FitSugar

A Little Sanskrit Lesson: Counting

FitSugar — Tue, 11 Sep 2007 02:30:00 -0700

The thing I love about Ashtanga yoga classes is that they are the same every time you go. Same poses, same order, same amount of breaths in each pose, and the class is always an hour and a half. There are no surprises, so you always know what to expect.

The teacher keeps everyone at the same pace by counting out loud. Many Ashtanga yoga instructors count in Sanskrit, the original language of yoga. Here are the numbers 1-10 written out, and what kind of breath you do for each one.

1: ekam (yekum) - Inhale
2: dve (dway) - Exhale
3: trini (treeny) - Inhale
4: catvari (chatwary) - Exhale
5: panca (pancha) - Inhale
6: sat (sut) - Exhale
7: sapta (supta) - Inhale
8: astau (ashtow) - Exhale
9: nava (nawa) - Inhale
10: dasa (dasha) - Exhale

Here is Pattabhi Jois (the father of Ashtanga Yoga) teaching Second Series with 6 students following. You can here him count in Sanskrit to get in and out of poses, but he counts the 5 breaths in English during the pose. Check it out.

Fit's Tips: Second Series is very challenging, and traditionally taught after mastering Primary Series, so don't be turned off by these difficult poses. If you've never tried an Ashtanga yoga class, take Primary Series first. You'll start off slow and build your way up when your body is ready.

Ashtanga Yoga: Why Avoid Drinking Water?

FitSugar — Tue, 21 Aug 2007 09:30:00 -0700

If you've ever walked into an Ashtanga Yoga class, I'm sure you've noticed that it's warm in the room, but not even close to as hot as Bikram. The warmth helps your muscles to loosen up slightly, but the quick-paced and strength building vinyasas between poses is what really heats up your body. Think of it as creating an inner fire that heats your body from the inside out, which helps you loosen up tight muscles. It also makes you sweat a lot, which helps in detoxification.

Drinking water during the practice prevents that heat and puts that internal fire out. Not only that, but if you stop every 10 minutes to take a sip of water, you interrupt your breathing and the flow of the sequence, which in turn will disrupt the moving meditation you've got going on.

It is very important to drink 10-12 glasses of water throughout the day so that you are well hydrated by the time you arrive at class. If you've been drinking all day, you shouldn't need to drink during class, however, if you are feeling nauseous, overheated, or dizzy - definitely listen to your body and drink water if necessary.

Fit's Tips: Depending on the class you go to, some Ashtanga Yoga instructors are very strict about this, which I personally don't agree with. As an instructor myself, I trust that my students are better able to make decisions about their own bodies. If an instructor you take class from makes you feel uncomfortable about your need for water (or anything else for that matter), talk to them after class about it. I'm sure they'd want to know how you feel.

Source

Move it at Home: David Swenson's Ashtanga Yoga: First Series

FitSugar — Fri, 26 Jan 2007 14:00:00 -0800

David Swenson is an incredibly well-known yoga instructor and practitioner. He began practicing when he was 13 and was introduced to Ashtanga at 19 by David Williams and Nancy Gilgoff (also very well known). Plus he studied with K. Pattabhi Jois, the master of Ashtanga.

His DVD, Ashtanga Yoga: First Series, available through Amazon for $24.95, is wonderful whether you are first learning or have been practicing for years.

There's a 30 minute intro explaining the foundations of the practice. Immediately following is the complete fully guided First Series, in the traditional flowing rhythm essential to Ashtanga Yoga. Ending with a guided deep relaxation, the series is about 1 1/2 hours long.

David's delivery of the basic principles is clear and down-to-earth. It's easy to follow along, and I love that he offers modifications so all levels of yogis will be able to follow along.

I definitely recommend this video if you want to learn First Series, or if you've already fallen in love with it. It's challenging both physically and mentally, yet very rewarding.

Class Act: Ashtanga Yoga's Primary Series

FitSugar — Mon, 04 Dec 2006 03:00:00 -0800

When you go to an Ashtanga Yoga class for the first time, you'll probably be learning Primary Series. In Sanskrit it is known as "Yoga Chikitsa" which means Yoga Therapy. Its purpose is to re-align the spine, detoxify the body, build strength, and increase flexibility.

The room is about 80°F, so your muscles can easily warm up. The instructor talks you though each pose and counts the breaths, so everyone is moving together in unison. (It's pretty amazing to see and experience.) The class is the same every time and anywhere. So if you love Primary Series, you can even find a class when you're travelling.

The basic sequence is as follows:

5 Sun Salutation A
5 Sun Salutation B
Standing Postures
Seated Postures
Closing Sequence (inversions and backbends)
Savasana (10 minute relaxation)

Want to know what makes it different from other kinds of Yoga? Then read more

The poses are linked together with vinyasas, or mini-Sun Salutations. Your breath (called ujayi) is loud and throaty, kind of like Darth Vader. Each inhale and exhale is linked to a movement, so Primary Series is a moving meditation, kind of like a dance.

Primary Series is excellent for runners, bikers, skiers, and riders because it involves a ton of forward bends to help loosen up your tight hips, hamstrings and the lower back. You warm up your muscles, really work them, and sweat a river. It's really difficult physically, so at the end of the 1 1/2 hour class, when you're lying in Savasana, you feel like you have taken quite a journey.

Fit's Tips: So you don't feel overwhelmed, it's a good idea to check out the poses ahead of time. Many studios encourage you to watch a class first. Or you can check out these helpful guides to learn the poses, and find out more about Ashtanga Yoga in general.

Strike a Yoga Pose: Seated Half Bound Lotus

FitSugar — Mon, 03 Aug 2009 10:00:41 -0700

Most of us suffer from stiff hamstrings and hips, so here's a pose that will increase flexibility in both. It's one of the seated postures in Ashtanga Yoga's Primary Series, and although it looks pretty basic, being in half lotus can be very challenging for those with tight hips.

Sanskrit Name: Ardha Baddha Padma Paschimottanasana
English Translation: Half Bound Lotus Western Intense Stretch Pose
Also Called: Seated Half Bound Lotus

To learn how to do this forward bend variation read more.

Begin sitting on the mat with both legs straight out in front of you. Bend your right knee and pull your right heel into half lotus, so it's in front of your left hip. Sit up tall and reach your right arm around your lower back and clasp your big toe with the first two fingers and thumb.

Now fold at your waist, rest your torso on your left thigh, and hold your left foot with your left hand. Lower your nose or forehead to your shin. As you breathe, continue to reach the crown of your head toward your left foot. This will help to lengthen the spine.
Be sure to relax your shoulders as you take five deep breaths. Then lift your torso up, release your right leg, take a vinyasa and do this pose with the left leg in half lotus.

Brain tumors - primary

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Causes
Prognosis
Diagnosis
Common Brain Tumors
Treatment
Surgery
Radiotherapy
Chemotherapy
Other Treatments
Treatment of Complications...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Radiation Therapy Complications

Radiation therapy in children with cancer increases the risk of new brain and spinal cord tumors, suggests a study in the Journal of the National Cancer Institute. The risk appears to increase along with the radiation dosage. Children who receive radiotherapy before age 5 are especially at risk for second primary tumors.
Survivors of childhood brain tumors who received cranial radiotherapy as part of their treatment are at risk for later having a stroke, indicates a study in the Journal of Clinical Oncology. The average length of time from brain tumor diagnosis to post-treatment stroke was 14 years.

Radiation Therapy for Elderly Patients

Radiotherapy provides modest improvement in survival for elderly patients (age 70 years and older) with glioblastoma, with no detriment to quality of life or cognition function, according to a 2007 study in the Journal of the American Medical Association.

Temozolomide (Temodar)

The chemotherapy drug temozolomide (Temodar) has become an important and effective treatment for patients newly diagnosed with glioblastoma. However, not all patients respond equally well to this drug. A 2007 study in the journal Neurology suggests that a patient’s genotype may explain differences in response. Though genetic testing, researchers found that temozolomide works best in people who are missing a particular gene.

Investigational Treatments

Vorinostat (Zolinza), a cancer drug used for T-cell lymphoma, may help patients with recurrent glioblastoma multiforme, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin), a targeted therapy drug used for lung and colorectal cancers, may help prolong survival in patients with advanced glioma, indicates a 2007 study in Clinical Cancer Research. Another anti-angiogenesis drug, cediranib (Recentin), may help make glioblastomas more responsive to chemotherapy and radiotherapy, according to recent interim trial results.
Vitespen (Oncophage), an experimental vaccine for glioma, is showing promise in early clinical trials, suggests research presented at the 2007 meeting of the American Association of Neurological Surgeons.

Introduction

Brain tumors are composed of cells that exhibit unrestrained growth in the brain.

The major areas of the brain have one or more specific functions.

They can be benign (noncancerous, meaning that they do not spread elsewhere or invade surrounding tissue) or malignant (cancerous).

Cancerous brain tumors are further classified as either primary or secondary tumors. Primary tumors start in the brain, whereas secondary tumors spread to the brain from another site such as the breast or lung. (In this report, the term "brain tumor" will refer mainly to primary malignant tumors, unless otherwise specified.)

Benign tumors represent half of all primary brain tumors. Their cells look relatively normal, grow slowly, and do not spread (metastasize) to other sites in the body. Benign tumors can still be serious and even life-threatening if they are in vital areas in the brain where they exert pressure on sensitive nerve tissue or if they increase pressure within the brain. While some benign brain tumors may pose a health risk, including risk of disability and death, most are usually successfully treated with techniques such as surgery.

Click the icon to see an image of a primary brain tumor.

A secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Usually, multiple tumors develop. Solitary metastasized brain cancers may occur but are less common. Most often, cancers that spread to the brain to cause secondary brain tumors originate in the lung, breast, kidney, or from melanomas in the skin.

A primary malignant brain tumor is one that originates in the brain itself. Although primary brain tumors often shed cancerous cells to other sites in the central nervous system (the brain or spine), they rarely spread to other parts of the body.

Brain tumors are generally named and classified according to the following:

The normal brain cells from which they originate, or
The location in which the cancer develops

The biologic diversity of these tumors, however, makes classification difficult, and some experts believe that more specific categories are needed.

About half of all primary brain tumors are known collectively as gliomas. They are cancerous forms of glial cells, the building-block cells of the connective, or supportive, tissue in the central nervous system. There are several glial cells types from which gliomas form. Their names are:

Astrocytomas are primary brain tumors derived from astrocytes, which are star-shaped glial cells. Normal astrocytes provide nutrients, support, and insulation for nerve cells and are one of the primary neurologic cells in the body. The malignant astrocytomas called glioblastomas account for 23% of brain tumors and are the most common ones.
Oligodendrogliomas develop from oligodendrocyte glial cells, which form the protective coatings around nerve cells. Although oligodendrogliomas were thought to represent about 5% of all gliomas, more recent evidence suggests they may comprise about 20% of gliomas. Pure oligodendrogliomas, however, are rare. In most cases they occur in mixed gliomas.
Ependymomas are derived from ependymal cells, which line the ventricles (fluid-filled cavities) in the lower part of the brain and the central canal of the spinal cord. They constitute about 6% of all primary tumors in the central nervous system. About 30% of these tumors occur in the spinal cord.
Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

It should be noted that gliomas may also contain cancer cells derived from brain cells other than glial cells.

Some brain tumors are categorized by their location in the brain. Such tumors often contain gliomas but are also frequently a mixture of different cell types.

Meningiomas. Meningiomas are usually benign tumors that develop in the membranes that cover the brain and spinal cord (the meninges).

Click the icon to see an image of the meninges.

They are not technically classified as brain tumors, but they have similar symptoms and develop within the brain. So in practical terms, they are considered brain tumors. In fact, meningiomas comprise 20% of all primary brain tumors. They occur more often in women than in men. Most grow very slowly, and the majority of people who have them never know they are present. Malignant forms called anaplastic meningiomas and hemangiopericytomas are less common and are difficult to remove surgically.

Cerebral Astrocytomas. Gliomas that develop inside the brain often occur in the cerebral hemispheres (the right and left sides of the brain). In such cases, they are referred to as cerebral astrocytomas. Gliomas sometimes occur in another part of the brain, called the cerebellum. The cerebellum is responsible for balance and coordination. In such cases, the term cerebellar astrocytoma is used.

Click the icon to see an image of the function of the left cerebral hemisphere.

Click the icon to see an image of the function of the right cerebral hemisphere.

Brain Stem Gliomas. Brain stem gliomas develop in the lowest portion of the brain. The brain stem connects the cerebrum (the higher centers of the brain) to the spinal cord. The brain stem is thought to be the primitive brain because it controls the most basic functions.

Click the icon to see an image of the function of the brainstem.

The brain stem consists of three primary parts:

The medulla regulates breathing, swallowing, blood pressure, and heart rate.
The pons links the cerebellum to the cerebrum.
The midbrain helps control vision and hearing.

Click the icon to see an image of the structures of the brain.

Medulloblastomas. Medulloblastomas are always located in the cerebellum, which is at the base and toward the back of the brain. They represent about 3% of all brain tumors.

Click the icon to see an image of the function of the cerebellum.

Pituitary Tumors. Pituitary tumors comprise about 10% of primary brain tumors and are often benign, slow-growing masses in the pituitary gland.

Click the icon to see an image of the pituitary gland.

Other Brain Tumor Locations. Optic nerve gliomas occur in the optic nerve, which is located behind the eye. Acoustic neuromas make up 7.5% of brain tumors.

Click the icon to see an image of the optic nerve.

Symptoms

Brain tumors produce a variety of symptoms, ranging from headache to stroke. They are great mimics of other neurologic disorders. Symptoms occur if the tumor directly damages the nerves in the brain or central nervous system or if its growth imposes pressure on the brain. Some gliomas develop gradually, and symptoms may be subtle for a long time, making an early diagnosis difficult.

Headache is probably the most common symptom of a brain tumor. It should be strongly emphasized, however, that everyone has headaches, and they rarely represent an underlying brain tumor. Headaches caused by brain tumors may vary depending on the location, and many different features.

Steady and worse upon waking in the morning and clears up within a few hours
Persistent non-migraine headache that occurs while sleeping and is also accompanied by at least one other symptom (such as vomiting or confusion)
May or may not be throbbing, depending on location of the tumor
Accompanied by double vision, weakness, or numbness
May worsen with coughing or exercise or with a change in body position
Sometimes accompanied by neck pain

Gastrointestinal symptoms, including nausea, are also common. Nausea and vomiting, in fact, often occur in children with brain tumors and in all people with brain stem cell tumors.

Seizures occur in between 15 - 95% of patients, depending on the location of the tumor.

Tumors are more likely to be localized and affect one area of the brain. In such cases they can cause partial seizures. In this case, a person does not lose consciousness but may experience confusion, jerking movements, tingling, or odd mental and emotional events.
Generalized seizures, which can cause loss of consciousness, are less common, since they are caused by disturbances of nerve cells in diffuse areas of the brain.

Sometimes the only symptoms are mental changes, which may include the following:

Memory loss
Impaired concentration
Problems with speech and reasoning
Increased sleep

Gradual loss of movement or sensation in an arm or leg
Unsteadiness
Unexpected visual disturbance (especially if it is associated with headache), including vision loss (usually of peripheral vision) in one or both eyes or double vision
Hearing loss with or without dizziness
Speech difficulty

Specific symptom syndromes may help identify the tumor. The following are some examples.

Symptoms of Brain Stem Gliomas. Sudden onset of symptoms that include vomiting (usually just after waking), a clumsy walk, muscle weakness on one side of the face, difficulty in swallowing, slurred or nasal speech, as well as impaired hearing or vision.

Symptoms of Glioblastoma Multiforme. Rapid onset and worsening of symptoms that include headaches, seizures, memory loss, and changes in behavior.

The below symptoms indicate an emergency condition and require immediate medical attention:

Pupil dilation
A fixed gaze
Paralysis on one or both sides of the body
Blindness or defective vision in one eye

Risk Factors

Nearly 360,000 people in the U.S. are living with brain cancer. Men are at higher risk than women for most brain tumors. Primary malignant brain tumors are still uncommon and represent only 1.3% of all cancers diagnosed in the United States and 2.4% of all deaths due to cancer.

Primary brain cancers are rare, occurring in slightly more than 11 people per 100,000 per year. There has been some evidence of a growing incidence of brain cancer among the elderly since the 1980s. The increase, however, is most likely due to the rise in incidence of non-Hodgkin's lymphomas -- which can occur in the brain. When this malignancy is eliminated, any increase in other tumors is not significant.

The average age of diagnosis for brain tumors is 57, and about 90% of primary brain tumors occur in adults. These tumors can develop at all ages, usually peaking in two age groups.

In adults, ages 55 - 65
In children, ages 3 - 12

Risk Factors in Children. Tumors in the central nervous system are now the most common primary cancers in children, but they are still rare. An estimated 3,110 benign or malignant brain tumors are expected to be diagnosed in children each year. Brain tumors in children are more likely to occur in the cerebellum, the midbrain, or the optic nerve.

The incidence has increased over the past years, but there is some evidence that this increase is only due to better diagnostic procedures. The mortality rate has actually decreased. Researchers have attempted to uncover risk factors for childhood brain cancer. There may be some association between a higher risk and the following conditions:

Children treated with radiation to the head for leukemia and who have a specific genetic defect may face a high risk for brain cancer. (It should be noted that for children without this defect, the risk is very small.)
Having parents with specific cancers. (According to one study, having parents with nervous system cancers, colon cancer, or cancer in the salivary glands increased the risk of specific brain tumors in their children.)

Click the icon to see an illustrated series detailing colon cancer surgery.

The risk for primary brain tumors in Caucasians is higher -- as much as twofold depending on type -- than in African-Americans.

Radiation Exposure. People who receive radiation therapy to the head during cancer treatment have an increased risk of developing brain tumors 10 - 15 years later. Workers in the nuclear industry are also at increased risk.

There is no evidence that electromagnetic field exposure from power lines or household appliances poses any risk. Several recent epidemiological studies, including a 2006 study in the British Medical Journal, found that cell phones, cordless phones, and wireless devices are also safe and do not increase the risk for gliomas.

Chemical and Metals in Brain Tumors. High exposure to numerous metals and chemicals have been associated with brain tumors:

Industrial chemicals, including vinyl chloride and petroleum products
Lead, arsenic, or mercury exposure
Exposure to pesticides. A major study of pesticides is underway, but results are not in yet. A 2003 study indicated that parental exposure to pesticides or herbicides did not appear to be important in increasing risk for brain cancer in their children.

Brain cancer is uncommon, and, over the course of their lifetime, many people are exposed to these chemicals, many of which are very common. To date, there has been no clear evidence that implicates any specific industrial chemical or metal.

One study reported a higher risk for brain cancers in patients who had undergone organ transplantations. Researchers believed that the drugs used to suppress the immune response after the procedures may increase the risk.

One study reported lower risks for brain cancers in individuals with allergies and autoimmune diseases (such as type 1 diabetes). Autoimmune diseases were also associated with a lower risk for meningiomas. The cause of this possible association remains unknown.

Studies have also found an association between lower risk for gliomas and a history of infection with varicella zoster, the virus that causes chicken pox and shingles.

Click the icon to see an image of the chicken pox.

Causes

Only 5 - 10% of primary brain tumors are associated with genetic disorders. These inherited conditions and associated genes include:

Von Recklinghausen disease, also called neurofibromatosis 1 (NF1 gene) and neurofibromatosis 2 (NF2 gene)
Turcot's syndrome (APC gene)
Gorlin syndrome, also called basal cell naevus syndrome (PTCH gene)
Tuberous sclerosis (TSC1 and TSC2 genes)
Li-Fraumeni syndrome (TP53 gene)

Certain types of brain tumors are specifically linked with these genetic conditions. For example, neurofibromatosis 1 is associated with about 15% of cases of pilocytic astrocytomas, the most common type of childhood glioma. Neurofibromatosis results from defects in the tumor suppressor genes NF1 and NF2. Li-Fraumeni syndrome results from mutations in the tumor suppressor gene TP53. These mutations affect the production of tumor suppressor protein p53.

Tumor suppressor genes regulate cell division and help repair DNA damage. When mutations that affect protein encoding occur, unregulated cell division and growth can lead to the development of a tumor. Tumor suppressor genes are sometimes described as being in a tug-of-war with cancer-causing genes called oncogenes. Oncogenes derive from mutations or overexpressions of proto-oncogenes. Proto-oncogenes encode for proteins that regulate cell growth and differentiation. When proto-oncogenes become oncogenes, normal cells start to grow uncontrollably. Cancer can occur when tumor suppressor genes are turned off, or when oncogenes are turned on.

Many different oncogenes are involved in cancer. Growth factors are a particularly important type of oncogene associated with brain tumors. Growth factors attach to receptors (connectors) that stimulate cell growth. Epidermal growth factor receptor (EGFR) has been shown to play a role in high-grade brain tumors such as glioblastoma multiforme. In 2007, scientists identified insulin-like growth factor binding protein (IGFBP2) with an oncogene that may be associated with the development of astrocytoma and oligodendroglioma.

Knowing the molecular origin of a brain tumor may help determine the treatment course, both for standard chemotherapy and "targeted therapy" biologic drugs. For example, patients with tumors marked by high EGFR proliferation may benefit from treatment with the EGFR kinase inhibitor drugs gefitinib (Iressa) or erlotinib (Tarceva).

Most genetic abnormalities that cause brain tumors are not inherited but occur as a result of environmental or other factors that affect genetic materials (DNA) in the cells. Researchers are studying various environmental factors (viruses, hormones, chemicals, radiation) that may trigger the genetic disruptions that lead to brain tumors in susceptible individuals. They are also working to identify the specific genes that are affected by these environmental triggers. For example, in a 2007 study, scientists proposed that genetic susceptibility may explain why some people develop meningioma, a rare type of brain tumor, following exposure to ionizing radiation. Future investigations will hopefully identify the specific genes involved and help determine which people would potentially be most at risk.

Prognosis

About 13,100 people die from cancerous brain tumors each year. Recent advances in surgical and radiation treatments have significantly extended average survival times and can reduce the size and progression of malignant gliomas. In general, survival rates are highest in younger people and lowest in the elderly.


Age	Survival Rates
0 - 19 years	63.1%
20 - 44 years	50.4%
45 - 64 years	14.2%
Over 65	4.9%
Data From: 2002 - 2003 Primary Brain Tumors in the United States Statistical Report. Fact Sheet (1973- 1999 data). Brain Tumor Registry of the United States www.cbtrus.org/factsheet/factsheet.html.

In general, studies are reporting that patients who survive the first 2 years after a diagnosis of a brain tumor have at least a 70% chance of surviving for at least 5 years. The best recent progress has been made for:

Medulloblastomas in both children and adults. Long-term survival rates are now about 60% in children after treatment for medulloblastomas, the most common malignant brain tumor in this age group. (New treatments, however, may significantly improve these rates.)
Nonmalignant astrocytomas and oligodendrogliomas in adults.

Unfortunately, the majority of primary brain tumors, notably anaplastic astrocytomas and glioblastoma multiforme, are only rarely curable.

The specific effects of tumors on the brain can cause seizures, mental changes, and mood, personality, and emotional changes. Such effects can be devastating to the patient and the caregivers. Numerous treatments are available that help alleviate these complications, and patients and family members should discuss these with their doctors.

Diagnosis

A neurological exam is usually the first test given when a patient complains of symptoms that suggest a brain tumor. The exam includes checking eye movements, hearing, sensation, muscle movement, sense of smell, and balance and coordination. The doctor will also test mental state and memory.

X-rays of the skull were once standard diagnostic tools but are now performed only when more advanced procedures are not available. Advanced imaging techniques have dramatically improved the diagnosis of brain tumors in recent years.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is the gold standard for diagnosing a brain tumor. It does not use radiation and provides pictures from various angles that can enable doctors to construct a three-dimensional image of the tumor. It gives a clear picture of tumors near bones, smaller tumors, brainstem tumors, and low-grade tumors. MRI is also useful during surgery to show tumor bulk, for accurately mapping the brain and for detecting response to therapy.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI creates a three-dimensional picture of the brain, which allows doctors to more precisely locate problems such as tumors or aneurysms.

A variant called magnetic resonance spectroscopy (MRS) is capable of providing information on the activity of the brain using magnetic resonance imaging. MRS is proving to be accurate for distinguishing dead (necrotic) tissue caused by previous radiation treatments from recurring tumor cells in the brain, a difficult diagnostic issue.

Computed Tomography. Computed tomography (CT) uses a sophisticated x-ray machine and a computer to create a detailed picture of the body's tissues and structures. It is not as accurate as an MRI and does not detect about half of low-grade gliomas. It is useful in certain situations, however. Often, doctors will inject the patient with an iodine dye, called contrast material, to make it easier to see abnormal tissues. A CT scan helps locate the tumor and can sometimes help determine its type. It can also help detect swelling, bleeding, and associated conditions. In addition, computed tomography is used to check the effectiveness of treatments and watch for tumor recurrence.

Click the icon to see an image of a CT scan of the brain.

Positron Emission Tomography. Positron emission tomography (PET) provides a picture of the brain's activity rather than its structure by tracking substances that have been labeled with a radioactive tracer. As with magnetic resonance spectroscopy (MRS), it is also able to distinguish between recurrent tumor cells from dead cells or scar tissue, although MRS is more widely available. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. Data from PET may also help improve the accuracy of newer radiosurgery techniques.

Other Imaging Techniques. Numerous other advanced imaging techniques may be used for specific purposes, if available or under investigation.

Single photon emission tomography (SPECT) is similar to PET but is not as effective in distinguishing tumor cells from destroyed tissue after treatments.
Magnetoencephalography (MEG) scans measure the magnetic fields created by nerve cells as they produce electrical currents.
Cerebral angiography involves x-rays of blood vessels in the brain. A long, thin tube (catheter) is threaded through blood vessels from a distant site to the brain, and a radiopaque substance (a substance that is impenetrable to x-rays) is injected through it. The role of angiography in glioma is usually limited to planning surgical removal of a tumor suspected of having a large blood supply.
Radionuclide brain scintigraphy uses a radioactive substance that is administered and absorbed by capillaries in the tumor, which are then viewed using imaging techniques.
Digital holography, a new technique that provides full three-dimensional mapping, is under investigation.

A lumbar puncture is used to obtain a sample of spinal fluid, which is examined for the presence of tumor cells. A computed tomography (CT) scan or magnetic resonance imaging (MRI) should generally be performed before a lumbar procedure to be sure that the procedure will be safe.

Click the icon to see an image of a lumbar puncture.

A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor and examined under a microscope for malignancy. The results of the biopsy also provide information on the cancer cell type.

In some cases, such as brain stem gliomas, a biopsy might be too hazardous because removing any healthy tissue from this area can affect vital functions. In such cases, diagnosis must rely on less invasive and possibly less accurate measures. Of promise is the stereotactic technique (also called stereotaxy), which uses computers to provide three-dimensional views of very small areas. This may allow precise biopsies of cancer cells without affecting healthy brain tissue. Expertise in this technique is extremely important, however, and the technique is not widely available.

The survival rates in people with brain tumors depend on many different variables:

Whether the tumor is malignant or benign
Cancer cell type and location (location affects whether the tumor can be removed surgically or not)
The tendency to spread and the growth rate (tumor grade)
Patient's age
Patient's ability to function
Duration of symptoms

The outlook is poorer in the very youngest and very oldest patients, although younger patients who survive 2 years after diagnosis have a much better outlook than older patients.

Grading Tumors. Malignant primary brain tumors are classified according to tumor grade. Grade I is the least cancerous, and Grades IV and V are the most dangerous. Grading a tumor attempts to predict its tendency to spread and its growth rate. It is based on the appearance of the tumor cells as seen under a microscope.

Lower-grade (I and II) tumor cells are well defined and almost normal-shaped. (Some primary low-grade brain tumors are curable by surgery alone, and some are curable by surgery and radiotherapy. Low-grade tumors tend to have the most favorable survival rates and high-grade the least. However, this is not always the case. For example, some low-grade II gliomas are at very high risk for progression.)
Higher-grade (III and IV) tumor cells are abnormally shaped and are more diffuse, which indicates more aggressive behavior. (High-grade brain tumors usually require surgery, radiotherapy, chemotherapy, and possibly investigational treatments.)
In tumors that contain a mixture of different-grade cells, the tumor is graded using the highest-grade cells in the mixture, even when there are very few of them.

Biologic Markers. Elevated levels of certain cancer-associated molecules or compounds may be correlated with prognosis. For example, evidence of genetically mutated p53 indicates a poorer prognosis in younger patients with glioblastoma multiforme.

Elevations of epidermal growth factors (EGF) or vascular endothelial growth factors (VEGF) suggest aggressive tumors. High levels of the receptor for EGF (EGFR), in fact, are found in 70% of glioblastoma specimens.

Genetic Profiles of Cancer Cells. Analyses that identify genetic types may soon help clinicians determine if patients with specific brain tumor cells might respond better to one treatment than another. For example, specific genetic profiles of oligodendrogliomas can help predict how patients respond to nitrosourea alkylating drugs such as carmustine. Genetic variation tests are also being used to determine how patients may respond to epidermal growth factor receptor (EGFR) kinase inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa).

A genetic profile can also help give doctors a better idea of a patient’s prognosis and survival. In a 2006 study of patients with anaplastic oligodendroglioma, the status of specific chromosomal deletions within tumors was a better predictor of survival than which kind of treatment patients received. In fact, the researchers suggested that gliomas be classified according to chromosomal deletion status, and recommended that chromosomal testing be a regular part of diagnosis and treatment decisions.

Common Brain Tumors


GENERAL DESCRIPTION OF ASTROCYTOMAS: Derived from star-shaped glial cells called astrocytes.

Low-Grade (Usually I) Astrocytomas. Pilocytic gliomas.	Pilocytic gliomas occur mostly in children. Tumors are well differentiated. Cells are relatively normal and rarely metastasize. They grow relatively slowly. Pilocytic astrocytomas have the highest 5-year survival rates (greater than 70%). However, even well differentiated astrocytomas are life threatening if they are inaccessible.	Cancer may sometimes be completely removed through surgery, particularly if it occurs in the cerebellum. For recurrence or residual tumors, reoperation, radiotherapy, or chemotherapy may be given, depending on the circumstances. Repeat surgery for cerebellar astrocytoma is often very successful. For those who fail radiotherapy and chemotherapy, investigative drugs are used.
Low-Grade (II) Astrocytomas. Fibrillary, protoplasmic, and protoplasmic astrocytomas. Some pleomorphic xanthoastrocytomas.	Tumors are well differentiated. Cells are relatively normal and less malignant than those in higher grades. They grow relatively slowly but can spread. Survival rates average 5 years, but people can survive for a decade or more. Pleomorphic xanthoastrocytomas have a relatively favorable prognosis, but can recur and demonstrate aggressive clinical behavior. Low-grade astrocytomas generally occur in young adulthood, with a peak incidence in 30s and 40s.	Surgery, if possible, plus radiotherapy. Surgery alone in certain children, if possible. Trials on postoperative radiotherapy include the following: radiotherapy with or without chemotherapy; low-versus-high radiotherapy doses (studies suggest results are the same and high-dose causes more side effects); deferring radiotherapy until tumor progresses and symptoms occur. (A major study confirmed earlier ones that suggest that this approach has the same 5-year survival benefits -- about 65% -- as immediate postoperative radiotherapy.)
Malignant (High-grade III and IV) Astrocytomas. Anaplastic astrocytoma (gemistocytic and some pleomorphic xanthoastrocytomas). Usually mid-grade (III).	Tumors grow more rapidly than lower grades and infiltrate other nearby healthy cells. Not well-differentiated. Five-year survival rates are about 30%. Recurrence is common.	Treatment same for all high-grade malignant astrocytomas. Surgery, with removal of as much of tumor as possible followed by radiotherapy, with or without chemotherapy. The addition of chemotherapy, particularly being able to take more than 6 cycles, appears to improve survival rates. Carmustine (BCNU) most effective drug at this time. Other drugs and treatment sequences are under investigation. For example, temozolomide is showing promise for many patients, including the elderly. Topotecan may also be useful with other drugs or with radiation. For recurring gliomas, surgery with placement of wafers that release carmustine (Gliadel wafers) is the only proven beneficial therapy to date. Combinations, such as procarbazine and carmustine, provide benefits for recurrent anaplastic astrocytomas. Single drugs may be less toxic and as helpful for other recurrent gliomas. Temozolomide has been approved in Europe for high-grade recurrent gliomas and is proving to be beneficial. Other trials include the following: drugs that block small molecules involved in tumor growth; radioimmunotherapy using monoclonal antibodies; advanced radiotherapy techniques; intraarterial chemotherapy.
High-grade (IV and V). Glioblastoma (notably glioblastoma multiforme or GBM).	Very rapidly growing tumors that spread quickly. Represents about 25% of all primary brain tumors. Most common in older adults (over age 55) and affect more men than women. Recurrences are common in patients who achieve long-term survival.


GENERAL DESCRIPTION OF EPENDYMOMAS: Derived from cells that line the ventricles (fluid-filled brain cavities) and spinal cord central canal. Do not usually spread into normal brain tissue. Can block exits for cerebrospinal fluid and cause hydrocephalus. They constitute about 4% of all central nervous system tumors in adults and 10% of these tumors in children. About 30% of ependymomas develop in the spinal column.

Low-grade (I). Myxopapillary ependymoma (found in the spine). Subependymoma (found in one of the ventricles).	No or very slow growth. In addition to grade, risk is also based on location of the tumor. Tumors on the spinal cord are more accessible than those in the fourth ventricle or in the middle of the lower back portion of the brain.	Can often be removed and cured with surgery, particularly those on spinal cord. Radiation may be needed. Chemotherapy (avoid radiation, if possible) in children under age 6).
Low-grade (II). Papillary, cellular, and clear cell ependymomas.	Slow growth. Usually affect adults.	Surgery alone or followed by radiotherapy. For those who fail radiotherapy, possible use of nitrosourea-based chemotherapies or investigative drugs.
Grade III. Anaplastic ependymomas.	Spreads to the spinal fluid.	Surgery followed by radiotherapy to brain and spinal cord. Possible shunt.
Grade IV. Primitive neuroecto-dermal tumor (PNET). Composed of malignant forms of early, undeveloped nerve cells called neuroblasts. (This malignancy is also referred to as neuroblastoma.)	Very rare, but more common in children. Primitive nerve cells that grow very rapidly. Usually occur in cerebellum.	Surgery followed by radiotherapy to brain and spinal cord. Chemotherapy in young children. Investigative high-dose chemotherapy with stem cell rescue for children with relapsed cancer.


DESCRIPTION OF OLIGODENDROGLIOMAS: They develop from oligodendrocyte glial cells. These cells form the protective coatings around nerve cells. Pure cell types are rare. Most often occur in mixed gliomas. Categorized as either low- or high-grade. Most are low-grade II.

Low-grade: Low grade difficult to tell from astrocytomas, although they are usually calcified. Very likely to bleed. Usually spread along nerve pathways of the brain and spine and rarely outside this area. In spite of difficulty in removing surgically, in some patients survival can be 30 - 40 years. Usually have better prognosis than astrocytomas of equal grade. Occur mostly in middle-aged adults, although there is also a small peak of incidence in children.	Treatment usually delayed until progression causes symptoms. Surgery to remove whole tumor. Radiotherapy often follows in all adults over age 40 or in anyone in which tumor cannot be completely removed. Solid evidence is lacking on this approach, however, and there is some debate on its benefits. Trials using chemotherapy after radiation are promising. Two-thirds of patients respond to PCV (combination of procarbazine, lomustine and vincristine.) Sustained remissions averaging 16 years often achieved. Pure oligodendrogliomas respond better than mixed gliomas. Temozolomide is showing promise as second-line treatment. Others under investigation. Trials of additional chemotherapy for less well-differentiated tumors or for residual tumors after surgery.
High-grade. Anaplastic oligodendrogliomas.	Immediate treatment. Surgery to remove the whole tumor, if possible. Radiation typically follows surgery. Chemotherapy treatments either before or with radiation. Standard drugs are limited. Experts recommend trying investigative drugs. Temozolomide and retinoic acid may be useful. Possible additional drugs include melphalan, thiotepa, carboplatin, cisplatin, and etoposide. (Numerous biologic markers may help identify specific oligodendrogliomas that will respond better or worse to specific treatments.)


GENERAL DESCRIPTION OF MIXED GLIOMAS: Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

Grade determined by the highest-grade cell present in the tumor.	Same as for oligodendroglioma.



Meningiomas	They are found in the membranes around the brain and spinal column. They are usually benign and rarely invasive. In such cases, long-term outlook is very favorable. (Malignant forms, anaplastic meningiomas, and hemangiopericytomas are uncommon and occur in about 2% of cases.)	Usually watchful waiting. Aggressive surgery the treatment of choice, if possible, although 20% recur after 10 years. Malignant forms and those at the base of the skull difficult to impossible to remove surgically. Stereotactic radiosurgery or fractionated external beam radiotherapy showing promising results for some patients.
Cerebellar astrocytomas (located in cerebellum)	Located in the cerebellum. Usually low-grade, but depends on cell type. If surgical removal is complete, up to 90% survival rates. More common in children than adults.	Surgery primary treatment. Radiotherapy if removal is incomplete.
Brain Stem Gliomas	About 60 - 70% of brain stem tumors are diffuse, which are likely to spread and have a rapid onset of symptoms. Focal tumors tend to be solid or cyst-like. They generally develop gradually. Occurs in both children and young adults.	Radiation is usual treatment. Tumors in this area are rarely removed surgically since the nerve tissue in this area is responsible for vital life functions. Slow-growing tumors may only require watchful waiting. Trials using advanced radiotherapy techniques, gene therapy, immunotherapy, and other experimental drugs.
Medulloblastomas	Occurs in cerebellum (the lower portion of the brain), brainstem, and spinal cord. Usually fast-growing aggressive cells. Most common brain tumors in children and young people, causing between 15 - 20% of brain tumors. With aggressive therapy, in children 5-year survival rates between 60 - 80%. In patients who survive for 2 years after diagnosis, long-term survival rate is nearly 80%.	Treatment is usually surgery and radiotherapy followed by chemotherapy. A 2005 study found that a combination chemotherapy regimen may replace radiation for very young children. A 2006 study suggested that radiation and chemotherapy doses should be adjusted based on disease severity.
Optic Tract Gliomas	Spread along the optic nerve. Usually slow growing. Most often in children under age 10. Children with these tumors often have vision and hormonal problems.	Usually surgery if one eye is involved. Possible chemotherapy or radiation.

Treatment

The approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation treatment (also called radiotherapy), chemotherapy, or investigative procedures. Such treatments are used alone or, more commonly, in combinations. With some very slow-growing cancers, such as those that occur in the midbrain or optic nerve pathway, patients may be closely observed and not treated until the tumor shows signs of growth. The intensity, combination, and sequence of these treatments depends on the glioma subtype, its size and location, and patient age, health status, and medical history.

Recent advances in surgical and radiation treatments have significantly extended average survival times compared to those of standard therapy. Investigative treatments, such as monoclonal antibodies, are also showing promise. Patients or their caretakers should discuss all options thoroughly with a specialist in brain cancer. Different specialists may be needed to help manage symptoms.

Because of the low-cure rates of most malignant brain tumors, support for the patients and their families is a critical component of treatment and management. In response to one survey of patients with gliomas, experts made several recommendations to help both patients and caregivers:

Any physical impairment that could benefit from home equipment or physical therapy should be identified and treated.
Patients should discuss emotional as well as physical issues with their doctors. Depression, for instance, can be medically treated. Caregivers should also seek help for the inevitable stress, depression, and tension arising from their difficult role.
Relaxation techniques, meditation, and spiritual resources can be extremely helpful. Support groups are beneficial, but experts recommend separate groups for patients and their families.

Surgery

Surgery is usually the first step in treating most brain tumors. In some cases, however, such as most brain stem gliomas, it may be too dangerous to perform surgery. The object of most brain tumor surgeries is to remove or reduce as much of its bulk as possible. By reducing the size, other therapies, particularly radiotherapy, can be more effective. (Although there have been significant advances in brain surgeries, some experts argue that in high-grade gliomas extensive surgery may not improve survival rates at all and patients are best served by radiation therapy.)

The standard procedure is called craniotomy.

The neurosurgeon removes a piece of skull bone to expose the area of brain over the tumor.
The tumor is located and then removed.

Click the icon to see an illustrated series detailing craniotomy surgery.

There are various surgical options for breaking down and removing the tumor. They include:

Standard surgical procedures
Laser microsurgery (which produces great heat and vaporizes tumor cells)
Ultrasonic aspiration (which uses ultrasound to break the glioma tumor into small pieces, which are then suctioned out)

Relatively benign, grade I gliomas may be treated only by surgery. Some controversy exists over whether surgery for low-grade astrocytomas improves survival, although insufficient research has been conducted to prove its benefits for these gliomas. Most malignant tumors require additional treatments, including repeat surgery.

The surgeon's skill in removing the tumor as completely as possible is critical to survival. No one should be shy about asking the surgeon the number of similar procedures they have performed. (Asking for complication rates may not be useful, since a very experienced surgeon might operate on many high-risk patients.)

In most cancers outside the brain, surgical removal of a tumor usually involves taking out surrounding healthy tissue to be sure all cancer cells are gone. In the brain, however, removing healthy nearby nerve tissue can be as disastrous for the patient as the cancer itself. Special techniques have been developed to allow maximum removal of tumors while protecting healthy brain cells.

Stereotaxy. Stereotaxy has become a useful adjunct to both surgery (stereotactic surgery) and radiotherapy (stereotactic radiotherapy).

Cortical Localization. Cortical localization, or stimulation, uses a probe that passes a tiny electrical current to delicately stimulate a specific area of the brain. This produces a visible response of the body part (such as a twitch in a leg), which the stimulated region of the brain controls. The surgeon then knows to avoid those areas during the operation.

Image-Guided Surgery. Image guided surgery uses a three-dimensional picture of the patient's brain derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans. An advanced technique called high-field interventional MR imaging (iMRI) is particularly accurate in identifying the tumor, but it is not widely available. The image, with various views of the brain, is displayed on a monitor in the operating room. During surgery, as the surgeon's instrument touches a part of the brain, a camera sends the image to a computer, which calculates the position of the surgical tool and displays it in its proper location on the 3-D image. The surgeon then can look at the monitor and see what structures to avoid.

Magnetic-Tipped Catheters. Neurosurgeons are investigating a technique in which external magnetic fields direct a magnet-tipped flexible catheter to the tumor site through a path that avoids harming certain important areas of the brain.

Heparin. Heparin, a blood-thinning drug, should be given at the time of surgery to help prevent blood clots.

Radiotherapy

Radiotherapy plays a central role in the treatment of most brain tumors, whether benign or malignant.

Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may require radiation, since they may be life-threatening if their growth is not controlled.

Radiotherapy When Surgery Is not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.

Radiotherapy and Chemotherapy (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors.

Various radiation treatments are now available.

Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues 5 days per week for 6 weeks. Older adults tend to have a more limited response to external-beam radiation therapy than younger people. According to a 2007 study in the New England Journal of Medicine, radiotherapy leads to a modest improvement in survival in elderly patients (70 years or older) with glioblastoma, and causes few negative impacts on quality of life or cognition.

For tumors that are highly localized, the radiation therapist has a choice of other radiation treatments:

Brachytherapy (also called interstitial radiation) uses radioactive "seeds" implanted directly in the tumor site. It is used as a booster to external beam radiation for patients with malignant astrocytoma. Brachytherapy appears to prolong survival in some aggressive gliomas. It may also be a safe and effective treatment for some children.
Intensity-modulated radiation therapy (IMRT) uses high-dose radiation beams that conform to the three-dimensional shape of the tumor.
Hyperfractionated radiation uses many small radiation doses to deliver a high total dosage of radiation.
A balloon catheter (GliaSite) that delivers radiation to the tumor cavity after surgery is showing promise.

Stereotactic radiosurgery has been developed to allow highly targeted radiation to be delivered directly to the small tumors while avoiding healthy brain tissue. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife. Some studies suggest that stereotactic radiosurgery improves survival, even in patients with the highly aggressive glioblastoma multiforme brain cancer. The procedure is being tested to boost standard radiotherapy.

Benefits of Stereotaxy. There are numerous benefits for stereotaxy:

Stereotaxy allows precisely focused, high-dose beams to be delivered to gliomas less than 1.25 inch in diameter.
Investigators have found that stereotactic radiosurgery can help them reach small tumors located deep in the brain that were previously considered inoperable.
Sometimes with stereotaxy only a single treatment may be needed.
Unlike traditional radiotherapy, stereotactic radiotherapy can be repeated, so it is useful for recurrent tumors when a patient has already received standard radiation treatments.
Combining stereotaxy with techniques that gauge speech and other mental functions in patients who are awake during the procedure can allow removal of brain tissue with a lower risk for complications in areas that affect such functioning.

The Planning Procedure. Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:

First, the patient is given a local anesthetic. In the standard operation, the patient's head must be totally immobilized by screwing a device known as a stereotactic frame into the patient's skull. (The frame procedure is effective only on brain tumors that have regular margins.) The frame is removed as soon as the whole procedure has been completed (about 3 - 4 hours).
A three-dimensional map, usually using magnetic resonance imaging (MRI) scans, is made of the patient's brain.
A computer program calculates dosage levels and specific areas for radiation targeting.

Advanced imaging techniques are now allowing frameless stereotaxy, which eliminates the frame and may be effective on more tumors. For example, high-field interventional MR imaging (iMRI) uses a guidance system based on cruise-missile technology to calculate the slightest variations in movements of the head and the location of the tumor relative to these movements. These calculations are then used to target the radiation beams directly on the tumor, even if the patient's head is moving slightly.

Delivery of Radiation Beams. Once the preliminary planning stage has been completed, treatment begins. Several advanced machines, such as the gamma knife, adapted linear accelerator (LINAC), and cyclotron, are being used with stereotaxy and can deliver very focused beams of radiation. Actual treatment takes 10 minutes to 1 hour.

The gamma knife uses gamma rays that are sent from multiple points to converge at a single point on the tumor. Although each gamma-ray beam is very low dosage, when the beams converge, the intensity and destructive power is very high. The gamma knife is limited to very small tumors and so is generally useful as a booster after standard radiation, surgery, chemotherapy, or combinations.
The linear accelerator (LINAC) produces photons (positively-charged atomic particles) in patterns that are matched to the tumor shape. The patient is positioned on a bed that can be moved to allow flexible positioning. It allows treatment over multiple sessions of small doses (fractionated stereotactic radiotherapy), instead of a single session. This means that larger tumors can be treated.
The cyclotron is basically an atom smasher, which produces protons that can be directed toward the tumor. As part of this procedure, some researchers are using boron neutron capture therapy (BNCT). BNCT employs intravenous administration of a boron compound, which is picked up more selectively by tumor cells than by normal brain tissue. The cyclotron delivers a single dose of radiation that triggers the release of high-energy particles from the boron to destroy nearby tumor cells. The cyclotron is available only in a very few locations, and there have been few trials to date.

Researchers are studying drugs that may be used along with radiation to increase the effectiveness of the treatment.

Radioprotectors. Drugs such as amifosistine (Ethyol) may protect healthy cells during radiation.

Radiosensitizers. Drugs such as fluorouracil (5-FU) and cisplatin (Platinol) may help make cancerous cells more sensitive to radiation.

Common Side Effects. Side effects of radiotherapy may vary depending on the tumor type and radiation treatment. Side effects may include hair loss, fatigue, and nausea and vomiting. Skin irritation and sensitivity may develop in the areas being treated. To prevent further irritation, avoid scratching or rubbing, avoid direct sunlight and heating pads, and do not attempt to treat the symptoms yourself. (Ask your doctor or radiation therapist for advice.) Brain swelling (edema) is another common radiotherapy side effect, which can sometimes cause an increase in brain tumor symptoms. Edema can be treated with steroids.

Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in about 25% of patients treated with intensive radiation. Radiation necrosis can cause brain swelling and reduction in mental functions. The condition is treated with steroids. If steroids prove ineffective, surgery may be required to remove the damaged tissue.

New Tumors. Radiation therapy for childhood cancer is the most important risk factor for developing new brain and spinal column tumors, according to a 2006 study. The risk appears greatest for children who received radiation therapy before age 5. Researchers found that the risk of second primary tumors increased in relation to the radiation dose used to treat the first cancer.

Stroke. Survivors of childhood brain tumors who were treated with high doses of cranial radiation (especially doses greater than 50Gy) may be at increased risk of having a stroke later in life. In a study of nearly 2,000 brain tumor survivors, the average length of time from cancer diagnosis to stroke was 14 years.

Chemotherapy

Chemotherapy involves the use of drugs to kill or alter cancer cells. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs cannot pass through the blood-brain barrier, the functional system that protects the brain by preventing certain molecules from reaching the central nervous system. In addition, not all types of brain tumors respond to chemotherapy. In general, chemotherapy for brain tumors is usually administered following surgery or radiation therapy.

The type of drug determines how it is administered. "Systemic delivery" drugs, which pass to the brain from the bloodstream, may be given by mouth, injected into a vein through an IV, or injected into an artery or a muscle. "Local delivery" drugs are placed within or around the brain tumor.

Scientists are working on several approaches to overcome the blood-brain barrier. Newer delivery methods include:

Interstitial chemotherapy uses disc-shaped polymer wafers (known as Gliadel wafers) soaked with carmustine, the standard chemotherapeutic drug for brain cancer. The surgeon implants the wafer directly into the surgical cavity after a tumor is removed.
Intrathecal chemotherapy delivers chemotherapeutic drugs directly into the spinal fluid.
Intraarterial chemotherapy delivers high-dose chemotherapy into arteries in the brain using tiny catheters. In one study, this approach was used within 2 weeks of radiotherapy in patients with high-grade astrocytomas, and the survival rates for glioblastoma multiforme tripled (20 months) compared to those who had chemotherapy and radiation at the same time.
Convection-enhanced delivery (CED) involves placing catheters into the brain tumor or nearby brain tissue to deliver slowly and continuously a cancer drug over several days.

Many different drugs, and drug combinations, are used for chemotherapy. Standard ones include:

Temozolomide (Temodar). Temozolomide, the first new drug approved for brain tumors in several decades, is taken by mouth as a pill. Temozolomide was first approved in 1999 for adult patients with anaplastic astrocytoma that did not respond to other treatments. In 2005, it was approved for use during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. The current first-line treatment for patients with glioblastoma is combined radiotherapy and temozolomide, followed by monthly doses of temozolomide after radiation treatment ends. A 2005 study, published in the New England Journal of Medicine, reported that adults with newly diagnosed glioblastoma who received temozolomide during and after radiation therapy had a higher rate of 2-year survival than patients who received radiation alone. A 2007 study in Neurology suggested that temozolomide works best for patients who are missing a particular gene (1p/19q). Temozolomide’s side effects are relatively minor, but may include constipation, nausea and vomiting, fatigue, and headache.

Carmustine (BCNU, BiCNU). Carmustine is used to treat many types of brain tumors, including glioblastoma, medulloblastoma, and astrocytoma. Carmustine is usually administered into the vein by IV. It can also be delivered through a wafer implant (Gliadel), which is surgically placed into the brain cavity after tumor removal. If carmustine is administered intravenously, side effects may include nausea and vomiting, fatigue, respiratory problems, and lung scarring (pulmonary fibrosis). Intravenous carmustine may cause bone marrow impairment, which results in decreased production of blood cells (a condition called myelosuppression). If carmustine is delivered through a wafer, side effects may include seizures, brain swelling, and infection within the brain cavity.

PCV Drug Regimen. PCV is an abbreviation for a chemotherapy regimen that combines procarbazine (Matulane), lomustine (CCNU), and vincristine (Oncovin). PCV is commonly used to treat oligodendrogliomas and oligoastrocytomas. The drugs may also be used alone or in other combinations. Procarbazine and lomustine are taken by mouth. Vincristine is given by either injection or IV. These drugs can cause significant side effects, including a drop in blood cell counts, nausea and vomiting, constipation, fatigue, and mouth sores. Procarbazine can cause high blood pressure when taken with foods high in tyramine. Patients should avoid foods such as beer, red wine, cheese, chocolate, processed meat, yogurt, and certain fruits and vegetables.

Platinum-Based Drugs. Cisplatin (Platinol) and carboplatin (Paraplatin) are standard cancer drugs that are sometimes used to treat glioma, medulloblastoma, and other types of brain tumors. These drugs are delivered by IV. In addition to nausea and vomiting, carboplatin can cause hair loss, and cisplatin can cause muscle weakness.

Patients with brain tumors, especially tumors that are in advanced stages, should consider enrolling in clinical trials. Many clinical trials are conducted through academic medical centers. Some promising areas of drug research include:

Other Chemotherapy Drugs. Researchers are investigating whether drugs used to treat other types of cancer may have benefits for brain tumors. These drugs include tamoxifen (Nolvadex) and paclitaxel (Taxol), which are used to treat breast cancer; topotecan (Hycamtin), which is used to treat ovarian and lung cancers; and vorinostat (Zolinza), which is approved for treatment of cutaneous T-cell lymphoma. Research presented at the 2007 meeting of the American Society of Clinical Oncology indicated that vorinostat may help patients with glioblastoma multiforme. Irinotecan (Campath) is another cancer drug that is being studied in combination treatment.

Molecular Targeted Therapy Drugs. One of the most promising developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotypes.

Promising targeted therapies for brain tumors include:

Anti-angiogenesis drugs block molecules involved with the growth of blood vessels that feed the tumor (a process called "angiogenesis," which is particularly important in the growth of glioblastomas.) These drugs starve tumors of vital nutrients and oxygen. Bevacizumab (Avastin) is being studied in combination with irinotecan for treatment of recurrent malignant gliomas. Bevacizumab targets vascular endothelial growth factor (VEGF), a specific angiogenesis growth factor. Cediranib (Recentin, AZD2171) is another VEGF inhibitor. In 2007 clinical trials, cediranib appeared to help make recurrent glioblastomas more responsive to chemotherapy and radiation treatment.
Tyrosine kinase inhibitor drugs block proteins involved in tumor cell growth and production. Drugs that specifically target epidermal growth factor receptors (EGFR) are a type of tyrosine kinase inhibitor of special interest in brain tumor research. These drugs include erlotinib (Tarceva), imatinib (Gleevac), and gefitinib (Iressa).
Farnesyl protein transferase inhibitors, such as tipifarnib (Zarnestra) and lonafarnib (Sarasar), are drugs that target a protein involved in the functioning of the cancer-causing Ras protein. Lonafarnib is being studied in combination with temozolomide, and tipifarnib in combination with radiation therapy.
MTOR inhibitors target other enzymes involved in cell growth and replication. Everolimus (RAD-001) is being studied for glioblastoma multiforme and astrocytoma. Everolimus is related to rapamycin (Siroliumus) and tacrolimus (Prograf), which are also being investigated for brain tumor treatment. These drugs are commonly used to suppress the immune system to prevent rejection after organ transplantation.

Other Treatments

Researchers are testing several drugs that target specific mechanisms associated with brain cancer. Combinations of some of these drugs, with or without standard chemotherapy and radiotherapy, may prove to be more effective than the use of any one treatment. It should be noted that none of these drugs at this time are producing cures, although some are improving survival.

Immunotherapy aims at using modalities that boost the patient's own immune system's ability to seek out and destroy cancerous cells.

Radioimmunotherapy with Monoclonal Antibodies. Radioimmunotherapy is showing special promise as a treatment approach to brain tumors. It typically uses monoclonal antibodies (MAbs), genetically engineered drugs designed to work against a specific target. MAbs are bound with radioactive substances and delivered directly into the brain and sometimes into the tumor. The MAbs are specifically designed to lock with the surface of certain cells in the tumor. Once they do so, the radioactive substances destroy the cell. The approach is essentially mini-radiation therapy without the damage or severe side effects of standard radiation treatments. Numerous different radioimmunotherapies are being investigated, and trials of some are reporting improved survival rates in high-grade gliomas. Some doctors believe this approach could prove to be the most effective therapy against these cancers.

Interleukins. Interleukins are natural proteins created by the immune system. Certain tumor cells carry receptors for specific interleukins, which are being investigated for a possible therapeutic role. For example, some drugs combine an interleukin with a drug that is toxic to cancer cells. The interleukin locks onto the receptor on the cancer cell, and the toxic chemical enters the tumor with the intent to kill it. Some interleukins are also being investigated alone for their own tumor-cell killing properties.

Tumor Vaccines. Tumor vaccines are being created, in which tumor cells are removed from the patient and inactivated. When the tumor cells are transferred back to the patient, they are harmless but can elicit a powerful immunologic response against the tumor. Vitespan (Oncophage) is a tumor vaccine that is showing promise against recurrent high-grade glioma, according to preliminary results from early trials presented at the 2007 annual meeting of the American Association of Neurological Surgeons.

Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Such drugs, when effective, would starve tumors of vital nutrients and oxygen. Angiogenesis is particularly important in the growth of glioblastomas, the most malignant brain tumors. Of particular promise are drugs that inhibit enzymes called tyrosine kinase, farnesyl protein transferase, and matrix metalloproteinase, which play critical roles in angiogenesis.

Farnesyl Protein Transferase Inhibitors. Farnesyl protein transferase inhibitors, such as tipifarnib, also called R115777 (Zarnestra) and lonafarnib (Sarasar), are drugs in a new class that block a mutated gene called the Ras gene, which is responsible for about 30% of cancers. Lonafarnib is in early trials in combination with temozolomide. Tipifarnib is also currently in early trials and may prove to be effective.

Tyrosine Kinase Inhibitors. Drugs that target growth factor receptors, such as tyrosine kinase, interfere with the pathway leading to angiogenesis. Some tyrosine kinase inhibitors -- including erlotinib (Tarceva), imatinib (Gleevac), gefitinib (Iressa), and others -- are being investigated in early trials for brain tumor treatment. Side effects include rash, diarrhea, nausea and vomiting. Some of these drugs may reduce white blood cell count or cause liver damage. Researchers are trying to identify biomarkers that could help predict which patients would best respond to tyrosine kinase inhibitor therapy.

Matrix metalloproteinase Inhibitors. Matrix metalloproteinase is an important enzyme in angiogenesis. Inhibitors of these enzymes, including marimastat, metastat, and prinomastat, are in early trials. Marimastat has been studied and has shown some benefits in early trials for patients with recurrent glioblastoma and anaplastic gliomas, particularly in combination with temozolomide.

Phophoinositide 3-Kinse (Pi3K) Inhibitors. Rapamycin and its analog (CCI-779) inhibit Pi3K, an enzyme involved in cell growth. Early trials using CCI-779 are underway. (Another rapamycin analog, everolimus, has different effects but is also being studied for its actions in inhibiting cell growth.)

Other Drugs that Block Angiogenesis. Thalidomide was one of the first drugs used to inhibit angiogenesis and has undergone several trials. There is some evidence that it may work more effectively for metastasized brain tumors than primary tumors. Other drugs in early trials with various effects on tumor growth include suramin, cilengitide, semaxanib, PTK787, and atrasentan.

Retinoids. Retinoids are vitamin A derivatives and act as differentiating drugs in cancer treatments. That is, they can convert immature, dividing tumor cells into mature cells, stopping tumor growth. Studies suggest that they have little benefits as single drugs. Combination with radiotherapy and other drugs may hold promise.

Inactivated Viruses. Investigators are finding that certain genetically inactivated viruses, such as the poliovirus or herpes virus, may prove to be valuable fighters of brain cancers. Such viruses can enter cells and destroy them but do not pose any danger for infection. For example, one specially designed herpes virus targets the enzyme thymidine kinase (an enzyme that promotes tumor growth). Some researchers believe that a combination of this virus with retinoids may be effective with few serious side effects. Other viruses are being investigated. A drug based on this model is years away, however.

Immunotoxins. Drugs called immunotoxins use natural toxins to kill malignant brain cells.

Drugs that use diphtheria toxins, including TransMID-107R and DAB(389)EGF), are the first immunotoxins to show some promise. Clinical trials are investigating them for gliomas and metastatic brain cancers. Other toxins under investigation include irofulven (a mushroom toxin) and chlorotoxin (a substance derived from scorpions).

Taurolidine. Taurolidine is a unique drug that prevents tumor formation and growth in animals. An early clinical trial in patients with high-grade gliomas is under way.

Protein-Blocking Drug. Another development is the discovery of a protein called BEHAB (Brain-Enriched Hyaluronan Binding Protein). BEHAB is produced only by invasive glioma tumor cells, not by normal brain tissue or noninvasive tumor cells. Breakdown of BEHAB releases a substance called HABD (hyaluronan-binding domain), which appears to give glioma cells the ability to invade other areas of the brain. Both BEHAB and HABD represent potential targets for new therapies.

Chemotherapy destroys not only cancer cells but also healthy cells, including special blood cells in the bone marrow called stem cells. Stem cells are immature cells from which all blood cells develop. Transplantation procedures using bone marrow or stem cells allow high-dose chemotherapy to be administered while protecting blood cells. The procedures are being tested for patients with recurrent brain tumors, such as medulloblastoma, primitive neuroectodermal tumors, and germ cell tumors. A 2003 study reported long-term survival in some patients who underwent this procedure

Photodynamic therapy uses a special drug (Photofrin) that is absorbed by the tumor and causes the cancer cells to become fluorescent when a laser is directed at them. It is being investigated in trials in combination with other treatments. A 2003 study reported encouraging results, notably in patients with recurring glioblastoma multiforme. In the study, more than half of these patients survived for at least a year.

Treatment of Complications

Some tumors, particularly medulloblastomas, interfere with the flow of cerebrospinal fluid and cause hydrocephalus (accumulation of fluid in the skull). This causes a build-up fluid in the ventricles (the cavities) in the brain. Symptoms include nausea and vomiting, severe headaches, lethargy, difficulty staying awake, seizures, visual impairment, irritability, and tiredness.

The ventricles of the brain are hollow chambers filled with cerebrospinal fluid (CSF), which supports the tissues of the brain.

Corticosteroids (commonly called steroids) such as dexamethasone (Decadron), prednisolone, and prednisone are used to treat hydrocephalus. Side effects include high blood pressure, mood swings, increased risk of infection, stronger appetite, facial swelling, and fluid retention.

Human corticotropin-releasing factor (hCRF), a naturally occurring neurohormone, appears to possess substantial anti-swelling properties and thus has been proposed as an alternative to corticosteroids in brain edema, with potentially fewer side effects. A hCRF drug called Xerecept is currently in clinical trials.

A shunt procedure may be performed to drain fluid. Shunts are flexible tubes used to reroute and drain the fluid.

Seizures are common in brain tumor cases, with younger patients having higher risks than older ones. Anti-epileptic medications, such as carbamazepine or phenobarbital, may treat seizures and are helpful in preventing recurrence. These drugs are not useful in preventing a first seizure, however, and they should not be used routinely to treat patients with newly diagnosed brain tumors. Anti-seizure medications should be used only for patients who are experiencing seizures. Despite these guidelines, a 2005 study in the Journal of the American Medical Association reported that nearly 90% of patients with newly diagnosed malignant glioma are treated with anti-epileptic drugs, although only 32% of the patients actually have seizures. Anti-seizure medications can interact with some of the chemotherapies used to treat brain cancers, including paclitaxel, irinotecan, interferon, and retinoic acid. Patients should discuss these interactions with their doctors.

Antidepressants are very useful for treating the emotional side effects of this disease. However, according to a 2005 Journal of the American Medical Association study, only 8% of patients with malignant gliomas receive antidepressant medication even though over 90% report depressive symptoms. Support groups can also have great benefit for both patients and families.

Resources

www.abta.org -- American Brain Tumor Association
www.cbtf.org -- Children's Brain Tumor Foundation
www.virtualtrials.com -- Musella Foundation for Brain Tumor Research and Information
www.braintumor.org -- National Brain Tumor Foundation
www.neurosurgery.org -- American Association of Neurologic Surgeons
www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.asco.org -- American Society for Clinical Oncology
www.cancer.gov/clinicaltrials -- Find clinical trials
www.radiologyinfo.org -- RadiologyInfo
www.plwc.org -- People Living with CAncer

References

Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2006 Nov 20;24(33):5277-82. Epub 2006 Nov 6.

Dunlap SM, Celestino J, Wang H, Jiang R, Holland EC, Fuller GN, et al. Insulin-like growth factor binding protein 2 promotes glioma development and progression. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11736-41. Epub 2007 Jul 2.

Flint-Richter P, Sadetzki S. Genetic predisposition for the development of radiation-associated meningioma: an epidemiological study. Lancet Oncol. 2007 May;8(5):403-10.

Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, et al. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology. 2007 May 22;68(21):1831-6.

Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35.

Neglia JP, Robison LL, Stovall M, Liu Y, Packer RJ, Hammond S, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37.

Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, et al. Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007 Feb 1;67(3):890-900.

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA,et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Cirrhosis

FitSugar — Wed, 08 Oct 2008 17:35:41 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration approved HepaGram B, an injectable immune globulin that can help prevent recurrence of hepatitis B following liver transplantation.

Primary Biliary Cirrhosis

Primary biliary cirrhosis is an autoimmune liver disease that increases the risk for liver cancer. According to a 2007 study, specific risk factors may help predict which patients with primary biliary cirrhosis are at particularly high risk of developing liver cancer. These risk factors include older age, being male, history of blood transfusion, and any signs of portal hypertension (high pressure of the blood in the portal vein, which leads to the liver) or cirrhosis.

Hepatitis C and Cirrhosis

Patients with cirrhosis who are infected with a particular hepatitis C genotype (1b) have a high risk of developing liver cancer, indicates a 2007 study. These patients should receive regular monitoring so that liver cancer can be detected in its earliest stages.
Interferon drug therapy can help reduce -- but not entirely eliminate -- the risk of liver cancer developing in patients with hepatitis C-related cirrhosis.

Hemochromatosis

Hemochromatosis, also called “iron overload,” is an iron disorder that increases the risk for cirrhosis. Hereditary hemochromatosis is one of the most common genetic diseases in the United States, and experts have debated whether all people should get screened for it. In 2006, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines concerning hemochromatosis screening. The USPSTF does not recommend routine screening in the general population. However, people who have family histories of hemochromatosis, or who show signs or symptoms of this disorder, should get tested.

Encephalopathy

Lactulose, a drug that helps remove ammonia from the body, can help improve cognitive function and quality of life for people with hepatic encephalopathy, suggests a 2007 study. Hepatic encephalopathy, a complication of liver disease, affects the brain and nervous system.

Introduction

Cirrhosis is an irreversible result of various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis - nodular regeneration), progressive decrease in liver function, excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

The disease process often takes the following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs from injuries due to alcohol, viruses, or other assaults. Normal clumps and form nodules around the scarred areas. The scar tissue and regenerated nodules act like small dams and alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant consequences, with both the liver and other organs responding to the altered flow:

The spleen overproduces nitric oxide, a gas that causes blood vessels in the spleen to relax and open.
The small blood vessels and bile ducts in the liver itself, however, narrow (constrict). (Blood vessels in other organs, including the kidney, also narrow.)
Blood flow coming from the intestine into the liver is slowed by the narrow blood vessels. It backs up through the portal vein and seeks other routes.
New, abnormally twisted and swollen veins called varices form in the stomach and lower part of the esophagus in order to compensate for the backup blood.
Bile also builds up in the bloodstream, resulting in high levels of bilirubin, which causes a yellowish cast in the skin called jaundice.
Fluid buildup also occurs in the abdomen (called ascites), and swelling in the arms and legs is common.

Changes in Liver Size. The liver enlarges in the first phases of the disease. In advanced stages, the liver sometimes shrinks, a condition called postnecrotic cirrhosis.

The liver is the largest organ in the body. In the healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located immediately below the diaphragm and occupies the entire upper right quadrant of the abdomen.

Vital Functions. The liver performs over 500 vital functions. Damage to the liver can impair these and many other processes. Among them are the following:

Processing Healthful Nutrients. It processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile, a green-colored fluid that helps the body absorb fats and fat-soluble vitamins. Bile is formed from bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin, the oxygen-carrying component in red blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile travels from the liver to the gallbladder, where it is stored until after a meal. It is then secreted into the intestines where it helps digest fat.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

Recycling Blood. The liver and spleen removes old red blood cells from the blood. The iron contained in them is recycled in the bone marrow to make new red blood cells.

The Liver's Architecture. The vital processes the liver performs rely on well-organized liver architecture.

The Building Blocks. The basic building blocks of the liver are the following structures:

Bile ducts
Blood vessels
Working liver tissue (called the parenchyma)
Supportive (connective) tissue

The Architecture. The liver is a built on a framework of lobes:

The lobes. The liver is divided into two major lobes, a right and a smaller left, that are separated by tough, fibrous connective tissue.
The lobules. The liver's two major lobes contain about 100,000 smaller lobes, called lobules. Each lobule contains microscopic columns of liver cells and blood vessels. Bracing the corners of each lobule column are an artery and a vein that carry blood and a bile duct that drains bile.
The arteries and veins. The arteries bring oxygen-rich blood to nourish the liver cells. The veins supply the liver cells with blood containing the nutrients and toxins that the liver cells process. A central vein runs through each column and collects the processed blood from both sources. These veins join to form the hepatic vein.
The bile ducts. The bile ducts in the column corners collect bile draining from tiny canals around the liver cells. These ducts eventually join to form the large common bile duct that leads from the liver to the gallbladder.

The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the body's supply. It is furnished with blood from two large vessels, the hepatic artery and the portal vein, and is drained of blood by the hepatic vein. (The word "hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating through the stomach, spleen, and intestine. The liver processes this blood, extracting nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena cava, a large vein that carries blood back to the heart.

Click the icon to see an image of the liver.

Causes

Several processes can lead to cirrhosis.

Alcoholism particularly endangers the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. It is estimated to be responsible for 44% of deaths from cirrhosis in North America. Some experts believe this estimate is low. One Canadian study found alcohol to be the major contributor in 80% of all cirrhosis deaths.

The relationship between alcohol and cirrhosis is generally as follows:

Alcohol is absorbed from the small intestine, and the blood carries it directly into the liver, where it becomes the preferred energy source.
In the liver, alcohol converts to toxic chemicals, such as acetaldehyde (AcH), which trigger the production of powerful immune factors called cytokines. These molecules in large amounts can cause inflammation and tissue injury. They are proving to be major culprits in the destructive process in the liver. AcH is particularly being researched because it plays a role in most actions of alcohol, including damaging effects on the liver that may lead to cirrhosis.
The injured liver eventually is unable to break down fatty acids, compounds that make up fat. Over time, then, fat accumulates, further impairing the liver's ability to absorb oxygen and increasing its susceptibility to injury. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as cirrhosis develops.

Chronic hepatitis, both hepatitis B and hepatitis C, is the second leading cause of cirrhosis. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. About 5 - 20% of patients with chronic hepatitis C, and 5 - 10% of patients with chronic hepatitis B, eventually develop cirrhosis over the course of several decades. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis. A 2005 study indicated that cirrhosis develops in 70% of patients who have had hepatitis C for more than 60 years.

The hepatitis virus can produce inflammation in liver cells, causing injury or destruction. If the condition is severe enough, the cell damage becomes progressive, building a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Hepatitis C is a virus-caused liver inflammation which may lead to jaundice, fever, and cirrhosis. The people most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs and health care workers or emergency workers who may be exposed to contaminated blood.

Autoimmune liver diseases include autoimmune hepatitis and primary biliary cirrhosis. Like other autoimmune disorders, these conditions most likely develop because a genetically defective immune system attacks the body's own cells and organs. People who have one of these liver diseases also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia.

Autoimmune Hepatitis. Autoimmune chronic hepatitis occurs when an abnormal immune response causes an attack on the liver cells. It accounts for about 20% of all chronic hepatitis cases. Autoimmune chronic hepatitis typically occurs in women age 20 - 40 who have other autoimmune diseases. Some research indicates that the postmenopausal period may be another peak in incidence of AIH among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, no major risk factors have been discovered for this condition.

Suspects for triggering this hepatitis include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in some people.

Click the icon to see an image of mononucleosis.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver’s bile ducts. Like many autoimmune disorders, the causes of PBC are unknown. Recent research indicates the following risk factors:

Family history of PBC
Family history of Sjögren syndrome (another autoimmune disorder)
Individual history of urinary tract infections (UTI)
History of smoking
History of nail polish use
Hormone replacement therapy
Exposure to toxins from hazardous waste sites

This research suggests that environmental factors (chemicals, cigarette smoke) or infectious organisms (bacteria that causes UTI) may trigger PBC in patients who are genetically susceptible to the disease. Women who have never been pregnant appear less likely to develop PBC.

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

Nonalcoholic fatty liver disease can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain patients it can lead to cirrhosis, liver failure, or liver cancer. About 8 - 20% of people with nonalcoholic steatohepatitis go on to develop cirrhosis. A 2006 study indicated that NASH-related cirrhosis causes fewer deaths than cirrhosis that is caused by chronic hepatitis C. However, many patients with NASH have coronary artery disease and heart failure and have a high risk of dying from heart disease.

Weight reduction and diabetes and cholesterol management are the primary approaches to controlling these diseases.

Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally gets rid of iron. People with hemochromatosis absorb too much more iron from the food that they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

There are two main forms of hemochromatosis:

Primary hemochromatosis, also called hereditary hemochromatosis, is an inherited genetic disease.
Secondary hemochromatosis results from other conditions, such as anemia and alcoholism.

Hereditary hemochromatosis is one of the most common genetic diseases, especially among Caucasians. About 1 in every 200 Americans carries the gene that causes this disease. Although experts do not recommend that everyone get screened for hemochromatosis, people who have a family history of this disease, or who show symptoms (joint pain, fatigue, abdominal pain), should get tested. Left untreated, hemochromatosis can lead to serious damage of the liver, heart, and pancreas.

Hemochromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week. Starting phlebotomy treatment before organ damage occurs can help prevent cirrhosis. If, however, cirrhosis has already developed, patients have a high risk for developing liver cancer even if iron levels are normalized.

Inherited Diseases. Cirrhosis can be caused by several inherited diseases, including:

Cystic fibrosis
Alpha-1 antitrypsin deficiency
Galactosemia
Glycogen storage diseases
Wilson's disease

Other Rare Causes. Rare causes of cirrhosis include:

Schistosomiasis, caused by a parasite found in the Far East, Africa, and South America.
Small intestine bypass surgery (rarely, if ever, performed anymore).
Long-term or high level exposure to certain chemicals and drugs can cause cirrhosis, including arsenic, methotrexate, and toxic doses of vitamin A.

Cancers that have metastasized to the liver, blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

Risk Factors

Cirrhosis affects about 3 million Americans a year. However, because about 2.7 - 4 million people harbor hepatitis C, the rates of cirrhosis could dramatically increase over the next few years.

Only 10% of heavy drinkers develop advanced liver disease. Not eating when drinking and consuming a variety of alcoholic beverages are factors that increase the risk for liver damage. Still, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Other risk factors have been identified that may increase the danger to the liver:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men. The reason for this may be due to women's inability to metabolize alcohol as quickly as men, so it stays in the bloodstream longer.
Genetic factors that regulate the immune responses in the intestine also play a role in increasing the risk for liver injury from alcoholism.

Risk Factors for Developing Cirrhosis from Hepatitis C. Overall, between 10 - 15% of patients with chronic hepatitis C develop cirrhosis. The risk varies widely, however. The following conditions put people with hepatitis C at higher risk for liver damage:

Overall the risk for progression is highest in men -- particularly African-Americans -- who were older at the time of infection. The risk is much lower in women and children (2 - 4%).
Moderate-to-heavy alcohol users. (Even one or two alcoholic drinks a day increase the risk for liver injury in hepatitis C patients.)
Having a specific genetic type of the virus. There are six main genetic types and more than 90 subtypes, which can differ significantly in their effects and response to treatment. Genotype 1 is the most serious and is the cause of up to three quarters of the cases in the U.S. The other common forms are types 2 (15%) and 3 (7%), which pose less danger.
Co-infection with hepatitis B. Co-infection with B significantly affects the outcome of these patients and may be more common than previously believed. This co-condition may cause superinfections with very serious consequences, reduce these patients' responses to interferon therapy, and increase their risk of liver cancer. Patients with hepatitis C should be immunized against hepatitis B.
Co-infection with HIV.
A history of transfusions. (In one report, the risk in middle-aged patients with a history of transfusions was 20 - 30%).
Being diabetic and overweight, particularly if fat is distributed in the abdomen (an apple-shape). This condition poses a higher risk for nonalcoholic fatty liver disease (NASH), which in turn is apt to become scarred and cirrhotic.

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

Having large iron stores in the liver.
High exposure to toxic chemicals or environmental contaminants.

Because there are millions of Americans now infected with chronic hepatitis C, doctors have been justifiably concerned that there will be a significant number of cases of liver failure and liver cancer in the coming years. Computer analyses have suggested that mortality rates from hepatitis C-related cirrhosis or liver cancer will double or triple over the next 20 years. Fortunately, improved therapies may significantly reduce these discouraging estimates.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Risk Factors for Developing Cirrhosis from Hepatitis B. The great majority of people with chronic persistent hepatitis B have a good long-term outlook. Between 5 - 10%, however, become carriers of the virus, and 5 - 10% of these individuals eventually develop cirrhosis. The addition of hepatitis D is a particular danger and increases the risk for cirrhosis. Seven genetic types of hepatitis B virus (designated A to G) have now been identified, which may help researchers determine the patients who may have a better outlook than others. Genotype C is the most common form and is more aggressive than genotype B, which also responds better to treatment.

Primary biliary cirrhosis accounts for only 0.6 - 2% of deaths from cirrhosis. In patients with chronic persistent autoimmune hepatitis, the outlook is very favorable, and survival rates are equal to the general population. If it becomes active, it must be treated. Left untreated, the 5-year survival rates of primary biliary cirrhosis are 50%.

Obesity increases the risk for nonalcoholic fatty liver disease (NAFLD), a condition that can lead to nonalcoholic steatohepatitis (NASH). Studies estimate that 8 - 20% of people with NASH eventually develop cirrhosis. A 2006 study found that people with NAFLD and elevated liver enzymes have a high risk of developing end-stage liver disease. People with NASH had an especially poor prognosis for survival. Losing weight is important for overweight people with NASH and may help to delay disease progression. A 2003 study of more than 11,000 patients indicated that obesity increases the risk of death from cirrhosis in people who drink little or no alcohol, but not among those who drink alcohol.

Symptoms

Many people experience few symptoms at the onset of cirrhosis.

Early symptoms include:

Fatigue and loss of energy.
Loss of appetite and nausea.
Spider angiomas may develop on the skin. These are pinhead-sized red spots from which tiny blood vessels radiate.

Patients in later stages may develop the following symptoms:

Jaundice. This yellowish cast to the skin and eyes occurs because the liver cannot process bilirubin for elimination from the body.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The palms of the hands may be reddish and blotchy, a condition known as palmar erythema.
Loss of body hair.
Abnormalities in hormone-affected organs. In men with alcoholic cirrhosis, the testicles may atrophy, and their breasts may become swollen, sometimes painfully.
Ascites. A swollen belly is a sign of ascites, the most common major complication of cirrhosis, which occurs when fluid accumulates in the abdomen. Fever, abdominal pain, and tenderness when the belly is pressed indicate that the fluid is infected, but infection can occur without any symptoms.
Fluid buildup and swelling (edema) in legs.

People with primary biliary cirrhosis may have severe generalized itching and often develop small fatty yellow lumps called xanthomas on the eyelids, hands, and elbows. They may have an unpleasant condition called steatorrhea, in which the feces contain excessive fat, causing them to float and to be very foul smelling.

Click the icon to see an image of a xanthoma.

Complications

Cirrhosis is the eleventh leading cause of death by disease in the United States, killing more than 25,000 people each year. A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. The most serious complications are those associated with so-called decompensation, which occur when cirrhosis progresses. They include the following:

Bleeding and fluid buildup (ascites).
Infections.
Damage to the brain (encephalopathy). Impaired brain function occurs when the liver cannot detoxify harmful substances.

Liver cancer is also a long-term risk with cirrhosis.

Cirrhosis is irreversible, but the rate of progression can be very slow, depending on its cause and other factors. Five-year survival rates are about 85% and can be lower or higher depending on severity.

For example, alcoholics with cirrhosis who abstain can have a 5-year or more survival rate of as high as 85%. For those who continue drinking, the chance for living beyond 5 years is no higher than 60%.
In patients with hepatitis B or C, the 5-year survival rate after a diagnosis of cirrhosis is 71 - 85%.
About two-thirds of patients with primary biliary cirrhosis never develop symptoms and can have a normal lifespan. Once symptoms of liver damage, such as jaundice, occur, however, the average survival time declines. In one study of women diagnosed with primary biliary cirrhosis, about 36% developed symptoms over an 11-year period, and 11% either died or required liver transplantation.

Unfortunately, doctors are usually unable to determine when cirrhosis first occurred, which makes it difficult to determine prognosis.

In cirrhosis, liver cell damage slows down blood flow. This causes a backup of blood through the portal vein, a condition called portal hypertension. The effects of portal hypertension can be widespread and serious, including fluid buildup and bleeding.

Ascites and Fluid Buildup. Ascites is fluid buildup in the abdomen. It is uncomfortable and can reduce breathing function and urination. Ascites is usually caused by portal hypertension, but it can result from other conditions. Swelling can also occur in the arms, legs, and spleen. Although ascites itself is not fatal, it is a marker for severe progression. Once ascites occurs, only half of patients survive after 2 years. Some doctors refer to the phases of cirrhosis as preascitic and ascitic. Some doctors even believe that ascites signals the need for liver transplantation, particularly in alcoholic cirrhosis.

Variceal Bleeding. One of the most serious repercussions of portal hypertension is the development of varices, blood vessels that enlarge to provide an alternative pathway for blood diverted from the liver. In about two-thirds of patients, they form in esophagus. Varices pose a high risk for rupture and bleeding because of the following characteristics:

They are thin-walled.
They are often twisted.
They are subject to high pressure.
Internal bleeding from these varices (variceal bleeding) occurs in 20 - 30% of patients with cirrhosis. The risk of death from a single episode can reach 70%.

Bleeding commonly recurs within 2 weeks of the first episode, but after 6 weeks, the risk for recurrence is the same as for patients who have not had a bleeding event.

Factors that predict variceal bleeding include:

Ascites
Encephalopathy
Large veins

Factors that can increase the danger for a bleeding episode in high-risk individuals include the following:

Moderate-to-intense exercise
Bacterial infection
Certain times of the day. Eating increases portal pressure, and there is a greater risk for bleeding in the evening. A lesser but still significant risk occurs in the early morning.

It is important for patients to be screened for esophageal varices and treated with preventive beta blockers if they show signs of risk. Between 30 - 40% of patients with cirrhosis have bleeding. The risk of dying from this complication is 20 - 35%. Some doctors recommend that all newly diagnosed patients be screened using endoscopy. Screening should also be considered for all previously diagnosed patients who have not been screened but would benefit from preventive treatments.

Portal hypertension can cause several secondary complications, including kidney failure. Non-steroidal anti-inflammatory drugs, such as naproxen, may increase the risk for kidney failure.

Gastrointestinal bleeding can occur from abnormal blood clotting, which can be a result of a combination of complications associated with cirrhosis. They include vitamin K deficiencies and thrombocytopenia -- a drop in platelets (the blood cells that normally initiate the clotting process). Some research now suggests that thrombocytopenia itself may be associated with more advanced liver failure.

Bacterial infections are very common in advanced cirrhosis, and may even increase the risk for bleeding. Most bacterial infections, including those in the urinary, respiratory, or gastrointestinal tracts, develop when patients are in the hospital. Abdominal infections are a particular problem in cirrhosis and occur in up to 25% of patients with cirrhosis within a year of diagnosis.

Mental impairment is a common event in advanced cirrhosis. In severe cases, the disease causes encephalopathy (damage to the brain), with mental symptoms that range from confusion to coma and death. A combination of conditions associated with cirrhosis causes this serious complication:

Buildup in the blood of harmful intestinal toxins, particularly ammonia.
An imbalance of amino acids that affect the central nervous system.

Encephalopathy is often triggered by certain conditions, including:

Gastrointestinal bleeding
Constipation
Excessive dietary protein
Infection
Surgery
Dehydration

Alcoholics with cirrhosis are believed to be at higher risk for this complication than are nonalcoholic cirrhosis, but one study suggested that alcoholics simply tend to have more severe cirrhosis. Even minimal hepatic encephalopathy (MHE) can have detrimental effects on functional ability. One study suggested that MHE impairs the ability to safely drive a car, and that all patients with cirrhosis be tested for MHE.

Symptoms of Encephalopathy. Early symptoms of hepatic encephalopathy include forgetfulness, unresponsiveness, and trouble concentrating. Sudden changes in the patient's mental state, including agitation or confusion, may indicate an emergency condition. Other symptoms include bad fruity-smelling breath and tremor. Late stage symptoms of encephalopathy are stupor and eventually coma.

Hepatorenal syndrome occurs if the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication of late-stage liver disease that occurs in patients with ascites. Symptoms include dark colored urine and a reduction in volume, yellowish skin, abdominal swelling, mental changes (delirium, confusion), jerking or coarse muscle movement, nausea, and vomiting.

People with cirrhosis have an increased risk for liver cancer. Hepatitis B and C themselves increase the risk for liver cancer, regardless of the presence of cirrhosis. Hepatitis B infection is the leading cause of liver cancer.

For hepatitis C-related cirrhosis, a 2007 study indicated that patients with cirrhosis who are infected with genotype 1b hepatitis C have a greater risk of developing liver cancer than patients infected with other types of hepatitis C genotypes. (Genotype 1 is the most common type of hepatitis C in the United States.)

People with primary biliary cirrhosis also face a high risk of liver cancer. According to a 2007 study, several factors can indicate the increased likelihood of developing liver cancer. These factors include older age, male gender, history of blood transfusion, and signs of portal hypertension or cirrhosis.

About 30% of patients with chronic liver disease develop osteoporosis (loss of bone density), which is twice the usual incidence. Patients with primary biliary cirrhosis have a particularly high risk for osteoporosis. Treating osteoporosis in patients with cirrhosis can be complicated. One study found that calcitriol (a form of vitamin D) is especially helpful in preventing bone loss in patients with cirrhosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements may reduce and even reverse loss of bone density.

Nearly all patients with cirrhosis are insulin resistant. Insulin resistance is a primary feature in type 2 diabetes and occurs when the body is unable to use insulin. This hormone is important for delivering blood sugar and amino acids into cells and helps determine whether these nutrients will be burned for energy or stored for future use.

One study reported that nearly a quarter of patients with cirrhosis had gallstones.

Click the icon to see an image of gallstones.

They may also face a higher than average risk for certain abnormal heart rhythms. Peptic ulcers, sleep disorders, and respiratory problems are also more common in people with cirrhosis than in the general population.

Diagnosis

A physical examination may reveal the following in a patient with cirrhosis:

The cirrhotic liver is firm and often enlarged. The liver may feel rock-hard. (In advanced stages of cirrhosis, the liver may become small and shriveled.)
The left side can often be felt by the doctor when pressing on the abdomen.

If the abdomen is swollen, the doctor will check for ascites by tapping the flanks and listening for a dull thud and feeling the abdomen for a shifting wave of fluid.

Measuring Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Radioimmunoassays. To identify a particular virus that may be causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous, and can be targeted by antibodies.)

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be enough antibodies for blood tests to detect for up to weeks or months after hepatitis develops. Blood tests that are taken too early, then, may miss these signs of infection.
Antibodies also persist after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. A PCR is able to make multiple copies of the genetic material (the RNA) of the virus to the point where it is detectable.

Screening for Hepatitis C Virus. In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against routine screening for the hepatitis C infection in the general population due to low prevalence of the disease. In addition, it "found no evidence that screening for HCV infection in adults at high risk leads to improved long-term health outcomes" and found insufficient evidence to recommend for or against such screening. However, the USPSTF did advise testing in those with signs or symptoms of liver disease. The failure to recommend testing in the high-risk population goes against current recommendations made by the Centers for Disease Control and Prevention, the National Institutes of Health, and other professional organizations. In response to the study, published in the Annals of Internal Medicine, the American Association for the Study of Liver Diseases issued a statement saying that halting such screening would be a "terrible mistake with grave consequences," pointing out that the study itself underscored some key infection-related data that strongly emphasizes the need for screening in high-risk populations.

A liver biopsy is the only definite method for diagnosing cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied appear to have a low risk for cirrhosis.

The biopsy may be performed using various approaches, including:

Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity.

Click the icon to see an image of liver biopsy.

Transjugular Liver Biopsy. This approach uses a catheter (a thin tube) that is inserted in the jugular vein in the neck and threaded through the hepatic vein (which leads to the liver). A needle is passed through the tube, and a suction device collects liver samples. This procedure is risky but may be used for patients with severe ascites.
Laparoscopy. This procedure requires a small abdominal incision through which the doctor inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes.

Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate clotting problems, on those who have had previous liver biopsies, or who have ascites.

Certain blood tests are used to determine liver function. They include the following:

Serum albumin concentration. Serum albumin measures protein in the blood (low levels indicate poor liver function).
Prothrombin time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).
Bilirubin. One of the most important factors indicative of liver damage is bilirubin, a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice.

The results of these tests along with the presence of specific complications (ascites and encephalopathy) are used for calculating the Child-Pugh Classification. This is a staging system (A to C) that helps doctors determine the severity of cirrhosis.

Very high levels of serum alkaline phosphatase, an enzyme produced in the liver, and high levels of immune factors called mitochondrial antibodies are usually present in blood tests of patients with primary biliary blood cirrhosis. Bilirubin measurements appear to be important factors in determining its severity.

Fatty liver is suspected when a patient has elevated liver enzymes. The doctor will take imaging tests of the liver using ultrasound, computed tomography, or magnetic resonance imaging. A liver biopsy is the standard test for confirming a diagnosis of fatty liver disease and for distinguishing NAFLD from nonalcoholic steatohepatitis (NASH). Several studies in 2006 and 2007 suggested that a blood test for cytokeratin-18 (CK-18), a protein found in liver cells, may be an effective noninvasive approach for diagnosing NASH. Doctors hope that this simple blood test may eventually be able to replace liver biopsy.

Several imaging tests can be used to diagnose cirrhosis and its complications.

Imaging Techniques. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the extent of cirrhosis. Such tests can reveal ascites, an enlarged spleen, an irregular liver surface, reversed portal vein blood flow, and liver cancer. Sometimes they can even detect abnormally large blood vessels in the liver. In some cases, images from ultrasound and CT can be misinterpreted as cancer. MRI is most useful for ruling out or confirming cancer.

Click the icon to see an image of an MRI scan.

Click the icon to see an image of a CT scan.

Liver Scans. Sometimes liver scans are performed using a small radioactive tracer and a special camera that records information provided by the tracer as it passes through the liver:

Arteriography uses dye injected into the hepatic arteries that show up on x-ray.
Splenoportography uses dye injected into the spleen, which allows the doctor to measure portal vein pressure. This procedure is risky.

Hepatic vein wedge pressure involves insertion of a catheter into the hepatic veins. The blood pressure in the veins of the liver is then measured. The result is an indicator of portal vein pressure. If pressure is high, cirrhosis is likely. A low measurement is a favorable sign.

Endoscopy. Some doctors recommend endoscopy for patients newly diagnosed with mild-to-moderate cirrhosis in order to screen for esophageal varices. (These are abnormal blood vessels in the esophagus that increase the risk for bleeding). In this test, a fiber optic tube is inserted down the throat. The tube contains tiny cameras to view the inside of the esophagus, where varices are most likely to develop. Endoscopy is the only procedure for detecting varices, but it is not clear if screening for varices in patients without severe cirrhosis is any more beneficial than simply putting them immediately on preventive drugs -- whether or not varices have been identified.

Paracentesis. If ascites is present, paracentesis is performed to determine its cause. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors to determine the cause of ascites:

Bacteria cultures and white blood cell counts. (These are used to determine the presence of infection.)
Protein levels. Low levels of protein in the fluid plus a low white blood cell count suggest that cirrhosis is the cause of the ascites.

The appearance of the fluid is helpful in determining problems:

A cloudy fluid plus a high white blood cell count means an infection is present.
Bloody fluid suggests the presence of a tumor.

Screening for Liver Cancer. Patients with cirrhosis are usually screened for liver cancer using ultrasound and tests for a substance called alpha-fetoprotein (AFP). It is not known whether such screening has much impact on survival, because it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

Treatment

The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with alcoholic cirrhosis are typically malnourished and require increased calories and rigorous nutritional support, which can improve survival rates.

Interferons Alone and in Combination with Ribavirin. Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with HCV genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavarin.

A 2005 clinical trial of patients with chronic hepatitis C and cirrhosis found that interferon treatment reduced the risk of liver cancer and significantly improved chance of survival. The study emphasizes the importance and substantial benefits of interferon therapy. A 2007 study of patients with hepatitis C-related cirrhosis also indicated that interferon therapy can help reduce the risk of liver cancer and overall risk of death from liver disease.

A number of natural and synthetic interferons are available:

Natural interferons include interferon alfa-2a (Intron) and interferon alfa-2b (Roferon).
Pegylated interferons (PegINF) are long-acting formulations of interferon. They include alfa-2b (Peg-Intron) or alfa-2a (Pegasys). These drugs are used in combination with ribavarin (Copegus, Rebetol).
Alfacon-1 (Infergen), also called consensus interferon, is a genetically modified interferon. A combination of alfacon-1 with ribavirin is proving to help some patients who had been resistant to ribavirin with interferon.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavarin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations are proving to slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.
Flu-like symptoms, such as fever, headaches, and muscle aches, are the most common side effect.
Reduced white blood cell count.
Skin disorders, such as dry skin and rash.
Coughing and shortness of breath.
Gastrointestinal symptoms (nausea, indigestion, lack of appetite).
Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.
Combination treatment in pregnant women poses a very high risk for birth defects.

The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs showing promise include:

Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavarin in Phase II trials for patients with genotype 1 chronic hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It is being used for hepatitis B and is under investigation for hepatitis C in combination with interferon.
Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.
Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.
Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Of interest are studies using phlebotomy (which is simply drawing blood) to reduce iron levels. In one study, maintenance therapy with this procedure reduced liver inflammation and possibly slowed progression of cirrhosis.

An ounce of prevention is worth a pound of cure, and the phrase resoundingly holds true in the case of hepatitis B. Today, a vaccine against hepatitis B is available. It can prevent hepatitis B and, therefore, also prevent liver cancer. The American Academy of Pediatrics and the Centers for Disease Control and Prevention currently recommend that all babies born in the United States receive a hepatitis B vaccine at birth.

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

Peginterferon alfa-2a (Pegasys)
Interferon-alfa-2b (Intron)
Adefovir (Hepsera)
Lamivudine (Epivir)
Entecavir (Baraclude)
Telbivudine (Tyzeka)

These drugs block the replication of hepatitis B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the Food and Drug Administration (FDA) approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitis B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitis B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitis B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitis Bas the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitis B. Patients with lymphoma should be screened for hepatitis B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitis Band HIV should take entecavir only if they are also taking antiviral HIV drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitis B.
Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitis B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Ursodeoxycholic Acid (UDCA) and Drugs Used to Slow Progression. At this time no medication can cure primary biliary cirrhosis. Ursodiol, ursodeoxycholic acid (Actigall), or UDCA has been the standard drug used for primary biliary cirrhosis. Several studies have reported that it slows progression and helps prevent the need for liver transplantation.

It has no effect on symptoms, including itching and fatigue. Some drugs, such as colchicine, corticosteroids, or immunosuppressants, are being investigated for use in combination with UDCA. Long-term controlled trials are needed to determine the value of UDCA alone or with other drugs.

Drugs for Itching. Itching is a major problem with this disease. Cholestyramine, taken with meals, is the first choice for relieving itching. Several other drugs have been used or investigated, including low doses of the drug naltrexone and phototherapy.

Drugs for Impaired Fat Absorption. Because primary biliary cirrhosis affects fat absorption, patients may need high doses or injections of important fat-soluble vitamins, including K, D, A, and E.

Treatment of Nonalcoholic Fatty Liver Disease. Weight loss is the most important method for managing nonalcoholic fatty liver disease (NAFLD) and preventing progression to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis. Diabetes and cholesterol control are also important. Investigators are studying whether various drugs used to treat type 2 diabetes may help treat NAFLD and NASH.

Other research is focusing on antioxidant vitamins, such as vitamin E.

In 2005, the National Institutes of Health launched two trials to study treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitisin adults and children. Children with NAFLD will receive vitamin E, metformin, or placebo. In the adult trial, patients with NASH will receive vitamin E, pioglitazone, or placebo.

Secondary Biliary Cirrhosis. Secondary biliary cirrhosis caused by blockage in the bile ducts can be relieved by surgery.

Autoimmune Hepatitis. Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Hemochromatosis. For hemochromatosis, weekly bleedings (phlebotomies) may be performed until iron levels are normal, then repeated as needed. If treatment is given before cirrhosis develops, life expectancy may be normal.

Wilson's Disease. D-penicillamine is the drug most used for Wilson's disease.

There are no current safe and effective therapies for liver scarring (fibrosis). However, recent insights into the cellular and molecular mechanisms responsible for scarring have led to the development of specific, antifibrotic drugs that target the primary injury and inhibit abnormal cell mechanisms. Such drugs, now in very early testing, could one day help prevent or reduce the progression of liver scarring or the progression to liver cancer.

Liver transplantation may be indicated for the following:

Patients who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.
Patients with liver cancer that has not spread beyond the liver.

Survival rates after transplantation are similar among those who have hepatitis B, hepatitis C, or alcoholic liver disease. Current 5-year survival rates after liver transplantation are about 75%. Patients also report improved quality of life and mental functioning after liver transplantation. Patients should seek medical centers that perform more than 50 transplants per year and produce better-than-average results.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Fortunately, more procedures are now being performed using liver tissue from a living donor. In these cases, surgeons replace the patient’s diseased liver with a part of the liver taken from a donor. The donor’s liver regenerates to full size within a few weeks of surgery, and the recipient’s liver also regrows.

Transplantation surgery generally takes 4 - 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most patients return to normal or near-normal activities 6 - 12 months following the transplant. For the rest of their lives, patients need to take immunosuppressive medication to prevent rejection.

Liver Transplantation in Patients with Hepatitis. One of the primary problems with many hepatitis patients is recurrence of the virus after transplantation.

One study of patients with hepatitis C reported 5-year risks of 80% for viral recurrence and 10% for cirrhosis. A 2004 study found that the hepatitis C virus recurs with more severity with liver donations from living donors than livers taken from cadavers.
Viral recurrence is also high in patients with hepatitis B. In 2007, the FDA approved HepaGram B, an immune globulin, to prevent recurrence of hepatitis B after transplantation. Patients need to receive HepaGram B injections on a lifelong basis.

Liver Transplantation in Autoimmune Liver Diseases. Patients who require transplantation for primary biliary cirrhosis are those who develop major complications of portal hypertension and liver failure or who have poor quality of life and short survival without the procedure. Survival rates after transplantation are excellent.

The outlook is also good for patients who have autoimmune hepatitis who require a transplant. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years. Rejection usually occurs in those patients whose immune systems are very compromised.

Liver Transplantation in Alcoholism. There is considerable controversy over whether liver transplantation should be performed in alcoholics with cirrhosis who are unlikely to abstain. One French study reported no differences in survival, transplant rejection, and other indicators of success and failure after transplantation between alcoholics and non-alcoholics and between alcoholics who abstained and those who relapsed after the procedure.

Click the icon to see an illustrated series detailing a liver transplant.

Lifestyle Changes

A healthy lifestyle is particularly important for people with cirrhosis.

Healthy Foods. Because important antioxidant vitamins are depleted in the cirrhotic liver, patients should maintain a diet rich in fresh fruits, vegetables, and whole grains.

Coffee and Tea. Coffee appears to help lower the risk of cirrhosis, especially among heavy drinkers. A 2006 study indicated that people who drank 1 - 3 cups of coffee a day reduced their risk of alcoholic cirrhosis by 40%. Those who drank 4 or more cups reduced their risk by 80%. Researchers think that there is some ingredient in coffee (other than caffeine) that is responsible for this apparent protection. Studies on tea have been mixed. Some studies report that tea also lowers the risk of chronic liver disease, while others have found no effect.

Antioxidant Supplements. There is some preliminary laboratory evidence that various antioxidant supplements -- including vitamin E, selenium, and S-adenosylmethionine (SAMe) -- may help protect against liver damage and cirrhosis. Supplements, however, are not recommended for people with liver disease except with the advice of a doctor. Some vitamins, such as vitamins D and A, are metabolized in the liver and can be toxic.

Iron Restrictions. Elevated iron levels have been associated with cirrhosis from many causes. Patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals, and should avoid cooking with iron-coated cookware and utensils.

Supplemental Nutritional Products. Supplemental nutritional beverages may be helpful, particularly for patients with both alcoholism and cirrhosis. In one study, patients with both alcoholism and cirrhosis drank Ensure every day as a supplement to their regular diet. After 6 months they showed significant improvement in many signs of overall health compared to those who did not consume the beverage.

Vitamin B1 (Thiamine). Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. It is not known if it has any benefit for cirrhosis. Pork is high in the vitamin, but more healthful sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

Like most vitamins, vitamin B1 may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Omega-3 Fatty Acids. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

Click the icon to see an image of omega-3 fatty acids.

Protein and Soy. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.

Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.

Zinc. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy.

Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their doctors.

Exercise increases the risk for portal pressure and variceal bleeding. One study reported that taking a beta-blocker may reduce this risk, although patients should discuss this with their doctor.

Infections can have a severe impact on the liver. Although most respiratory infections generally affect only the lungs, one small study suggested influenza may directly affect the liver in patients with cirrhosis and exacerbate the disease process. Researchers in the study advise annual flu shots for people with cirrhosis.

Patients should be aware that manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Among the natural substances being investigated for liver disease are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), SAMe, and silymarin (found in milk thistle).

Silymarin. Silymarin is a chemical found in the milk thistle herb. It is one of the most popular, and most studied, herbal remedies for liver disease. Some studies have indicated that silymarin may help improve liver enzyme levels. However, a 2005 review found that milk thistle did not help reduce deaths from liver disease caused by alcohol or hepatitis.

S-adenosylmethionine. S-adenosylmethionine (SAMe) is a chemical found in all parts of the body, which declines with age. It has been investigated for years in Europe for arthritis, depression, and liver disease. Some preliminary studies suggest it may provide some protection against liver damage and scarring and may improve survival rates in alcoholic patients with cirrhosis. It is very expensive, however, and as with all unregulated products, long-term side effects, drug interactions, and other factors are not fully known.

The following warnings are of particular importance for people with liver disease:

Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.

Abdominal Infections

Antibiotics are administered when fluid examination and tests for ascites indicate infection. For a first episode, the antibiotic cefotaxime is typically administered intravenously, requiring hospitalization. Treatment usually lasts 10 days, but research indicates that 5 days may be sufficient for certain patients. Some research indicates that the oral antibiotic ofloxacin may work as well with fewer complications, allowing patients to be treated at home.

In advanced cirrhosis, the risk for serious abdominal infection is high, and the antibiotic norfloxacin is often prescribed preventively against specific organisms that infect the abdominal cavity. One study reported, however, that patients who took norfloxacin became susceptible to Staphylococcal infections. Long-term treatments with norfloxacin or similar antibiotics may increase the risk for fungal infections after liver transplantation.

Encephalopathy

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

High ammonia levels
Bleeding
Low oxygen
Dehydration
Infection
Use of sedatives

Some studies indicate that manganese poisoning may be partially responsible for encephalopathy in cirrhosis. Studies are needed to determine if drugs that remove manganese improve this complication.

Ammonia is the leading toxin in causing encephalopathy related to cirrhosis. Mild encephalopathy is managed by directing therapy toward eliminating ammonia in the intestine:

The first step is to restrict animal protein, substituting meats and dairy products with vegetable protein, such as soy, and amino acid supplements.
Enemas, which clean out the intestine, may be effective.
Lactulose (Cephulac, Chronulac, Constulose, Duphalac, Enulose) and lactitol, known as disaccharides, help lower blood ammonia levels and have been shown to be effective in improving cognitive function and quality of life in people with mild encephalopathy.
Antibiotics, such as metronidazole, rifamycin, or neomycin, are effective in reducing levels of ammonia-producing bacteria in the intestine, although long-term use of these drugs can cause toxic side effects. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.
L. acidophilus is the probiotic found in live culture yogurt. Researchers are studying whether L. acidophilus food or supplements can aid in improving liver and cognitive functions.
Researchers are investigating whether exercise can help remove ammonia from the body and improve encephalopathy.

Investigational Drugs. Certain drugs, such as rifaximin (Xifaxan) and flumazenil (Mazicon, Romazicon), are under investigation for treating encephalopathy. Flumazenil is typically administered to counteract the effects of sedatives.

Ascites

Nearly all patients with ascites (fluid accumulation in the abdomen) can benefit from the following measures:

Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to improve this complication.)
Restricting salt.
Taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix). Previously, spironolactone was usually given alone, but experts now use it by itself only in patients with minimal fluid buildup. Patients should be monitored carefully for excessive and too-fluid loss, which can set off complications, including hypokalemia (dangerously low potassium levels), kidney failure, or encephalopathy. Weight loss from diuretics usually should not exceed 1 - 2 pounds per day, but there is no limit for patients with massive swelling.

Doctors often recommend bed rest for patients with ascites, but studies do not support its benefits. Restricting fluid is not usually necessary unless sodium levels in the blood are very low.

Patients with recurring ascites, or ascites that does not respond to standard diuretics after a month (refractory ascites), may require procedures to reduce fluid.

Large-Volume Paracentesis. Large-volume paracentesis is the current standard procedure and involves the following:

Large volumes of fluid are removed through a tube in the abdomen. Research indicates that 4 - 6 liters are usually effective and safe.
Albumin (protein) may be administered intravenously. This helps prevent a sudden drop in blood flow in the arteries. One study suggested that terlipressin, a drug that constricts blood vessels, may be as effective.
If the ascites does not respond to treatments, the patient may need paracentesis every 2 weeks or more frequently, and up to 10 liters may need to be removed.

Patients who need this procedure are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt. Studies have been mixed on whether transjugular intrahepatic portosystemic shunt (TIPS) improves survival without transplantation compared to large-volume paracentesis. An important 2003 study reported that although TIPS reduced the number of paracenteses, there was no improvement in survival rates. In addition, patients who were given TIPS had a higher risk for encephalopathy than those given large-volume paracentesis. In general, TIPS should be a second-line option for ascites that does not respond to diuretics.

Peritoneovenous Shunting. Peritoneovenous shunting is an older, more invasive, procedure involving insertion of a tube, or shunt, under the skin that routes the fluid from the abdomen into the jugular vein. The procedure can have serious complications, including infection, blood clots, encephalopathy, and rupture of blood vessels in the esophagus. It is now generally reserved for patients who are not candidates for repeat paracentesis or liver transplantation.

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Studies suggest that terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Researchers are testing certain drugs that may correct the imbalances in circulation that lead to portal hypertension and ascites. Of particular interest are drugs called nonpeptide vasopressin antagonists, also referred to as aquaretics. They may reverse the dilation in blood vessels that lead to salt and fluid retention.

The prognosis for patients with ascites is poor, even with intensive procedures. Liver transplantation should be considered for patients when ascites does not respond to treatments and when poor liver function or other complications, such as peritonitis or kidney failure, are present.

Bleeding Episodes

Preventing an Initial Bleeding Episode. About half of patients with mild-to-moderate cirrhosis have esophageal varices (enlarged veins in the esophagus). In such patients, the risk for bleeding within 2 years is as high as 35%. Bleeding is fatal in half of these patients. In general, experts recommend preventive drugs for such patients, even if they have not been screened with endoscopy -- the procedure needed to actually detect varices. Beta-blockers are the only medications to date that have some preventive effects, but others are under investigation.

Guidelines for Treating Bleeding Episodes. The doctor should first be certain that bleeding is caused by portal hypertension and ruptured varices and not by other conditions. For example, patients with cirrhosis are also at higher than average risk for bleeding peptic ulcers.

Saline or Ringers solution (a fluid and electrolyte replenisher) followed by red blood cells and plasma is administered immediately to replace lost blood.

The next step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode and prevent early recurrence, which typically occurs 3 - 5 days after a bleeding episode.

In general it is a two-pronged approach using drugs and endoscopy procedures.

Drugs. Either octreotide or vasopressin are typically used to reduce portal pressure and blood flow.
Endoscopy. Endoscopy involves insertion of a thin tube containing a tiny camera followed by surgery to make repairs. Endoscopic sclerotherapy is the most common procedure. Emergency sclerotherapy is often used as first-line therapy for variceal bleeding, but a major 2002 analysis suggested that it is no more effective than drugs for stopping bleeding, and it has potentially serious adverse effects.

A combination of drugs and endoscopy is the best approach for stopping bleeding compared to endoscopy alone. It is not clear if there is any difference in long-term survival, however.

Prevent Bleeding Recurrence. Rebleeding is common after an episode. Beta-blocker drugs are typically used, although they are not effective for many patients.

Preventing Complications. The patient who is experiencing a bleeding episode is at high risk for other complications, including pneumonia, bacterial infections, and hepatic encephalopathy. Bacterial infections can also impair blood clotting. Preventive oral antibiotics are often problematic in these patients. One study suggested that intravenous ciprofloxacin may be helpful.

Beta-Blockers. Beta-blockers, typically propranolol (Inderal) or nadolol (Corgard), reduce the heart rate and can lower portal vein pressure in many patients and so reduce variceal bleeding. Carvedilol (Coreg), a newer drug, may be even more effective, but more research is needed. Beta-blockers are also used as a primary approach for prevention of recurring bleeding. Nevertheless, they fail to reduce portal pressure in nearly 40% of patients with cirrhosis. They may not be appropriate for patients with type 1 diabetes, asthma, emphysema, and chronic bronchitis. They must be taken for at least 2 years and most likely longer to sustain a survival advantage.

Other Drugs. Other drugs are being used or investigated, mostly in combination with beta-blockers, to reduce recurrence rates.

Isosorbide mononitrate is a nitrate, a type of drug commonly used for angina. Combinations with beta-blockers appear to prevent rebleeding more effectively than beta-blockers alone. It is not clear if the combination improves any other aspects of the disease. The nitrate may also be an alternative drug for patients who cannot tolerate beta-blockers. Studies have failed to show any survival advantage, however, when isosorbide mononitrate is used alone.
The diuretic spironolactone may be helpful in combination with a beta-blocker for reducing both ascites and rebleeding after an initial episode.
Angiotensin II receptor antagonists, including losartan (Cozaar), are being studied for lowering portal pressure.

Somatostatinand Similar Drugs. Somatostatin is a natural hormone that constricts blood vessels. This drug or synthetic derivatives (octreotide and vapreotide) may be more effective than the common procedure, endoscopic sclerotherapy, for controlling bleeding. No single drug is more effective than another. Their benefits for improving overall survival, however, are still uncertain, and a major analysis of current studies found no effects on survival rates with either octreotide or somatostatin.

Somatostatin, the natural hormone, controlled variceal bleeding in 87% of patients in one study, but it is short acting.
Octreotide (Sandostatin) is a derivative of somatostatin and is longer acting. It has largely replaced the older drug. It is very safe, even for heart patients, and has few serious side effects.
Vapreotide (Octastatin) also resembles somatostatin. One study concluded that a combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone for controlling bleeding, but the combination therapy did not improve mortality rates at 42 days. The study suggested that these drugs should be taken for 5 days.

Vasoconstrictors. Vasoconstrictors narrow the blood vessels and reduce flow in the spleen. They are particularly effective when used with nitroglycerin.

Vasopressin (Pitressin) is the most commonly used vasoconstrictor. It poses a risk to the heart, however, and it is not clear whether it is actually helpful.
Terlipressin is a synthetic version of vasopressin that is proving to be as effective as sclerotherapy in controlling bleeding. It also lacks vasopressin's side effects and may prove to prolong survival and serve as a bridge for patients waiting for liver transplantation.

Endoscopic procedures use a tube inserted down through the esophagus, containing microcameras and tiny instruments. Endoscopy is used both to diagnose the disease and stop bleeding. The two standard procedures are band ligation and sclerotherapy. In general, a combination of drug therapies and an endoscopic procedure is the usual approach for preventing a bleeding recurrence.

Endoscopic Band Ligation. In endoscopic band ligation, latex bands are wrapped around the bleeding varices, shutting off the blood supply. It is the method of choice to control of bleeding and, in weekly sessions, to prevent rebleeding, because it has a lower risk for complications than sclerotherapy. Recurrence rates are higher with band ligation, however. Studies are mixed on whether weekly treatments with band ligation are any more effective in preventing rebleeding than beta-blockers plus isosorbide mononitrate. A combination of medications plus band ligation is under investigation.

Investigators are studying argon plasma coagulation (APC) after band ligation to prevent variceal recurrence and rebleeding. This procedure uses argon gas to deliver electric currents that coagulate and stop bleeding.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against bleeding in the esophagus. The endoscopic tube is inserted through the mouth. A sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding. The procedure is repeated over a period of 2 - 3 months. Repeat treatments appear to reduce rebleeding and death. Minor complications (usually ulcers in the mucus membranes) are common, and serious complications can occur (narrowing or perforation of the esophagus and leakage at the injection site.)

Balloon tamponade has been available for years, but it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses a tube inserted through the nose and down through the esophagus until it reaches the upper part of the stomach. A balloon at the tube's end is inflated and positioned tightly against the esophageal wall. It is usually deflated in about 24 hours. Serious complications can occur, the most dangerous being rupture of the esophagus. Recurrence of bleeding is common.

Shunts are used for patients who are still bleeding in the esophagus after endoscopic sclerotherapy or who are bleeding in the stomach. Choices include the following:

Transjugular intrahepatic portosystemic shunt (TIPS)
A surgical shunt

Shunt operations usually eliminate variceal bleeding, but encephalopathy and shunt failure are frequent complications. Doctors do not recommend shunts as elective surgery for high-risk patients who are candidates for liver transplantation, since shunts make this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt.A transjugular intrahepatic portosystemic (or portal-systemic) shunt (TIPS) involves the following:

The patient only requires a local anesthetic and a sedative.
A long needle is inserted into the jugular vein in the neck and passed down through the vena cava, a large vein that conducts blood back to the heart. This serves to widen the vein.
The surgeon makes an incision in the hepatic vein in the liver and creates a connection to the portal vein.
A cylindrical wire-mesh stent is inserted into this connecting vein.
The stent now acts as a shunt, which reroutes blood around the scarred liver.

TIPS is a good choice for bleeding that is not controlled by endoscopy, particularly when it is performed shortly after a bleeding episode. It also reduces ascites.

It is not useful as the first choice for stopping an initial bleeding episode or for preventing rebleeding, however, since it poses a high risk for encephalopathy. This complication outweighs its benefits compared to endoscopy for initial treatment and to beta-blockers for preventing recurrence. Blockage or closure of the shunt can develop over time.

TIPS is generally recommended for only patients who:

Cannot tolerate sclerotherapy
Are unlikely or unable to comply with the repeated procedures necessary for sclerotherapy
Have poor blood circulation

Surgical Shunts. There are two types of surgical shunts:

A portal shunt, or portal systemic shunt. It was introduced in 1945 and was the first significant treatment for bleeding varices. It relieves pressure in the portal vein by surgically joining it to the inferior vena cava, a large vein that conducts blood back to the heart. It poses a high risk for encephalopathy and does not appear to improve survival, so is not used often.
A variation called the H-graft portacaval shunt is a partial shunt that is proving to be effective for treating bleeding. It controls bleeding in 90% of patients and has a lower encephalopathy rate than the complete portal shunt or TIPS. In fact, early studies report that it may have lower rates for transplantation and death than TIPS.
A distal splenorenal shunt (DSRS) preserves blood flow through the portal vein while relieving pressure on the varices by joining the left kidney vein to the splenic vein. (The splenic vein returns blood from the spleen and is one of two veins that form the portal vein.) Studies show that DSRS has similar mortality rates compared to the portal shunt but lower rates of encephalopathy afterwards. Patients with alcoholic cirrhosis fare worse with DSRS than nonalcoholic patients. It is probably best used as an elective operation in patients with good liver function who continue to bleed in spite of endoscopy.

Resources

www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.aasld.org -- American Association for the Study of Liver Diseases
www.liverfoundation.org -- American Liver Foundation
www.gastro.org -- American Gastrointestinal Association
www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
www.hepfi.org -- Hepatitis Foundation International
www.pbcers.org -- Primary Biliary Cirrhosis Organization
www.organdonor.org -- National Transplant Society
www.unos.org -- United Network for Organ Sharing
www.organdonor.gov -- US government organ donor site

References

Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: A seventeen-year prospective cohort study. Hepatology. 2007 Aug 6; [Epub ahead of print]

Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007 Mar;45(3):579-87.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life inpatients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007 Mar;45(3):549-59.

Suzuki A, Lymp J, Donlinger J, Mendes F, Angulo P, Lindor K. Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007 Feb;5(2):259-64. Epub 2006 Dec 15.

U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med. 2006 Aug 1;145(3):204-8.

Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2006 Aug 1;145(3):209-23.

Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Parker Posey Is a Fan of Ashtanga Yoga

FitSugar — Fri, 20 Mar 2009 04:30:00 -0700

Ashtanga Yoga is one of my favorite types of yoga, and according to People magazine, Parker Posey is a big fan too. She says, "It centers me. I like the community," and I totally agree.

The thing that's so great about Ashtanga is that you can step into any class, and it'll be the same no matter what studio or state you're in. That's because this type of yoga follows a sequence known as Primary Series, that never changes. It includes Sun Salutations (five A's and five B's), standing postures such as Triangle, seated postures such as Butterfly, the entire Closing Sequence, and ends with Savasana. The flow of the postures is guided by ujayii breath, and each posture is linked with a series of movements known as a vinyasa, so you're always moving. Primary Series is mostly about poses that stretch your hamstrings, but Ashtanga has another series (that some think is more advanced) known as Second Series, that involves backbends and arm balancing poses.

If you're a runner, dancer, athlete, or someone who likes to work hard and sweat a lot, you'll love Ashtanga yoga. It will strengthen your muscles and increase flexibility in every area of your body. If you can't make it to a class, check out this DVD.

Source

Menstrual disorders

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Menstrual Disorders
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

“No-Period” Pill Approved

In May 2007, the FDA approved Lybrel, the first birth control pill that completely eliminates monthly menstrual periods. Lybrel contains low doses of the estrogen estradiol and the progesterone levonorgestrol. The active pills are taken 365 days a year -- with no inactive pill breaks. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, continued to have occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Other Options for Eliminating Menstrual Periods

In addition to Lybrel, women with menstrual problems have several other options for stopping periods:

Levonorgestrol-Releasing Intrauterine System (LNG-IUS). The LNG-IUS is an intrauterine device (IUD) that is placed in the uterus. The LNG-IUS releases levonorgestrol for up to 5 years. Over the course of the first year, it reduces menstrual bleeding. Many women find that their periods completely stop. Doctors often recommend this contraceptive device as a treatment for menorrhagia (heavy bleeding) and an alternative to hysterectomy. In the U.S., the LNG-IUS is marketed as Mirena.
Depo-Provera. Depo-Provera is an injectable progestin contraceptive. Most women who use Depo-Provera stop menstruating after a year. However, Depo-Provera is associated with serious side effects, including loss of bone density. Because of this risk, the FDA recommends that Depo-Provera should not be used for more than 2 years. Weight gain is also a common side effect.
Hysterectomy. Hysterectomy, the surgical removal of the uterus, is a permanent cure for menorrhagia, but it is an invasive procedure that also ends fertility.

Menstruation in Girls and Adolescents

According to a 2006 report from the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists:

Most girls begin to menstruate when they are between 12 - 13 years old.
Menstruation usually starts 2 - 3 years after initial breast development.
Girls who have not begun menstruation by the age of 15 should see a doctor for an evaluation.

Introduction

The Primary Organs and Structures in the Reproductive System.

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy, the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium, and during pregnancy it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed and a woman starts her menstrual flow (or "period"). Menstrual flow also consists of blood and mucus from the cervix and vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland control the reproductive hormones. In women, six hormones help regulate the reproductive system:

Click the icon to see an image of the hypothalamus and pituitary gland.

Gonadotropin-releasing hormone (GnRH) is released by the hypothalamus.
GnRH stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH.

Click the icon to see an image of the pituitary gland.

Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of two sets of organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this astonishing process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months.

A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process to conception is complex:

With the start of each menstrual cycle, FSH stimulates several follicles to mature over a two-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle.
FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls.
Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of LH.

LH serves two important roles:

First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization.
Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm.
If the egg is fertilized, it moves about 2 - 4 days later from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its nine-month incubation.
The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.
The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy.

Click the icon to see an image of the placenta.

Click the icon to see an image of the corpus luteum.

If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.


Menstrual Phases	Typical No. of Days	Hormonal Actions
Follicular (Proliferative) Phase	Cycle Days 1 through 6: Beginning of menstruation to end of blood flow.	Estrogen and progesterone start out at their lowest levels. FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.
	Cycle Days 7 - 13: The endometrium thickens to prepare for the egg implantation.
Ovulation	Cycle Day 14:	Surge in LH. Largest follicle bursts and releases egg into fallopian tube.
Luteal (Secretory) Phase, also known as the Premenstrual Phase	Cycle Days 15 - 28:	Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.
	If fertilization occurs:	Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.
	If fertilization does not occur:	Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Click the icon to see an animation about the menstrual cycle.

What is Menstruation? Menstruation, also called a "period," is the cyclical flow of blood from the uterus in women between the ages of puberty and menopause.

Onset of Menstruation (Menarche). The onset of menstruation, called the menarche, typically begins between the ages of 12 - 13 years. Menarche generally occurs 2 - 3 years after initial breast development (breast budding). African-American and Hispanic girls tend to mature slightly earlier than Caucasian girls. A higher body mass index (BMI) during childhood is associated with an earlier onset of puberty. Environmental factors and nutrition may also affect menarche timing.

Length of Monthly Cycle. The menstrual cycle can be very irregular during the first 1 - 2 years, ranging from 21 - 45 days. The length then generally stabilizes to an average of 28 days, although the cycle length may range from 21 - 34 days and still be considered normal. A variation of 10 days or more -- either more or fewer days -- may have an impact on fertility, however. The cycle lengthens when a woman is in her 40s, reaching an average of 31 days by age 49. A number of factors can affect cycle length at any age.


Shorter Cycles	Longer Cycles
Regular alcohol use.	Being under 21 and over 44.
Stressful jobs.	Being very thin (also at risk for short bleeding periods).
	Competitive athletics (also at risk for short bleeding periods).

Length of Periods. Periods average 6.6 days in adolescent girls. By the age of 21, menstrual bleeding averages 6 days until women approach menopause. However, about 5% of healthy women menstruate fewer than 4 days and 5% menstruate more than 8 days.

Normal Absence of Menstruation. Normal absence of periods can occur in any woman under the following circumstances:

Menstruation stops during the duration of pregnancy. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the doctor.
When women breastfeed they are unlikely to ovulate. After that time, menstruation usually resumes and they are fertile again.
Perimenopause starts when the intervals between periods begin to lengthen, and it ends with menopause itself (the complete cessation of menstruation). Menopause usually occurs at about age 51, although smokers often go through menopause earlier.

Menstrual Disorders

There are a number of different menstrual disorders. Problems can range from heavy, painful periods to no period at all.

Dysmenorrhea is severe, frequent cramping during menstruation. Pain occurs in the lower abdomen but can spread to the lower back and thighs. Dysmenorrhea is usually referred to as primary or secondary.

Primary dysmenorrhea. Cramps occur from contractions in the uterus. These contractions are a normal part of the menstrual process. With primary dysmenorrhea, cramping pain is directly related to and caused by menstruation. About half of menstruating women experience primary dysmenorrhea. It usually begins 2 - 3 years after a women begins to menstruate. The pain typically develops when the bleeding starts and continues for 32 - 48 hours. Cramps are generally most severe during heavy bleeding.

Secondary dysmenorrhea. Secondary dysmenorrhea is menstrually related pain that accompanies another medical or physical condition, such as endometriosis or uterine fibroids.

During a normal menstrual cycle, the average woman loses about 1 ounce (30 mL) of blood. Most women change their tampons or pads around 3 - 6 times per day. Menorrhagia is the medical term for significantly heavier bleeding. Menorrhagia occurs in 9 - 14% of all women and can be caused by a number of factors. Women often overestimate the amount of blood lost during their periods. Clot formation is fairly common during heavy bleeding and is not a cause for concern. However, women should consult their doctor if any of the following occurs:

Soaking through at least one pad or tampon every 1 - 2 hours for several hours
Heavy periods that regularly last 10 or more days
Bleeding between periods or during pregnancy. Spotting or light bleeding between periods is common in girls just starting menstruation and sometimes during ovulation in young adult women, but it is still a good idea to speak with a doctor.

Amenorrhea is the absence of menstruation. There are two categories: primary amenorrhea and secondary amenorrhea. These terms refer to the time when menstruation stops:

Primary amenorrhea occurs when a girl does not begin to menstruate. Girls who show no signs of sexual development (breast development and pubic hair) by age 13 should be evaluated by a doctor. Any girl who does not have her period by age 15 should be evaluated for primary amenorrhea.
Secondary amenorrhea occurs when periods that were previously regular become absent for at least three cycles.

Oligomenorrhea is a condition in which menstrual cycles are infrequent. It is very common in early puberty and does not usually indicate a medical problem. When girls first menstruate they often do not have regular cycles for a couple of years. Even healthy cycles in adult women can vary by a few days from month to month. In some women, periods may occur every 3 weeks and in others, every 5 weeks. Flow also varies and can be heavy or light. Skipping a period and then having a heavy flow may occur; this is most likely due to missed ovulation rather than a miscarriage. Women should be concerned when periods come less than 21 days or more than 3 months apart, or if they last more than 10 days. Such events may indicate ovulation problems.

Premenstrual syndrome (PMS) is a set of physical, emotional, and behavioral symptoms that occur during the last week of the luteal phase (a week before menstruation) in most cycles. The symptoms typically do not start until at least day 13 in the cycle, and resolve within 4 days after bleeding begins. Women may begin to experience premenstrual syndrome symptoms at any time during their reproductive years. Once established, the symptoms tend to remain fairly constant until menopause, although they can vary from cycle to cycle. About 100 symptoms have been identified with the premenstrual phase. [See In-Depth Report #79: Premenstrual syndrome.]

Causes

Menstrual disorders can be triggered by a number of different factors, such as hormone imbalances, genetic factors, clotting disorders, and pelvic diseases.

Contraction-Causing Chemicals. Powerful chemicals known as prostaglandins and arachidonic acid can induce uterine muscle contractions. Prostaglandins also play a large role in the heavy bleeding that causes dysmenorrhea.
Abnormal Nervous System Response. Some women with primary dysmenorrhea may have autonomic nervous systems that are overly sensitive to menstrual cycle changes. The autonomic nervous system regulates heart rate and blood pressure, and it contains the pain receptors in nerve fibers in the uterus and pelvic area. As a result, women with autonomic nervous system abnormalities may have a more intense response to pain.
Abnormalities in the Arteries in the Uterus.Impaired blood flow through the arteries in the uterus may cause severe dysmenorrhea for some women.
Genetic Factors. Genetic factors may play an important role in over half of primary dysmenorrhea cases.
Endometriosis. Endometriosis is a chronic and often progressive disease that develops when the tissue that lines the uterus (endometrium) grows onto other areas, such as the ovaries, bowels, or bladder. [See In-Depth Report #74: Endometriosis.]

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Uterine Fibroids. Fibroids are noncancerous growths that grow on the walls of the uterus. They can cause heavy bleeding during menstruation and cramping pain. [See In-Depth Report #73: Uterine fibroids.]
Other Causes. Pelvic inflammatory disease, ovarian cysts, and ectopic pregnancy. The intrauterine device (IUD) contraceptive can also cause dysmenorrhea.

Hormonal imbalances and uterine fibroids are the most common causes of menorrhagia. Other causes of menorrhagia include:

Dysfunctional Uterine Bleeding (DUB). DUB is a general term for abnormal bleeding. It is usually caused by hormonal problems and is one of the primary causes of menorrhagia. DUB usually occurs either when girls begin to menstruate or when women approach menopause, but it can occur at any time in during a woman's reproductive life. About 90% of DUB events occur when ovulation is not occurring (anovulatory DUB). In such cases, women do not properly develop and release a mature egg. When this happens, the corpus luteum does not form. As a result, estrogen is produced continuously, causing an overgrowth of the uterus lining. The period is delayed in such cases, and when it occurs menstruation can be very heavy and prolonged. The other 10% of DUB cases occur in women who are ovulating (ovulatory DUB), but progesterone secretion is prolonged because estrogen levels are low. This causes irregular shedding of the uterine lining and break-through bleeding.
Von Willebrand Disease and Other Bleeding Disorders. Bleeding disorders that stop blood from clotting can cause heavy menstrual bleeding. Most of these disorders have a genetic basis. Von Willebrand disease is the most common of these bleeding disorders and may be underdiagnosed in many women with unexplained menorrhagia.
Abnormal Blood Vessel Growth. Every month, blood vessels regrow in the uterus to replace the blood-rich uterine lining lost during menstruation. Abnormalities in this growth process (called arteriogenesis or angiogenesis) may occur in some women with menorrhagia.
Abnormalities in the Uterus. Structural problems or other abnormalities in the uterus may cause bleeding. They include uterine polyps (small benign growths in the uterus), uterine fibroids, endometriosis, adenomyosis, and miscarriage. Infections or inflammation in the vagina or pelvic area can also cause heavy bleeding.
Medications. Certain drugs, including anticoagulants and anti-inflammatory medications, can cause heavy bleeding.
Cancer. Uterine, ovarian, and cervical cancer can cause excessive bleeding but these are rare causes.
Other Medical Conditions. Systemic lupus erythematosus, diabetes, pelvic inflammatory disorder, and thyroid disorders can cause heavy bleeding. Women who have migraine headaches may be more likely to experience menorrhagia and endometriosis.

Fibroid tumors may not need to be removed if they are not causing pain, bleeding excessively, or growing rapidly.

Normal causes of skipped or irregular periods include pregnancy, breastfeeding, hormonal contraception, and perimenopause. Skipped periods are also common during adolescence, when it may take a while before ovulation occurs regularly. Consistently absent periods may be due to the following factors:

Delayed Puberty. The most common cause of primary amenorrhea is delayed puberty due to some genetic factor that delays physical development.
Weight Loss and Eating Disorders. Extreme weight loss and reduced fat stores lead to hormonal changes that include low thyroid levels (hypothyroidism) and elevated stress hormone levels (hypercortisolism). These changes produce a reduction in reproductive hormones. A syndrome known as the female athlete triad is associated with hormonal changes that occur with eating disorders in young women who excessively exercise. It comprises anorexia (severe weight loss), amenorrhea, and osteoporosis (decrease in bone density).
Polycystic Ovarian Syndrome (PCOS). PCOS is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to some studies, nearly 30% of obese women with PCOS have amenorrhea.
Elevated Prolactin Levels (Hyperprolactinemia). Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) in women who are not pregnant or nursing can reduce gonadotropin hormones and inhibit ovulation, thus causing amenorrhea. It is the cause of between 10 - 40% of cases of secondary amenorrhea.
Premature Ovarian Failure (POF). POF is the early depletion of follicles before age 40. In most cases it leads to premature menopause. POF is a significant cause of infertility.
Structural Problems. In some cases, structure problems or scarring in the uterus may prevent menstrual flow. Inborn genital tract abnormalities may also cause primary amenorrhea. A specific malformation called Mullerian agenesis, in which no vagina or uterus develops, is rare but still causes about 16% of primary amenorrhea cases.
Stress. Physical and emotional stress may block the release of luteinizing hormone, causing temporary amenorrhea
Other Medical Conditions. Epilepsy, thyroid problems, celiac sprue, metabolic syndrome, and Cushing's disease are associated with amenorrhea.

If the ovaries produce too much androgen (hormones such as testosterone) a woman may develop male characteristics. This ovarian imbalance can be caused by tumors in the ovaries or adrenal glands, or polycystic ovarian disease. Virilization may include growth of excess body and facial hair, amenorrhea (loss of menstrual period) and changes in body contour.

Risk Factors

Age plays a key role in menstrual disorders. Girls who start menstruating at age 11 or younger are at higher risk for severe pain, longer periods, and longer menstrual cycles. Between 20 - 90% of teenage girls report menstrual pain and about 15% report that it is severe. Adolescents may experience amenorrhea before their ovulating cycles become regular.

Women who are approaching menopause (perimenopause) may also skip periods. Occasional episodes of heavy bleeding are also common as women approach menopause.

Other risk factors include:

Weight. Being either excessively overweight or underweight can increase the risk for dysmenorrhea and amenorrhea.
Smoking and Alcohol Use. Smokers have a 50% higher risk than nonsmokers for menstrual pain. Alcohol does not cause menstrual pain, but in women with existing dysmenorrhea, alcohol consumption may prolong the pain.
Stress. Physical and emotional stress may block the release of luteinizing hormone, causing temporary amenorrhea. Emotional problems, including history of sexual abuse, may predispose to dysmenorrhea.
Menstrual Cycles and Flow. Longer and heavier menstrual cycles can cause dysmenorrhea.
Pregnancy History. Women who have had a higher number of pregnancies are at increased risk for menorrhagia. Women who have never given birth are at increased risk of dysmenorrhea, while women who first gave birth at a young age are at lower risk.
Chronic Pelvic Pain. Many women experience chronic pain in the pelvic area. This pain can be due to gynecologic reasons (fibroids, endometriosis, pelvic inflammatory disease) or non-gynecologic causes (irritable bowel syndrome, interstitial cystitis, diverticulitis).

Exercise and oral contraceptive use may help protect against dysmenorrhea.

Complications

An estimated 10 - 15% of all women in their reproductive years have chronic gynecologic problems. Nearly 30% of women reporting such problems spend one or more days in bed per year because of them. In fact, menstrual pain is the primary cause of short-term absences in school age girls. In adult women, who have not received treatment, it is an important cause of reduced work productivity.

Menorrhagia is the most common cause of anemia in premenopausal women. A blood loss of more than 80mL per menstrual cycle can trigger anemia. According to one report, 10% of women in their reproductive years have iron deficiencies, and between 2 - 5% have iron levels low enough to cause anemia. Although poor diets play a role in many cases, the problem is compounded in women who have heavy periods.

Most cases of anemia are mild. Nevertheless, even mild anemia can reduce oxygen transport in the blood, causing fatigue and a diminished physical capacity. (Some studies indicate that even iron deficiency without anemia can produce a subtle but still lower capacity for exercise.) Moderate-to-severe iron-deficiency anemia is known to reduce endurance.

Moderate-to-severe anemia can also cause shortness of breath, rapid heart rate, lightheadedness, headaches, ringing in the ears (tinnitus), irritability, pale skin, restless legs syndrome, and mental confusion. Heart problems can occur in prolonged and severe anemia that is not treated. Pregnant women who are anemic, particularly in the first trimester, have an increased risk for a poor pregnancy outcome. [See In-Depth Report #57: Anemia.]

Amenorrhea caused by reduced estrogen levels increases the risk for osteoporosis (loss of bone density). Conditions that are associated with low estrogen levels include eating disorders, the female-athlete triad (excessive exercise and weight loss), pituitary tumors, and premature ovarian failure. Because bone growth is at its peak in adolescence and young adulthood, losing bone density at that time is very dangerous, and early diagnosis and treatment is essential for long-term health. [See In-Depth Report #18: Osteoporosis.]

Some conditions associated with heavy bleeding, such as ovulation abnormalities, fibroids, or endometriosis, are important contributors to infertility. Many conditions that cause amenorrhea, such as ovulation abnormalities and polycystic ovary syndrome, can also cause infertility. Irregular periods from any cause may make it more difficult to conceive. In some cases treating the underlying condition can restore fertility. In other cases, specific fertility treatments that use assisted reproductive technologies may be beneficial. [See In-Depth Report #22: Infertility in women.]

Diagnosis

A doctor needs to have a complete history of any medical or personal conditions that might be causing menstrual disorders. This information can help determine whether a menstrual problem is caused by another medical condition. For example, non-menstrual conditions that may cause abdominal pain include appendicitis, urinary tract infections, ectopic pregnancy, and irritable bowel syndrome. Endometriosis and fibroids may cause heavy bleeding and pain. Doctors may ask questions concerning:

Menstrual cycle patterns -- length of time between periods, number of days that periods last, number of days of heavy or light bleeding
The presence or history of any medical conditions that might be causing menstrual problems
Any family history of menstrual problems
History of pelvic pain
Regular use of any medications (including vitamins and over-the-counter drugs)
Diet history, including caffeine and alcohol intake
Past or present contraceptive use
Any recent stressful events
Sexual history (it is very important that patients trust their doctor enough to describe any sexual activity that might be risky)

Menstrual Diary. A menstrual diary is a helpful way to keep track of changes in menstrual cycles. Patients can record when their period starts, how long it lasts, and the amount of bleeding and pain that occurs during the course of menstruation.

Pelvic Examination. A pelvic exam is a standard part of diagnosis. A Pap test may be done during this exam.

Blood tests can help rule out other conditions that cause menstrual disorders. For example, a doctor may test thyroid function to make sure that low thyroid (hypothyroidism) is not present. Blood tests can also check follicle-stimulating hormone, estrogen, and prolactin levels. Patients who have menorrhagia may get tests for bleeding disorders. If patients are losing a lot of blood, they should also get tested for anemia.

Patients who have amenorrhea may need to receive special hormonal tests. The progestational challenge test uses oral or injected progesterone to test for a functional uterine lining (endometrium):

Bleeding that occurs up to 3 weeks after the progesterone dose suggests that the woman has normal estrogen levels but is not ovulating, particularly if thyroid and prolactin levels are normal. In such cases, the doctor will check for stress, recent weight loss, and any medications. Such results could also suggest polycystic ovaries or stress.
A failure to bleed could indicate an abnormal uterus that prevents outflow or insufficient estrogen. In such cases, the next step may be to administer estrogen followed by progestin. If bleeding occurs after that, then the cause of amenorrhea is related to low estrogen levels. The doctor will then check for ovarian failure, anorexia, or other causes of low estrogen. If bleeding does not occur, then the doctor would check for obstructions that are preventing outflow of menstruation.

Imaging techniques are often used to detect certain conditions that may be causing menstrual disorders. Imaging can help diagnose fibroids, endometriosis, or structural abnormalities of the reproductive organs.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and finding obstructions in the urinary tract. It uses sound waves to produce an image of the organs. Ultrasound carries no risk and causes very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline injected into the uterus to enhance the visualization of the uterus.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of fibroids, polyps, or other causes of bleeding. It may miss cases of uterine cancer, however, and is not a substitute for more invasive procedures, such as D&C or endometrial biopsy, if cancer is suspected.

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This can cause cramping.

Hysteroscopy is non-invasive, but 30% of women report severe pain with the procedure. The use of an anesthetic spray such as lidocaine may be highly effective in preventing pain from this procedure. Other complications include excessive fluid absorption, infection, and uterine perforation. Hysteroscopy is also performed as part of surgical procedures.

Laparoscopy. Diagnostic laparoscopy, an invasive surgical procedure, is currently the only definitive method for diagnosing endometriosis. Laparoscopy normally requires a general anesthetic, although the patient can go home the same day. The procedure is as follows:

Click the icon to see an image of laparoscopy.

The surgeon makes tiny abdominal incisions through which a fiber optic tube, equipped with small camera lenses, is inserted. The doctor uses these devices to view the uterus, ovaries, tubes, and peritoneum (lining of the pelvis) on a video monitor.
Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away so that the doctor has a wider view.
A blue dye may be flushed through the fallopian tubes to determine blockage; if there is an obstruction, the dye will not flow through the tube.
If the surgeon needs to remove small endometrial cysts or other lesions during the procedure (operative laparoscopy), tiny surgical instruments are passed through a tube.

The procedure is used for detecting and staging endometriosis to determine its severity. In some cases, the procedure itself will restore fertility in women with endometriosis.

Transvaginal Hydrolaparoscopy. Transvaginal hydrolaparoscopy is a new and less invasive approach than laparoscopy, since the instruments are inserted through the vagina, not through incisions in the abdomen. It requires only sedation, does not use CO2 to distend the abdomen, and has a much shorter and easier recovery than with standard laparoscopy. When used by a skilled professional, it is as accurate as laparoscopy, but is not yet widely available.

Endometrial Biopsy With or Without Dilation and Curettage (D&C). When heavy or abnormal bleeding occurs, an endometrial (uterine) biopsy can be performed in the office along with an ultrasound. It is usually used with a procedure called dilation and curettage (D&C), which is particularly important to rule out uterine (endometrial) cancer. A D&C is a somewhat invasive procedure:

A D&C is usually done in an outpatient setting so that the patient can return home the same day, but it sometimes requires a general anesthetic. It may need to be performed in the operating room to rule out serious conditions or treat some minor ones that may be causing the bleeding.
The cervix (the neck of the uterus) is dilated (opened).
The surgeon scrapes the inside lining of the uterus and cervix.

The procedure is used to take samples of the tissue and to relieve heavy bleeding in some instances. D&C can also be effective in scraping off small endometrial polyps, but it is not very useful for most fibroids, which tend to be larger and more firmly attached.

Click the icon to see an image of a D&C.

Treatment

Making dietary adjustments starting about 14 days before a period may help some women with certain mild menstrual disorders, such as cramping. The general guidelines for a healthy diet apply to everyone; they include eating plenty of whole grains, fresh fruits and vegetables, and avoiding saturated fats and commercial junk foods.

Dietary Fats. A 2000 study reported that women who followed a low-fat vegetarian diet for two menstrual cycles experienced less pain and bloating and a shorter duration of premenstrual symptoms than those who ate meat. Women who are losing too much blood, however, may need meat to help maintain iron levels. Choosing more fish and eggs may be a helpful alternative.

More than one study has reported less menstrual pain with a higher intake of omega 3 fatty acids (fat compounds found in oily fish, such as salmon and tuna). In one study, supplements of fish oil also appeared to reduce heavy bleeding in adolescent girls.

Salt Restriction. Limiting salt may help bloating.

Reducing Caffeine, Sugar, and Alcohol. Reducing caffeine, sugar, and alcohol intake may be beneficial. The effects of alcohol are mixed. One study found that women who drank less wine had less menstrual pain than those who drank more wine. Another reported that regular consumption of alcohol lowered the risk for developing cramps, but it actually increased the length of cramping time in certain women. In any case, alcohol is certainly not recommended for relieving menstrual disorders.

Forms of Iron. Women who have heavy menstrual bleeding can sometimes become anemic. Eating iron-rich foods can help prevent anemia. Iron found in foods is either in the form of heme or non-heme iron. Heme iron is better absorbed than non-heme iron.

Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
Non-heme iron is less well absorbed. About 60% of iron in meat in non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables only have the non-heme form. Such vegetable products include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron:

Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.
Increasing intake of vitamin C rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin C rich foods are healthful and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or six ounces of orange juice can double the amount of iron the body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on iron stores.)

Exercise may help reduce menstrual pain. It is not clear, however, how intense the exercise should be to reduce dysmenorrhea. For example young female athletes in a 2001 study were only half as likely to suffer from dysmenorrhea as their non-active peers. However, they were also three times more likely to experience an absence of periods. Exercise may be very helpful for women with menstrual pain due to endometriosis. It relieves stress and tension and may reduce hormonal levels that could contribute to endometrial growth.

Sexual Activity. There have been reports that orgasm reduces the severity of menstrual cramps.

Applying Heat. One study found that continuously applying a heated abdominal pad for 12 hours 2 days in a row was as effective in reducing menstrual cramps as ibuprofen (Advil). A warm bath may also be helpful.

Menstrual Hygiene. Tampons should be changed every 4 - 6 hours. Scented pads and tampons should be avoided; feminine deodorants can irritate the genital area. Women should not douche during or between periods. Women who douche on a weekly basis are more likely to contract cervical cancer than those who do not. Douching may destroy the natural bacteria normally present in the vagina. Bathing regularly is sufficient.

Acupuncture and Acupressure. Some studies, including a small well-conducted trial, have reported relief from pelvic pain after acupuncture or acupressure, a technique that applies small pins or pressure to specific points on the body. Some women report relief with reflexology, an acupuncture technique that uses manual pressure on acupuncture points on the ears, hands, and feet.

Yoga and Meditative Techniques. Yoga and meditative techniques that promote relaxation may help relieve menstrual cramps.

Chiropractic. Some women with primary dysmenorrhea have sought help from chiropractors trained in spinal manipulation. One study compared a high-force spinal manipulation technique with a low-force maneuver used as a placebo technique. Both showed lower scores on tests that measure pain, perhaps indicating that a simple back rub by a sympathetic partner or friend may be helpful.

Herbs and Supplements. Studies have not generally found herbal or natural remedies to be any more effective than placebos for reducing menstrual disorders. Natural remedies for menstrual symptoms include:

Evening primrose oil. Evening primrose oil contains a polyunsaturated fatty acid known as gamma linolenic acid. This compound seems to block the release of cytokines and prostaglandins, immune system factors that are manufactured by the endometrium. These factors are involved in uterine muscle contraction and cramping. Foods that contain gamma linolenic acid include black currant oil and cold-water fish.
Omega-3 fatty acids. There is some evidence that the fatty acids found in fish oil have anti-inflammatory properties that may help relieve menstrual cramps. Omega-3 fatty acids are available in supplement pill form, but diets that include cold-water fish (tuna, salmon, mackerel) provide the best source for these nutrients.
Ginger. Ginger tea or capsules may help to relieve nausea and bloating.
Aromatherapy. Aromatherapy with topically-applied lavender, sage, and rose oils may help ease menstrual cramps, according to a small 2006 study.
Pycnogenol. Pycnogenol, an extract from the bark of the French maritime pine tree, may help reduce menstrual pain and discomfort, according to some small studies.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like with drugs, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for menstrual disorders:

Valerian has been used by some women for menstrual cramps. This herb is listed on the FDA's list of generally safe products. However, its calming effects can be dangerously increased if it is used with sedative drugs. Other interactions and long-term side effects are unknown.
Black cohosh (also known as Cimicifuga racemosa or squawroot) contains a plant estrogen and is the most studied herbal remedy for treating menopausal symptoms, although a 2006 study indicated it is ineffective. Some women also use it for dysmenorrhea. Black cohosh has been used for decades in Germany and appears to be safe, but because its actions resemble estrogen more clinical studies are needed to confirm both long-term safety and effectiveness. Headaches and gastrointestinal problems are common side effects. At this time, experts do not recommend taking it for more than 6 months.

Medications

There are a number of different medicines prescribed for menstrual disorders.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that increase uterine contractions. They are effective painkillers that also help control the inflammatory factors that may be responsible for heavy menstrual bleeding. Aspirin is the most common NSAID, but there are dozens of others available over the counter or by prescription.

Among the most effective NSAIDs for menstrual disorders are ibuprofen (Advil, Motrin, Midol PMS), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and mefenamic acid (Ponstel). In a comparison study of ibuprofen and naproxen, both were effective, but the effects of naproxen lasted longer. Naproxen, however, may carry a higher risk for gastrointestinal (GI) effects than ibuprofen. Long-term use of any NSAID can increase the risk for GI bleeding and ulcers. Long-term NSAID use can also increase the risk for heart attack and stroke.

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. To avoid irritating an ulcer a person can try eliminating certain substances from their diet such as caffeine, alcohol, aspirin, and avoid smoking. Patients can take certain medicines to suppress the acid in the stomach causing the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

Acetaminophen. Some evidence suggests that acetaminophen (Tylenol) reduces levels of female hormones (gonadotropins and estradiol, an estrogen), which may have some beneficial effect on menstrual disorders. A combination of acetaminophen and pamabrom (Women's Tylenol Menstrual Relief) is specifically aimed at treating menstrual pain and bloating. (Pamabrom is a diuretic, a drug used to reduce fluid build-up and bloating.) One study indicated that acetaminophen is less effective than NSAIDs for dysmenorrhea, but does not have the same potentially harmful effects on the gastrointestinal tract.

Oral contraceptives (OCs), commonly called "the Pill" collectively, contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestogen). The estrogen compound used in most combination OCs is estradiol. There are many different progestins, but commonly used types include levonorgestrol, drospirenone, norgestrol, norethindrone, and desogestrel. (Combination contraceptives are also available in other forms, including patches and vaginal rings, but they may increase the risk for menstrual cramping and bleeding.)

Click the icon to see an image of hormone-based contraceptives.

OCs are often used to regulate periods in women with menstrual disorders, including menorrhagia (heavy bleeding), dysmenorrhea (severe pain), and amenorrhea (absence of periods). Oral contraceptives are as effective for treating pain from endometriosis as the more potent gonadotropin releasing hormone agonists. They also protect against ovarian and endometrial cancers.

High-dose OCs have been specifically helpful for adolescents with severe dysmenorrhea. Studies with low-dose OCs have also shown they can reduce menstrual pain for adolescents and adults.

OCs may be taken in cycles that include pills of the same or different strengths. These are categorized as monophasic (one-phase), biphasic (two-phase), or triphasic (three-phase). Monophasic pills contain the same amount of hormones in each dose. Biphasic and triphasic pills contain different dosages of hormones with the pill packs. The monophasic regimen is the most studied regimen and is usually recommended for dysmenorrhea as well as premenstrual symptoms.

Continuous-Dosing OCs. Standard OCs usually come in a 28-pill pack with 21 days of “active” (hormone) pills and 7 days of “inactive” (placebo) pills. Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly menstrual periods. These OCs contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.

Seasonale, the first continuous-dosing contraceptive, was approved in 2003. It contains 81 days of active pills followed by 7 days of inactive pills. Women who take Seasonale have on average a period every 3 months. Seasonique, a follow-up to Seasonale, was approved in 2006. As with Seasonale, it produces about 4 periods a year. With Seasonique, a woman takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.

In 2007, the FDA approved Lybrel, which supplies a daily low dose of levonorgestrol and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Side effects. Common side effects of combination OCs include headache, nausea, bloating, breast tenderness, and bleeding between periods. The estrogen component in combination OCs is usually responsible for these side effects. In general, today’s OCs are much safer than OCs of the past because they contain much lower dosages of estrogen.

However, all OCs can increase the risk for migraine, stroke, heart attack, and blood clots. The risk is highest for women who smoke or who have a history of heart disease risk factors (such as high blood pressure or diabetes) or past cardiac events. Women who have certain metabolic disorders, such as polycystic ovary syndrome (PCOS), are also at higher risk for the heart-related complications associated with these pills.

Progestins (either natural progesterone or synthetic progestogen) are used by women with irregular or skipped periods to restore regular cycles. Because of this, they may also help menstrual pain. They also reduce heavy bleeding and may protect against uterine and ovarian cancers. Progestin-only contraceptives may be a good option for women who are not candidates for estrogen-containing OCs, such as women smokers over the age of 35.

Progestins can be delivered in various forms:

Levonorgestrel-Releasing Intrauterine System (LNG-IUS). An intrauterine device (IUD) that releases progestin can be very beneficial for menstrual disorders, regardless of its contraceptive effects. In the United States, a levonorgestrel-releasing intrauterine system, also called an LNG-IUS, is sold under the brand name Mirena. The LNG-IUS has been proven to reduce heavy bleeding and pain in many women who suffer from menorrhagia and dysmenorrhea. In a 3-year study, the proportion of women with dysmenorrhea using the LNG-IUS dropped from 60% to about 30%. Some studies suggest that the LNG-IUS is more effective than oral contraceptives for controlling heavy menstrual bleeding.

Many experts now recommend the LNG-IUS as a first-line treatment for menorrhagia, particularly for women who may face hysterectomy (removal of uterus), conservative surgery such as endometrial resection (removal of endometrial lining), or endometrial ablation (destruction of endometrial lining). Studies report that about 60% of women with menorrhagia who use the LNG-IUS are able to avoid hysterectomy. Some clinical trials suggest that endometrial resection or ablation may be better at reducing menstrual bleeding than the LNG-IUS. Other studies report that the device is as effective as conservative surgery. Research also indicates that women who choose the LNG-IUS are as satisfied with their quality of life as those who choose surgery.

The LNG-IUS remains in place in the uterus and releases the progestin levonorgestrel for up to 5 years. Progestin released by an IUD mainly affects the uterus and cervix, and so it causes fewer widespread side effects than progestin pills do. (However, the other major IUD -- the Copper T -- may increase bleeding.)

After the LNG-IUS is inserted, heaver periods may occur during the first 3 - 6 months as the lining of the uterus is shed. This shedding may also cause irregular periods and light bleeding (“spotting”) between menstrual cycles. Eventually, the LNG-IUS results in a shorter period, with little or no blood flow. For many women, the LNG-IUS completely stops menstrual periods.

Common side effects include cramping, acne, back pain, breast tenderness, headache, mood changes, and nausea. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually cause no symptoms and resolve on their own. Women who have a history of pelvic inflammatory disease or who have had a serious pelvic infection should not use the LNG-IUS.

Injections (Depo-Provera). Depo-Provera uses a progestin called medroxyprogesterone. Most women who use Depo-Provera stop menstruating altogether after a year. Depo-Provera may be beneficial for women with heavy bleeding, severe cramps, or both. Women who eventually want to have children should be aware that Depo-Provera can cause persistent infertility for up to 22 months after the last injection, although the average is 10 months.

Weight gain can be a problem, particularly in women who are already overweight. Women should not use Depo-Provera if they have a history of liver disease, blood clots, stroke, or cancer of the reproductive organs.

Long-term (more than 2 years) use of Depo-Provera can cause loss of bone density. In 2004, the FDA added a “black box” warning to the Depo-Provera label advising of this risk. The warning notes that the decline in bone density increases with duration of use and may not be completely reversible even after the drug is discontinued. Based on this information, the FDA recommends that Depo-Provera should not be used for longer than 2 years unless other birth control methods are inadequate. [See In-Depth Report #91: Birth control options for women.]

Gonadotropin releasing hormone (GnRH) agonists are sometimes used to treat menorrhagia. GnRH agonists block the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, Nafarelin (Synarel). Such drugs may be used alone or in preparation for procedures used to destroy the uterine lining. They are not generally suitable for long-term use.

Commonly reported side effects, which can be severe in some women, include menopausal-like symptoms. These symptoms include hot flashes, night sweats, changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women ordinarily should not take these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist.
Intermittent leuprolide, which uses repeated 6-month courses of GnRH agonists followed by an average of 9 months of symptom control only.
Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
Adding a bone-protective drug called a bisphosphonate (alendronate or etidronate) may be helpful.
Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include parathyroid hormone or selective estrogen-receptor modulators (SERMs).

GnRH treatments used alone do not prevent pregnancy. Furthermore, if a woman becomes pregnant during their use, there is some risk for birth defects. Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Danazol (Danocrine) is a synthetic substance that resembles a male hormone. It suppresses estrogen, and therefore menstruation, and is used (sometimes in combination with an oral contraceptive), to help prevent heavy bleeding. It may also improve surgical success rates in women with menorrhagia when used before ablation or resection to destroy the uterine lining. It is not suitable for long-term use.

Adverse side effects include facial hair, deepening of the voice, weight gain, acne, and dandruff. It may also increase the risk for unhealthy cholesterol levels. Pregnant women or those trying to become pregnant should not take this drug because it may cause birth defects. [See In-Depth Report #74: Endometriosis or In-Depth Report #63: Uterine fibroids.]

Surgery

Women with heavy menstrual bleeding, dysmenorrhea, or both have medical and surgical options available to them. Most procedures eliminate the possibility for childbearing, however. Hysterectomy removes the entire uterus while ablation and resection destroy most or all of uterine lining.

For some women, an intrauterine device (IUD) that releases hormones is proving to be a good medical alternative to surgery. The levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena), is increasingly being used to treat menorrhagia. Many experts recommend it as a first-line treatment for heavy bleeding. Studies have found the LNG-IUS to work just as well as ablation and resection. Women should be sure to ask their doctors about all medical options before undergoing surgical procedures.

In either standard endometrial resection or ablation, the entire lining of the uterus (the endometrium) is removed or destroyed. The standard endometrial ablation and resection techniques are equally effective in reducing bleeding. In general, either one reduces bleeding by about half. About 15% of women require a hysterectomy later on. Some recent studies report that microwave endometrial ablation may work better than resection, and considerably reduce the need for future hysterectomy. Women should discuss with their surgeon which procedure may be best for them.

Hormonal Pretreatment. Hormonal drugs, such as GnRH analogs or danazol, are sometimes used before the procedures to help prepare the uterus by thinning the endometrial lining. However, a 2005 study suggested that drug preparation may not be required before microwave endometrial ablation.

Postoperative Effects of Endometrial Ablation or Resection Procedures. Postoperative effects of either procedure include the following:

Anesthesia may cause nausea and even vomiting for a few hours following the operation.
Cramping and pain occurs but can usually be relieved using over-the-counter painkillers.
Patients may experience frequent urination for the first day after the procedure and blood-tinged, watery vaginal discharge for more than a month.

Complications of Endometrial Ablation or Resection Procedures. Complications from either procedure may include perforation of the uterus, injury to the intestine, hemorrhage, or infection.

In standard resection and ablation, the uterine cavity is expanded by filling it with fluid. In rare instances, excess glycine from the fluid instilled in the uterus builds up in the bloodstream and causes an abnormal drop in sodium levels. This can be a serious event resulting in mental confusion, convulsions, and, very rarely, death. General anesthesia may pose a lower risk for this complication than local. Some of the newer ablation procedures do not require fluid instillation.

In a 2002 study, 10% of patients who were given standard ablation using the roller ball technique experienced blockage or blood build-up in the fallopian tubes that require a follow-up procedure or a hysterectomy later on.

Resection procedures benefit those women who have very heavy menstrual bleeding but do not have any other underlying uterine problems, such as polyps, hyperplasia of the endometrium, or cancer. Resection also seems to have a higher success rate in reducing bleeding and relieving pain in older women than younger women.

Resection procedures typically involve the following:

The patients are given a local or general anesthesia.
The surgeon dilates (widens) the cervix and fills the uterine cavity with fluid to improve visualization.
The surgeon then removes the uterine lining.

Endometrial ablation involves the destruction of the uterine lining using a number of approaches that include heat, electricity, laser energy, and other methods. The standard ablation approach uses hysteroscopy to allow the doctor to view the uterus.

A typical procedure uses the following approach:

The doctor uses hysteroscopy to view the uterine cavity. This is a fiber optic light source inside a long flexible or rigid tube, which is inserted into the uterus in order to view the cavity. The image of the uterine cavity is transmitted by camera lenses to a video screen.
The uterine cavity is filled with fluid for better visualization. A special substance such as glycine, sorbitol, or mannitol may be added to the fluid so that it does not conduct electricity. This process prevents accidental burns.
With ablation, uterine tissue is usually vaporized using a thin powerful laser beam or high electric voltage. One ablation technique, known as electrocautery with roller ball diathermy, uses a device that looks like a tiny steamroller. This device applies heat and destroys endometrial tissue as it rolls across the uterine lining.
The procedure typically takes 15 - 45 minutes. Although a general anesthetic is usually required, the patient can go home the same day.

It takes about 3 months to determine whether the procedure has been effective. There should be a follow-up appointment about 2 weeks after the procedure. One study revealed 80% of the women were satisfied with ablation. However, this was lower than the 89% satisfaction rate reported by women who had hysterectomy. About 30% of women who have this procedure still require additional surgeries, including hysterectomies, within 5 years. The risk is higher in younger women. The risk for complications increases with repeat ablations.

Newer endometrial ablation techniques (described below) do not use the hysteroscopy. These “second-generation” procedures are technically easier to perform than standard ablation and may be less dependent on the skill of the surgeon. A 2005 review found that second-generation procedures reduce surgery time. Women who had the newer procedures were less likely to experience fluid buildup, perforation of the uterus, cervical cuts and tears, or accumulation of blood in the uterus. However, women did experience more nausea, vomiting, and cramping.

Balloon Endometrial Ablation. Balloon ablation (ThermaChoice in the U.S., Cavaterm in Europe) is proving to be very effective:

A balloon at the tip of a catheter tube is filled with fluid and inflated until it conforms to the walls of the uterus.
A probe in the balloon heats the fluid to destroy the endometrial lining.
After 8 minutes the fluid is drained out and the balloon is removed.

Studies show that bleeding is controlled in 70 - 90% of patients for at least 5 years. It is fast, simple to perform, and comparison studies suggest that it is as effective as resection and standard ablation.

Treatment is less likely to succeed in younger women, those with a tipped uterus, when the uterine lining is 4 mm or thicker, and when menstrual bleeding is prolonged. Pregnancy is possible if some of the lining is maintained, but generally women should not depend on it to preserve fertility.

Electric Wand Ablation. This approach involves inserting a slender wand up through the cervix (the NovaSure System). A triangular mesh-like device is then passed through the wand and expands to fit the uterus. Electrical energy is passed through it for about 90 seconds and the mesh and wand are then withdrawn. As with many other second-generation ablation techniques, it is quick, effective, and does not require pretreatment to expand the uterus. In a 2003 study, it achieved significantly lower bleeding rates than balloon ablation.

Freezing (Cryoablation). With cryoablation (Her Option Uterine Cryoablation Therapy System), the uterine tissue is frozen, which destroys the lining. The procedure takes about 10 minutes to destroy the lining, and it requires no fluid to expand the uterus and little anesthetic. Ultrasound is used to guide the procedure so that the surgeon can view the depth of the ablation. In a 2003 study, cryoablation was slightly less successful than a standard ablation procedure. However, bleeding still declined by 92% with the freezing technique, and quality of life significantly improved.

Hot Saline. Another recently approved technique [Hydro-Therm-Ablator (HTA) system] uses hot saline (salt water) to destroy the lining. It takes about 10 minutes to do this. This is not a "blind" procedure but uses hysteroscopy so that the surgeon can view the uterus.

Laser Ablation. Endometrial laser intrauterine thermotherapy (ELITT) is an ablation technique that does not require either fluid or devices for expanding the uterus or direct contact with the endometrium. This appears to be a very effective approach.

Microwave Endometrial Ablation. Microwave endometrial ablation applies very low-power microwaves to the uterus, which limits tissue destruction only to the lining without causing any unnecessary harm to other tissues. It takes about 3 minutes. Studies report success rates equal to standard ablation and resection procedures.

Until recently, hysterectomy was the only surgical option for uterine fibroids. Other procedures, however, are now available:

Myomectomy. Myomectomy is the surgical removal of only one or more fibroids. Myomectomy usually involves a laparotomy (a procedure that uses a wide abdominal incision) or less invasive surgical techniques, such as laparoscopy and hysteroscopy. In such cases, unlike with hysterectomy, this technique may preserve fertility.
Uterine Artery Embolization (UAE). UAE, also called uterine fibroid embolization (UFE), is a non-surgical radiology procedure. An interventional radiologist injects small plastic particles through a catheter placed in the uterine artery. The particles block the blood supply to the fibroids and cause them to shrink.
Other Procedures. Endometrial ablation (destruction of the lining of the uterus) may be useful in women with small fibroids and heavy bleeding. Myolysis is another procedure best suited for women with specific types of small fibroids. Magnetic resonance-guided focused ultrasound (MRgFUS) is the newest type of fibroid procedure. Myolysis and MRgFUS use heat to cut off the blood supply to fibroids.

Women should discuss each option with their doctor. Deciding on the surgical procedure depends on the location, size, and number of fibroids. Certain procedures affect a women’s fertility and are recommended only for women who are past childbearing age or who do not want to become pregnant. The risk for bleeding increases with the surgeon's inexperience, so patients are urged to investigate the surgeon's track record. [See In-Depth Report #73: Uterine fibroids.]

Hysterectomy is the surgical removal of the uterus and is the second most frequently performed surgery in premenopausal women (Cesarean sections are first). About 600,000 hysterectomies are performed each year in the U.S., which is among the highest rate of all countries. By age 60, about a third of American women have had this procedure. The highest hysterectomy rates are in women age 40 - 44. Women in the southern and midwestern areas of the United States are more likely to have the operation than those in the northeast and west.

Click the icon to see an illustrated series detailing a hysterectomy.

A 2007 study suggested that a combination of factors predicts whether a woman will decide to have a hysterectomy. A woman who meets all three of these factors has a 95% chance of having a hysterectomy:

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement or resolution despite treatment
Previous use of GnRH agonist drugs

Heavy bleeding, often from fibroids, is the reason for about two-thirds of all hysterectomies. However, in about half of these hysterectomies, no abnormalities are detected to explain the bleeding. In one European study, women with menorrhagia were more likely to choose hysterectomy over conservative treatment if they also had pelvic pain and were inconvenienced by the heavy bleeding. The number of procedures has continued to increase, but the rise has slowed substantially in recent years.

In its support, hysterectomy, unlike medical treatments and less invasive procedures, cures menorrhagia completely, and most women are satisfied with the procedure. Less invasive hysterectomy procedures are also improving recovery rates and increasing satisfaction afterward.

Still, in one study in 70% of cases when doctors recommended hysterectomies, they did not give their patients alternative choices or adequate diagnostic evaluations. Some studies suggest that the levonorgestrel-releasing intrauterine system (Mirena) might help avoid hysterectomy in 80% of cases. Any woman, even one who has reached menopause, uncertain about a recommendation for a hysterectomy for fibroids or heavy bleeding should certainly seek a second opinion.

[See In-Depth Report #73: Uterine fibroids or In-Depth Report #74: Endometriosis.]

Some evidence suggests that surgically cutting the pain-conducting nerve fibers leading from the uterus diminishes the pain from dysmenorrhea. Two procedures, uterine nerve ablation and laparoscopic presacral neurectomy, can block such nerves. Small studies have shown benefits from these procedures, but stronger evidence is needed before they can be recommended for women with severe primary dysmenorrhea.

Laparoscopic Uterosacral Nerve Ablation (LUNA). LUNA is a recent approach that uses either laser or cauterization to destroy nerves in a small segment of the ligaments that connect the cervix with the lower back. The ligaments do not appear to provide any structural support. There are few side effects from the procedure. The patient does not lose any sensations associated with sexual activity.

Laparoscopic Presacral Neurectomy (LPSN). LPSN uses laser techniques to sever a web of nerves between the lower spine and tail bone that transmit pain from the uterus. The procedure does not affect fertility. Studies suggest that it may work better than LUNA in the long term, but it also poses a higher risk of complications. These complications include constipation, diarrhea, and urinary problems. However, many women find that these symptoms eventually improve.

Resources

www.acog.org -- American College of Obstetricians and Gynecologists
www.resolve.org -- National Infertility Association
www.asrm.com -- American Society for Reproductive Medicine
www.endometriosisassn.org -- Endometriosis Association
www.pelvicpain.org -- International Pelvic Pain Society

References

American Academy of Pediatrics Committee on Adolescence; American College of Obstetricians and Gynecologists Committee on Adolescent Health Care; Diaz A, Laufer MR, Breech LL. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006 Nov;118(5):2245-50.

Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. Epub 2006 Sep 18.

Han SH, Hur MH, Buckle J, Choi J, Lee MS. Effect of aromatherapy on symptoms of dysmenorrhea in college students: A randomized placebo-controlled clinical trial. J Altern Complement Med. 2006 Jul-Aug;12(6):535-41.

Learman LA, Kuppermann M, Gates E, Gregorich SE, Lewis J, Washington AE. Predictors of hysterectomy in women with common pelvic problems: a uterine survival analysis. J Am Coll Surg. 2007 Apr;204(4):633-41. Epub 2007 Feb 23.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Headaches - tension

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Managing Tension-Type Heada...
Medications
Treatment
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Global Prevalence of Tension-Type Headache

Tension-type headaches account for nearly half of all headaches, according to a 2007 study in Cephalagia. The researchers estimated that more people are disabled by tension-type headache than by migraine.

Causes of Tension-Type Headaches

Doctors are not really sure why tension-type headaches occur. Possible causes include muscle contractions or changes in brain chemicals. Several studies in 2006 and 2007 presented the theory that tension-type headaches may be due to myofascial trigger points in the shoulders and neck, as well as poor head posture. Some researchers suggest that tension-type headaches may be related to fibromyalgia, a condition that is also characterized by myofascial pain.

Tension-type headaches may be triggered by:

Chronic poor posture
Overwork and stress
Lack of sleep
Dental problems, including temporomandibular joint disorder (TMJ)
Certain types of foods
Skipping meals
Medication overuse
Hormonal changes related to menstruation

Managing Tension-Type Headaches

Acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), or ketoprofen (Actron, Orudis KT) can usually provide pain relief for tension-type headache attacks. Patients who have chronic headaches sometimes take amitriptyline (Elavil), a prescription tricyclic antidepressant, to help prevent attacks. Exercise, stress reduction, and relaxation techniques are very important lifestyle approaches for controlling tension-type headaches.

Introduction

Most people are familiar with headaches, the all too common affliction marked by throbbing, piercing, or vise-like pain around much or a part of the head. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.

The brain itself is insensitive to pain, so that is not what hurts when a headache arises. The pain, instead, occurs in the following locations:

The tissues covering the brain
The attaching structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Doctors categorize headaches as either primary or secondary, which helps to distinguish the many different kinds of headaches and to determine appropriate treatments for each.

Primary Headaches. A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: Tension-type, migraine, and cluster headaches.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Neurovascular headaches are the second most frequently occurring primary headaches and include migraines (the more common) and cluster headaches. Such headaches are caused by an interaction between blood vessel and nerve abnormalities. [See In-Depth Report #97: Migraine headaches and In-DepthReport #99: Cluster headaches.]

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Over-the-counter pain medications can relieve most headaches.

Symptoms of migraine and tension-type headaches often overlap, and a diagnosis is sometimes difficult.

Secondary Headaches. Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.

Chronic Daily Headaches. The International Headache Society's classification system includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.

Click the icon to see an image of the different types of headache.

Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily, or almost daily, and they can be quite debilitating.

Chronic daily headaches are, in turn, subdivided into two categories:

Short-duration headaches last fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
Long-duration headaches last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.

General Description. Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and have the following characteristics:

The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.
Sufferers of tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)

Types of Tension Headache. In 2004, the International Headache Society updated its original 1988 classification criteria. Tension-type headaches are now divided into the following four classifications:

Frequent episodic tension-type headache. Headaches occur at least once but not more than 15 days per month for at least 3 months (a minimum of 12 days but not more than 180 days per year). Headaches last from at least 30 minutes to 7 days.
Infrequent episodic tension-type headache. At least 10 episodes of headache that occur less than 1 day per month (12 days per year). Because these headaches occur infrequently, they do not impact a patient's quality of life as severely as frequent episodic headaches and may not require attention from a medical professional.
Chronic tension-type headache. Headaches occur at least 15 days per month for at least 3 months (180 days per year). The headache persists for hours at a time and may be continuous.
Probable tension-type headache. Probable tension headaches may be classified as probable frequent episodic, probable infrequent episodic, or probable chronic. They have most, but not all, of the symptoms of tension-type headaches and are not attributed to migraine without aura or other neurological disorders. Probable chronic tension-type headache may be related to medication overuse.

Migraine Headache: General Description of Its Course. Migraine is now recognized as a chronic illness, not simply as a headache. These headaches are often classified by whether or not auras accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four symptom phases to a migraine (although they may not all occur in every patient): the prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in between 20 - 25% of patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from four to 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity.
Nausea, sometimes with vomiting.
Visual symptoms.
Facial tingling or numbness.
Extreme sensitivity to light and noise.
Looking pale and feeling cold.
Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

Cluster Headache. Cluster headaches are very painful events. Patients typically awaken a few hours after they go to sleep with the following symptoms:

Very severe, stabbing pain centered in one eye.
Excessive tearing, a drooping eyelid, and one stuffy or runny nostril, all on the same side as the pain.
Feelings of intense restlessness are common. People in the throes of a cluster headache may pace the floor or may even bang their heads against the wall in an attempt to cope with the pain.
Cluster headaches often have a cycle with the following pattern:
Attacks themselves are usually brief, lasting 30 - 90 minutes, although they can persist for up to 3 hours.
During an active period, sufferers can experience as few as one attack every other day to one or more daily. In a rare form of cluster headache, known as chronic paroxysmal hemicrania, as many as six attacks per day can occur.
An active period of recurrent cluster attacks typically extends over 4 - 12 weeks.
Headache-free periods last several months to even years.

Hemicrania Continua. Hemicrania continua is a rare form of chronic headache. Such headaches occur on one side of the face, mostly in women. The patient generally experiences continuous low-level headache with periodic attacks that can last days to weeks. (About 10% of patients experience remissions.) The actual attacks can be mild to severe, and may resemble migraines. The headaches can usually be treated successfully with NSAIDs such as indomethacin (Indocin). Migraine medications are typically not as helpful.

Prognosis

Both episodic tension-type headache and chronic daily headache affect quality of life. Tension-type headache episodes are rarely disabling, however, and rarely require emergency treatment. If they do, usually there is a migraine component occurring with the tension-type headache.

Nevertheless, although they are not medically dangerous, chronic tension headaches have a negative impact on quality of life, families, and work productivity. Several studies have reported lower quality of life with any chronic daily headache compared to those with no headaches or who have only episodic ones. In one study, people with tension-type headaches tended to have higher anxiety and lower quality of life during a headache attack than people with migraines (who, however, were less able to cope during a migraine attack).

In one study, two-thirds of patients with chronic tension-type headaches reported daily or near daily headaches for an average of 7 years. Only 12% reported headaches occurring less than 20 days a month. In the study, 74% of the patients had to take some time off from work because of the headaches, and about a third reported impaired sleep, less energy, and reduced emotional well-being on 10 or more days a month. Most were able to carry out their daily responsibilities even when in pain, although at lower than normal capacity. This and other studies report a strong association between anxiety and depression and chronic tension-type headaches.

Causes

There does not appear to be a single cause of chronic tension-type headache. Many factors are likely involved.

One of the most popular theories on the cause of tension-type headaches involves muscle contraction in the head, neck, and shoulders. There are several ideas about how muscle tension may produce these headaches.

The most common cause of tension-type headaches is muscle contraction in the head, neck or shoulders.

Studies have suggested that tension-type headache sufferers may have higher-than-average muscle tenderness in the face and head that make them more susceptible to headache after muscle contractions. A few studies suggest that some patients with chronic headaches may be overly sensitive to pain in general or may overestimate muscle contraction pain.

One theory suggests that sustained tension or stress that produces muscle contractions in the tender areas around the skull constrict blood vessels. Blood flow is reduced so oxygen is blocked and waste matter builds up, resulting in pain.

Still, pain can last long after the muscles have relaxed, and clear evidence is lacking on how or even if muscle contractions are a major cause of tension headache.

Researchers are increasingly finding evidence to support factors that are common to both migraine and tension-type headache. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Serotonin and Other Neurotransmitter Levels. Neurotransmitters are chemical messengers in the brain. Serotonin is a neurotransmitter (chemical messenger in the brain) that is important for sleep, well-being, and other factors that affect quality of life. Abnormalities in serotonin levels have been observed in both tension-type and migraine headache sufferers. Altered levels of other neurotransmitters, importantly dopamine and stress hormones, also occur with migraine and tension-type headaches.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people oversensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Reduced Magnesium Levels. Magnesium deficiencies have been observed in people with both tension-type and migraine headaches. Researchers have noted a drop in magnesium levels before or during a migraine attack. Magnesium plays a role in nerve cell function. Reduced levels could be a destabilizing factor, causing the nerves in the brain to misfire, possibly even accounting for the auras that many sufferers experience.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger, which may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

Inflammation in the Maxillary Nerve. Early studies suggest that some chronic tension-type and migraine headaches may be caused by inflammation in the nerve that runs behind the cheekbone (the maxillary nerve) -- not around the covering of the brain. In fact, some work using ice water for reducing swelling in areas of the gums above the last upper molars has relieved some severe migraine and tension-type headaches.

Genetic factors appear to play a role in predisposing people to recurrent tension headaches. One study of twins suggested that the chances of inheriting the susceptibility to recurring headaches (both migraine and tension) were about 70% in close relatives. The trait is equal in both boys and girls. Because such headaches tend to occur more in females, however, hormonal, social, psychological, or other factors must play a role in their development.

Tension-type headache has been highly associated with an intense response to stress. Some studies suggest that patients with chronic tension-type headaches have more general feelings of anxiety or depression and are less able to express their emotions. One study indicated that patients with tension headaches tend to perceive everyday events as more stressful than those without headaches. Some research even suggests that tension-type headache victims may have some biological predisposition for translating stress into muscle contraction. Still, the link between stress and tension-type headaches is not fully understood, and some evidence challenges any causal association.

Whiplash, concussions, and other head and neck injuries, even mild ones, may result in persistent tension-type or migraine headaches in both adults and children. Such headaches should be treated as if they were the primary types. The risk for tension headaches may persist for years after the injury.

Myofascial pain involves the fascia (connective tissue) and muscles. Some researchers think that tension-type headaches may be linked to myofascial trigger points in the neck and shoulder muscles. Trigger points are knots in the muscle tissue that can cause tightness, weakness, and intense pain in various areas of the body. (For example, a trigger point in the shoulder may result in headache.) Because fibromyalgia is also characterized by myofascial pain, researchers are exploring whether there may be an association between this condition and tension-type headache. [See In-Depth Report #76: Fibromyalgia.]

Medication Overuse (Rebound) Headache. About a third of persistent headaches -- whether chronic migraine or tension-type -- are medication-overuse headaches. These are the result of a rebound effect caused by the regular overuse of headache medications. Nearly any headache medication can produce this effect. In one study of headache sufferers, medication-overuse headaches developed after an average of 1.7 years of regular use of triptans (18 doses a month), after 2.7 years of ergot use (37 doses as month), and after 4.8 years using painkillers (114 doses a month). Regular use of painkillers for any chronic problem (such as arthritis) poses a 2% risk for medication-overuse headache, with risk being highest in people who already have primary headaches, especially migraines.

Chronic Migraines. In some cases, migraines naturally evolve into chronic, daily headaches referred to as transformed migraines.

About 90% of people seeking help for headaches have a primary headache. The rest are secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. They even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck).

Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also known as TMD), which is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders. This condition often coexists with chronic tension headache.

Click the icon to see an image of temporomandibular joint dysfunction.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Brain Tumor. Fear of brain tumor is common among people with headaches, but headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, evidence suggests that hypertension does not cause headaches. An exception is malignant hypertension, an uncommon medical emergency in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same way as the primary headache. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain, which may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Risk Factors

Tension-type headaches are the most common headaches, accounting for nearly half of all headaches. According to one study, nearly 40% of Americans have at least one episode of tension headache during the course of a year. Some reports estimate that over 85% of women and about 63% of men will have a tension-type headache at some point during a year. Nearly everyone has at least one tension-type headache during their lifetime.

Surveys indicate that about 3 - 5% of the general population has chronic tension-type headache, with the prevalence being higher in women.

About 40% of people with tension-type headaches first have them before they are age 20, and another 40% first experience them between ages 20 - 40. Most of the remaining headache sufferers first have tension-type headaches in the decade between ages 40 - 50. Chronic tension-type headache tends to occur in older adults.

Headaches in Children. Headaches are rare before age 4 but increase in prevalence throughout childhood, reaching a peak around age 13. In one large study, about 7% of seven year olds and 15% of 11 year olds had headaches. Ten percent of these childhood headaches were recurrent. In many of these patients, chronic headaches persist into adulthood. In addition, as adults these patients have a tendency to develop multiple physical or psychiatric complaints, such as back pain, muscle aches, digestive complaints, and depression.

Studies have found that only a minority of chronic childhood headaches are due to physical conditions, such as head injuries or medical problems. In one study, over 62% of children with tension-type headache episodes suffered some form of emotional disorder. In the study, every child reported the presence of a stress factor.

Psychological factors associated with childhood tension-type headaches include:

Sleep problems. According to one study, more than two-thirds of children who experience chronic daily headaches suffer from sleep disturbances, especially difficulty falling asleep.
Moderate or severe depression.
Emotional rigidity in a child and more repressed anger than their peers.
Family stress. This includes maternal illness or separation, family bereavement, relationship problems, mental illness in a family member, and other stressful family events.
Problems at school. According to a National Headache Foundation survey, nearly 30% of children miss school because of headaches. For many children, the start of the school season can be a particularly stressful time.

The National Headache Foundation recommends these tips for parents:

Keep a diary of child’s headaches noting time of onset, length and intensity of attack, location of pain, and food triggers.
Make sure child gets plenty of sleep at regular times.
Avoid changes in child’s eating routing (hunger and eating at irregular times can trigger headaches).
Discuss any headache concerns with child’s doctor.

The following conditions can make people susceptible to tension-type headaches.

Chronic poor posture
Chronic overwork
Upper respiratory tract infections, such as colds and flu
Sleep disorders. Sleep problems, such as insomnia, sleep apnea, or habitual snoring, are common in all primary headaches. Headache can disturb sleep, but sleep disorders may also contribute directly to tension headache, particularly those that occur at night or early morning. (In one study, treating people who had chronic headaches for sleep apnea cured the headaches in many cases.)
Obesity
Hypothyroidism (decreased thyroid function)
Dental problems
Allergies
Substance or alcohol abuse
Temporomandibular joint dysfunction (TMJ, also called TMD). This is a condition in which there are abnormalities in the jaw joints. TMJ itself can cause headache, and it also often coexists with chronic tension headache.

Certain triggers, including the following, may cause headache episodes in people with chronic tension-type headaches:

Specific stressful events
Not eating on time
Fatigue or lack of sleep
Crying. In one study, only stress, anxiety, and menstruation were more important headache triggers in women.
Withdrawal from over-used substances (caffeine, nicotine, alcohol, pain relievers)
Eyestrain
Intense physical exertion, including sexual activity. Athletes are at higher risk for headaches. Patients with tension-type headaches should not avoid exercise, however. Ordinary levels of physical activity do not usually precipitate these headaches. Furthermore, a sedentary lifestyle may increase the risks for stress and obesity and thereby for tension headaches in susceptible people.
Certain foods, such as chocolate, cheese, and the flavor enhancer monosodium glutamate (MSG), are commonly cited as triggers for tension headaches as they are for migraines.
Medications (overuse of headache medications, nitrates, certain anti-depressants, some drugs used to treat high blood pressure, and many others.)
Hormonal changes, such as specific menstrual phases, in women.

Weather conditions, certain smells, smoke, and light, which can set off migraines, are not common triggers for tension-type headaches.

The rapid consumption of ice cream or other very cold foods or beverages is a well-known trigger of sudden headache pain -- the so-called "ice cream" headache. It can be easily prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Drinking a glass of room-temperature water quickly relieves the pain.

Diagnosis

Diagnosing the cause of persistent daily headache is difficult, even for expert doctors. Studies report that people who visit the emergency room with disabling headache are often misdiagnosed as tension-type headaches instead of migraines. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

According to the International Headache Society, a diagnosis of tension-type headache is suggested by the following symptoms:

Pressing or tightening (but non-pulsating) feeling
Mild-to-moderate pain on both sides of the head
Not aggravated by routine physical activity (walking, etc.)

In episodic tension-type headaches:

No nausea or vomiting
Photophobia (intolerance of light) or phonophobia (intolerance of sound) may be absent or one of these symptoms (but not both) may be present

In chronic tension-type headaches:

No vomiting
No moderate or severe nausea
No more than one of the following symptoms: Mild nausea, photophobia, or phonophobia
Some types of chronic tension headache may include tenderness upon manual palpitation of the head (pericranial tenderness).

Differentiating Medication-Overuse (Rebound) Headache from Tension-Type Headache. About a third of persistent headaches are the result of the rebound effect caused by the overuse of headache medications (formerly called rebound headaches).

Usually in such cases, medications have been taken on an ongoing basis for more than 3 days each week. If patients stop taking these drugs, the headaches come back. The patient then starts taking the drugs again. Eventually the headache simply persists and medications are no longer effective. Even after successful medication withdrawal, relapse is common, particularly with drugs that contain caffeine, so doctors should check for this type of headache even in patients who have previously been treated.

Medications implicated in medication-overuse headache include barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.) Simple painkillers, such as aspirin or ibuprofen, are less likely causes of medication-overuse headaches.

Differentiating Tension Headaches from Chronic Migraines. It is often difficult to differentiate between chronic migraine and chronic tension-type headaches. The McGill Pain Questionnaire may be useful for ruling out migraine. According to a 2003 study, patients with migraine who answer the questionnaire report significantly more severe specific symptoms (throbbing, stabbing, gnawing, hot, sickening, exhausting) than those with tension-type headaches. There is very little difference between these headaches, however, in scores of overall severity of the pain.

For an accurate diagnosis, the patient should describe the following:

Duration and frequency of headaches
Recent changes in their character
Location of the pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting. (These are seen most often with migraines.)
Behaviors during a headache. Different behaviors may help distinguish between migraine and tension headaches. People with tension headaches tend to relieve pain by massaging the scalp, temples, or the nape of the neck. People with migraines are more likely to compress the forehead and temples (tying a scarf around the head) or to apply cold to the area. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches. Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.

Researchers are investigating triggers of headaches to determine if certain ones are more likely to set off different primary headaches. In general, however, the same stimuli seem to trigger any of the primary headaches, although people with migraines may be more sensitive to some of them (weather, certain smells, light, and smoke) than people with tension headaches.

Tracking medications is an important way of identifying medication-overuse headache or transformed migraine.

Be sure to attempt to define the intensity of the headache. There are different scoring symptoms available that help communicate the severity of the pain to the doctor. For instance, the following is a number system that can be helpful:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to the following:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
An uncharacteristic dietary changes
Any current medications or recent withdrawal from any drugs, including over-the-counter or natural remedies
Any history of caffeine, alcohol, or drug abuse
Any serious stress, depression, and anxiety
The doctor will also need the patient's general medical and family history, particularly concerning headaches or other diseases such as epilepsy. Migraine, in particular, tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headache that wakes them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headache.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out other conditions, particularly chronic sinusitis, which, in one study, occurred in 20% of patients with chronic headache. Other findings include aneurysms, benign or cancerous growths, and other abnormalities in the brain.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition believing it to be one of their usual headaches. Such patients should immediately call a doctor if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea, and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Managing Tension-Type Headaches

Given the very high prevalence of tension-type headaches, some experts express frustration over the lack of serious scientific attention given to this problem. Unfortunately, few tension headache sufferers seek medical help for their problem, and 60% of those with severe headaches use only over-the-counter medications. Many patients fear that they will not be taken seriously by their doctor or believe the widespread misperceptions that their problem is due solely to stress. With medications, relaxation training, lifestyle changes, and other therapies, over 90% of patients can be helped.

Fortunately, most acute tension-type headaches get better without any treatment, and simple over-the-counter pain relievers such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) can treat mild symptoms.

The most common pain relievers are:

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol)
Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail)

Acetaminophen may be effective for moderate-to-severe headaches only at high doses (1,000 mg), while NSAIDs can be effective at lower doses. One study indicated that ibuprofen and naproxen were more effective than aspirin or acetaminophen.

There are few proven therapies for treating or preventing chronic tension-type headaches, and studies are weak. To date, the major treatments used for chronic tension-type headache are a group of antidepressants called tricyclics, and cognitive-behavior therapy. Used alone either of these approaches achieves modest benefits, at best. A combination, however, may be very helpful in some cases.

Some research suggests the following steps in treating this condition:

Because many chronic daily headaches are due to over-use of headache medications, withdrawal from such drugs is the first action. (NSAIDs or other painkillers should not be used to prevent chronic tension-type headaches.)
Cognitive behavioral therapies, including relaxation and stress-reduction techniques, should be used next for managing headaches. They should be the first option for children and adolescents with chronic headaches.
If medication withdrawal and psychological methods fail to bring improvement, tricyclic antidepressants are tried next in combination with cognitive therapy.
Physical therapy, massage therapy, or acupuncture may help some people.

If headaches develop because of medication overuse, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may only need to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient usually has the option of stopping abruptly or gradually and should expect the following course:

Most headache drugs can be stopped abruptly, but the patient should be sure to check with the doctor before withdrawal. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days or shorter. Otherwise the patient may become discouraged.
No matter which approach is used for stopping medication, the patient must expect a period of worsening headache for a few days afterward. Alternative pain relievers may be administered during the first days to help withdrawal.
Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).

Studies suggest that nearly half of patients with medication-overuse headaches relapse. According to one study, the relapse rate may be much higher for tension headaches (73%) than for migraine headaches (22%). More research is needed to determine the optimal methods for drug withdrawal. On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward.

Medications

The standard treatments for tension-type headaches are non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, and tricyclic antidepressants, usually amitriptyline (Elavil, Endep).

Several pain relievers are helpful for mild-to-moderate headaches. They should not be used to prevent headaches, however.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs are common pain relievers that block prostaglandins, substances that dilate blood vessels and cause inflammation and pain. NSAIDs are usually the first drugs tried for almost any kind of headache. There are dozens of NSAIDs. Aspirin is the most common, but it is not as effective for acute tension-type headache as other NSAIDs. Common NSAIDs include:

Over-the-counter NSAIDs. Aspirin, ibuprofen (Motrin), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs. Diclofenac (Voltaren, Cataflam, Solaraze), tolmetin (Tolectin), indomethacin (Indocin)

Patients should be aware that long-term use of high-dose NSAIDs may increase the risk for stomach bleeding and heart problems, including heart attack and stroke.

Acetaminophen. Acetaminophen (Tylenol) is a good alternative to NSAIDs when stomach distress, ulcers, or allergic reactions prohibit their use. A high dose (1,000 mg), however, is needed for this drug to be effective for headaches. Midrin (a combination of a drug that narrows blood vessels, a mild sedative, and acetaminophen) may be very helpful for tension-type headaches.

Acetaminophen does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly. Acetaminophen may cause serious kidney problems in people who already have kidney disease. It also may interact with certain medications, including the blood thinner warfarin.

Antidepressants known as tricyclics are most often used for prevention of severe chronic tension-type headaches. Newer selective serotonin-reuptake inhibitors (SSRIs) antidepressants are also sometimes used in milder cases.

Tricyclic Antidepressants. Tricyclics are not only useful for depression but also appear to help relieve muscle pain and improve sleep. They are sometimes classified in one of two categories: tertiary or secondary amines:

Tertiary amines include amitriptyline (Elavil) and imipramine (Tofranil). Amitriptyline is the tricyclic most commonly used for tension-type headache. These drugs tend to cause more drowsiness than secondary amines, which may be helpful for patients with sleep problems.)
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects than tertiary amines, but they are just as toxic in high amounts.

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).

Unfortunately, these drugs can lose effectiveness over time. Side effects are also fairly common with these medications. Drowsiness is the most common, but may vary by specific drug. In addition, side effects most often reported include dry mouth, constipation, blurred vision, sexual dysfunction, weight gain, trouble urinating, heart rhythm problems, and dizziness. Blood pressure may also drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects, including heart rhythm problems, which can be dangerous for some patients with certain heart diseases. These drugs can be fatal with overdose.

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). Because they act on serotonin specifically, they have fewer side effects than the older antidepressants, such as monoamine oxidase inhibitors (MAOIs), which affect a number of chemicals in the body. SSRIs take 2 - 4 weeks to be effective in most adults and sometimes longer, up to 12 weeks, so their value for treating headaches is limited.

Side effects may include nausea, stomach problems, agitation, insomnia, mild tremor, impulsivity, temporary weight gain or loss, and sexual dysfunction. Death from overdose is extremely rare. Serious interactions can occur with other antidepressants, such as tricyclics and MAOIs.

Designer Antidepressants. Several drugs target other neurotransmitters, such as norepinephrine, alone or in addition to serotonin, and are showing promise for prevention of tension-type headache. The following are some examples:

In one study, bupropion (Wellbutrin) was as effective as a tricyclic in preventing tension-type headaches.
Nefazodone (Serzone), a fast-acting designer antidepressant, was particularly beneficial in a study of patients with chronic daily headaches. After 3 months of treatment, symptoms were reduced by half in over 70% of patients. Nearly 60% of them said their symptoms improved over 75%.
Venlafaxine (Effexor), a designer antidepressant that targets both serotonin and the brain chemical norepinephrine, is showing promise for preventing chronic tension-type headaches (as well as migraines). In one study, patients who took the extended-release form of the drug for 6 months went from an average of 24 tension headaches a month to 15.
Mirtazapine (Remeron) is a unique antidepressant known as a 5-HT2 blocker. It may indirectly enhance the affects of both serotonin and norepinephrine. In one study, it was as effective in treating chronic tension-type headache as the tricyclic Elavil. Mirtazapine has significantly fewer side effects than tricyclics, although it may slightly raise cholesterol and triglyceride levels. It may also cause blurred vision and slight weight gain.

Mild anti-anxiety drugs are occasionally used as an adjunct in treating chronic headaches to decrease muscle contraction or to calm anxiety symptoms during periods of extreme stress. They include alprazolam (Xanax) and clonazepam (Klonopin). They tend to be highly addictive, however, and patients should therefore use them only on a short-term basis.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these drugs.

Opioids. Opioids, such as codeine or hydrocodone, are sometimes prescribed for severe headaches, although their use is controversial because of the risk for addiction. Methadone is showing promise for patients who do not respond to standard treatments. These drugs are narcotics, however, and may be subject to abuse. Patients must be monitored and reevaluated regularly. Overuse of these drugs can reduce their effectiveness and lead to medication-overuse headaches, so it is important for a doctor to supervise this type of medication. Long-term, high-dosage use of some of these drugs can also lead to kidney disease and ulcers. Other, less serious side effects include gastrointestinal upset, dizziness, and ringing in the ears (tinnitus).

Sedatives. Barbiturates, particularly butalbital (Butalan) and its combinations (Fioricet, Axocet), are occasionally prescribed if other medications fail to provide relief. These drugs are sedatives that also contain pain relievers. Because they pose a very high risk for alcohol-like intoxication, dependence and drug-induced headaches during withdrawal, they should be used very sparingly. Some experts believe they should not be used at all for headaches.

Valproate. In some studies, the anticonvulsant medication valproate has been effective for stopping headaches in some patients with persistent migraines and tension-type chronic daily headaches. In one study, 75% of patients with either type of headache experienced at least a 50% reduction in headache frequency and severity. Minor side effects occurred in a third of the patients. Other anti-seizure medications are under investigation.

Botulinum Toxin. Botulinum toxin A (Botox) injections are now widely used to relax muscles and reduce skin wrinkles. They are also being investigated for chronic daily headaches, which include tension-type headache. This potentially deadly toxin is very safe when tiny amounts are injected into small muscles. In a 2003 study of various headache types (including tension-type headache), over 85% of all the patients had fewer headaches per month and the intensity of the pain. Several 2005 studies reported that Botox injections every 3 months might help patients with chronic daily headaches have fewer headaches. However, other studies have reported no benefit. Botox is not approved for headache treatment.

It should be noted that Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Tizanidine. Tizanidine (Zanaflex) is a muscle relaxant that is emerging as a possible effective preventive drug in chronic tension-type headaches. Called an alpha2-adrenergic agonist, it blocks the release and effectiveness of a stress chemical in the body called norepinephrine and may also help prevent muscle spasms. Studies have reported that nearly 70% of patients with chronic tension-type headaches experienced a reduction in headache symptoms of 50% or more. It also appears to help patients experiencing medication-overuse headache to withdraw from medications. Side effects are usually minor and include fatigue and dry mouth, although patients taking the drug need to be monitored periodically for potential liver damage.

Nitric Oxide Synthase Inhibitors. Nitric oxide synthase inhibitors block nitric oxide, which may play a role in increasing nerve activity that leads to headache. Drugs being investigated include L-NG methyl arginine hydrochloride (L-NMMA) and L-NG-nitro-arginine. Studies suggest they may be very helpful in reducing chronic tension-type pain.

Treatment

In cases where abnormalities or injuries in the cervical spine (the spinal bones in the neck) cause headaches, a cervical epidural nerve block may be beneficial in treating and preventing further pain. This procedure involves injecting small amounts of a corticosteroid and anesthetic into spaces between the vertebrae in the neck to block the nerves. Some patients have reported significant pain relief from this procedure.

Dental Adjustment. Some reports suggest that dental adjustment to help teeth bite down evenly might help some people with temporomandibular joint disorder and chronic headaches. The results indicated that dental adjustments may be helpful. A systematic review in 2003, however, reported no headache relief from this approach.

Nociceptive Trigeminal Inhibition. A dental device called the NTI (nociceptive trigeminal inhibition) tension suppression system has been approved for relief of headaches due to jaw clenching during the night. The small plastic mouthpiece is fitted by a dentist and slips over the two front teeth, preventing teeth clenching at night. Preliminary studies report some benefits for relief of migraines and associated tension-type headaches.

Techniques using acupuncture points on the body have become popular for managing pain. Studies do show some benefits.

Standard Acupuncture. A major 2001 analysis of 26 trials of acupuncture suggested that it may have some benefit for tension headache, but the evidence to date is not completely convincing. Some studies comparing short-term acupuncture to sham (dummy) procedures report no benefits. A 2005 study suggested that acupuncture may help tension-type headache, but needling at non-acupuncture points worked just as well. This suggests a placebo effect may account for the headache relief experienced by acupuncture patients.

Acupuncture, hypnosis and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Percutaneous Electrical Nerve Stimulation. A technique called percutaneous electrical nerve stimulation (PENS) uses low-level electrical pulses delivered through acupuncture needles into soft tissue. Patients are barely aware of the sensation. Some studies are showing some benefits, but strong evidence is still lacking to confirm or refute its benefits.

Acupressure. One acupressure practitioner reports that pressing for 60 seconds on the web space between the forefinger and thumb of the dominant hand erases headache in patients with migraine and tension-type headaches. The specific spot pressed should be the most tender point in the web area. The patient should then lie down for about 15 minutes.

Two investigational procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and relax, and then the process is stopped. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including tension headache.

Spinal manipulation by chiropractors or osteopaths may have some benefits for preventing tension-type headaches. Evidence is stronger on benefits of spinal manipulation for patients with headaches originating from nerve or muscular problems in the neck. Some researchers believe that tension-type headaches relieved by spinal manipulation are probably really caused by neck problems.

In a small 2006 study, daily relaxation exercises combined with three sessions of osteopathic treatment helped reduce the frequency -- but not the intensity -- of tension-type headaches. Another 2006 study suggested that physical therapy that incorporates a craniocervical (head and neck) training program may help reduce tension-type headache frequency, intensity, and duration as well as reduce the need for pain medication. In the 6-week program, patients performed 10-minute exercises twice a day. The exercises were designed to retrain muscles in the head, neck, and shoulders. The benefits of these exercises lasted up to 6 months after the program had ended.

Lifestyle Changes

Good health habits -- including adequate sleep, healthy diet, regular exercise, and good stress management -- are important, along with the following specific measures for headache management. Quitting smoking is essential in reducing the risks for all headaches.

An ancient and potentially effective remedy for tension headaches uses pressure applied to the head (such as a headband or a towel wrapped around the head) plus either heat or cold. In one study, 87% of headache sufferers experienced significant relief, and the rest reported moderate relief while they were wearing special headbands that could be tightened. They applied packs that were frozen or heated in a microwave. (Either heat or cold packs were useful, although people with tension headaches generally preferred cold packs.)

A healthy diet rich in fresh fruits and vegetables and whole grains and low in saturated fats (animal fats) is important to everyone. Fish (particularly oily fish, such as salmon and tuna) and soy are protein sources that may be a good alternative to red meats.

Caffeine. In some people with headaches, caffeine appears to be an excellent companion to medications. One study found that the caffeine equivalent of two and a half of cups of coffee can help treat a tension-type headache by itself. Many medications contain combinations of pain or anxiety relievers and caffeine, which boosts pain-relieving potency and counters drowsiness. Taking ibuprofen along with caffeine is even more effective than either substance alone. (It should be noted that in some people with migraines, the tannin found in coffee or tea may be a trigger for the headache. In addition, withdrawal from caffeine is a major cause of headache.)

Headaches that occur during the night and early morning may be related to sleep disorders. One study reported that treating an underlying sleep disorder, such as sleep apnea or insomnia, in patients who also had headaches resulted in headache cure or improvement in all patients except those who suffered from restless legs syndrome.

Several stress-reduction methods are available that may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. Such approaches may be especially helpful for children and pregnant women with chronic headaches. (For information on acupuncture and spinal manipulation, see the Treatment section of this report.)

Among the stress reduction techniques that may be helpful are:

Guided imagery. (This uses body awareness and visualization of pleasant or positive images.)
Biofeedback. This technique works when patients develop awareness of their physical responses and learn to feed this information back to the brain for the purpose of replicating that response. It is often used to reduce muscle tension. One interesting and sometimes effective technique for headaches is called thermal biofeedback. It is based on the concept that hand-warming reduces blood flow to the brain and so relieves headache. The patient learns techniques (such as using specific images) that can raise the temperatures of the hand during a headache. Studies suggest the approach has been helpful in children with tension and migraine headaches.
Autogenic training. This approach combines elements of meditation, relaxation, and self-hypnosis. In one study, it reduced headache frequency and use of medications in patients with tension-type and migraine headaches. It was more successful for tension-type headache.
Massage therapy. In one study, massage therapy of the neck and shoulder muscles reduced the frequency of chronic daily tension-type headaches within the first week of treatment. (It did not have any effect on the intensity of headaches, however.)
Reflexology, an alternative massage method that manipulates the feet, was associated with improvement in 81% of patients with tension or migraine headaches. Patients reported an improvement in energy, well-being, and increased ability to understand the cause of the headaches. In the study, 19% went off medication.
Muscle relaxation exercises.
Self-hypnosis.
Breathing exercises. Studies have reported that correct and rhythmic breathing from the diaphragm can sometimes relieve tension-type headaches. Such breathing exercises may be particularly beneficial when performed with physical movements. (Yoga, in fact, is a practice that combines both and has been helpful in people with headaches.)

Any of these therapies may be used in conjunction with drug therapy.

Numerous herbal remedies are promoted for tension-type headache. It is important that anyone taking herbal or so-called natural remedies be aware of the lack of regulations governing their quality and effectiveness.

Essential Oils. Some patients find relief using two drops of peppermint, eucalyptus, or lavender oil added to one cup of water. The patient soaks a cloth in the solution and applies it as a compress to the head.

Herbs. Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration (FDA) to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for headache:

Feverfew is the most studied herbal remedy for headaches. It does appear to help some people. However, like all effective headache remedies, long-term use can cause a rebound effect. Some experts recommend purchasing feverfew in dried leaf form. Feverfew is generally safe, but side effects can be distressing, particularly canker sores in the mouth (5 - 15% of cases) and stomach distress. Pregnant women or women hoping to become pregnant should not take this herb. People with any blood-clotting disorders should not take it.
Valerian has sedative qualities and is listed on the FDA's list of generally safe products. However, its effects can be dangerously increased if it is used with pharmaceutical sedatives. High doses of valerian can cause blurred vision, excitability, vivid dreams, and changes in heart rhythm.
Comfrey is an herbal remedy used to treat several inflammatory problems. Evidence suggests that comfrey is toxic to the liver. Animal studies have reported a possible cancer risk. It is banned in several countries.

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.i-h-s.org -- International Headache Society

References

Anderson RE, Seniscal C. A comparison of selected osteopathic treatment and relaxation for tension-type headaches. Headache. 2006 Sep;46(:1273-80.

Fernandez-de-Las-Penas C, Alonso-Blanco C, Cuadrado ML, Gerwin RD, Pareja JA. Myofascial trigger points and their relationship to headache clinical parameters in chronic tension-type headache. Headache. 2006 Sep;46(:1264-72.

Fernandez-de-Las-Penas C, Cuadrado ML, Pareja JA. Myofascial trigger points, neck mobility, and forward head posture in episodic tension-type headache. Headache. 2007 May;47(5):662-72.

Lenaerts ME, Gill PS. At the crossroads between tension-type headache and fibromyalgia. Curr Pain Headache Rep. 2006 Dec;10(6):463-6.

Stovner Lj, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007 Mar;27(3):193-210.

van Ettekoven H, Lucas C. Efficacy of physiotherapy including a craniocervical training programme for tension-type headache; a randomized clinical trial. Cephalalgia. 2006 Aug;26(:983-91.

Zissis NP, Harmoussi S, Vlaikidis N, Mitsikostas D, Thomaidis T, Georgiadis G, et al. A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache. Cephalalgia. 2007 Apr;27(4):315-24. Epub 2007 Mar 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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