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 third 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 between 200,000 and 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 as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones. The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system. The hypothalamus first releases the gonadotropin-releasing hormone (GnRH). This chemical, in turn, 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 and complete the hormonal group necessary for reproductive health.

The menstrual cycle reflects the changes that occur in the endometrium -- the membrane lining the uterus. Layers of the endometrium are shed at the end of the cycle as part of menstrual flow. The menstrual cycle is generally divided into phases: the follicular (proliferative) phase; ovulation; and the luteal (or secretory) phase.

The follicular phase includes menstrual bleeding followed by proliferation -- growth and thickening -- of the endometrium. It usually lasts 10 to 14 days. For a clear picture of the process it is important to understand how to count days in a menstrual cycle. Day one is generally considered to be the first day of bleeding. The menstrual flow lasts an average of six days. Estrogen and progesterone levels are at their lowest during this time. At the end of the menstrual flow, the proliferative phase begins and the endometrium starts to grow and thicken. FSH levels rise and stimulate several ovarian follicles to mature over a two-week period until their eggs nearly triple in size. During this period, FSH also signals the ovaries to produce estrogen, which, in turn, stimulates a great surge of LH around day 14. This surge of LH then triggers ovulation by causing the largest follicle to burst and release its egg into one of the two fallopian tubes.

At ovulation (usually day 14 in a 28-day cycle), the proliferative stage ends and the secretory (luteal) phase begins, which lasts about 14 days. This is also commonly known as the premenstrual period. Once ovulation has occurred, LH causes the ruptured follicle to develop into the corpus luteum, a mound of yellow tissue that produces progesterone. Acting together, progesterone and estrogen stimulate the tissue lining the uterus to prepare a thick blanket of blood vessels where a fertilized egg can attach and develop. If an egg is fertilized, this blood-vessel blanket develops into the placenta. The corpus luteum continues to produce progesterone and estrogen. When fertilization does not occur, the corpus luteum degenerates to a form called the corpus albicans (Latin for "white body"), and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.

The onset of menstruation, called the menarche, usually occurs at 12 or 13 years. A recent study, however, has indicated that girls may be starting puberty earlier than in the past. By the age of eight, 48% of African-American girls and 15% of white girls were showing pubic hair and developing breast buds. It was previously thought that only 1% of girls exhibited such changes at that age. Being overweight is a risk factor for early puberty, and the increasing trend toward early obesity in the U.S. may play a role in the decreasing age of menarche. Some experts believe, however, that this trend may be due to environmental estrogens found in chemicals and pesticides. They are especially concerned about hair products that contain estrogens, which are being used by some young girls.

Menstruation can be very irregular for the first one or two years. Then the cycle stabilizes and averages about 28 days. The cycle, however, may range from 20 to 40 days and still be normal. Age is a major factor in cycle variation. In one long-term study of midwestern women, the monthly cycle averaged 33 days for women under 21; 28 days after age 21; and 26 days by age 40. Cycle time lengthened by age 46, reaching an average of 31 days by age 49. Thin women and athletes tend to have longer cycles. Women who drink alcohol regularly tend to have shorter cycles.

Periods average 6.6 days in young girls; by the age of 21, menstrual bleeding averages six days until women approach menopause. It should be noted, however that about 5% of healthy women menstruate less than four days and 5% menstruate more than eight days. Thin women, particularly those who smoke, tend to have longer periods, while athletes tend to have shorter ones. Women who use oral or injected contraceptives generally have longer periods.

During pregnancy menstruation stops, of course. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the physician. When women breast feed they are unlikely to ovulate during the first eight weeks after delivery. 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.

As they approach menstruation, about three-quarters of all women report some symptoms related to fluctuating hormone levels. For about half, these symptoms are mild and do not affect normal daily life; the other half report more severe symptoms, including depression. Premenstrual symptoms may result from physiological events or psychological and cultural attitudes. Most often, premenstrual syndrome (PMS) is likely to be a combination of these factors. Studies indicate that women in different cultures experience premenstrual events differently. For example, a study of Chinese women in Hong Kong reported that pain was the most significant PMS symptom, while depression predominated in Western women. Some people cite studies showing an increased incidence of low self-esteem in women who report severe premenstrual symptoms. They argue that, perhaps, most cases can be remedied with self-reassessment therapies that build confidence. It is certainly possible, however, that monthly recurring physical symptoms that impair normal activities can also eventually effect a loss of confidence. Certainly, the association between specific phases of the menstrual cycle and attacks of asthma, migraines, seizures, heart attacks, and other acute events in women with these physical disorders indicates the importance of biologic factors. Whether the basic cause is emotional or hormonal, however, PMS is undoubtedly real and causes genuine distress in many women, preventing them from functioning at full capacity during the luteal phase.

Some experts diagnose PMS by having women rate 17 PMS symptoms on a score of zero (no symptoms) to four (very severe). (See below for a list of symptoms.) Women are defined as having PMS if they meet the following criteria: a premenstrual symptom score of at least 70, which is also 50% greater than the score following menstruation, and an impaired ability to function before a period. Only 3% to 5% of women actually meet these stringent criteria, although far more report having PMS.

Nearly all women experience bloating, breast tenderness, and slight, temporary weight gain. About 11% of women who experience breast pain associated with their menstrual cycle have a condition called cyclic mastopathy, in which the pain occurs after ovulation, increasing in intensity during the luteal phase, and then receding at menstruation. Other PMS symptoms may include gastrointestinal distress, headaches, rashes, muscle and joint pains, fatigue, gingivitis, heart pounding, imbalance, hot flashes, oversensitivity to sounds and smells, agitation, and insomnia. Dysmenorrhea (cramps) and menorrhagia (heavy bleeding) are separate diagnostic conditions and are not considered as part of PMS.

Emotional hypersensitivity is common with PMS, and women report a wide range of related symptoms, including depression, anxiety, anger, and agitation. They also report impaired concentration and some memory loss, although a recent small study found that women with PMS, in spite of feelings of inadequacy, scored as well on tests of mental acuity during the premenstrual stage as women without PMS. Carbohydrate cravings are common. Premenstrual dysphoric disorder (PMDD) -- also called late-luteal dysphoric disorder -- is a condition marked by severe depression, irritability, and tension before menstruation. PMDD affects an estimated 3% to 8% of women in their reproductive years. A diagnosis of premenstrual dysphoric disorder depends on having at least five symptoms of depression that occur during most menstrual cycles, with symptoms worsening a week or so before the menstrual period and resolving afterward (see below). In rare cases, delusions and hallucinations occur. Sexual drive may also fluctuate in individual women; some experience diminished sexual interest and others have a heightened drive. Some women even experience very positive bursts of creative energy before a period.

Symptoms must occur during the last week of the luteal phase in most menstrual cycles. They should resolve within a few days after the period starts.

Five or more of the following symptoms must be present:

1. Feeling of sadness or hopelessness, possible suicidal thoughts
2. Feelings of tension or anxiety
3. Mood swings marked by periods of teariness
4. Persistent irritability or that anger affects other people
5. Disinterest in daily activities and relationships
6. Trouble concentrating
7. Fatigue or low energy
8. Food cravings or bingeing
9. Sleep disturbances
10. Feeling out of control
11. Physical symptoms, such as bloating, breast tenderness, headaches, and joint or muscle pain

From The American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Washington, DC, Copyright American Psychiatric Association 1994.

Researchers are still uncertain about the causes of premenstrual syndrome. Some experts are concerned that the inclusion of premenstrual dysphoric disorder (PMDD) in the psychiatric diagnostic literature may misrepresent the full problem. They warn that such categorization may restrict research on PMS only to psychiatric areas and, furthermore, that both women with PMDD and their physicians may view their PMS only as a psychiatric disorder and not as condition that may have physiologic causes unrelated to classic depression.

Drugs known as gonadotropin-releasing hormone (GnRH) agonists relieve PMS symptoms by suppressing the hormones that cause ovulation. As a result, researchers can assume that reproductive hormones play an important role in PMS. Exactly what their roles are, however, is unclear. Premenstrual syndrome appears to be a complicated interaction between these reproductive hormones and neurotransmitters -- chemical messengers in the brain. The two neurotransmitters most likely to be involved in PMS are serotonin and gamma-aminobutyric acid (GABA). Low levels of serotonin are associated with depression and carbohydrate cravings, and GABA deficiences are linked to anxiety and susceptibility to seizures. Progesterone converts to pregnanolone, a compound known as a neurosteroid, which is essential for enhancing the effects of GABA, while estrogen appears to play an essential role in maintaining sufficient levels of serotonin. It should follow, then, that these hormones should protect against PMS. Nevertheless, a number of studies have indicated that progesterone may intensify symptoms, and a recent study has demonstrated that estrogen also appears to worsen symptoms in women with PMS (but not in women without the syndrome). Some studies are indicating PMS patients may be less responsive to the anti-anxiety effects of progesterone than women without PMS. The findings on estrogen are unexpected, however, since during the follicular phase, when progesterone levels are low and estrogen levels are high, women do not experience PMS symptoms. The researchers concluded that women with PMS have an abnormal response to normal hormonal variations. Another study found that high concentrations of both estrogen and luteinizing hormone, which is released by the pituitary gland during the premenstrual phase, were associated with severe symptoms in women with PMS.

Calcium and magnesium levels vary widely during the menstrual cycle, and some researchers believe certain imbalances in these minerals may play a part in premenstrual disorder. One study observed very low levels of magnesium and high levels of calcium during the premenstrual phase. Calcium and magnesium affect communication between nerve cells and the opening and closing of blood vessels -- functions that may be important in the development of PMS symptoms. Some experts hypothesize that deficiences in magnesium or excess amounts of calcium may be responsible for triggering symptoms. The effects may be more complicated than this, since taking calcium supplements appears to reduce PMS symptoms, and taking magnesium seems to have no effect.

Other hormones under investigation are the neurotransmitters and hormones related to stress. Following a stressful event, the part of the brain called the hypothalamic-pituitary-adrenal (HPA) system releases certain neurotransmitters called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (adrenaline). These chemicals trigger the release of the steroid hormones known as glucocorticoids, which in turn produce cortisol -- the primary stress hormone. Cortisol affects systems throughout the body. Some studies indicate that the stress response in women with PMS may be more intense than in those without the syndrome.

Some researchers are studying certain peptides and other hormones that vary during the menstrual cycle among women with and without PMS. These substances include arginine vasopressin (AVP), which affects water retention, and atrial natriuretic peptide (ANP), which increases sodium elimination. Some PMS symptoms, particularly breast pain, may be caused by excess levels of prolactin, a hormone produced by the pituitary gland that stimulates the glands in the breasts. Results of a study of women who had both PMS and heavy bleeding (menorrhagia) suggested that substances in the endometrium might cause PMS symptoms, at least in women who also have menorrhagia (heavy menstrual bleeding).

Premenstrual syndrome is reported in women in all cultures worldwide. Although only 2% of women fit the strict criteria for premenstrual syndrome, an estimated 40% of women in their reproductive years experience PMS symptoms severe enough to impair daily activities. In a survey of adolescents, 88% reported moderate to severe premenstrual symptoms. In another study, younger women also had a higher risk for severe premenstrual syndrome than older women, and women with more children were more likely to experience severe symptoms than those with fewer children. Other risk factors included having a mother with PMS and being sedentary. The results of this study indicated that genetic susceptibility and stress probably play a role in the severity of symptoms.

Some studies have reported that half of women with migraines experience them during menstruation, although a recent one suggested that a true menstrual migraine (one that occurs regularly and only between two days before and three days after a period) occurs only in a small group of women.

The menstrual cycle may also affects diabetes, a disease that is defined by low levels of insulin or resistance to this hormone that is critical for efficient use of sugar (glucose) in the body. High estrogen and progesterone levels, which occur in the luteal phase, affect insulin, although their effects vary widely among individuals. In one study of women with insulin-dependent diabetes, 27% experienced higher blood sugar levels and 12% lower levels in the week before their period than at other times in the cycle. Some experts argue, however, that these blood sugar changes are due to cravings and dietary responses to PMS, not to insulin changes.

Women with asthma are at higher risk for asthma attacks during the premenstrual phase. One study found that a combination of asthma-inducing effects, including lower resistance to stress and infections and increased hyperreactivity in the airways of the lungs, occurred during this time.

Many other chronic disorders may be exacerbated during the premenstrual phase, including epilepsy, multiple sclerosis, systemic lupus erythematosus, and irritable bowel syndrome. Women are also more prone to seasickness in the premenstrual phase.

Premenstrual syndrome, particularly premenstrual dysphoric disorder (PMDD), can have an adverse effect on a woman's relationships with co-workers, partners, and children. No studies, however, have found that women become mentally incompetent because of PMDD. Adolescents with severe PMS may be prone to high-risk behavior and suicidal thoughts. One study suggested that women who attempt suicide, in fact, are more likely to do so during the premenstrual phase or in the first week of the period. Women who are alcoholics or have close relatives who are alcoholics have a much higher risk for drinking during the premenstrual period. Alcohol increases the risk for prolonged cramping (dysmenorrhea) in women with severe PMS. One study showed a strong association between PMDD and eating disorders.

Many women with severe breast pain (cyclic mastalgia) are worried about an increased risk for breast cancer. It is not yet known if such concern is warranted. One study found that women with cyclical mastalgia had a greater incidence of abnormal breast cells than those without severe premenstrual breast pain, although more research is needed to confirm any actual increased risk for breast cancer. Such women are more likely to have mammograms at an early age than others, although such tests are not generally useful in detecting breast cancer in women under 35.

The only method for obtaining a clear picture of premenstrual syndrome is charting the symptoms over two or three months using a severity index of one to 10, with 10 being the most severe. Women should begin recording their symptoms on day one of the cycle, which is the day bleeding begins. Symptoms should be divided into physical (e.g., bloating, headaches, weight gain, aches and pains, breast tenderness) and emotional (e.g., depression, anger, changes in sexual drive, irritability). Menstrual cramps (dysmenorrhea) are not part of PMS. The record should also include specific events that might contribute to emotional or physical responses. If the symptoms consistently resolve at the onset of menstruation, then they are most likely caused by hormonal fluctuations. If certain symptoms, such as depression or breast pain, continue or do not follow a menstrual pattern, they are probably due to other conditions. Depression that persists could indicate a serious mood disorder. Breast pain that is not cyclical can be due to injury, a previous biopsy (pain can last for two years after this event), lung infection, or arthritis. A condition called costochondritis, in which the joint between the ribs and breastbone is inflamed, can cause breast pain. This can be detected if pain is triggered by pushing down on the breastbone near the rib or by taking a deep breath.

Making dietary adjustments starting about 14 days before a period may help some women with premenstrual syndrome and, perhaps, some mild menstrual disorders. Some experts suggest eating frequent small meals with no more than three hours between snacks. The general guidelines for any healthy diet are recommended, including eating plenty of whole grains, fresh fruits and vegetables and avoiding saturated fats and commercial junk foods. Avoiding red meats and dairy products during the premenstrual period may be beneficial for some women. A recent study found that reducing salt does not alleviate bloating or other symptoms, but salt reduction in the study was modest and may have been too small to effect improvement. Moderating salt intake is always wise, in any case. Reducing caffeine, sugar, and alcohol intake may be beneficial. While regular consumption of alcohol can reduce the risk for developing cramps in women who don't have them, it increases the length of cramping time in women who ordinarily do experience pain during menstruation. It should also be noted that having even one drink a day increases the risk for breast cancer, so alcohol is never recommended to prevent menstrual cramps, and any women with severe menstrual pain who drinks should consider stopping altogether. Increasing the amount of fish in the diet may help reduce menstrual disorders. In one study of Danish women, menstrual pain was greater in women with lower levels of omega 3 fatty acids, which is found in fish oil. In another study, supplements of fish oil appeared to reduce heavy bleeding in adolescent girls.

A complex carbohydrate powdered drink mix called PMS Escape appears to alleviate symptoms in some women and is available over the counter. In one study, patients reported improvement in anger, depression, tension, and confusion between an hour and a half and three hours after drinking the mixture. Within that time cravings for sweet and starchy foods diminished. Other studies have also found that the carbohydrate drink helps reduce food cravings as well as mood swings and problems in concentration. The powder is made of compounds that increase levels of tryptophan, a substance that is important in the production of serotonin, the chemical messenger in the brain that affects appetite and mood.

Exercise is very important in maintaining good health. One study indicated that PMS is more severe in women who do not exercise. (Exercise, however, does not appear to have any affect on menstrual cramps, either in decreasing or increasing them.) Even just taking a 30-minute walk every day is beneficial. Although very vigorous exercise can cause menstrual irregularity and even amenorrhea, few women exercise to the extent that these occur. For those who do, a recent study found that simply adding calories can restore menstruation in women who experience amenorrhea from extreme weight loss, excessive exercise, or both. Competitive athletes do not have to stop exercising, then, to restore fertility; they simply need to eat more.

During PMS magnesium and calcium levels fluctuate. In one study, taking 1200 mg of calcium daily reduced all PMS symptoms by nearly half after three months, and some experts now recommend taking calcium before trying antidepressants. Some women take magnesium supplements for PMS symptoms, but studies have not confirmed any benefit.

There have been some reports that premenstrual symptoms or menstrual disorders may be caused by deficiencies of vitamins A, E, B-6, and thiamin or other nutrients, including the minerals zinc and magnesium. No studies, however, have confirmed this. Some women report that taking between 50 mg and 300 mg of vitamin B6 daily alleviates their PMS symptoms. It should be noted that very high doses (500 mg to 2,000 mg daily over long periods) can cause nerve damage with symptoms of instability and numbness in the feet and hands. Food sources of B6 are meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast. (Women prone to Candida vaginitis -- the so-called yeast infection -- should not increase their intake of dietary yeast.) One study reported relief from menstrual pain using vitamin B1 (thiamin). Thiamin is found in almost all foods, but the best source is pork and other, good sources are dried B-fortified cereals, oatmeal, and sunflower seeds. Vitamin E supplements have also been tried for PMS symptoms and cramps, but no studies have shown them to be more effective than placebos.

Studies have not found herbal or other so-called natural remedies to be any more effective than placebo for relieving PMS symptoms or reducing menstrual disorders, and they can be expensive. It is certainly possible that some herbal medicines may be helpful, but patients should always be wary of unproven claims for quick cures. Some women have reported that taking evening primrose oil helped symptoms of bloating, depression, and breast tenderness. An analysis of the few studies done on primrose oil found no value for PMS, however. Ginger tea is safe and may help in relieving nausea. The Chinese herb dong quai has chemical properties that dilate blood vessels and may prevent blood vessel spasms. It has traditionally been used for helping to relieve menstrual cramps, although no studies have proven its effectiveness. The herb increases the skin's sensitivity to the sun and should not be taken in high amounts. Another herbal remedy commonly used for PMS is black cohosh. It has properties that open blood vessels and may also affect estrogen levels. It can cause dizziness and headache in high amounts. Women with PMS appear to have lower levels of melatonin, a powerful hormone that regulates sleep, but there are no studies to indicate whether taking melatonin supplements is beneficial.

Until scientific studies determine actual benefits, proper doses, and side effects of unregulated herbal and other natural products, the patient is at risk for ineffective or even harmful treatments. It is dangerous to assume that simply because a substance is "natural", it has no side effects and is completely safe. High doses of any herbal or so-called natural medicine are not necessarily safer than traditional drugs, and because of the lack of manufacturing standards and knowledge about toxicity or interactions with other drugs, they may be even more dangerous.

Selective serotonin-reuptake inhibitors (SSRIs) are drugs that keep increased levels of serotonin (also called 5-HT) available in the brain. Serotonin is important in the regulation of depression, sleep, and appetite. These drugs are also useful for reducing anxiety, which may account for their greater success in treating PMS compared to other antidepressants. Standard SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxitine (Paxil), and fluvoxamine (Luvox). Studies using Prozac and Zoloft have reported that they relieve premenstrual depression, irritability, and tension. Other SSRIs are also being investigated for this benefit.

Women who become pregnant while taking SSRIs should not be unduly alarmed. A number of studies have indicated that SSRIs are generally safe for pregnant women, although one study found an increase in minor birth defects, such as smaller than normal fingernails when women took Prozac in the first trimester.

Overdose of SSRIs is much less harmful than with the other types of antidepressants. SSRIs can cause agitation, nausea, and sexual dysfunction, including delay or loss of orgasm and low sexual drive. Taking a drug "holiday" on weekends may improve sexual function during that time, although this should be done under a physician's direction. Withdrawal symptoms can include sleep problems, exhaustion, and dizziness, and returning depression. Such a tactic for improving sexual drive may not work for those taking Prozac, which is longer-acting than other SSRIs and so takes longer than a weekend for the drug's effects to lessen. Intermittent Prozac therapy (taking the drug only during the 14-day premenstrual period) may be as effective as continuous therapy for PMS and would considerably reduce the risk for adverse effects. Prozac does have some major side effect, however, and all unorthodox uses of the medication should be conducted under the careful supervision of a physician. During the first few weeks of treatment, some patients lose a small amount of weight, but they generally regain it. Other side effects include dizziness, headaches, insomnia, increased anxiety, and exhaustion. High doses or interactions with other drugs may cause hallucinations, confusion, changes in blood pressure, stiffness, and irregular heartbeats. Drugs that may have particularly dangerous interactions with SSRIs include other antidepressants and illegal drugs (e.g., LSD, cocaine, or "ecstasy").

Injections of potent hormonal agents, particularly gonadotropin-releasing hormone (GnRH) agonists, such as nafarelin (Synarel), goserelin (Zoladex), leuprolide (Lupron Depot), and histrelin (Supprelin) have been used for the treatment of PMS. Ovulation is suppressed during this treatment, creating a temporary menopause-like state. Certain symptoms of PMS improve, including breast tenderness, fatigue, and irritability; GnRH analogs, however, appear to have little effect on depression. They are useful for relieving symptoms of severe endometriosis, fibroids, or menorrhagia. GnRH agonists are also used to determine if symptoms are actually caused by PMS. If they persist after the drug is taken, then PMS is unlikely to be the cause.

Because loss of estrogen can lead to irreversible osteoporosis (bone loss), the drugs are not taken for more than six months. If they are, low-dose estrogen replacement, called add-back therapy, is needed. Some experts do not believe GnRH analogs should be used as primary treatment for PMS for even as short a period as six months. Women who are at risk for osteoporosis should consider GnRH analogs with caution. Risk factors for osteoporosis include smoking, alcohol abuse, long-term use of certain drugs (such as corticosteroids) that reduce bone density, and a family history of osteoporosis. Women should be sure they are not pregnant before using these drugs, because they increase the risk for miscarriage. Other common side effects include hot flashes, mood swings, reduced sexual drive, headache, nausea and vomiting, memory loss, changes in the skin and hair, rapid heartbeat, vaginitis, and weight changes. The risks and benefits of long-term therapy are not known. Small studies of women who used leuprolide for up to three years have not reported any permanent pituitary damage that could affect fertility. To help offset side effects, researchers are testing the use of add-back therapy, which provides low doses of estrogen and progestin. These hormones are added to the GnRH analog regime at levels that are too low to offset the beneficial effects of the GnRH analog, but which are high enough to reduce its side effects and prevent bone loss. Studies have shown this add-back regimen to be helpful for endometriosis and fibroids, but in severe PMS, the beneficial effects of GnRH are diminished. Women who are taking GnRH analogs or other non-contraceptive hormones should use non-hormonal birth control methods (such as the diaphragm, cervical cap, or condoms) while on these treatments, because the drugs can increase the risk for birth defects if pregnancy occurs.

Both estrogen and progesterone are elevated during the luteal phase when PMS occurs. Progesterone has been thought for some time to be a factor in worsening symptoms, although rectal or vaginal progesterone suppositories have had some success in reducing symptoms, including improving mood. Experts have believed that estrogen, on the other hand, may be beneficial, but a recent study indicated that it, too, might also worsen PMS symptoms. In one study, however, about half of the women who used estrogen skin patches reported reduced PMS symptoms after eight months. In women with asthma, the use of estrogen may reduce the severity of symptoms during the premenstrual phase, when they are often worse than at other times. Oral contraceptives containing estrogen appear to reduce hyperreactivity in the airways associated with asthma attacks.

Antianxiety drugs may be helpful for women with severe PMS who also suffer from anxiety. The most common of these are the benzodiazepines. In one three-month study, 37% of women taking alprazolam (Xanax), a common benzodiazepine, felt that symptom severity was reduced by half compared to 30% of those taking either progesterone or a placebo. Common side effects are daytime drowsiness and a hung-over feeling. Respiratory problems may be exacerbated. Overdose is very serious, although rarely fatal. Benzodiazepines are potentially dangerous when used in combination with alcohol. The drug must be used sparingly, because dependence is a common danger and can occur after as short a time as three months of use. By using Xanax for only a few days per month when symptoms are most severe, the risk of dependence is reduced. A unique anti-anxiety drug, buspirone (BuSpar), may have some value for premenstrual symptoms of anxiety and depression, although in one study it was not as effective as the SSRI antidepressant Prozac. BuSpar belongs to a class of drugs called azapirones, which have less severe side effects than benzodiazepines and no significant potential for addiction.

Clomipramine (Anafranil) is one of the tricyclic antidepressants. It has also been effective in treating obsessive-compulsive disorders. Patients report more side effects with Anafranil than with SSRIs, although low doses are used for premenstrual syndrome. It is important that this drug not be taken with the antidepressants known as monoamine oxidase inhibitors (MAOIs).

Diuretics are prescription drugs that increase urination and help eliminate water and sodium from the body. They reduce bloating in women with PMS and also have a beneficial effect on mood, breast tenderness, and food craving. Spironolactone (Aldactone) is most commonly used for this purpose. Other common diuretics include hydrochlorothiazide (Esidrix, HydroDiuril) and furosemide (Lasix). Unless potassium is replaced, many diuretics deplete the body's supply of potassium, possibly leading to heart rhythm disturbances. Spironolactone, however, is known as a potassium-sparing drug and does not have this problem. Diuretics should not be used for mild or moderate PMS symptoms. Diuretics should not be taken with certain antidepressants; women taking other medications should check with their doctors about possible drug interactions.

Danazol (Danocrine) is a synthetic substance that resembles male hormones. It suppresses estrogen and menstruation and is used, sometimes in combination with an oral contraceptive, to reduce dysmenorrhea, menorrhagia, fibroids, and symptoms of endometriosis. It has also been used for pain relief from cyclical mastalgia -- severe breast pain. In one study, 65% of women who took it for six consecutive menstrual cycles achieved pain relief. Adverse side effects include facial hair growth, deepening of the voice, weight gain, acne, and dandruff. It may increase the risk for unhealthy cholesterol levels. There is no experience to date with long-term use. Pregnant women or those trying to become pregnant should not take this drug, because it may cause birth defects.

Tamoxifen is a drug used for treating and, possibly, for preventing breast cancer. In one study it was more effective in relieving breast pain from cyclical mastalgia than danazol. Tamoxifen also has properties that may benefit the heart, although it increases the risks for blood clots and endometrial (uterine) cancer.

Bromocriptine (Parlodel) is a drug that is useful for breast pain caused by abnormalities in prolactin secretion.

Cognitive-behavioral methods are effective ways to reduce stress and may be useful for women with PMS. They include identifying sources of stress, restructuring priorities, and finding methods for managing and reducing stress. Some work is aimed at reframing women's perception of menstruation as a more positive experience in order to reduce functional impairment during the days around menstruation. One study showed promise with this technique and the researchers stressed the need for further work.

Often women do not recognize that the decline in their mood and the premenstrual phase coincide. It is useful to start the process of stress reduction with an informal diary of daily events and activities tracked by days of the menstrual cycle. The first step is to note those activities that put a strain on energy and time, trigger anger or anxiety, or precipitate a negative physical response (e.g., a sour stomach or headache). Positive experiences should also be noted -- those that are mentally or physically refreshing or produce a sense of accomplishment. While this exercise might itself seem stress producing -- yet one more chore -- it need not be done in painstaking detail. A few words accompanying a time and date will usually be enough to serve as reminders of significant events or activities. Women should try to identify two or three events or activities that have been significantly upsetting or overwhelming. Priorities and goals should then be carefully examined. Women should question whether the stressful activities meet their own goals or someone else's, whether they have taken on tasks that they can reasonably accomplish, and which tasks are in their control and which ones aren't, particularly during the premenstrual phase.

The next step is to attempt to shift the balance from stress-producing to stress-reducing activities. A recent study indicated that daily pleasant events have positive effects on the immune system. In fact, adding pleasurable events has more benefit than simply reducing stressful or negative ones. Planning ahead for such activities during the premenstrual phase may be very helpful. When eliminating stress is not practical, there may be ways to reduce its impact. Making time for recreation is as essential as paying bills or shopping for groceries. Many people are afraid of being perceived as selfish if they make decisions that benefit only themselves; the truth is that self-sacrifice may be inappropriate and even damaging if the person making the sacrifice is unhappy, angry, or physically unwell as a result. In most cases, small daily decisions for improvement can accumulate and work to reconstruct a stressed existence into a pleasant and productive one.

The concept of communication and "letting your feelings out" has been so excessively promoted and parodied that it has nearly lost its value as good psychological advice. Nevertheless, feelings of anger or frustration that are not expressed in an acceptable way may lead to hostility, a sense of helplessness, and depression. Expressing feelings does not mean venting frustration on waiters and subordinates, boring friends with emotional minutia, or wallowing in self-pity. The primary goal is to explain and assert one's needs to a trusted individual in a positive way. Direct communication with another person may not even be necessary; relief from stress can sometimes be achieved by writing in a journal or composing a letter that is never mailed. Expressing one's feelings is not enough, however; learning to listen, empathize, and respond to others with understanding is just as important for maintaining the strong relationships necessary for emotional fulfillment and reduced stress.

Negative feelings not only foster hostility but also hamper people from achieving goals. Learning to focus on positive outcomes helps to reduce tension levels. Knowing intellectually that the premenstrual phase will end does not always relieve emotional stress, but it is important to keep the end in mind. It may also be helpful to envision undertaking activities during other times of the month when symptoms are not as severe.

Keeping a sense of humor during any difficult situation is a common recommendation from stress management experts. Laughing releases the tension of pent-up feelings and helps keep perspective. Research has shown that humor is a very effective coping mechanism for acute stress.

Some women have reported relief from pelvic pain after acupuncture. Of particular interest is reflexology, a technique that uses manual pressure on acupuncture points on the ears, hands, and feet. In one study comparing this technique to a sham procedure, those who had true reflexology had significantly fewer PMS symptoms than did women in the other group. Yoga, other exercises, and meditative techniques that promote relaxation may also be helpful.

Phototherapy, which uses fluorescent light up to 50 times more intense than ordinary light, is now a recommended treatment for seasonal affective disorder (SAD), which is a form of depression related to reducing sunlight in winter months. Some experts now believe that phototherapy may be useful for premenstrual dysphoric disorder, in which there appear to be low levels of melatonin, the hormone in the brain that regulates sleep. There are a few side effects, including headache, eyestrain, and irritability. Patients taking drugs for psoriasis or vitiligo, certain antibiotics, or antipsychotic drugs should not use light therapy.

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