PMS

Premenstrual Syndrome Symptoms

Premenstrual syndrome (PMS) can appear as physical or emotional and behavioral symptoms.

Physical symptoms of PMS include:

• Breast engorgement and tenderness
• Abdominal bloating
• Constipation or diarrhea
• Headache and migraine
• Swelling of the hands or feet
• Weight gain
• Clumsiness
• Nausea and vomiting
• Muscle and joint aches or pains

Emotional and behavioral symptoms of PMS include:

• Depression (severe depression before menstruation, called premenstrual dysphoric disorder, occurs in about 5% of women with PMS)
• Anxiety and panic attacks
• Insomnia
• Change in sexual interest and desire
• Irritability
• Hostility and outbursts of anger
• Increased appetite often with specific food cravings (especially salt and sugar)
• Mood swings
• Inability to concentrate
• Lethargy and fatigue

Premenstrual Dysphoric Disorder

Premenstrual dysphoric disorder (PMDD) is a specific psychiatric condition marked by severe depression, irritability, and tension before menstruation. For a doctor to confirm a diagnosis of PMDD, the patient must have symptoms during the last week of the premenstrual phase and that resolve within a few days after menstruation starts.

Five or more of the following symptoms must occur:

• Feeling of sadness or hopelessness, possible suicidal thoughts
• Feelings of tension or anxiety (panic attacks, in fact, may be much more common in patients with PMDD than in the general population)
• Mood swings marked by periods of teariness
• Persistent irritability or anger that affects other people
• Disinterest in daily activities and relationships
• Trouble concentrating
• Fatigue or low energy
• Food cravings or bingeing
• Sleep disturbances
• Feeling out of control
• Physical symptoms, such as bloating, breast tenderness, headaches, and joint or muscle pain

The Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are:

• 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. During pregnancy it thickens and becomes enriched with blood vessels, which 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.

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

Menstrual cycle - interactive tool

Stages and Features of Menstruation

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. When a woman reaches her 40s the cycle lengthens, reaching an average of 31 days by age 49. A number of factors can affect cycle length at any age.

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 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.

Nearly every woman at some point has some symptoms as menstruation approaches. For about half of these women, symptoms are mild and do not affect normal daily life. The other half report symptoms severe enough to impair daily life and relationships. Between 3 - 5% of women report extremely severe symptoms.

In general, premenstrual syndrome (PMS) is a set of physical, emotional, and behavioral symptoms that occur during the last week of the luteal phase (1 - 2 weeks before menstruation) in most cycles. The symptoms typically go away within 4 days after bleeding starts and do not start again until at least day 13 in the cycle. 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.

Physical Symptoms

• Breast engorgement and tenderness
• Abdominal bloating
• Constipation or diarrhea
• Headache and migraine (migraine may increase severity of PMS symptoms)
• Swelling of the hands or feet
• Weight gain
• Clumsiness
• Nausea and vomiting
• Muscle and joint aches or pains

Emotional and Behavioral Symptoms

• Depression (severe depression before menstruation, called premenstrual dysphoric disorder, occurs in about 5% of women with PMS)
• Anxiety and panic attacks
• Insomnia
• Change in sexual interest and desire (although some women lose interest, others have a heightened drive)
• Irritability
• Hostility and outbursts of anger (in severe cases, violence toward self and others)
• Increased appetite often with specific food cravings (especially salt and sugar)
• Mood swings (although angry outburst or negative emotions are common, some women experience very positive bursts of creative energy before a period)
• Inability to concentrate and some memory loss (although women often report these symptoms, studies have indicate no actual differences in mental and thinking tasks between women with PMS or premenstrual dysphoric disorder and women without these syndromes)
• Withdrawal from other people
• Confusion
• Being accident prone
• Lethargy and fatigue

Premenstrual Dysphoric Disorder

The U.S. National Institutes of Health and the American Psychiatric Association have developed criteria which defines the more severe form of premenstrual syndrome. Premenstrual dysphoric disorder (PMDD), also called late-luteal dysphoric disorder, is a condition marked by severe depression, irritability, and tension before menstruation. PMDD has features of both anxiety and depression disorders, although increasingly experts believe it is a distinct disorder with specific biochemical actions.

Diagnostic Criteria. Symptoms must occur during the last week of the premenstrual (luteal) phase in most menstrual cycles. They should resolve within a few days after the period starts. They should markedly interfere with work or social functioning. Also, symptoms should not just be another underlying disorder.

Five or more of the following symptoms must occur:

• Feeling of sadness or hopelessness, possible suicidal thoughts
• Feelings of tension or anxiety (panic attacks, in fact, may be much more common in patients with PMDD than in the general population)
• Mood swings marked by periods of teariness
• Persistent irritability or anger that affects other people
• Disinterest in daily activities and relationships
• Trouble concentrating
• Fatigue or low energy
• Food cravings or bingeing
• Sleep disturbances
• Feeling out of control
• Physical symptoms, such as bloating, breast tenderness, headaches, and joint or muscle pain

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

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

During a doctor's visit, the patient may be asked about her symptoms or to fill out a questionnaire.

The only method for obtaining a clear picture of premenstrual syndrome, however, is for the woman to chart her symptoms over 2 - 3 months. The following is an example of such a process:

• Divide symptoms into physical (such as bloating, headaches, weight gain, aches and pains, breast tenderness) and emotional and mental (such as depression, anger, changes in sexual drive, irritability). Note: Menstrual cramps are NOT part of PMS.
• Begin recording symptoms on day 1 of the cycle, which is the day bleeding begins.
• Record symptom severity using an index from 1 - 4, with 1 being no symptoms and 4 being the most severe.
• Include any medications taken or events that might contribute to emotional or physical responses. (For example, taking oral contraceptives may worsen PMS and cause symptoms that confuse the diagnosis.)

The American College of Obstetricians and Gynecologists asks that a pattern of symptoms:

• Be present in the 5 days before a woman's menstrual period for a least three cycles in a row and
• Within 4 days after the beginning of the menstrual period
• Interfere with normal daily activities

The Premenstrual Shortened Form

A number of questionnaires are used for identifying PMS. A simple scoring system called The Premenstrual Shortened Form is often used during an office visit. The woman is asked to rate the following symptoms on a score of 1 - 6, with 1 equal to no change and 6 equal to very severe.

1. Breast tenderness, pain, or swelling
2. Inability to cope and being overwhelmed by ordinary demands
3. Feeling under stress
4. Sudden bursts of irritability or anger
5. Sadness, depression
6. Muscle and joint pain
7. Weight gain
8. Steady feeling of heaviness, discomfort, or pain in the abdomen
9. Swelling or puffiness from fluid retention
10. Feeling bloated

In order to be diagnosed with PMS, a woman must score a 5 or 6 on at least 5 of the symptoms and at least 1 of the symptoms must be numbers 2, 3, 4, or 5.

Ruling Out Other Conditions Causing Similar Symptoms

If the symptoms consistently resolve at the onset of menstruation, they are most likely caused by hormonal fluctuations. If they persist, however, or do not appear to be associated with a regular cycle, other conditions may be causing them. Among the possible conditions that mimic some PMS symptoms are:

• Psychiatric disorders (depression or anxiety that persists suggests serious mood disorders that are unrelated to PMS)
• Eating disorders
• Anemia
• Thyroid disorders
• Diabetes
• Endometriosis
• Chronic fatigue syndrome
• Side effects of oral contraceptives
• Perimenopausal symptoms in women over age 40 (these can include breast tenderness, headaches, sleep disturbances, and mood swings)

Researchers are still uncertain about the causes of premenstrual syndrome. Evidence suggests that fluctuations in gonadal hormones (progesterone or estrogen) and brain chemicals play a role. However, exactly how these fluctuations play a role in premenstrual syndrome is not clear. Hormonal levels seem to be the same in women whether or not they have premenstrual syndrome. It is possible that women with premenstrual syndrome are somehow more responsive to these changing levels of hormones.

Activity in the Hypothalamic-Pituitary-Adrenal (HPA) System

The hypothalamic-pituitary-adrenal (HPA) system controls reproduction, appetite, and feelings of well-being. The HPA is also involved in regulating the stress response. A number of reproductive hormones and neurotransmitters (chemical messengers in the brain) play important and complicated interrelated roles in the activity of the HPA system. Disruptions in these chemicals may be important in PMS and premenstrual dysphoric disorder (PMDD).

• Reproductive hormones. The two important female hormones, progesterone and estrogen, are at their highest levels during the premenstrual period. Evidence indicates that an abnormal response to progesterone, rather than estrogen, is the primary factor in PMS.
• Neurotransmitters. Each hormone is involved in the regulation of two neurotransmitters, serotonin and gamma-aminobutyric acid (GABA). These brain chemicals have properties that protect against PMS symptoms.
• Stress hormones.

The exact roles and relationships of any of these substances in PMS or premenstrual dysphoric disorder (PMDD) are still unclear. Evidence increasingly suggests that fluctuations in some of these hormones -- not whether they are high or low -- may be the important factors in premenstrual problems.

Progesterone and GABA. Changes in progesterone and a potent progesterone derivative called allopregnanolone (ALLO) are proving to play important roles in PMS. ALLO in turn regulates gamma-aminobutyric acid (GABA). Imbalances in the hormones that reduce GABA levels have been associated with depression, anxiety, and agitation. GABA is an amino acid that acts as a neurotransmitter to inhibit transmission of impulses from one nerve cell to another. It plays a very important role in the stress response.

Serotonin. Some women with PMS and premenstrual dysphoric disorder have been found to have abnormal levels of serotonin. Abnormalities in this important neurotransmitter are associated with depression, anger, irritability, poor impulse control, and carbohydrate cravings, all symptoms of PMS.

Stress Hormones. After a stressful event, the HPA system releases certain neurotransmitters called catecholamines, particularly dopamine 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 activates systems throughout the body to respond to this stressful event (the fight or flight response). Low levels are associated with depression.

Other Factors

Calcium and Magnesium. Calcium and magnesium help nerve cells to communicate and blood vessels to widen and narrow. Hormonal swings during the premenstrual phase cause variations in these important minerals. Some researchers believe that imbalances in these minerals may contribute to PMS.

Peptides. Some researchers are studying certain peptides 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.

Thyroid Hormone. A few studies report that women with PMS may be more sensitive to variations in thyroid hormone, which can impact both physical and emotional well-being.

Prolactin. 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.

Endometrial Abnormalities. Results of a study of women who had both PMS and heavy bleeding (menorrhagia) suggested that substances in the endometrium (the lining of the uterus) might cause PMS symptoms.

Premenstrual syndrome (PMS) is reported in women in many cultures worldwide. About 80% of women in their reproductive years have some emotional and physical symptoms before their periods that impair daily activities. An estimated 30% of women feel they need treatment for symptoms. Between 3 - 8% of women report very severe symptoms, notably premenstrual dysphoric disorder (PMDD). A number of factors may put a woman at higher risk for PMS.

Age

The risk for severe PMS is higher in younger women, and onset usually begins around the mid-twenties. Some evidence has suggested that PMS symptoms diminish after age 35. Naturally, PMS and any manifestation of it end at menopause.

Psychologic Factors

Psychologic factors often play an important role in a woman's risk for PMS and premenstrual dysphoric disorder (PMDD). Studies indicate that strong psychologic support can significantly reduce some PMS symptoms. Studies have shown that women with signs of depression or who have seasonal affective disorder (characterized by annual episodes of depression during fall or winter that remit in the spring or summer when daylight hours increase) have a higher prevalence of premenstrual syndrome or PMDD.

Personality Factors. Some studies suggest an increased incidence of low self-esteem in women who report severe premenstrual symptoms.

Cultural Factors

Studies indicate that cultural factors affect the perception and severity of PMS symptoms.

Other Factors Associated with PMS

Studies have found some factors associated with a higher risk for PMS or more severe symptoms, (although the evidence behind these claims is not very strong):

• Having a mother who had PMS
• Being sedentary
• Stress
• High-sugar diet
• Consumption of large amounts of caffeine
• Alcohol abuse
• Women with more children may experience more severe symptoms than those with fewer children

PMS, and in particular premenstrual dysphoric disorder (PMDD), can have an adverse effect on women's relationships with co-workers, partners, and children.

Risk for Major Depression

Depression and PMS often coincide, and may in some cases be due to common factors. Some studies suggest that PMDD may lead to or predict perimenopausal depression in some women.

Substance Abuse

Women who abuse alcohol or have close relatives who are alcoholics, have a much higher risk for drinking during the premenstrual period. Alcohol worsens PMS symptoms and may increase the risk for prolonged cramping (dysmenorrhea) during menstruation.

Studies also have found a higher incidence of smoking in women with premenstrual dysphoric disorder than in women without PMDD.

Magnification of Other Medical Conditions

A number of conditions worsen during the premenstrual or menstrual phase of the cycle, a phenomenon sometimes referred to as menstrual magnification.

Migraines. Although half of women with migraines report they are related to menstruation, experts believe that true menstrual migraines are less common than originally thought. Typical menstrual migraines are usually without auras and regularly occur during the first 3 days of menstruation, but not during ovulation or right before a period. Although researchers are not certain what causes menstrual migraines, some evidence suggests that progesterone may be protective. Menstrual migraines have also been associated with magnesium deficiencies. (Magnesium levels drop during the premenstrual period.)

Asthma. It has long been known that asthma often worsens during the premenstrual period, with one study estimating that 40% of women with asthma are affected at that time. Some research suggests that during the premenstrual period there is increased activity of a combination of asthma-inducing effects, including lower resistance to stress and infections and increased hyperreactivity in the airways of the lungs.

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

Some experts recommend a gradual approach for treatment of symptoms that meet the full criteria for PMS or premenstrual dysphoric disorder (PMDD).

• First-line therapies do not include prescription medications. Lifestyle modifications, especially exercise, are advised for any stage of treatment. Over-the-counter pain relievers may be helpful. Vitamin B6 and calcium supplements are sometimes recommended.
• In severe cases, particularly in women who have PMDD, antidepressants may be helpful. The first options are usually antidepressants known as serotonin-reuptake inhibitors.
• Cognitive behavioral therapy may be an alternative to antidepressants.
• Hormonal drugs, such as birth control pills, may help some women. Certain types of oral contraceptives may especially help mood symptoms associated with PMDD.
• Patients with severe anxiety sometimes receive anti-anxiety drugs. The standard drugs are benzodiazepines, usually alprazolam (Xanax), but they can become addictive and subject to abuse. Newer antianxiety drugs, notably buspirone (BuSpar), may work better and have fewer side effects.
• Diuretics may help women with severe fluid retention.

A healthy lifestyle, including regular exercise and a healthy diet, is the first step towards managing premenstrual syndrome. For many women with mild symptoms, lifestyle approaches are sufficient to control symptoms.

Dietary Factors

Women should follow the general guidelines for a healthy diet. These guidelines include eating plenty of whole grains and fresh fruits and vegetables and avoiding saturated fats and commercial junk foods. Making dietary adjustments starting about 14 days before a period may help some women control premenstrual symptoms.

Fluid. Drinking plenty of fluids (water or juice, not soft drinks or caffeine) may help reduce bloating, fluid retention, and other symptoms.

Frequent Small Meals of Complex Carbohydrates. Increasing complex carbohydrate intake has been found to be helpful. Carbohydrates increase blood levels of tryptophan, an amino acid that converts to serotonin, the brain chemical important for feelings of well-being. Meals should be high in complex carbohydrates, which are found in whole grains and vegetables. (Complex carbohydrates should always be preferred over simple carbohydrates found in sugar and starch-heavy foods, such as pastas, baked goods, white-flour products, and white potatoes.)

Experts suggest eating frequent small meals with no more than 3 hours between snacks. It is important to avoid overeating. Unfortunately many women not only overeat during the premenstrual stage but also tend to eat sugar-rich foods or high-fat salty snack foods -- the worst choices for PMS. Overeating such foods may worsen some PMS symptoms, including water retention and negative moods.

Salt Restriction. Limiting salt may help bloating.

Reducing Caffeine, Sugar, and Alcohol. Reducing caffeine, sugar, and alcohol intake may be beneficial.

Exercise

Evidence suggests that exercise, especially aerobic exercise, increases natural opioids in the brain (endorphins) and improves mood. Exercise is also very important for maintaining good physical health. In one study, women who jogged an average of 12 miles a week for 6 months had reduced PMS symptoms while a comparable group of women who remained sedentary did not improve. Even taking a 30-minute walk every day is beneficial. Although not an aerobic exercise, yoga releases muscle tension, regulates breathing, and reduces stress.

Minerals (Calcium, Magnesium, and Manganese)

Calcium. Some evidence supports the use of calcium and vitamin D to reduce PMS symptoms. Food sources provide the most nutritional value, but studies also suggest that supplements may be helpful. The recommended dietary intake is 1,200 mg/day for calcium and 400 IUD/day for vitamin D. Calcium-rich foods include dairy products, dark green vegetables, nuts, grains, beans, and canned salmon and sardines.

Click the icon to see an image of sources of calcium

Magnesium. The effects of magnesium are not as well established as with calcium, but some evidence suggests that it may be helpful in reducing fluid retention in women with mild PMS. A number of conditions can cause magnesium deficiencies, including intake of too much alcohol, salt, soda, coffee, as well as profuse sweating, intense stress, and excessive menstruation. Magnesium can be toxic in high amounts and can interact with certain drugs. Women should discuss supplements with their doctor.

Vitamins

Researchers have investigated certain vitamins.

Vitamin B6. Limited clinical evidence suggests that vitamin B6 may help reduce PMS symptoms, including depression, although comparison studies with a placebo reported no additional benefits with this vitamin. Typically, women take 100 mg per day. Very high doses (500 - 2,000 mg daily over long periods) can cause nerve damage with symptoms of numbness in the feet and hands. When stopping vitamin B supplementation, it is best to taper off slowly.

Food sources of B6 include 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.)

Click the icon to see an image of the benefits of vitamin B6.

Click the icon to see an image of vitamin B6 sources.

Improved Sleep

Many women with PMS suffer from sleep problems, either sleeping too much or too little. Achieving better sleep habits may help relieve symptoms. [For more information, see In-Depth Report #27: Insomnia .]

Cognitive-Behavioral Therapy

Evidence is mixed on whether cognitive-behavioral therapy (CBT) may help reduce PMS symptoms and improve functioning. CBT techniques include:

• Identifying sources of stress
• Restructuring priorities
• Reframing perception of menstruation as a positive experience
• Defining and practicing methods for managing and reducing stress

Acupuncture and Acupressure

Some women have reported relief from pelvic pain after acupuncture or acupressure (a needleless approach). Studies evaluating this technique have not been considered to be high quality. Therefore, acupuncture treatment of premenstrual syndrome does not have good evidence to support a benefit. More research is needed.

Chiropractic Treatments

Studies evaluating this technique have not been considered to be high-quality. It is not clear if chiropractic treatment is any more effective than a sham treatment. More research is needed.

Meditative Exercises

Meditative techniques include yoga or other exercises that use meditation, promote relaxation, and reduce stress. They may be particularly helpful.

Phototherapy

Phototherapy, which uses fluorescent light up to 50 times more intense than ordinary light, is now a recommended treatment for seasonal affective disorder (SAD), a form of depression related to the reduction of sunlight in winter months. Women with SAD may have a higher prevalence of premenstrual dysphoric disorder, and some experts believe that phototherapy may be useful for PMS-related depression. 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.

Herbs and Supplements

Generally, 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 a number of 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.

A number of herbal remedies are used for PMS symptoms. With a few exceptions, studies have not found any herbal or dietary supplement remedy to be any more effective than placebo for relieving PMS symptoms. It is certainly possible that some herbal medicines may be helpful, but patients should always be wary of unproven claims for quick cures.

Evening Primrose Oil. Some women have reported that taking evening primrose oil helped PMS. However, studies vary as to its effectiveness for PMS symptoms and two rigorous studies reported no benefit. It may be helpful for relieving breast symptoms.

Ginger Tea. Ginger tea is safe and may help soothe mild nausea and other minor symptoms of PMS.

Melatonin. Women with PMS appear to have lower levels of melatonin, a powerful hormone that regulates sleep. One small study that simulated air travel reported that melatonin was helpful in reducing stress in PMS women, but controlled studies are needed to determine any real benefit.

The following are special concerns for people taking natural remedies for PMS:

• St. John's wort (Hypericum perforatum) is an herbal remedy that may help some patients with mild-to-moderate depression. It can increase the risk for bleeding when used with blood-thinning drugs. It can also reduce the effectiveness of certain drugs, including cancer and HIV treatments. St. John's wort can increase sensitivity to sunlight.
• Dong quai is a Chinese herb used to treat menstrual symptoms. Dong quai can lengthen the time it takes for blood to clot. People with bleeding disorders should not use dong quai. Dong quai should not be taken with drugs that prevent blood clotting, such as warfarin or aspirin.
• L-tryptophan supplements have caused eosinophilia-myalgia syndrome (EMS) in some people. EMS is a disorder that elevates certain white blood cells and can be fatal.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Acetaminophen

Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, substances that dilate blood vessels and cause inflammation. NSAIDs are usually among the first drugs recommended for almost any kind of minor pain. There are dozens of NSAIDs. Aspirin is the most common. Among the most effective NSAIDs for menstrual disorders are ibuprofen (such as Advil, Motrin, and Midol PMS), naproxen (such as Aleve, Naprosyn, Naprelan, and Anaprox), and mefenamic acid (Ponstel). Studies have also indicated that they are most helpful when started 7 days before menstruation and continued for 4 days into the cycle. Long-term use of any NSAID can increase the risk for gastrointestinal bleeding and ulcers. Long-term NSAID use can also increase the risk for heart attack and stroke.

Acetaminophen (Tylenol) is a good alternative to NSAIDs, especially when stomach problems, ulcers, or allergic reactions prohibit their use. Products that combine acetaminophen with other drugs that reduce PMS symptoms may be helpful. Brands include Pamprin and Premsyn. Such drugs typically also include a diuretic to reduce fluid and an antihistamine. Little evidence exists to indicate whether they are more or less effective than NSAIDs or other mild pain relievers.

Antidepressants

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) are drugs that keep higher levels of serotonin available in the brain. They have become the most effective treatments for premenstrual dysphoric disorder (PMDD) and for severe PMS symptoms. SSRIs currently approved by the FDA for the treatment of PMDD symptoms include fluoxetine (Prozac, Sarafem), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro).

SSRIs may help not only premenstrual dysphoric disorder but also premenstrual physical symptoms, irritability, and tension. SSRIs appear to work much faster for relieving PMS-related depression than when used in major depression. These drugs are typically prescribed with either continuous (daily) dosing throughout the month or an intermittent dosing regimen. With intermittent dosing, women take the antidepressant during the 14-day premenstrual period of their luteal phase. This approach is also associated with fewer adverse effects than the standard regimens for major depression.

General side effects of SSRIs may include nausea, drowsiness, headache, weight gain and sexual dysfunction. In May 2007, the FDA proposed that all antidepressant medications should carry a warning about increased risks for suicidal thinking and behavior in young adults ages 18 - 24. This risk for “suicidality” generally occurs during the first few months of treatment.

Other Antidepressants. Non-SSRI antidepressants sometimes prescribed for PMDD include:

• Venlafaxine (Effexor) is a serotonin-noradrenaline reuptake inhibitor. It is similar to fluoxetine (Prozac) in effectiveness and tolerability for most patients. Some trials have reported significant improvement in premenstrual dysphoria. Research is needed to determine whether intermittent treatment would be useful.
• Clomipramine (Anafranil), a tricyclic antidepressant, also affects serotonin and has been helpful for some women. Patients report more side effects with clomipramine than with SSRIs, although low doses are used for premenstrual syndrome and may be beneficial for some women. Patients should not take tricyclics with either SSRIs or other antidepressants known as monoamine oxidase inhibitors (MAOIs).

[For more information, see In-Depth Report #8: Depression .]

Antianxiety Drugs

Antianxiety drugs (called anxiolytics) may be helpful for women with severe premenstrual anxiety that is not relieved by SSRIs or other treatments.

Benzodiazepines. The standard anxiolytics are the benzodiazepines, with alprazolam (Xanax) most often used for PMS. Experts, however, generally do not recommend these drugs for PMS-related anxiety. Dependence is a common danger and can occur after as short a time as 3 months of use. (Using Xanax for only a few days per month when symptoms are most severe reduces this risk.) Common side effects are daytime drowsiness and a hung-over feeling. Respiratory problems may be worsened. Benzodiazepines also increase appetite, particularly for fats, during the premenstrual cycle. Overdose is very serious, although rarely fatal. Benzodiazepines are potentially dangerous when used in combination with alcohol.

Buspirone. Buspirone (BuSpar) is a unique anti-anxiety drug known as an azapirone. One study reported that it reduced premenstrual irritability. Unlike benzodiazepines, buspirone is not addictive. Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. [For more information, see In-Depth Report #28: Anxiety .]

Hormone Therapies

Hormone therapies are used in an effort to interrupt the hormonal cycle that triggers premenstrual syndrome symptoms. One method to accomplish this includes having patients take hormone pills in the form of estrogen, progesterone, or birth control pills.

Birth Control Pills. Oral contraceptives (OCs), commonly called "the Pill" collectively, contain combinations of an estrogen (usually estradiol) and a progestin (either a natural progesterone or the synthetic form called progestin). Some women may experience worsening of symptoms with oral contraceptives. [For more information, see In-Depth Report #91: Birth control options for women .]

Standard OCs come in a 28-pill pack that contains 21 active pills and 7 inactive (placebo) pills. Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These OCs contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills. Examples of these include:

• Seasonale, the first continuous-dosing contraceptive, 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 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.
• Lybrel, which supplies a daily low dose of levonorgestrol and estradiol, contains no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods in around 59% of women by the end of the first year. Some women, however, experience occasional unscheduled bleeding or spotting during the first 3 - 6 months. In clinical trials, women who took Lybrel experienced relief of PMS symptoms within a month of starting the drug.

OCs are also being developed to treat the physical and emotional symptoms associated with premenstrual dysmorphic disorder (PMDD). Yaz is a low-dose birth control pill that combines the estrogen estradiol with a new type of progestin called drospirenone. This type of progestin is related to spironolactone, a diuretic. In clinical trials, Yaz helped improve mood and relieve PMDD symptoms when used in a 24/4 dosing regimen (24 days active pills, 4 days placebo pills).

Side effects of OCs include nausea, breakthrough bleeding, breast tenderness, headache, and weight gain. Women who smoke, or who are at risk for blood clots or stroke, should avoid oral contraceptives or use them with caution.

Click the icon to see an illustrated series detailing the birth control pill.

GnRH Agonists. Gonadotropin-releasing hormone (GnRH) agonists (also called analogs) are powerful hormonal drugs that suppress ovulation and, thereby, the hormonal fluctuations that produce PMS. They are sometimes used for very severe PMS symptoms and to improve breast tenderness, fatigue, and irritability. (These drugs, in fact, are sometimes used to rule out or confirm a diagnosis of PMS. If symptoms persist while the drug is being taken, then PMS is unlikely to be their cause.) GnRH analogs, however, appear to have little effect on depression.

GnRH agonists include nafarelin (Synarel), goserelin (Zoladex), leuprolide (Lupron Depot), and histrelin (Supprelin). Some experts believe that GnRH analogs may be useful as first-line therapy for women with severe menstrual pain and irregular periods.

Commonly reported side effects (which can be severe in some women) include menopausal-like symptoms that include hot flashes, night sweat, weight change, and depression. The side effects vary in intensity, depending on the particular 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. Doctors recommend that women not take these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Click the icon to see an image of osteoporosis.

• 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 (such as alendronate or etidronate) may also be helpful.
• Other drugs are being tested in combination with a GnRH agonist to preserve bone. Some of these investigational drugs include selective estrogen-receptor modulators (SERMs), which have some of the effects of estrogen.

Danazol. Danazol (Danocrine) is a synthetic substance that resembles male hormones and should be used only if other therapies fail. It suppresses estrogen and menstruation and is used in low doses for severe PMS. It is particularly useful for premenstrual migraines. Taking it only during the luteal phase relieves cyclical mastalgia (severe breast pain) and avoids major side effects, but this intermittent regimen has no effect on other PMS symptoms.

Side effects from continuous use of Danazol can be severe. They include facial hair growth, deepening of the voice, weight gain, acne, and dandruff. Danazol also increases the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have been reported. Women who are trying to become pregnant should not take this drug, because it may cause birth defects.

Diuretics for Fluid Retention

Diuretics are drugs that increase urination and help eliminate water and salt from the body. They reduce bloating in women with PMS and also have a beneficial effect on mood, breast tenderness, and food craving. Diuretics can have considerable side effects and should not be used for mild or moderate PMS symptoms.

Spironolactone (Aldactone) is most commonly used for PMS. Other common diuretics include hydrochlorothiazide (Esidrix, HydroDiuril) and furosemide (Lasix). Unless potassium is replaced, many diuretics deplete the body's supply of potassium, which can lead to heart rhythm disturbances. Spironolactone, however, is known as a potassium-sparing drug and does not have this problem. (However, women should be sure not to take additional potassium if they are taking spironolactone.) Diuretics interact with a number of other drugs, including certain antidepressants. Women who are considering diuretics should let their doctors know of any other drugs or supplements that they are taking.

• www.4woman.gov -- National Women's Health Information Center
• www.endo-society.org -- Endocrine Society
• www.acog.org -- American College of Obstetricians and Gynecologists

Braverman PK. Premenstrual syndrome and premenstrual dysphoric disorder. J Pediatr Adolesc Gynecol. 2007 Feb;20(1):3-12.

Kwan I and Onwude JL. Premenstrual syndrome. BMJ Clinical Evidence. Web publication date: 01 May 2007.

Lentz GM. Primary and secondary dysmenorrheal, premenstrual syndrome, and premenstrual dysphoric disorder. Etiology, diagnosis, management. In: Katz VL, Lobo RA, Lentz G, Gershenson D, eds. Comprehensive Gynecology. 5th ed. St. Louis, MO: Mosby; 2007:chap 36.

Yonkers KA, O'Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008 Apr 5;371(9619):1200-10.