Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)

INTRODUCTION — Premenstrual syndrome (PMS) refers to a group of physical and behavioral symptoms that occur in a cyclic pattern during the second half of the menstrual cycle. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. Common symptoms are anger, irritability, and internal tension that are severe enough to interfere with daily activities.

Mild PMS is common, affecting up to 75 percent of women with regular menstrual cycles; PMDD affects only 3 to 8 percent of women. This condition affects women of any socioeconomic, cultural, or ethnic backgrounds.

PMDD is usually a chronic condition that can have a serious impact on a woman's quality of life. Fortunately, a variety of treatments and self-care measures can effectively control the symptoms in most women.

CAUSES — The first day of menstrual bleeding is the first day of a woman's cycle. Following this, levels of the hormones estrogen and progesterone increase until approximately day 21, when they begin to fall. Tissues throughout the body are sensitive to these changing hormone levels. Studies suggest that rising and falling hormone levels may also influence chemicals in the brain, including a substance called serotonin, that affect mood.

However, it is not clear why some women develop PMDD and others do not. Levels of estrogen and progesterone are similar in women with and without PMDD. The most likely explanation, based upon several studies, is that women who develop PMDD are exquisitely sensitive to changes in hormone levels.

SYMPTOMS

Common symptoms — The most common symptoms of PMS and PMDD are fatigue, bloating, irritability, and anxiety. Other symptoms include the following: Feeling sad, hopeless, or worthless Feeling tense, anxious, or "on edge" Variable moods with frequent tearfulness Persistent irritability, anger, and conflict with family, coworkers, or friends Decreased interest in usual activities Difficulty concentrating Feeling fatigued, lethargic, or lacking in energy Changes in appetite, which may include binge eating or craving certain foods Sleeping excessively or difficulty sleeping Feeling overwhelmed or out of control Breast tenderness or swelling, headaches, joint or muscle pain, weight gain

Disorders that mimic PMDD — Other conditions can have similar signs and symptoms, including depression, anxiety disorders, and perimenopause. It is important to distinguish between underlying depression (which often worsens before menses) and true PMDD because the treatments are quite different.

Women with underlying depression often feel better during or after menses, but the symptoms do not resolve completely, whereas the symptoms of PMDD do resolve completely when menses begin. Some women who think they have PMDD actually have depression or an anxiety disorder. (See "Patient information: Depression in adults").

There are other medical disorders that worsen before or during menstruation that have features similar to PMDD, such as migraine, chronic fatigue syndrome, or irritable bowel syndrome. A careful medical history should be able to distinguish among these disorders. It is also possible for a woman to have PMDD in addition to another medical condition. (See "Patient information: Headache causes and diagnosis" and see "Patient information: Irritable bowel syndrome").

DIAGNOSIS — There is no single, definitive test for the diagnosis of PMDD. To be diagnosed with PMS or PMDD a woman must have both physical and behavioral symptoms. The symptoms of PMS/PMDD must occur only during the second half (luteal phase) of the menstrual cycle, most often during the five to seven days before the start of the menstrual period. These symptoms are not present between days 4 through 12 of a 28-day menstrual cycle.

Medical history — During a medical history, a healthcare provider will ask about when symptoms started, if symptoms have worsened or improved, severity of symptoms, and how long symptoms occur with each cycle. The provider will also ask about symptom timing in relation to the menstrual cycle and whether menstrual cycles are regular (every 21 to 35 days). The provider will also ask about factors that improve or worsen the symptoms, about other medical conditions, and about other medications, herbs, or vitamins used.

Physical examination — A general physical examination is done to rule out other possible causes of symptoms.

Blood tests — Blood tests are usually normal in women with PMDD. A routine blood count provides a general screening for other medical conditions that cause fatigue, such as anemia. Thyroid function tests can detect hypothyroidism (underactive thyroid gland) or hyperthyroidism (overactive thyroid gland), which can have signs and symptoms similar to PMS. (See "Patient information: Hypothyroidism" and see "Patient information: Hyperthyroidism").

Recording symptoms — Although a woman's symptoms may suggest PMDD, a clinician may request that she carefully record her symptoms on a daily basis for two full menstrual cycles (show figure 1). Using this calendar, a woman can rate the severity of 10 physical symptoms and 12 behavioral symptoms on a 4-point scale.

TREATMENT — Healthcare providers usually recommend conservative treatment of PMS first, which may include regular exercise, relaxation techniques, and vitamin and mineral supplementation. These therapies relieve symptoms in some women and have few or no side effects. If these therapies do not bring sufficient relief, drug therapy can be considered as a second option.

Drug therapy is generally recommended first for women with PMDD because of the severity of symptoms.

Highly effective treatments — Several drugs have proven effectiveness for relieving the symptoms of PMDD.

Serotonin reuptake inhibitors — There is good evidence that serotonin reuptake inhibitors (SRIs) are highly effective for the symptoms of PMDD. The SRIs include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), and paroxetine (Paxil®). In studies, all of these drugs reduced the symptoms of PMDD much more effectively than placebo. Some women find that they do not have to take the medication every day; taking them only during the second half of the menstrual cycle (ie, beginning on day 14 of the cycle and continuing until the bleeding begins) may be sufficient.

Fluoxetine reduces the symptoms of PMDD in up to 75 percent of women and remains effective for many years. The usual dose is 20 mg/day; higher doses have not been proven to be more beneficial. Some women have sexual side effects while using fluoxetine, including anorgasmia (inability to achieve orgasm). If this occurs, using a lower dose or trying an alternate drug in the same drug class may be helpful.

SRIs should be taken for at least two menstrual cycles to determine their effect on the symptoms of PMDD. About 15 percent of women do not achieve relief with these drugs after two cycles, in which case an alternate treatment is recommended.

Other antidepressants that inhibit serotonin reuptake (but are not SRIs), such as clomipramine (Anafranil®) (which can be taken daily or only during the second half of the cycle). Venlaxafine (Effexor®) selectively inhibits the reuptake of two neurotransmitters, serotonin and norepinephrine, and is also more effective than placebo.

Gonadotropin-releasing hormone agonists — A gonadotropin-releasing hormone (GnRH) agonist is an injectable medication that suppresses the pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). As a result, the ovaries temporarily stop making estrogen and progesterone, causing a temporary menopause. Leuprolide (Lupron®) is a GnRH agonist.

Side effects occur due the loss of estrogen, and include hot flashes, thinning of the bones, and an increased risk of osteoporosis with long-term use. GnRH agonists are effective for relieving the physical symptoms of PMS, but the side effects of these drugs limit their use. Side effects can be treated by adding back small doses of estrogen or medications that protect the bones (See "Patient information: Osteoporosis prevention and treatment").

Danazol — Danazol (Danocrine®) is an injectable medication that works similarly to the GnRH agonists in suppressing ovulation. It can improve the symptoms of PMS, but has side effects similar to those of testosterone (acne and growth of facial hair); its use is generally reserved for women who do not improve with other medications.

Other treatments — The effectiveness of some treatments is not as clear. These treatments may relieve the symptoms of PMS or PMDD in some women, and women may use a short trial of these treatments to determine if they are effective.

Alprazolam — The drug alprazolam (Xanax®) may reduce the symptoms of PMS or PMDD in some women. However, it can be addictive and is therefore reserved as a second-line treatment.

Oral contraceptives — PMDD is equally common among women who take oral contraceptives and women who do not. However, some women with PMDD have relief of their symptoms when they begin taking an oral contraceptive (while other women feel worse). Some providers recommend that the pill be taken continuously by women with PMDD (ie, skipping the placebo week of the pill for several months in a row). By doing this, the woman will not have a menstrual period, and in theory, will not have the usual cyclic changes in hormones that could affect mood. This is not, however, a proven treatment for PMDD.

Exercise and relaxation techniques — Some studies suggest that regular exercise, relaxation, and reflexology can improve the symptoms of PMS. However, these techniques are not recommended as the sole treatment for women with PMDD.

Agnus castus fruit extract — The fruits of Vitex agnus castus (the chasteberry tree) have been used to treat the symptoms of PMS. In one clinical trial of women with PMS, agnus castus (one dry extract tablet daily for 3 cycles) resulted in a significant decrease in irritability, anger, headache, and breast fullness when compared with placebo [1]. No significant side effects were seen. While this appears to be a potential therapy for PMS/PMDD, further study is needed before it is recommended. In addition, consumers should use caution with herbal products because their purity is not regulated.

Vitamin and mineral supplements — Several clinical trials have evaluated the benefit of calcium treatment for women with PMS. The women who took 600 mg of calcium twice daily had fewer symptoms compared to those who took a placebo [2]. This is an inexpensive treatment with few side effects, and a trial should be considered by women with mild to moderate symptoms of PMS.

Some smaller clinical trials have studied the benefit of vitamin B6 (up to 100 mg/day), magnesium (200 to 360 mg up to three times per day), and vitamin E (400 IU per day). There may be modest improvement of PMS symptoms with these supplements.

Ineffective treatments — Several treatments are of no proven benefit in relieving the symptoms of PMS. These treatments include progesterone, diuretics such as spironolactone, other antidepressant drugs (tricyclic antidepressants and monoamine oxidase inhibitors), and lithium. There is also no proven benefit of certain popular dietary supplements, including evening primrose oil, essential free fatty acids, and ginkgo biloba.

SUMMARY Premenstrual syndrome (PMS) causes symptoms one to two weeks before a woman's menstrual period. Common symptoms include feeling tired, bloated, irritable, and anxious. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. PMDD can cause a woman to feel very sad or nervous, to have trouble with friends or family (eg, disagreements with husband or children), and can cause problems with paying attention to work or school (see "Symptoms" above). The cause of PMS and PMDD is not known. Some women may be very sensitive to changes in hormone levels. Hormone levels normally change before and during the menstrual period (see "Causes" above). Other problems, such as depression and anxiety, are similar to PMDD. The main difference is that PMS and/or PMDD only occur before the period. Depression and anxiety are usually noticeable all the time. The treatments of PMDD and depression are quite different. There is no test for PMS or PMDD. To be diagnosed with PMS or PMDD, a woman must have physical symptoms (eg, breast tenderness, muscle pain) and mood changes (eg, sadness, crying). These symptoms must occur before the menstrual period (not after). (see "Diagnosis" above). Some women are asked to keep a record of their feelings every day for two full menstrual cycles (for example, show figure 1). PMS may be treated with behavior changes (eg, exercise, relaxation) first. These treatments are helpful for some women and have few or no side effects. A medication may be tried if behavior changes are not helpful. A medication is usually the best treatment for women with PMDD (see "Treatment" above). The best medications for PMS or PMDD include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), or paroxetine (Paxil®). Some women take this medication every day. Others take medication for two weeks before their menstrual period (see "Serotonin reuptake inhibitors" above).

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The Hormone Foundation

(www.hormone.org/public/pms.cfm)
National Institutes of Health

(www.nlm.nih.gov/medlineplus/healthtopics.html)
United States Department of Health and Human Services

(www.4woman.gov/faq/pms.htm)
American Academy of Family Physicians

(http://familydoctor.org)
The Mayo Clinic

(www.mayoclinic.com)


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