Patient information: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)

PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER OVERVIEW

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.

PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER CAUSES

Tissues throughout the body are sensitive to hormone levels that change throughout a woman's menstrual cycle (figure 1). Studies suggest that rising and falling hormone levels may also influence chemicals in the brain, including a substance called serotonin, which affects mood.

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

PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER 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 have symptoms that are similar to those of PMS and PMDD, including depression, anxiety disorders, and perimenopause. It is important to distinguish between underlying depression (which often worsens before menses) and true PMS or PMDD because the treatments are quite different.

Women with underlying depression often feel better during or after menses, but their symptoms do NOT resolve completely. On the other hand, women with PMS or PMDD have a complete resolution of symptoms when their menses begin. Some women who think they have PMS or 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, such as migraines, chronic fatigue syndrome, pelvic and bladder pain, 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 in adults" and "Patient information: Irritable bowel syndrome" and "Patient information: Painful bladder syndrome and interstitial cystitis".)

PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER DIAGNOSIS

There is no single test that can diagnose PMS and PMDD. The symptoms must occur only during the second half (luteal phase) of the menstrual cycle, most often during the five to seven days before the menstrual period, and there must be physical as well as behavioral symptoms. In women with PMS or PMDD, these symptoms should not be present between days 4 through 12 of a 28-day menstrual cycle.

Blood tests — Blood tests are not necessary to diagnose PMS/PMDD. A blood count may be recommended to screen for other medical conditions that cause fatigue, such as anemia. Thyroid function tests can detect hypothyroidism (an underactive thyroid gland) or hyperthyroidism (an overactive thyroid gland), both of which have similar signs and symptoms to PMS/PMDD. (See "Patient information: Hypothyroidism" and "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 (algorithm 1). Using this calendar, a woman can rate the severity of 10 physical symptoms and 12 behavioral symptoms on a 4-point scale.

PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER TREATMENT

Conservative treatments — Conservative treatments for PMS may be recommended first, including 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, prescription medication can be considered as a second option.

Conservative treatments are also recommended for women with PMDD, along with a prescription medication.

• Exercise — Exercise can help to reduce stress, tension, anxiety, and depression. A simple way to start exercising is to walk at a comfortable speed for a distance that is easily tolerated.

The greatest benefits of exercise are seen when it is done at least 5 days per week for at least 30 minutes. However, exercising only one or two days per week is better than not exercising at all. In addition, exercise does not need to be continuous to be beneficial; it can be broken up into three or four ten-minute sessions per day. (See "Patient information: Exercise".)

• Relaxation therapy — PMS and PMDD can be worsened by stress, anxiety, depression, and other psychological factors. Furthermore, living with PMS or PMDD can cause difficulties in interpersonal relationships, at work or school, and with general day to day living. Relaxation therapy can help to ease the stress and anxiety of daily life, and may include techniques such as meditation, progressive muscle relaxation, self-hypnosis, or biofeedback.
• Agnus castus fruit extract — The fruits of Vitex agnus castus (the chasteberry tree) have been used to treat the symptoms of PMS. In one small trial, women with PMS felt an improvement in PMS symptoms after three months of treatment with chasteberry [1]. However, further study is needed to ensure that chasteberry is safe and effective. Updated information about chasteberry can be found at the National Center for Complementary and Alternative Medicine's web site (http://nccam.nih.gov/health/chasteberry/).
• Vitamin and mineral supplements — Several clinical trials have evaluated the benefit of calcium supplements for women with PMS. After three months, women who took 600 mg of calcium twice daily had fewer symptoms compared to those who took a placebo [2]. Calcium is an inexpensive treatment with few side effects and is a reasonable option for women with mild to moderate symptoms of PMS.

A small clinical trial studied vitamin B6 (up to 100 mg/day) and found that it may have some benefit for women with mild PMS. No more than 100 mg of vitamin B6 should be taken per day.

Antidepressant medications

Selective serotonin reuptake inhibitors (SSRIs) — Selective serotonin reuptake inhibitors (SSRIs) are a highly effective treatment for the symptoms of PMS and PMDD. The SSRIs include fluoxetine (Prozac® and Sarafem®), sertraline (Zoloft®), citalopram (Celexa®), and paroxetine (Paxil®). In studies, SRIs reduced the symptoms of PMDD significantly compared to placebo; between 60 and 75 percent of women with PMDD improve with an SSRI. It may not be necessary to take the medication every day. Taking the SRI only during the luteal phase (starting 14 days before the next period) may be sufficient.

Some women have sexual side effects with SSRIs. The most common sexual side effect is difficulty having an orgasm. If this occurs, using a lower dose or trying an alternate drug in the same drug class is recommended.

SSRIs should be taken for at least two menstrual cycles to measure their benefit. 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 SSRIs) include clomipramine (Anafranil®), which can be taken daily or only during the second half of the cycle. Venlafaxine (Effexor®) selectively inhibits the reuptake of two neurotransmitters, serotonin and norepinephrine, and is also more effective than placebo for treatment of PMDD. Other antidepressant medications, including escitalopram (Lexapro®), bupropion (Wellbutrin®), buspirone (BuSpar®), duloxetine (Cymbalta®), and mirtazapine (Remeron®), may be used for treatment of PMDD, although there are fewer data about effectiveness.

Anti-anxiety medications — Antianxiety medications such as alprazolam (Xanax®) are sometimes prescribed for treatment of anxiety. It may reduce the symptoms of PMS or PMDD in some women when taken during the luteal phase (14 days before the next menstrual period). However, alprazolam can be addictive and is generally reserved as a second-line treatment.

Medications that affect hormone production

Gonadotropin releasing hormone agonists — Gonadotropin-releasing hormone (GnRH) agonists (eg, leuprolide acetate or Lupron®) are a type of medication that causes the ovaries to temporarily stop making estrogen and progesterone. This causes a temporary menopause and may improve the physical symptoms (eg, bloating) and irritability caused by PMS and PMDD. However, GnRH agonists are not helpful for treatment of depression. Women who have mild ongoing depression that worsens premenstrually and women with severe premenstrual depression are not good candidates for treatment with a GnRH agonist.

GnRH agonists must be injected every one to three months. The side effects of these drugs can be bothersome and often include hot flashes, thinning of the bones, and an increased risk of osteoporosis with long-term use. Many of these side effects can be minimized by giving estrogen (and progesterone if necessary) or a bone strengthening drug along with the GnRH agonist. (See "Patient information: Osteoporosis prevention and treatment".)

GnRH agonists have traditionally been recommended for no more than six months due to the risk of bone thinning. It may be possible to use a lower dose of the GnRH agonist for longer than six months; this would reduce bone loss and would allow a woman whose PMS or PMDD is well-controlled with a GnRH agonist to continue it. Monitoring of bone density is usually recommended if GnRH agonists are used for more than six months.

Danazol — Danazol (Danocrine®) is an injectable medication that works similarly to the GnRH agonists to suppress 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.

Birth control pills — PMS and PMDD are equally common among women who take birth control pills and those who do not. However, some women with PMS/PMDD have relief of their symptoms when they begin taking a birth control pill (while other women feel worse).

The pill can be taken continuously to avoid having a menstrual period. To do this, the woman takes all of the active pills in a pack and then opens a new pack; the placebo pills are discarded. In theory, taking the pill continuously prevents the usual cyclical hormone changes that could affect mood.

In the United States, one birth control pill (Yaz®) is approved for the treatment of PMDD. Yaz® contains 24 tablets of 20 mcg ethinyl estradiol and 3 mg drosperinone. In one study, women with PMDD who took Yaz® for three months had a 62 percent decline in symptoms compared to a 38 percent decline in women who took the placebo [3].

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 several 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 'Premenstrual syndrome and premenstrual dysphoric disorder 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 'Premenstrual syndrome and premenstrual dysphoric disorder causes' above.
• Other problems, such as depression and anxiety, are similar to PMS and PMDD. The main difference is that PMS and 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 during or after). (See 'Premenstrual syndrome and premenstrual dysphoric disorder diagnosis' above.)

• Some women are asked to keep a record of their feelings every day for two full menstrual cycles before PMS or PMDD is diagnosed (for an example, (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 'Premenstrual syndrome and premenstrual dysphoric disorder 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 'Selective serotonin reuptake inhibitors (SSRIs)' 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 people 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.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Depression in adults
Patient information: Depression treatment options for adults
Patient information: Headache causes and diagnosis in adults
Patient information: Irritable bowel syndrome
Patient information: Painful bladder syndrome and interstitial cystitis
Patient information: Hypothyroidism
Patient information: Hyperthyroidism
Patient information: Exercise
Patient information: Osteoporosis prevention and treatment

Professional Level Information:
Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder
Epidemiology and pathogenesis of premenstrual syndrome and premenstrual dysphoric disorder
Treatment of premenstrual syndrome and premenstrual dysphoric disorder
Patient information: Depression treatment options for adults

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)

• 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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