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Premenstrual syndrome

Highlights

Premenstrual Syndrome Symptoms

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

Physical symptoms of PMS may 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 may 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

Introduction

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

Typical Menstrual Cycle

Menstrual Phases

Typical No. of Days

Hormonal Actions

Follicular (Proliferative) Phase

Cycle Days 1 through 6: Beginning of menstruation to end of blood flow.

Estrogen and progesterone start out at their lowest levels.

FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.

Cycle Days 7 - 13: The endometrium (the inner lining of the uterus) thickens to prepare for the egg implantation.

Ovulation

Cycle Day 14:

Surge in LH. Largest follicle bursts and releases egg into fallopian tube.

Luteal (Secretory) Phase, also known as the Premenstrual Phase

Cycle Days 15 - 28:

Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.

If fertilization occurs:

Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.

If fertilization does not occur:

Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Menstrual cycle - interactive tool

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

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.

Risk Factors for Shorter and Longer Cycles

Shorter Cycles

Longer Cycles

Regular alcohol use

Being under 21 and over 44

Stressful jobs

Being very thin (also at risk for short bleeding periods)

Competitive athletics (also at risk for short bleeding periods)

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

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

  • Menstruation stops during 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.

Causes

Researchers are still uncertain about the causes of premenstrual syndrome. Fluctuations in gonadal hormones (progesterone or estrogen) and brain chemicals may play a role although their exact significance is unclear. 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.

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. An abnormal response to progesterone, more so than estrogen, may be 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 appear to protect against PMS symptoms.
  • Stress hormones. Stress hormones include cortisol and norepinephrine.

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

Other Factors

Calcium and Magnesium. Calcium and magnesium help nerve cells to communicate and blood vessels to widen and narrow. Imbalances in these minerals may contribute to PMS.

Risk Factors

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. 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 suggests that PMS symptoms diminish after age 35. Naturally, PMS and any manifestation of it end at menopause.

Psychologic Factors

Women with a history of or susceptibility to depression may be at increased risk for PMS and premenstrual dysphoric disorder (PMDD). Cultural factors may also 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

Complications

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. About half of women with migraines report an association with menstruation, usually in the first days before or after menstruation begins. Compared to migraines that occur at other times of the month, menstrual migraines tend to be more severe, last longer, and not have auras.

Asthma. Asthma attacks often increase or worsen during the premenstrual period.

Other Disorders. Many other chronic medical conditions may be exacerbated during the premenstrual phase, including epilepsy and other seizure disorders, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and irritable bowel syndrome.

Symptoms

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.

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 American Psychiatric Association has specific criteria that defines premenstrual dysphoric disorder (PMDD). 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.

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 those of another underlying disorder.

Five or more of the following symptoms must occur:

  • Feelings of sadness or hopelessness, possible suicidal thoughts
  • Feelings of tension ,anxiety, or edginess
  • Sudden mood swings marked by feeling suddenly tearful or feeling increased sensitivity to rejection
  • Persistent irritability or anger that causes conflict with other people
  • Disinterest in daily activities and relationships
  • Trouble concentrating
  • Fatigue or low energy
  • Food cravings or bingeing
  • Sleep disturbances
  • Feeling overwhelmed or out of control
  • Physical symptoms, such as bloating, breast tenderness, headaches, and joint or muscle pain

Diagnosis

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)

Treatment

For many women, PMS symptoms can be relieved by lifestyle changes (food modifications, exercise, possibly vitamin B-6 and calcium supplements.)

Women with more severe PMS whose symptoms have not been helped by lifestyle changes should discuss drug treatment options with their doctors. Medications for PMS include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) to help reduce pain
  • Diuretics to reduce fluid retention
  • Certain types of birth control pills, which can reduce or eliminate menstrual periods
  • Serotonin-reuptake inhibitor antidepressants for premenstrual dysphoric disorder (PMDD). (Cognitive-behavioral psychotherapy may be an appropriate alternative to antidepressants for some women).
  • Benzodiazepine anti-anxiety drugs for patients with severe PMS-related anxiety.

Lifestyle Changes

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 may 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.)

It is best to eat frequent small meals, with no more than 3 hours between snacks, and 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 mo.

Salt Restriction. Limiting salt intake can help bloating.

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

Exercise and Stress Reduction

Exercise, especially aerobic exercise, increases natural opioids in the brain (endorphins) and improves mood. Exercise is also very important for maintaining good physical health. Even taking a 30-minute walk every day is beneficial. Although not an aerobic exercise, yoga releases muscle tension, regulates breathing, and reduces stress. Relaxation techniques, including meditation, can also help reduce stress.

Benefit of regular exercise
Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing the amount of bone loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, thereby helping in weight loss and maintenance. It can also increase basal metabolic rate, reduces appetite, and help reduce body fat.

Vitamins and Minerals

Some evidence indicates that calcium with vitamin D, and vitamin B6 supplements, may help with PMS symptoms.

Calcium. For calcium, the recommended dietary intake is 1,000 mg/day before age 50 and 1,200 mg/day after age 50. For vitamin D, the recommended daily intake is 400 IUD/day before age 50 and 600 IU a day after age 50. Calcium-rich foods include dairy products, dark green vegetables, nuts, grains, beans, and canned salmon and sardines. Food sources provide the most nutritional value, but studies also suggest that supplements may be helpful.

Calcium source

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 factors 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.

Vitamin B6. Limited clinical evidence suggests that vitamin B6 may help reduce PMS symptoms. 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.

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.)

Vitamin B6 benefit

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

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.]

Acupuncture and Acupressure

Some women have reported relief from pelvic pain after acupuncture or acupressure (a needleless approach). However, acupuncture treatment of premenstrual syndrome does not have good evidence to support it.

Acupuncture
Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

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.

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.

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.

Medications

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. The most common ones used for PMS are nonprescription ibuprofen (Advil, Motrin, Midol) and naproxen (Aleve) or prescription mefenamic acid (Postel). Studies indicate that NSAIDs are most helpful when started 7 days before menstruation and continued for 4 days into the cycle.

Long-term daily 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:

  • Fuoxetine (Prozac, Sarafem)
  • Sertraline (Zoloft)
  • Paroxetine (Paxil)
  • Citalopram (Celexa)
  • 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 the serotonin-noradrenaline reuptake inhibitor venlafaxine (Effexor) and the tricyclic antidepressant clomipramine (Anafranil). 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. Doctors, however, generally do not recommend these drugs for PMS-related anxiety. Dependence is a risk 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 an anti-anxiety drug that may help reduce 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 to interrupt the hormonal cycle that triggers premenstrual syndrome symptoms. One method to accomplish this is through 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.

One birth control pill, Yaz, is approved specifically for treatment of premenstrual dysmorphic disorder (PMSS). Yaz is a low-dose birth control pill that combines the estrogen estradiol with a newer type of progestin called drospirenone. This type of progestin is related to spironolactone, a diuretic. Yaz uses a 24-day dosing regimen (24 days active pills, 4 days 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.

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.

[For more information, see In-Depth Report #91: Birth control options for women.]

Birth control pill - series

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. GnRH analogs, however, appear to have little effect on depression.

GnRH agonists include nafarelin (Synarel), goserelin (Zoladex), leuprolide (Lupron Depot), and histrelin (Supprelin).

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.

Osteoporosis

Click the icon to see an image of osteoporosis.

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 and 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 masculinizing effects such as facial hair growth, deepening of the voice, and acne. 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 may 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 is 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, and patients with kidney disease should avoid this medication.)

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.

Resources

References

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

Brown J, O' Brien PM, Marjoribanks J, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001396.

Jarvis CI, Lynch AM, Morin AK. Management strategies for premenstrual syndrome/premenstrual dysphoric disorder. Ann Pharmacother. 2008 Jul;42(7):967-78. Epub 2008 Jun 17

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.

Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006586.

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


Review Date: 8/4/2009
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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