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Premenstrual syndromeHighlightsNew No-Period Birth Control Pill In May 2007, the FDA approved Lybrel, the first birth control pill that completely eliminates monthly menstrual periods. Lybrel contains low doses of the estrogen estradiol and the progesterone levonorgestrol. The active pills are taken 365 days a year -- with no inactive pill breaks. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, continued to experience occasional unscheduled bleeding or spotting during the first 3 - 6 months. New Oral Contraceptive for Premenstrual Dysphoric Disorder (PMDD) In October 2006, the FDA approved Yaz for treatment of PMDD. Yaz is a low-dose birth control pill that combines estradiol with the progesterone drospirenone. PMDDs physical and emotional symptoms include breast tenderness, bloating, headache, irritability, mood swings, and food cravings. In 2007, Yaz was also approved for treatment of acne. Antidepressants for Premenstrual Syndrome (PMS) and PMDD
IntroductionThe Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are:
![]() 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. Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones. The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:
Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of two sets of organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this astonishing process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months. A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process to conception is complex:
LH serves two important roles:
Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:
If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.
Stages and Features of MenstruationOnset 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:
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. SymptomsNearly 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 Pain (Cyclical Mastalgia)In one survey, 68% of women experienced breast symptoms associated with menstruation. According to studies, between 8 - 22% of women experience breast pain that is moderate to severe, a condition called cyclical mastalgia (also called cyclic mastopathy). (Some women experience breast pain that is unrelated to menstruation and is referred to as noncyclical mastalgia.) This condition occurs after ovulation, increasing in intensity during the premenstrual phase and then receding at menstruation. It is often associated with PMS, but studies report that most women with this disorder do not have PMS. Some experts believe that this condition may be a unique chronic pain syndrome and require treatments that are different from those of PMS. A 2003 study suggested that women with mastalgia, both cyclical and noncyclical, may have wider milk ducts than others. The wider the duct, the more severe and persistent the pain. Managing Cyclical Mastalgia Lifestyle approaches for relieving cyclical mastalgia include:
Some women have benefited from supplements such as vitamin E, primrose oil, or flaxseed oil Severe cases may require prescription drugs such as bromocriptine (Parlodel), danazol (Danocrine), or tamoxifen (Nolvadex). Researchers are also investigating the breast cancer drug toremifene (Fareston) for treatment of premenstrual breast pain. However, these drugs all have severe side effects, and lifestyle measures should be tried first. Breast Cancer Fears Many women with cyclic mastalgia are worried about an increased risk for breast cancer. It is not yet known if such concern is warranted. One study found that women with cyclical mastalgia had a greater incidence of abnormal breast cells than those without severe premenstrual breast pain. More research is still needed to confirm any increased risk for breast cancer. These women are more likely to have mammograms at an early age than others, although mammograms are not generally useful in detecting breast cancer in women younger than 35. Emotional Symptoms
Behavioral and Mental Symptoms
Premenstrual Dysphoric DisorderPremenstrual dysphoric disorder (PMDD), also called late-luteal dysphoric disorder, is a condition marked by severe depression, irritability, and tension before menstruation. Studies in Europe and the U.S. estimate that PMDD affects between 3 - 8% of women in their reproductive years. 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. Five or more of the following symptoms must be present:
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. DiagnosisDuring 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:
The Premenstrual Shortened FormA 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.
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 SymptomsIf the symptoms consistently resolve at the onset of menstruation, then they are most likely caused by hormonal fluctuations. If they persist, however, or do not appear to be associated with a regular cycle, then other conditions may be causing them. Among the possible conditions that mimic some PMS symptoms are:
Breast pain that is not cyclical can be due to:
Costochondritis. With this condition the region between the ribs and breastbone is inflamed, which can cause chest pain that seems to be in the breast. Costochondritis should be suspected if pain is triggered by pushing down on the breastbone near the rib or by taking a deep breath. CausesResearchers are still uncertain about the causes of premenstrual syndrome. Evidence suggests that fluctuations in hormones and brain chemicals play a role. Activity in the Hypothalamic-Pituitary-Adrenal (HPA) SystemThe 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).
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. An important 2002 study reported lower levels of GABA during menstruation in women with premenstrual dysphoric disorder (PMDD). In fact, GABA may become an important target for drugs aimed at relieving PMDD. 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).
One study observed that women with PMS-related depression had lower cortisol levels during the premenstrual phase and higher levels during menstruation compared to women with few PMS symptoms. Calcium and Magnesium ImbalancesCalcium and magnesium help nerve cells to communicate and blood vessels to widen and narrow. Female hormones, including estrogen, regulate calcium and magnesium. Hormonal swings during the premenstrual phase cause variations in these important minerals. Some researchers believe that imbalances in these minerals may contribute to PMS. (Vitamin D, which is essential for calcium absorption, may also be deficient in women with PMS.) One study observed very low levels of magnesium and high levels of calcium during the premenstrual phase. Some experts hypothesize that deficiencies in magnesium may be responsible for triggering symptoms. The effects are likely to be more complicated than this, however, since taking calcium supplements appears to reduce PMS symptoms in some women, while taking magnesium seems to have no effect. Other Physical FactorsPeptides. 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. Risk FactorsPremenstrual syndrome (PMS) is reported in women in many cultures worldwide. About 80% of women in their reproductive years experience 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. AgeThe risk for severe PMS is higher in younger women and onset usually begins around the mid-twenties. (In one survey of adolescents, however, 88% reported moderate-to-severe premenstrual symptoms.) Women typically first seek treatment when they are in their 30s. Although some evidence has suggested that PMS symptoms diminish after age 35, a 2002 study reported that 6.4% of women ages 36 - 44 had a diagnosis of premenstrual dysphoric disorder. Naturally, PMS and any manifestation of it end at menopause. Psychologic FactorsPsychologic 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. Depression. One large study of women ages 36 - 44, reported that 25% had symptoms indicative of major depression. Such women were significantly more likely to have PMS than those who were not depressed. PMDD can occur without any history or presence of major depression. Nevertheless, major depression is very common with PMDD. Studies have specifically found a high prevalence of PMDD in women who also suffer from seasonal affective disorder (SAD). This form of depression is characterized by annual episodes of depression during fall or winter that remit in the spring or summer when daylight hours increase. Some studies suggest that women with both PMDD and SAD may share genetic factors that make them vulnerable to these forms of depression. Personality Factors. Some studies suggest an increased incidence of low self-esteem in women who report severe premenstrual symptoms. Cultural FactorsStudies indicate that cultural factors affect the perception and severity of PMS symptoms. For example, a study of Chinese women reported that pain was the most significant PMS symptom, while depression predominated in Western women. A 2002 study reported that Asian American women reported fewer PMS symptoms than their Caucasian counterparts, while Hispanic American women reported more severe symptoms. Other studies have reported little difference between American and Northern European experiences of premenstrual symptoms and impact on daily life. Other Factors Associated with PMSStudies have found some factors associated with a higher risk for PMS or more severe symptoms, although there is no clear evidence that any of the following are actual risk factors:
ComplicationsPremenstrual syndrome (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 SuicideAs many as 10% of women who report PMS symptoms, especially PMDD, have had suicidal thoughts. One study suggested that women who attempt suicide are more likely to do so during the premenstrual phase or in the first week of the period. Risk for Major DepressionDepression and PMS often coincide, and may in some cases be due to common factors. Some studies suggest that PMDD may lead to or predict major depression in some women. Substance Abuse and Eating DisordersWomen 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. One study showed a strong association between PMDD and eating disorders. Magnification of Other Medical ConditionsA 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.) Diabetes. The menstrual cycle may also affect diabetes, a disease that is defined by low levels of insulin or resistance to this hormone that is critical for efficient use of sugar (glucose) in the body. High estrogen and progesterone levels, which occur in the luteal phase, affect insulin, although their effects vary widely among individuals. In one study of women with insulin-dependent diabetes, 27% experienced higher blood sugar levels and 12% lower levels in the week before their period than at other times in the cycle. Some experts argue, however, that these blood sugar changes are due to cravings and dietary responses to PMS, not to insulin changes. ![]() Islets of Langerhans contain beta cells and are located within the pancreas. Beta cells produce insulin which is needed to metabolize glucose within the body. 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. TreatmentSome experts recommend a gradual approach for treatment of symptoms that meet the full criteria for premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD).
Lifestyle ChangesA 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 FactorsWomen 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. In one major analysis of dietary changes involved with PMS, increasing carbohydrate intake was 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 worsens some PMS symptoms, including water retention and negative moods. Low-Fat, High-Fish Diets. A 2000 study reported that women who followed a low-fat vegetarian diet for 2 menstrual cycles experienced less pain and bloating and a shorter duration of premenstrual symptoms than those who ate meat. Women who lose a lot of blood during menstruation, however, may need meat to help maintain iron levels. Choosing more fish and eggs may be a helpful alternative. Salt Restriction. Limiting salt may help bloating. Reducing Caffeine, Sugar, and Alcohol. Reducing caffeine, sugar, and alcohol intake may be beneficial. ExerciseEvidence 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 experienced 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. ![]() 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 helps in the reduction of body fat. Minerals (Calcium, Magnesium, and Manganese)Calcium. Evidence now 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. Magnesium. The effects of magnesium are not as significant as with calcium, but some evidence suggests that it may be helpful in reducing fluid retention in women with mild PMS. (A 2001 analysis of three small studies also suggested that magnesium may help women with menstrual cramps.) 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. VitaminsSpecific vitamins have been investigated. 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, although one study suggested that a lower dose (50 mg) may have the same effect. 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.) Vitamin E. Several randomized controlled trials suggest that vitamin E may improve both physical and emotional symptoms. However, high doses of vitamin E may cause bleeding problems, particularly in people taking anti-clotting medications. Research also indicates that vitamin E, like other antioxidant vitamin supplements, may have damaging effects in high doses. Improved SleepMany women with PMS suffer from sleep problems, either sleeping too much or too little. Achieving better sleep habits may help relieve symptoms. TherapyCognitive-behavioral therapy (CBT) is proving to be very effective in reducing PMS symptoms and improving functioning. In one study of women who had undergone an intensive behavioral program, PMS symptoms were reduced by 75%, and well-being and self-esteem increased. Improvement was most significant in the first 3 months of treatment, but some benefits persisted. Several cognitive-behavioral strategies are being investigated for PMS. Techniques include:
The benefits of CBT are comparable to antidepressants. Identifying Sources of StressStep 1. The Daily Diary. Often, women do not recognize that the decline in their mood and the premenstrual phase coincide. Keeping a diary can help. It is useful to start the process of stress reduction with an informal record of daily events and activities tracked by days of the menstrual cycle. While this exercise might itself seem stress-producing, it need not be done in painstaking detail. A few words accompanying a time and date will usually be enough to serve as reminders of significant events or activities. Note negative experiences, such as those that:
Note positive experiences, including those that:
Step 2. Questioning the Sources of Stress. After reviewing the diary, women should try to identify two or three events or activities that have been significantly upsetting or overwhelming during the premenstrual phase. Priorities and goals should then be carefully examined. Women should ask themselves the following questions:
Restructuring PrioritiesThe next step is to attempt to shift the balance from stress-producing to stress-reducing activities. While it is impossible to completely eliminate stress, there are ways to reduce its impact. In most cases, small daily decisions for improvement can accumulate and work to reconstruct a stressed existence into a pleasant and productive one. Planning ahead for pleasurable activities during the premenstrual phase may be specifically helpful. In fact, adding pleasurable events has more benefit than simply reducing stressful or negative ones. (Studies suggest that daily pleasant events even have positive effects on the immune system and help protect health.) Making time for recreation is as essential as paying bills or shopping for groceries. Many people are afraid of being perceived as selfish if they make decisions that benefit only themselves. The truth is that self-sacrifice may be inappropriate and even damaging if the person making the sacrifice is unhappy, angry, or physically unwell as a result. Keep PerspectiveLearning to focus on positive outcomes during the premenstrual phase helps to reduce tension levels. Negative feelings not only foster hostility but also hamper people from achieving goals. Some of the following may be helpful:
Other TreatmentsAcupuncture and AcupressureSome women have reported relief from pelvic pain after acupuncture or acupressure (a needleless approach). Of particular interest is reflexology, a variant technique that uses manual pressure on acupuncture points on the ears, hands, and feet. In one study comparing this technique to a sham procedure, those who had true reflexology had significantly fewer PMS symptoms than women who received a sham treatment. ![]() 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. Chiropractic TreatmentsOne small study reported improvement in symptoms with the use of spinal manipulation and soft-tissue therapy 2 - 3 times a week in the week before menstruation. It was not clear, however, if the real treatment was any more effective than a sham treatment. More research is needed. Meditative ExercisesMeditative techniques include yoga or other exercises that use meditation, promote relaxation, and reduce stress. They may be particularly helpful. PhototherapyPhototherapy, 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. Sleep DeprivationSome studies suggest that sleep deprivation during the late premenstrual phase may improve premenstrual dysphoric disorder in some women by correcting underlying disturbances of circadian rhythms. This technique involves sleeping only 4 hours during one night and making up for it the next. More research is needed on this interesting approach. Herbs and SupplementsA 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. Flaxseed Oil. Flaxseed oil may help relieve breast pain and tenderness associated with menstruation. Agnus Castus Fruit Extract (Chaste Tree Berry). Several studies report that agnus castus fruit, also known as chaste tree berry, may help relieve PMS symptoms including breast pain and tenderness. Some evidence suggests that the compounds in this substance reduce prolactin levels. Prolactin is the important hormone in breast milk production. Women who are breastfeeding should not use this herb. 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. Herbs and SupplementsGenerally, 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. The following are special concerns for people taking natural remedies for PMS:
MedicationsNonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, substances that dilate blood vessels and cause inflammation. NSAIDs are usually the first drugs tried 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 (Advil, Motrin, Midol PMS), naproxen (Aleve, Naprosyn, Naprelan, 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. AcetaminophenAcetaminophen (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 are 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. AntidepressantsSelective 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), and paroxetine (Paxil). Other SSRIs, such as fluvoxamine (Luvox) and citalopram (Celexa), are also being investigated for PMDD treatment. 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. The following SSRIs are currently approved for PMS and PMDD:
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. Designer Antidepressants. Non-SSRI antidepressants sometimes prescribed for PMDD include:
Studies are needed to determine if these drugs offer any additional benefits compared to standard SSRIs. Tricyclics. Before the introduction of SSRIs, tricyclics, such as desipramine (Norpramin) or amitriptyline (Elavil, Endep), had been the standard treatment for depression. They are not very useful, in general, for premenstrual dysphoric disorder or other PMS symptoms. One exception may be clomipramine (Anafranil), which affects serotonin and has been helpful for some women. Patients report more side effects with Anafranil 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). [See In-Depth Report #8: Depression.] Antianxiety DrugsAntianxiety 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. A 2001 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. [See In-Depth Report #28: Anxiety.] Hormone TherapiesBirth 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). [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. Seasonale, the first continuous-dosing contraceptive, was approved in 2003. It 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, a follow-up to Seasonale, was approved in 2006. As with Seasonale, it 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. In 2007, the FDA approved Lybrel, which supplies a daily low dose of levonorgestrol and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced 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 mood symptoms associated with premenstrual dysmorphic disorder (PMDD). Yaz is a low-dose birth control pill that was approved in March 2006. It combines the estrogen estradiol with a new type of progestin called drospirenone. In October 2006, the FDA approved Yaz for treatment of physical and emotional symptoms of PMDD. 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). (In 2007, Yaz was also approved to treat moderate acne.) 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. 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:
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 RetentionDiuretics 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. Resources
ReferencesArcher DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. Epub 2006 Sep 18. Kornstein SG, Pearlstein TB, Fayyad R, Farfel GM, Gillespie JA. Low-dose sertraline in the treatment of moderate-to-severe premenstrual syndrome: efficacy of 3 dosing strategies. J Clin Psychiatry. 2006 Oct;67(10):1624-32. Landen M, Nissbrandt H, Allgulander C, Sorvik K, Ysander C, Eriksson E. Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder. Neuropsychopharmacology. 2007 Jan;32(1):153-61. Epub 2006 Oct 11.
Review Date:
6/16/2007 Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. 1997-
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