Premenstrual syndrome

Highlights

Premenstrual Syndrome Symptoms

Premenstrual syndrome (PMS) can produce physical and emotional or behavioral symptoms in the days before menstruation.

Physical symptoms of PMS may include:

Emotional and behavioral symptoms of PMS may include:

Premenstrual Dysphoric Disorder Symptoms

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 that resolve within a few days after menstruation starts.

Five or more of the following symptoms must occur:

Drospirenone and Blood Clots

In 2012, the Food and Drug Administration (FDA) completed its safety review of drospirenone-containing birth control pills and concluded that drospirenone has a much higher risk for causing blood clots than levonorgestrel or other types of progestin. Drospirenone is the progestin used in the Yaz and Beyaz brand birth control pills, which are approved specifically for treatment of premenstrual dysmorphic disorder (PMDD).

Introduction

Premenstrual Syndrome

Premenstrual syndrome (PMS) is a set of emotional and physical symptoms that typically occur about 5 - 11 days before a woman starts her monthly menstrual cycle. The symptoms usually stop when menstruation begins, or shortly thereafter.

A menstrual cycle usually lasts an average of 28 days, although the cycle length may range from 21 - 34 days and still be considered normal. When a woman reaches her 40s the cycle lengthens, reaching an average of 31 days by age 49.

Ovulation occurs mid-way through the menstrual cycle, around day 14 (in a 28-day cycle). A menstrual cycle has two main phases, which precede and follow ovulation:

PMS is associated with the luteal phase of the menstrual cycle. Estrogen and progesterone levels rise in the first part of the luteal phase to help prepare the endometrial lining of the uterus for an embryo. If conception (pregnancy) does not occur, the levels of these hormones decrease in the latter part of the luteal phase, and the lining is shed through menstruation in the beginning of the follicular phase. Levels of other types of hormones also rise and fall during the menstrual cycle.

Premenstrual Dysphoric Dysorder

Premenstrual dysphoric disorder (PMDD) is a condition marked by severe depression symptoms, irritability, and tension before menstruation. The symptoms of PMDD are similar to those of PMS, but they are generally more severe and debilitating. Like PMS, symptoms of PMDD occur during the luteal phase in the week before menstrual bleeding begins. Symptoms usually improve within a few days after the period starts.

Typical Menstrual Cycle

Menstrual Phases

Typical No. of Days

Hormonal Actions

Follicular (Proliferative) Phase

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

Estrogen and progesterone start out at their lowest levels.

Follicle-stimulating hormone (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 luteinizing hormone (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. 

Causes

Doctors don't know exactly what causes 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 sensitive 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).

While hormonal and brain chemical changes certainly play a role, it is not exactly clear how they cause PMS or PMDD. Cyclic fluctuations in some of these hormones -- not whether their levels are high or low -- may be the important factors in premenstrual problems.

Risk Factors

Many women in their reproductive years experience some of the emotional and physical symptoms of premenstrual syndrome (PMS). A small percentage 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

PMS tends to occurs in women who are in their late 20s to early 40s. Symptoms usually begin when a woman is in her mid-twenties. Naturally, PMS and other menstrual problems end at menopause when a woman stops having menstrual periods.

Family History

A woman whose mother had PMS is more likely to have PMS herself.

Psychologic Factors

Women with past or current mood or anxiety disorders, including depression, may be at increased risk for PMS and premenstrual dysphoric disorder (PMDD). A history of postpartum depression is a risk factor as is history of alcohol abuse.

Lifestyle Factors

Poor eating habits may contribute to PMS. Dietary issues associated with PMS include:

Stress does not cause PMS, but it may worsen symptoms. Exercise can help reduce stress and boost energy levels.

Complications

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.

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

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). The symptoms typically start in the 5 days before menstruation begins and go away within 4 days after bleeding starts. Symptoms do not start again until at least day 13 in the cycle. Once established, the symptoms tend to remain fairly constant until menopause, although they can vary from cycle to cycle.

Physical Symptoms

Emotional and Behavioral Symptoms

Premenstrual Dysphoric Disorder

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

Diagnosis

Your doctor will ask you about your symptoms and may ask you to fill out a questionnaire. The best method for determining your PMS patterns is to track your symptoms for 2 - 3 months:

Ruling Out Other Conditions

If the symptoms consistently resolve once menstruation begins, 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:

Treatment

For many women, PMS symptoms can be relieved by lifestyle changes (food modifications, exercise, and 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:

Cognitive-behavioral psychotherapy may be an appropriate alternative to antidepressants for some women.

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 control premenstrual symptoms:

Vitamins and Minerals

Some evidence indicates that calcium -- and possibly vitamin B6, other B vitamins, or magnesium -- may help with PMS symptoms.

Calcium. Calcium has the most evidence as an effective dietary treatment for PMS. The recommended dietary intake for women is 1,000 mg/day before age 50 and 1,200 mg/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 supplements may be helpful for certain women.

Calcium source

 Click the icon to see an image of sources of calcium. 

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. 

Other B Vitamins. Other B vitamins that may play a role in PMS include riboflavin (B2), niacin (B3), and folate (folic acid). Food sources for these vitamins include:

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 doctors.

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.

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.

Herbs and Supplements

Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration (FDA) 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.

Chasteberry Extract. Chasteberry (Vitex agnus castus) is a traditional herbal remedy for many gynecological conditions. Some small studies have indicated it may be helpful for PMS symptoms, including breast discomfort. However, the evidence is not strong.

Evening Primrose Oil. Some women have reported that taking evening primrose oil helped improve PMS and symptoms such as breast tenderness. However, several rigorous studies have reported no benefit.

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:

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, generic) and naproxen (Aleve, generic) or prescription mefenamic acid (Postel, generic). 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, generic) 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, which are also available as generics. Such drugs typically include a diuretic to reduce fluid and an antihistamine to reduce tension.

Antidepressants

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) are the main type of antidepressants used to treat premenstrual dysphoric disorder (PMDD) and severe PMS mood symptoms.

In the United States, three SSRIs are approved by the FDA for the treatment of PMDD:

Other SSRIs sometimes prescribed for PMDD include citalopram (Celexa, generic) and escitalopram (Lexapro, generic). The serotonin-noradrenaline reuptake inhibitor venlafaxine (Effexor, generic) has also shown benefit in some studies.

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.

General side effects of SSRIs may include nausea, drowsiness, headache, weight gain and sexual dysfunction. Antidepressants may increase the risk for suicidal thinking and behavior in young adults ages 18 - 24. This risk for “suicidality” generally occurs during the first few months of treatment.

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. Alprazolam (Xanax) is a benzodiazepine antxiolytic often prescribed for PMS. However, benzodiazepines have a lot of serious side effects. Dependence is a risk and can occur after as short a time as 3 months of use. (Using alprazolam 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. Overdose is very serious, although rarely fatal. Benzodiazepines are potentially dangerous when used in combination with alcohol.

Buspirone. Buspirone (BuSpar, generic) is a drug used to treat anxiety. It 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.

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) contain combinations of an estrogen (usually estradiol) and a progestin (the synthetic form of progesterone).

The birth control pill Yaz is approved specifically for treatment of premenstrual dysmorphic disorder (PMDD). A related birth control pill, Beyaz, which is supplemented with the B vitamin folate, is also approved for treatment of PMDD. Both of these pills contain a newer type of progestin called drospirenone. The FDA warns that birth control pills that contain drospirenone may increase the risk for blood clots much more than the progestin levonorgestrel contained in other types of birth control pills. Some studies have indicated that the risk for blood clots is 3 times higher with drospirenone.

Because of the high risk for blood clots, stroke, and heart attack Yaz and Beyaz should not be used by women who are over age 35 or by those who smoke. In addition, Yaz and Beyaz should not be used by women with kidney, liver, or adrenal disease. Drospirenone is related to spironolactone, a diuretic, and can increase potassium levels.

Some women with PMS use extended-cycle (continuous-dosing) OCs to reduce or eliminate their monthly periods:

Side effects of OCs include nausea, breakthrough bleeding, breast tenderness, headache (which may worsen in smokers or women with a history of migraine), and weight gain. Women who are over age 35 and smoke, or who are at risk for blood clots, heart attack, or stroke, should not take combination birth control pills.. Some women may experience worsening of PMS symptoms with oral contraceptives.

 
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 appear to have little effect on depression.

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

Common side effects (which can be severe in some women) include menopausal-like symptoms such as hot flashes, night sweat, weight change, and depression. The side effects vary in intensity, depending on the particular GnRH agonist. The most important concern is possible osteoporosis from estrogen loss. Doctors recommend that women not take these drugs for more than 6 months.

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, generic) is a synthetic substance that resembles male hormones. It has very severe side effects and is used only if other therapies fail. It suppresses estrogen and menstruation and is used in low doses for severe PMS and premenstrual migraines. Side effects include masculinizing effects such as facial hair growth, deepening of the voice, and acne.

Diuretics for Fluid Retention

Diuretics are drugs that increase urination and help eliminate water and salt from the body. They reduce bloating and breast tenderness in women with PMS. Diuretics can have considerable side effects and should not be used for mild or moderate PMS symptoms. Spironolactone (Aldactone, generic) is the most commonly prescribed diuretic for PMS.

Spironolactone can increase potassium levels in the body. 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

Biggs WS, Demuth RH. Premenstrual syndrome and premenstrual dysphoric disorder. Am Fam Physician. 2011 Oct 15;84(8):918-24.

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.

Chocano-Bedoya PO, Manson JE, Hankinson SE, Willett WC, Johnson SR, Chasan-Taber L, et al. Dietary B vitamin intake and incident premenstrual syndrome. Am J Clin Nutr. 2011 May;93(5):1080-6. Epub 2011 Feb 23.

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

Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ. 2011 Apr 21;342:d2151. doi: 10.1136/bmj.d2151.

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.

[No authors listed] ACOG Practice Bulletin No. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol. 2010 Jan;115(1):206-18.

Parkin L, Sharples K, Hernandez RK, Jick SS. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ. 2011 Apr 21;342:d2139. doi: 10.1136/bmj.d2139.

Pinkerton JV, Guico-Pabia CJ, Taylor HS. Menstrual cycle-related exacerbation of disease. Am J Obstet Gynecol. 2010 Mar;202(3):221-31.

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


Review Date: 9/25/2012
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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