Premenstrual Syndrome (PMS)

Premenstrual syndrome (known as PMS) involves a variety of physical, mental, and behavioral symptoms tied to a woman’s menstrual cycle. By definition, symptoms occur during the days before a woman's period starts. They usually go away after the first day or two of flow.

PMS is a complex health concern. Up to 80% of women experience some symptoms of PMS. Scientists cannot agree on its cause or the best way to treat PMS.

• PMS usually occurs in women in their fourth and fifth decades of life (aged 30-49 years). For a small number of women, it can be severely incapacitating. A woman who has had a hysterectomy (removal of the uterus) may still experience PMS if at least one ovary remains.

• Because many different processes may contribute to PMS, methods of treatment vary widely and can include medical and alternative approaches. Surgery is a last resort.

• As many as 3-8% of women may have a more severe condition called premenstrual dysphoric disorder (PMDD). PMS and PMDD are not the same. Women with PMDD become seriously depressed for a week or more before their periods. PMS is shorter, usually milder, and involves more physical symptoms. The two may occur together, or a woman may have one and not the other.

Premenstrual syndrome occurs during the luteal phase of the menstrual cycle. This phase occurs immediately after an egg is released from the ovary and lasts from day 14 through day 28 of a normal menstrual cycle (day 1 is the day your period begins).

During the luteal phase, hormones from the ovary cause the lining of the uterus to grow thick and spongy. At the same time, an egg is released from the ovary. If the egg meets sperm, it may implant in the lining of the uterus and grow. At this time, the level of a hormone called progesterone rises in the body, while the level of another hormone, estrogen, begins to drop. The shift from estrogen to progesterone may cause some of the symptoms of PMS.

• At first, some medical professionals believed that changing progesterone levels alone could account for a woman’s mood, behavior, and physical changes during the luteal phase (or second half) of the menstrual cycle. Progesterone interacts with certain parts of the brain that deal with relaxation. Newer studies suggest that other hormones and chemical changes may also be at work.

• For example, women develop deficiencies in a part of their nervous system called the endorphin system. Endorphins are "feel good" hormones. Normal levels contribute to cheerful, happy moods and also make people less sensitive to pain. (Drugs such as heroin and morphine act like super endorphins.) A small amount of these "feel good" endorphins usually circulate in the body, but these levels drop during the luteal phase of the menstrual cycle. In some women, falling endorphin levels may lead to nausea, jumpiness, and various types of pain.

• Many women with premenstrual syndrome retain water. This may occur because of cycling in hormones that affect the kidneys, the organs that control the balance of water and salt in the body. Fluid overload may cause some of the symptoms of PMS, especially swelling and weight gain, and may also aggravate some negative self perceptions and thus worsen emotional symptoms at this stage of the menstrual cycle.

• Diet may also be a factor in PMS. Progesterone, which affects insulin and levels of blood sugar, may affect alcohol tolerance and trigger the craving for sweets, especially simple sweets like candy and soda, that some women notice during the premenstrual phase. Such sweet foods break down very quickly in the body, so that blood sugar first goes up and then drops down low. Episodes of low blood sugar may contribute to both crying spells and the irritability that are part of PMS. Additionally, low levels of vitamin A, vitamin B6, and vitamin E may play a role in PMS.

• Hormonal cycling also affects the level of serotonin, a brain chemical that regulates many functions, including mood and sensitivity to pain. Compared to women who do not have PMS, some women who experience PMS have lower levels of serotonin in their brains prior to their periods. (Low serotonin levels are commonly associated with depression. Popular antidepressant medicines such as fluoxetine [Prozac] and paroxetine [Paxil] lift depression by raising levels of serotonin in parts of the brain.)

• Another theory explaining PMS involves inflammatory substances called prostaglandins. Prostaglandins are produced in the areas where PMS symptoms originate, namely, breast, brain, reproductive tract, kidney, and gastrointestinal tract. This suggests they may play a role in problems such as cramping, breast tenderness, gas, diarrhea, and constipation.

• Premenstrual syndrome (PMS): A woman with PMS will have monthly cycles of symptoms in mood, behavior, and/or physical functioning. Though bothersome, these symptoms are usually not severe enough to  interrupt a normal lifestyle. Most women who experience PMS symptoms cope with symptoms at home. A few may seek medical care for very severe symptoms. These symptoms affect the following:

• Mood - Anxiety, nervousness, mood swings, irritability, depression, forgetfulness, confusion, insomnia, hostility

• Behavior - Cravings for sweets, increased eating, crying, poor concentration, sensitivity to noise, changes in alcohol tolerance

• Physical functions - Headache, heart pounding, fatigue, dizziness, weight gain, bloating, breast swelling and tenderness, constipation or diarrhea

• Premenstrual dysphoric disorder (PMDD): This is a more severe condition than PMS. It is only diagnosed when symptoms are so bad that they make it hard for a woman to function normally. While the mood symptoms are similar to the mood symptoms of PMS, they are worse and cause more problems. The physical symptoms of PMS may or may not be present.

• Like PMS, the symptoms of PMDD start 7-14 days before a woman's period and go away once the period starts. Unlike PMS, PMDD can seriously affect a woman's daily activities. PMDD is diagnosed as a mental health disorder.

• A woman may have PMDD if she has 5 or more of the following symptoms during the premenstrual week and for most cycles during the past year:
  • Depression (feeling despair or hopelessness, not just sadness)

  • Anxiety (keyed up, on edge)

  • Severe mood swings (feeling suddenly sad or extremely sensitive to rejection)

  • Anger or irritability

  • Decreased interest in usual activities (work, school, friends, hobbies)

  • Difficulty concentrating

  • Decreased energy

  • Appetite changes (overeating or cravings for certain foods)

  • Sleep problems (can’t sleep or wake up early, or oversleeping)

  • Feeling overwhelmed or out of control

  • Physical symptoms, such as bloating, breast tenderness or headaches

• If these symptoms do not occur in sync with the menstrual cycle, the woman may have some other medical or mental health condition.

• The symptoms of PMDD end with menopause, when menstruation stops and the levels of hormones that regulate menstruation no longer rise and fall each month.

If you have symptoms of PMS that do not go away within 3-4 days of the start of your period, call your doctor. You may have a different medical problem.

When the typical symptoms of PMS become so severe that your lifestyle is drastically altered, talk with your health care provider.

• Your doctor will evaluate your symptoms for signs of premenstrual dysphoric disorder (PMDD), a mental health concern, which should be diagnosed and treated.
  
  
• Serious signs may also signify other mental or medical problems. Psychiatric diagnoses such as chronic depression, anxiety disorders, and personality disorders may overlap with the diagnosis of PMDD. Medical considerations include hormone imbalances, thyroid disorders, electrolyte problems, and low levels of red blood cells. Your doctor will want to rule out these more serious medical problems.
  
  
• If you have such serious mood changes or behavior changes that you feel you may hurt yourself or another person, seek medical care immediately at a hospital’s emergency department.

Your health care provider will talk with you about your symptoms and when they occur each month. Keep track of your symptoms, particularly noting when they occur during your menstrual cycle. If you have not already kept a diary, your provider may ask you to keep accurate records of your symptoms throughout the next month or two. This diary gives you and your provider a better understanding of your symptoms and how they relate to your menstrual cycle.

• Your provider may perform various blood tests to rule out other illnesses.
  
  
• Your provider may also ask you to see a mental health provider to rule out a mental health disorder or to confirm the diagnosis of PMDD.

Different treatments are aimed at different causes of PMS, and different approaches may relieve some symptoms but not others. Anti-inflammatory drugs are especially helpful for cramping, bowel symptoms, breast pain, and headaches. Diuretics (water pills) help with swelling and sometimes headaches. Antianxiety drugs and antidepressants (which usually also relieve anxiety) may help with mood, irritability, and concentration. For those women who also seek contraception, contraceptives such as pills and patches (all of which inhibit ovulation) may be of value as they reduce the hormonal variability of the natural menstrual cycle. Indeed, the progestin drospirenone (Yasmin) has been associated with a further decrease in PMS/PMDD symptoms because of its unique action as a mild diuretic, although it is not yet specifically approved for this indication. Supplements help some women as well.

You and your health care provider may need to try different medications before you find one that works for you. Medicines may not completely relieve all your symptoms, and they are not always necessary. You can often make lifestyle changes that help.

Changes in diet and exercise are usually recommended first. Eat a well-balanced diet and avoid salt, candy, sodas, and sugary foods during the week before your period. While it may also help to avoid caffeine, going on and off caffeine during the month may be difficult. You may have to cut out caffeine completely if it seems to contribute to your symptoms. Use alcohol in moderation, if at all. Small, frequent meals during the premenstrual week may help keep blood sugar at a steady level and reduce cravings. Keeping a consistent exercise program may also improve your well-being throughout the menstrual cycle.

|Self-Care at Home|

Self care reduces many premenstrual symptoms.

• Dietary strategies may help.
  
  
  • To lessen bloating and water retention, avoid foods high in salt (sodium), especially in the week before your period.
    
    
  • Because diet may play a role in symptoms associated with low blood sugar, avoid candy, soda, and other sugary foods, especially in the week before your period.
    
    
  • An adequate vitamin and mineral intake may also help with PMS symptoms.
    
    
    • Vitamin E: Studies do not agree about how much vitamin E may be helpful, but 300-400 IU per day is a safe dose that may be of benefit.
      
      
    • Calcium: Some women get relief being careful to take at least 1,200 mg of calcium per day, through a combination of normal eating and taking supplements.
      
      
    • Magnesium: Most studies that have evaluated magnesium have failed to show overall benefit. One study of magnesium (200 mg/day) with 50 mg of vitamin B6 showed a significant reduction in anxiety symptoms, compared to magnesium alone. Food sources of magnesium include nuts, legumes, whole grains, dark green vegetables, seafood (oysters), and meats.
      
      
• Regular aerobic exercise and relaxation techniques can help to relieve many of the mood symptoms found with PMS. Muscle relaxation techniques and massage therapy may help.

|Medications|

PMS treatment

• Anti-inflammatories: These drugs prevent the body from producing prostaglandins, which have been suggested as a cause of PMS. Reducing the amount of prostaglandins in the body may eliminate many of the inflammatory symptoms of PMS such as menstrual cramps, breast pain, headache, swelling, and other discomforts. Several types of anti-inflammatory agents are used for PMS. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended initially, and there are several that may be purchased without a prescription. COX-2 inhibitors are a new type of NSAID that must be obtained with a prescription. These are longer-acting than most NSAIDs and have less risk of causing stomach discomfort or ulcers.

• Alert: On September 30, 2004, Merck & Co, Inc, announced a voluntary withdrawal of the COX-2 inhibitor rofecoxib (Vioxx) from the US and worldwide market because of its association with an increased rate of cardiovascular events (including heart attacks and strokes) compared to that of placebo. A major US Food and Drug Administration (FDA) study of rofecoxib found an apparent 3-fold increase in the risk of sudden cardiac death or heart attack among patients who had taken higher doses of the drug compared to the risk of patients who had not recently received similar medication. The report showed that even patients taking the standard starting dose of 12.5 mg or 25 mg of rofecoxib had a 50% greater chance of heart attack or sudden cardiac death than patients on any dose of celecoxib (Celebrex). The large-scale study was conducted after analyzing the medical records of 1.4 million people insured by Kaiser Permanente in Oakland, Calif, between 1999-2001. Note: The study has inherent limitations in that it is observational, rather than randomized and controlled.

• Alert: On April 7, 2005, valdecoxib (Bextra, by Pfizer, Inc) was voluntarily withdrawn from the US market, pending further discussion with the FDA. The association of valdecoxib with potentially life-threatening risks, including myocardial infarction, stroke, and serious skin reactions, initiated an investigation to determine whether the benefits of the drug outweighed the risks. The serious skin reactions are most likely to occur in the first 2 weeks of treatment, but they can occur any time during therapy. Valdecoxib should be discontinued at the first sign of rash, mouth sores, and/or allergic reactions (eg, swelling, itching, shortness of breath). Other COX-2 inhibitors and traditional NSAIDs (eg, naproxen [Aleve, Naprosyn], ibuprofen [Motrin]) also have a risk for these rare, serious skin reactions, but the reported rate of the reaction appears to be greater for valdecoxib. New data regarding risks in individuals who take valdecoxib following heart bypass surgery showed an increased risk of heart attack, stroke, deep vein thrombosis (blood clots in the leg), and pulmonary embolism (blood clots in the lungs).

• NSAIDs
  • Diclofenac (Cataflam, Voltaren)

  • Ibuprofen (Motrin)

  • Ketoprofen (Orudis)

  • Meclofenamate (Meclomen)

  • Mefenamic acid (Ponstel)

  • Naproxen (Aleve, Naprosyn)
  
  
• COX-2 inhibitors: Celecoxib (Celebrex)

• Hormones: Hormones such as nafarelin (Synarel) and leuprolide (Lupron) prevent your body from releasing eggs and undergoing a menstrual cycle. Therefore, if you take these medications, you will not ovulate and will not menstruate. This treatment eliminates PMS symptoms in more than half of all women receiving it. These hormones are like birth control pills in that they suppress the menstrual cycle, but the cycle returns when they are stopped. However, women taking the birth control pill still bleed every month. Women on this therapy have no periods at all. However, most contraceptive pills and patches can be used in a continuous fashion to reduce or eliminate withdrawal bleeding. 

• Danazol (Danocrine) is another hormonal agent that blocks the production and the effects of certain female hormones. Danazol is a modified male sex hormone, which was shown to significantly decrease breast pain in clinical studies. However, it was not effective in treating other symptoms. Because danazol may increase certain fat levels in the blood, it is not recommended if you have high cholesterol levels. Because of the profound adverse side effect profile of danazol, its use continues to decrease.

• Anti-anxiety drugs: Benzodiazepines are drugs that decrease anxiety by depressing the central nervous system. Alprazolam (Xanax) is a member of this class. It can be effective in treating the anxiety associated with premenstrual syndrome. You may feel drowsy if you take this type of medicine. Benzodiazepines can be addictive.

• Antidepressants: Fluoxetine (Sarafem, also known as Prozac), sertraline (Zoloft), and paroxetine (Paxil) are medicines that help the body increase the activity of serotonin, a brain chemical that has been shown to be low in some women with PMS (and in those with PMDD). Clinical trials show that SSRIs effectively treat mood symptoms such as depression, anxiety, and anger. However, other symptoms of PMS, such as tiredness and decreased sexual drive, may not improve or may become worse on these drugs.

• Diuretics: Diuretics (commonly called water pills) are drugs that help the body to shed excess water through the kidneys. These medicines significantly help reduce the weight gain, breast swelling, and bloating associated with PMS. Metolazone (Mykrox, Zaroxolyn) and spironolactone (Aldactone) are 2 commonly used diuretics.

• Others: Other treatments that may work but not been evaluated in scientific trials include lithium, progesterone, and birth control pills. Case reports of progesterone organogel have shown promising results (especially in teenaged girls) in relieving mood symptoms.

PMDD treatment: The same lifestyle changes that sometimes help women with PMS may help relieve the symptoms of PMDD. In most cases, however, PMDD symptoms continue despite such efforts. Studies show that some women with PMDD benefit from treatment with antidepressants called selective serotonin reuptake inhibitors (SSRIs). These include fluoxetine (Sarafem, also known as Prozac), sertraline (Zoloft), and paroxetine (Paxil). The same medications are also commonly given to treat depression. If your doctor prescribes one of them for PMDD, you may be given a low dose and take it for just part of each month.

|Other Therapy|

Certain herbs have been evaluated for use in PMS. Many over-the-counter herbal preparations combine various herbs with certain vitamins to create a PMS formula. Although preliminary reports have been promising, more scientific research is needed to evaluate herbal treatment of PMS. Consult your health care provider before using any herbal supplement.

• Black cohosh: Black cohosh has been shown to positively impact the serotonin pathway and thus may have a beneficial impact for some women, especially those with vasomotor symptoms (hot flashes). Black cohosh does not affect estrogen levels or function.  
  
  
• St. John's wort: This herb may help elevate serotonin levels, possibly helping PMS symptoms. Studies do not agree on its effectiveness. St. John's wort should never be used if you take prescription antidepressants.
  
  
• Evening primrose oil: Gamma-linoleic acid (GLA) is the active agent found in evening primrose oil. Much like mefenamic acid, GLA blocks prostaglandin synthesis, resulting in decreased breast tenderness, bloating, and weight gain. The standard dose is 3 grams per day, and it should be started less than 1 week before the onset of your period. This agent is available without a prescription at health food stores and certain pharmacies. A review of the studies on evening primrose oil, however, showed no proven effect on the symptoms of PMS.
  
  
• Ginkgo biloba: Shown to reduce the symptom of breast pain but not other PMS symptoms.
  
  
• Chasteberry (Vitex; agnus castus fruit extract): A study in 2001 evaluated the use of agnus castus fruit extract (20 mg per day) for 3 months. The treated group showed a greater improvement on all scales (irritability, mood alteration, anger, headache, breast fullness) except for bloating. Do not use if you take birth control pills.

|Prevention|

• Lifestyle change
  
  
  • Perform aerobic exercise (if not daily, then 3-4 times a week, even a brisk walk).
    
    
  • Learn and use stress management techniques such as relaxation, deep breathing, meditation, a warm bath, listening to music, or yoga in your day.
    
    
  • Limit salt (to help reduce fluid retention, bloating, and swelling especially in your feet and hands).
    
    
  • Limit caffeine (caffeine can make breast tenderness worse and increase headaches).
    
    
  • Avoid alcohol (can often affect you differently before your period).
    
    
  • Eat small meals and snacks spread throughout your day so you don’t go for long periods of time without eating.
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• Vitamin therapy
  
  
  • Vitamin B6 — 100 mg per day maximum (larger doses sometimes cause serious side effects). You can also take a B-complex that includes all the B vitamins. Vitamin B6 may take the edge off irritability and reduce fatigue and depression.
    
    
  • Vitamin E — 400 IU per day (maximum) may be helpful in reducing breast tenderness.
    
    
  • Calcium — 1,000-1,200 mg per day of elemental calcium (the labels on foods and supplements give the amount of elemental calcium they contain) may reduce bloating, body aches, anxiety, or depression.
    
    
  • Magnesium — 400 mg per day in combination with vitamin B6 may reduce pain, water retention, and negative mood.

|Outlook|

The symptoms of premenstrual syndrome are usually gone within 3-4 days of the start of your period. If you have a severe case of PMS, some doctors will treat you with a variety of medications or with a combination of medicine, diet, and exercise. The only definitive cure for PMS is removal of the uterus and ovaries, which may have many other complications and unwanted long- and short-term consequences. Most women gain benefit from existing therapies without surgery.

|Support Groups and Counseling|

PMS symptoms are not "all in your head." Consider attending support groups to discuss your experiences and to hear those of other women and how they cope.

Author: Julia Frank, MD, Director of Medical Student Education in Psychiatry, Associate Professor, Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine.

Coauthor(s): Todd E Arkava, MD, Resident Physician, Department of Emergency Medicine, Darnall Army Community Hospital; John G McManus Jr, MD, Research Director, Department of Emergency Medicine, Darnall Army Community Hospital; Assistant Professor, Department of Emergency Medicine, Scott and White Medical Center, Texas A&M University.

Editors: Bryan D Cowan, MD, Director, Division of Reproductive Endocrinology, Professor, Department of Obstetrics and Gynecology, University of Mississippi College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, ; Lee P Shulman, MD, Professor of Obstetrics and Gynecology, Head, Section of Reproductive Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.