Most women experience some degree of emotional or physical discomfort a few days before and just after their menstrual period begins each month. About 5% of women of childbearing age, however, experience premenstrual symptoms that are so severe they cause significant mental distress and interfere with work, school, or relationships — thereby meeting the criteria for premenstrual dysphoric disorder, or PMDD. Another 18% to 35% of women suffer from less severe, but nevertheless bothersome, premenstrual symptoms.

Although sometimes dismissed as trivial, PMDD can disrupt a woman's life and relationships so completely, she may despair that life itself is not worth living. About 15% of women with PMDD attempt suicide. Fortunately, treatment options exist for PMDD — but the most effective are not always prescribed.

Key points Antidepressants that slow the reuptake of serotonin provide effective treatment for premenstrual dysphoric disorder (PMDD).

These drugs alleviate PMDD more quickly than depression, which means that women don't necessarily have to take the drugs every day.

Hormone therapies provide additional options, but are generally considered second-line treatments.

Some dietary and lifestyle changes may also help relieve symptoms.

PMDD Risk factors and diagnosis

Brain areas that regulate emotion and behavior are studded with receptors for estrogen, progesterone, and other sex hormones. These hormones affect the functioning of neurotransmitter systems that influence mood and thinking — and in this way may trigger PMDD. But it's not clear why some women are more sensitive than others. Genetic vulnerability likely contributes. Other risk factors for developing PMDD include stress, being overweight or obese, and a past history of trauma or sexual abuse.

Also, it's important to rule out other conditions that cause symptoms similar to PMDD, such as depression, dysthymia, anxiety, and hypothyroidism.

A key challenge in PMDD diagnosis is differentiating between mild premenstrual symptoms, which may be annoying but are not disabling, and those severe enough to interfere with daily life.

Proposed criteria for premenstrual dysphoric disorder (PMDD) Five or more of the following symptoms (at least one related to mood) for most menstrual cycles in the past year: Depression Anxiety or tension Sudden mood changes Irritability Loss of interest in daily activities Difficulty concentrating Decreased energy Food cravings and appetite changes Insomnia or sleepiness Physical symptoms, such as breast tenderness or bloating

Symptoms interfere with activities, work, school, or relationships

Symptoms are not due to a cyclical exacerbation of another disorder

Documentation by daily symptom ratings for at least two menstrual cycles

Serotonin reuptake inhibitors for PMDD

Antidepressants that slow the reuptake of serotonin are effective for many women with PMDD. Options include selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa) and fluoxetine (Prozac); the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor); and a tricyclic antidepressant that has a strong effect on serotonin, called clomipramine (Anafranil). Studies report that 60% to 90% of women with PMDD respond to treatment with drugs that block reuptake of serotonin, compared with 30% to 40% of those who take a placebo.

Other types of antidepressants, which target neurotransmitters other than serotonin, have not proven effective in treating PMDD. This suggests that serotonin reuptake inhibitors work in some way independent of their antidepressant effect — but their mechanism of action in PMDD remains unclear.

These drugs also alleviate symptoms of PMDD more quickly than depression, which means that women don't necessarily have to take the drugs every day. Instead, women can take them on an intermittent basis, also known as luteal-phase dosing because it coincides with the roughly 14-day span that begins just after ovulation and ends when menstruation starts.

The decision about whether to take a serotonin reuptake inhibitor every day or on an intermittent basis depends on the type of symptoms a particular woman experiences and if the symptoms of PMDD are superimposed on a more persistent depression. Intermittent dosing is sufficient for treating irritability or mood, but daily medication may be necessary to control somatic symptoms such as fatigue and physical discomfort.

Side effects of serotonin reuptake inhibitors are usually relatively mild and transient. Nausea, for example, typically subsides after several days of taking a drug for the first time — and the problem tends not to recur even when the drug is taken intermittently.

Sexual side effects, such as reduced libido and inability to reach orgasm, can be troubling and persistent, however, even when dosing is intermittent. Of course, PMDD can also lessen sexual desire, so as a practical matter, taking a serotonin reuptake inhibitor on an intermittent basis may still seem like an acceptable strategy.

Hormone therapies may be helpful for some women. They seem to work in PMDD act not by countering hormonal abnormalities, but by interrupting aberrant signaling in the hypothalamic-pituitary-gonadal circuit that links brain and ovaries and regulates the reproductive cycle

PMDD lifestyle changes

Lifestyle changes are always worth the effort.

Diet. The usual dietary advice given to women with mild or even moderate premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol, and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Preliminary evidence suggests that what may help PMDD is consuming more high-protein foods or complex carbohydrates to raise levels of tryptophan, a precursor of serotonin and other neurotransmitters.

Aerobic exercise. Although it has not been well studied for PMDD, a wealth of evidence concludes that aerobic physical activity, such as walking, swimming, or biking, tends to improve mood and energy levels.

Supplements. Vitamin B6, calcium, magnesium supplements, and herbal remedies have all been studied for use in PMDD — but as yet there is no consistent or compelling evidence leading to consensus about their efficacy.

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