Causes and Risk Factors of Premenstrual Dysphoric Disorder (PMDD)

Premenstrual dysphoric disorder (PMDD) is thought to be caused by disturbances that alter your brain's neurochemistry and communication circuits. Characterized by severe mood changes that occur a week or two before the start of menstruation, symptoms generally resolve shortly after your period arrives. Hormone changes are at the root of PMDD, but some women may be more prone to the disorder due to factors like genetics and stress.

While most women experience some unpleasant symptoms in the days before their period, PMDD is more serious. The mood disorder affects 3% to 8% of women in the second half of their menstrual cycle.

Common Causes

Estrogen and progesterone are produced by the ovaries, and levels of these reproductive hormones fluctuate during a regular menstrual cycle.

PMDD is believed to be triggered by these fluctuations, as the hormones interact with brain chemicals and can influence mood. Specifically, estrogen and progesterone can alter the production or effectiveness of neurotransmitters, including serotonin and dopamine—so-called "feel good" chemicals.

Progesterone/Allopregnanolone

PMDD symptoms are limited to the luteal phase of the menstrual cycle, which occurs between ovulation and the first day of bleeding. In a typical 28-day menstrual cycle, this corresponds to cycle days 14 to 28.

At ovulation, the ovaries begin to increase the production of progesterone, which is then converted into allopregnanolone (ALLO). Progesterone and ALLO levels continue to rise until the start of your period, at which point they rapidly drop. 

ALLO interacts with GABA receptors in parts of the brain that control agitation, anxiety, and irritability. ALLO typically has a calming effect, but women with PMDD appear to have an abnormal reaction to it.

The exact cause is not known, but researchers have two theories: Women with PMDD either experience a change in GABA-receptor sensitivity to ALLO in the luteal phase or there is a defect in ALLO production during the luteal phase.

Estrogen

After ovulation, estrogen levels drop. Estrogen interacts with several brain chemicals that control your mood, in particular, serotonin. Serotonin is important for regulating many functions, including mood, sleep, and appetite. Serotonin also influences your cognition, or how you acquire, process, and perceive information from your environment. Estrogen promotes the positive effects of serotonin.

Women with PMDD may experience an exaggerated drop in serotonin levels. Low serotonin levels are associated with the depressed mood, food cravings, and impaired cognitive functioning of PMDD. This is why selective serotonin receptor inhibitors (SSRIs) are the top treatment for PMDD.

PMDD is not necessarily the result of a hormonal imbalance or deficiency, but your doctor will probably run tests to rule that out.

Health Risk Factors

Some women are more susceptible to mood changes during hormonal fluctuation due to a combination of genetics, stress, and chronic medical conditions.

Genetics

There is a genetic basis for the hormonal sensitivities that appear to be at work in PMDD. Researchers at the National Institute of Health found that women with PMDD have changes in one of the gene complexes that control how they respond to estrogen and progesterone.

This discovery can be extremely validating if you have PMDD. It gives concrete scientific evidence that something biological and beyond your control is causing your mood changes.

Immune Activation and Inflammation

Mood disorders are linked to the immune system. Infections and other causes of systemic inflammation can trigger a worsening of symptoms in patients with mental health issues.

Early research in this area suggests that women with more significant premenstrual symptoms may have an increased inflammatory response during the luteal phase compared to women with minimal symptoms. The link between PMDD and inflammation, however, is still unclear.

Stress

Researchers are looking at the relationship between ALLO and the stress response in women with PMDD.

ALLO typically increases at times of acute stress and has a calming and sedative effect. However, experimental studies suggest this response is decreased in cases of chronic stress.

This may help explain why some, but not all, women with PMDD also have a history of significant stress exposure, such as childhood physical, emotional, or sexual abuse. Chronic everyday stress can also trigger symptoms or make them worse.

The correlation between stress and worsening PMDD symptoms is currently an area of active investigation. Certainly, the possibility of a connection between your stress response and PMDD supports the common sense first-line treatment interventions for PMDD, including lifestyle modifications and stress reduction.

History of Mood Disorders

Research shows that 50% of women diagnosed with PMDD also have an anxiety disorder, compared with 22% of women without PMDD. In addition, 30% of women with PMDD were also diagnosed with depressive disorder, compared to 12% of women without PMDD.

Having a family history of mood disorders increases the likelihood of PMDD as well.

Smoking

Cigarette smoking is linked to an increased risk of severe PMS and PMDD, according to a study published in the American Journal of Epidemiology.

Researchers tracked more than 3,000 women ages 27 to 44 over 10 years and found that those with a history of smoking were twice as likely to develop PMS than those who never smoked. What's more, those who started smoking before age 15 were 2.5 times more likely. PMDD risk may follow suit.

A Word From Verywell

PMDD is a real condition that, if left untreated, may have a serious impact on your health and well-being. There are likely variable causes of PMDD, which may explain why some women respond better to different treatments. If you believe you may be affected by PMDD, seek a medical evaluation—and, if needed, a second opinion.

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