Causes and Risk Factors of Premenstrual Dysphoric Disorder

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Premenstrual dysphoric disorder (PMDD) is a mood disorder that affects 3 to 8 percent of women in the second half of their menstrual cycle. It is thought to be the result of disturbances that alter your brain's neurochemistry and communication circuits.

While most women experience some unpleasant symptoms in the days before their period, PMDD is more serious. It presents as severe mood changes occurring seven to 14 days before the start of your period and resolves shortly after your period arrives.

Common Causes

As a mood disorder, PMDD is believed to be triggered by fluctuating hormone levels altering the production or effectiveness of neurotransmitters, including serotonin and dopamine.

The reason why some women are more susceptible to mood changes during hormonal fluctuation is a combination of genetics, stress, medications, and chronic medical conditions.


Reproductive hormones—namely estrogen and progesterone—interact with brain chemicals and can influence mood. Estrogen and progesterone are produced by the ovaries and the levels of these hormones fluctuate during a regular menstrual cycle.

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

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) is the top treatment for PMDD.

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.


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

Lifestyle Risk Factors

Some, but not all, women with PMDD have a history of significant stress exposure, such as a history of childhood physical, emotional, or sexual abuse. 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. 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. Experimental studies suggest the ALLO response to acute stress is decreased when exposed to chronic stress.

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.

A Word From Verywell

PMDD is a real condition and left untreated may have a serious impact on your health and well being. It is not something that can be wished away with willpower or corrected with better behavior.

There are likely variable causes of PMDD, which may explain why some women respond better to different treatments. It is important to keep this in mind as you and your doctor are exploring the various treatment options to help you live well with PMDD.

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