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In what is being hailed as a big development for women’s health, National Institutes of Health (NIH) researchers said they have discovered the molecular mechanisms that may be behind a woman’s likelihood to suffer from symptoms of premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS).

“We found dysregulated expression in a suspect gene complex which adds to evidence that PMDD is a disorder of cellular response to estrogen and progesterone,” Peter Schmidt, M.D., of the NIH’s National Institute of Mental Health, Behavioral Endocrinology Branch, said in a news release. “Learning more about the role of this gene complex holds more hope for improved treatment of such prevalent reproductive endocrine-related mood disorders.”

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Symptoms of PMDD can include disabling irritability, sadness and anxiety in the days leading up to a woman’s menstrual period. While PMDD affects between 2 to 5 percent of the patient population, PMS, a less severe syndrome, is more prevalent.

“This is a big moment for women’s health, because it establishes that women with PMDD have an intrinsic difference in their molecular apparatus for response to sex hormones – not just emotional behaviors they should be able to voluntarily control,” Dr. David Goldman, of the NIH’s National Institute on Alcohol Abuse and Alcoholism, said in the news release.

For the research, which was published January 3 in the journal Molecular Psychiatry, the team observed a cause and effect relationship with turning off and later adding estrogen and progesterone in women with PMDD. Turning off the hormones eliminated symptoms, while adding them back triggered a re-emergence, according to the news release.  Researchers determined the finding to confirm that women who suffer from PMDD have a biologically-based behavioral sensitivity to the hormones that may be identifiable in cellular molecular differences.

A later analysis of a genetic control of gene expression in cultured white blood cells from patients with PMDD and controls provided evidence of a large gene complex in which gene expression differed between PMDD suffers and others.

According to the news release, researchers found a large difference in the gene complex ESC/E(Z), which regulates epigenetic mechanisms that govern  the transcription of genes into proteins in response to environmental factors, including sex hormones and various stressors.

"For the first time, we now have cellular evidence of abnormal signaling in cells derived from women with PMDD, and a plausible biological cause for their abnormal behavioral sensitivity to estrogen and progesterone," Schmidt said in the news release.