Women who are especially irritable, sad or anxious in the days leading up to their periods might just respond differently to their own hormones on a microscopic level.

Researchers from the National Institutes of Health have found that genes in white blood cells express themselves differently in women with those mood changes, as compared to those without, as the body undergoes changes during the menstrual cycle, according to a statement from the NIH. The genes in question regulate how the body produces proteins in response to environmental factors — among them sex hormones like estrogen and progesterone that are involved in the menstrual cycle.

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A small percentage of women experiencing those mood changes suffer from premenstrual dysphoric disorder, also known as PMDD, while more women experience the long publicly maligned PMS: premenstrual syndrome. Those conditions may also come with aches, pains and bloating, but are frequently identified for making someone irritable or sad.

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

While researchers have long understood that women with mood symptoms leading up to their periods are unusually sensitive to normal levels of those sex hormones, the cause of that sensitivity has not been fully explained.

The findings, published in Molecular Psychiatry, noted that many of the genes identified in the examined blood cells also appear in brain cells, and the scientists said the next step is to take a deeper look at neurons created from the blood of PMDD patients “in hopes of gaining a more direct window into the [genes’] role in the brain,” according to the NIH.

Dr. Peter Schmidt, of the NIH’s National Institute of Mental Health, Behavioral Endocrinology Branch, said in a statement that scientists now have information of what happens on a cellular level in women with PMDD when they react with estrogen and progesterone, and learning more could lead to “improved treatment of such prevalent reproductive endocrine-related mood disorders.”

Source: Goldman D, Schmidt PJ, Dubey N, et al. The ESC/E(Z) complex, an intrinsic cellular molecular pathway differentially responsive to ovarian steroids in Premenstrual Dysphoric Disorder. Molecular Psychiatry. 2017.

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