Researchers have discovered that a minority of women go through severe premenstrual syndrome (PMS) symptoms due to a hormonal abnormality.

Expression of the ESC/E(Z) gene network was found to be systematically disturbed in PMDD. Credit: Peter Schmidt, M.D., NIMH., David Goldman, M.D., NIAAAClose

National Institutes of Health (NIH) researchers report that 2 to 5 percent of women go through something called premenstrual dysphoric disorder (PMDD). During PMDD, their hormonal levels are unchanged but for some reason, they are much more sensitive to these hormones.

“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,” explained Peter Schmidt, M.D. of the NIH’s National Institute of Mental Health, Behavioral Endocrinology Branch. “Learning more about the role of this gene complex holds hope for improved treatment of such prevalent reproductive endocrine-related mood disorders.”

This is a groundbreaking study because it finally shows the molecular mechanisms that appear to be triggering the debilitating condition, demonstrating once and for all that extreme PMS is a real thing.

“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 behaviours they should be able to voluntarily control,” said David Goldman, from the US National Institutes of Health (NIH).

In order to reach this conclusion, they recruited 10 females suffering from PMDD and 9 control women, and turned off the progesterone and oestrogen in their system. The women with PMDD stopped exhibiting extreme symptoms, while the control women didn’t report similar changes – so scientists understood the reaction was connected to the hormones.

They then cultured the women’s white blood cells, which express many similar genes to the brain cells and are much easier to extract and handle. What they found was that a large gene complex called ESC/E(Z) (Extra Sex Combs/Enhancer of Zeste) was different in the two groups. In PMDD women, the genes were overexpressed, making researchers believe that something in the molecular pathway goes haywire

“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,” explained Schmidt.

Of course, this is just the first step – but if we at least have confirmation of some mechanism at work, then we can start taking action and look for ways to address this problem.

Journal Reference: N Dubey, J F Hoffman, K Schuebel, Q Yuan, P E Martinez, L K Nieman, D R Rubinow, P J Schmidt, D Goldman. The ESC/E(Z) complex, an effector of response to ovarian steroids, manifests an intrinsic difference in cells from women with premenstrual dysphoric disorder. Molecular Psychiatry, 2017; DOI: 10.1038/mp.2016.229

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