Scientists Have Found a Possible Cause of Severe PMS

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There’s no two ways about it: premenstrual syndrome (PMS) is awful. But for people with severe PMS (also known as premenstrual dysphoric disorder, or PMDD), “awful” is an understatement. Now scientists at the National Institutes of Health say they may have found the root of the problem: abnormal gene expression. They published their findings in the journal Molecular Psychiatry.

Experiencing PMDD symptoms is like having the volume turned up on the emotional elements of regular PMS. These extreme bouts of depression, anger, and anxiety can be so deep and persistent that they interfere with work or school, home, or relationships.

PMDD is not common; scientists estimate that it affects 2 to 5 percent of people who menstruate. But for those who have it, it can be disabling, and it sure would be nice to know what’s causing it.

Previous studies in the '90s concluded that people with PMDD appear to be hypersensitive to ordinary, menstrual-related fluctuations in steroid hormones like estrogen and progesterone. They still couldn’t tell us where this hypersensitivity came from, but they kept looking.

Fast-forward to 2015. Technology has advanced in ways that would have blown our minds 20 years ago. Behavioral endocrinologist Peter Schmidt, who led the earlier studies, teamed up with experts in neurogenetics and psychiatry to try a new approach.

They recruited 67 women between the ages of 18 and 48. Some of these women had been diagnosed with PMDD, while others said they had no trouble with severe PMS. One subgroup of participants with PMDD were given drugs that turned off their production of estrogen and progesterone. Their symptoms abated. When the researchers stopped the treatment, the women’s symptoms returned. These changes supported the theory that even normal changes in hormone levels could trigger big emotional changes for women with the condition. In other words, PMDD is quite literally PMS on steroids.

Next, the researchers extracted cell samples from 48 participants (24 with PMDD and 24 without) and sequenced their genetic code, looking for differences. They found them, all right: A large group of genes called the ESC/E(Z) complex was working overtime in women with PMDD. This makes a lot of sense, the researchers say, as the role of the ESC/E(Z) complex is to tell our genes how to respond to changes in our internal and external environment. Hypersensitivity there could definitely cause dramatic overreaction to hormonal changes.

The authors say these findings strike at the myth of the fragile, overly emotional woman. “This is a big moment for women’s health,” co-author and neurogeneticist David Goldman said in a statement. "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.”