Estrogen, Progesterone, Your Genes and Mood

It’s No Longer a Case of Trying Harder

Posted Jan 08, 2017

ZF foto at big
Source: ZF foto at big

This past week I read a press release on exciting news from NIMH, the National Institute of Mental Health.  It’s about a study on genes and PMDD and fairly technical, but I want to share it with you and will try to explain it as clearly as possible.  Dated January 3, 2017, the report announced that NIH researchers have discovered a link between a reproductive hormone-related set of genes and PMDD, or Premenstrual Dysphoric Disorder.  PMDD is a mood disorder with disabling sadness, irritability, and anxiety that occurs in the days right before a woman’s menstrual period.  It affects approximately 2-5% of women in their reproductive age.  A gene is made up of DNA and is found on our chromosomes, inherited from our parents.  Genes instruct the body to make proteins and molecules necessary for the body to function.  Reproductive hormones in women are estrogen and progesterone, which rise and fall with the cycles of her menstrual period.  This report adds to prior indications that PMDD is a disorder of a cell’s response to estrogen and progesterone.  It’s the first evidence that the cells from women who have PMDD don’t work together properly, and offers a credible explanation for a woman’s abnormal sensitivity to estrogen and progesterone. (1) 

This news is a big moment in women’s mental health because it verifies that women who have PMDD have a basic difference in the way their molecules respond to reproductive hormones.  It is evidence that PMDD is not just a problem of emotions and behavior that the woman should be able to control on her own, voluntarily.  Up until now there has not been a lot of scientific evidence linking reproductive hormones and mood disorders; many providers accepted patients’ accounts as valid anecdotal evidence for which there has been limited direct treatment.     

The report describes the history behind this research.  In the late 1990’s the NIMH team showed that women who experience mood symptoms right before their menstrual periods were particularly sensitive to the normal cyclic changes in reproductive hormones.   But at the time the cause was not clear.  Later, they tried to experimentally “shut off” estrogen and progesterone in these women with a medication and found that this eliminated their PMDD symptoms.  Re-starting the hormones was found to cause a return of the symptoms.  This established that women with PMDD have a biologically based sensitivity to these hormones that might be related to differences in the molecules in their cells.

A follow-up study was done on white blood cells, or wbc’s, in the laboratory from women with PMDD (a wbc cultured cell line).  They were able to identify a large gene complex (set of genes) in which the way the genes worked to instruct the body in making proteins (called gene expression) differed greatly in those who have PMDD compared to a healthy control group.  This gene complex, called ESC/E(Z), regulates mechanisms that control how genes make proteins – including hormones – in response to the environment.  The researchers found several instances of altered gene activity where there was abnormal regulation of the cell’s response to these hormones in PMDD. 

It’s a first step.  It’s exciting because of the future potential for improved treatment options in reproductive hormone-related mood disorders.  Research in ongoing to gain a better understanding of the role of this set of genes on the brain.


Dubey N, Hoffman JF, Schuebel K, et al.  The ESC/E(Z) complex, an intrinsic cellular molecular pathway differentially responsive to ovarian steroids in Premenstrual Dysphoric Disorder. Molecular Psych. Jan3, 2016, doi:10.1038/mp.2016.229