It's genetic – the debilitating form of premenstrual syndrome with very severe cramps, irritability, breast soreness and muscle aches known as premenstrual dysmorphic disorder has been linked to a group of genes that respond differently to sex hormones.
Researchers have now found that PMDD is caused by a group of genes that affects how sex hormones interact with other genes, according to a paper published in the journal Molecular Psychiatry.
The researchers studied women's white blood cells – which express many of the same genes as neurons in the brain – to see how they reacted to oestrogen and progesterone.
The cells from women who had PMDD expressed genes differently to women who didn't have PMDD. There was one large complex of genes that seemed to be the root of the difference, called Extra Sex Combs/Enhancer of Zeste, or ESC/E(Z).
This complex is involved in regulating how other genes respond to the sex hormones oestrogen and progesterone, which could explain why women with PMDD are so sensitive to sex hormones.
"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 study author David Goldman, a researcher at the US's National Institutes of Health.
"For the first time, we now have cellular evidence of abnormal signalling in cells derived from women with PMDD, and a plausible biological cause for their abnormal behavioural sensitivity to oestrogen and progesterone," said Peter Schmidt, a mental health researcher at the NIH and also an author of the study.
The finding is a significant one for women who suffer from PMDD. There has been relatively little research into PMDD or the more common condition PMS. For example, there are five times as many studies on erectile dysfunction than PMS, despite the fact that it affects less than 20 per cent of men.
Treatments for PMDD are few and far between, and so far have had little solid basis in evidence. Sadly, the only thing that stops PMS and PMDD altogether is the menopause.
But this finding may pave the way for better targeted treatments for the condition, which is so disruptive to women's lives that it drives 15 per cent of PMDD sufferers to attempt suicide.
"Learning more about the role of this gene complex holds hope for improved treatment of such prevalent reproductive endocrine-related mood disorders," said Schmidt.