Scientists think they might have figured out the cause of severe PMS

Women are often mocked about their bad moods at 'that time of the month'. But scientists have found evidence that women going through severe premenstrual syndrome (PMS) aren't just 'grumpy' - their mood fluctuations could be caused by a genetic mutation that's sending their cells haywire.

While regular PMS is bad enough, 2 to 5 percent of women suffer from an even more extreme version of the syndrome, called premenstrual dysphoric disorder (PMDD), which causes such intense irritability, sadness, anxiety, bloating, and general achiness in the days leading up to a woman's period that she's unable to go about her normal life. 

Researchers know that women with PMDD have normal hormone levels, but for some reason their bodies are much more sensitive to them, which sends their PMS into overdrive. But up until now, no one had been able to figure out what was causing this sensitivity.

The new study has finally revealed the molecular mechanisms that appear to be triggering the debilitating condition, showing once and for all that severe mood-related PMS is very real.

"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).

To figure out what was going on, the team took 10 women with PMDD and nine controls without the condition, and 'turned off' progesterone and oestrogen in their system.

The women with PMDD stopped having mood symptoms when the hormones stopped, and their symptoms started again when they reintroduced them, while the control group didn't experience the same change.

This indicated that the brain cells of the women with PMDD were reacting differently to the hormones somehow. To better understand why, the researchers cultured their white blood cells - which express many of the same genes as brain cells - both in the presence of hormones and without them. (They used white blood cells because brain cells are incredibly hard to harvest).

The researchers found that a large gene complex was different between the two groups.

The complex is known as the ESC/E(Z) (Extra Sex Combs/Enhancer of Zeste) gene complex, and it controls which genes are turned on and off in response to environmental inputs such as hormones and stressors.

It now appears that mutations in this gene complex could be the cause of many of the intense mood symptoms experienced by women with PMDD.

The team showed that in the cells of those with PMDD, many of the genes controlled by the ESC/E(Z) complex were over-expressed, while others were under-expressed compared to the control group.

And when the team added sex hormones, the differences were even more pronounced, suggesting that something about the ESC/E(Z) gene complex in women with PMDD is making their molecular pathways go haywire, and making them more sensitive to sex hormones that ramp up right before their periods.

To be clear, this is a small study performed on a limited group of women. More research needs to be done before we can say for sure what's causing PMDD. But this is the first time the underlying cellular activity has been identified, so it's a promising first step.

The good news is that now we have more insight into the condition, we might finally be able to find some effective treatments - currently, women have little options during intense PMS other than to take painkillers, 'cheer up' and 'get over it'.

"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," explained Peter Schmidt from the NIH's National Institute of Mental Health.

"Learning more about the role of this gene complex holds hope for improved treatment of such prevalent reproductive endocrine-related mood disorders."

The team is now looking at the role this gene complex plays in brains cells induced from the stem cells of PMDD patients, which should help them get a better idea of what's going on.