Your brain on PMS is like your brain on alcohol and depressants

One of those days.
One of those days.
Image: Reuters/Stefano Rellandini
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For some it’s unpredictable, and for many it’s hard to explain, but the feelings of worry associated with the menstrual cycle have a very specific cause—and it’s the same hormone used in much birth control.

As many as 85% of women experience pre-menstrual stress, or PMS, in the days leading up to their period, according to the American Congress of Obstetricians and Gynecologists (ACOG). The condition comes with physical symptoms like painful joints or breasts, headaches, and sleeplessness, but often it’s the sense of being overwhelmed by anxiety, stress, or anger that’s most troublesome. So what’s actually going on in the brain that makes PMS such a struggle?

It pretty much comes down to one hormone: progesterone, says Inger Sundström Poromaa at the University of Uppsala in Sweden, one of the leading experts on brain metabolism and sex hormones.

Progesterone, which appears after ovulation, is one of two main female hormones. The other, estrogen, is present in the first two weeks of the cycle, and has a broadly positive effect on mood. estrogen increases the brain’s serotonin, the hormone most associated with happiness. Progesterone, on the other hand, can have a depressing effect.

Recent research into hormonal contraceptives found a clear link between them and depression. That’s hardly surprising, the researcher says, when you consider that all hormonal contraceptives contain progesterone, and some are progesterone-only.

The mechanism

How and why progesterone alters moods is understudied, but there’s a growing body of research, based on the results of blood tests and brain scans, conducted by Poromaa and others. One discovery from this research is that progesterone can trigger the small, almond-shaped part of the brain called the amygdala.

The amygdala is the brain’s chief alert system. It responds to cues in the environment, quickly assessing whether they might represent threats, and triggering fear and anxiety if so—an early evolutionary defense mechanism. Other, more evolved parts of the brain, notably the frontal lobes, may later overrule the amygdala, but it is the first to respond.

And progesterone, says Poromaa, “seems to enhance amygdala reactivity.” That could explain the experience of feeling stressed for small or even unidentifiable reasons at particular times of the month.

As well as creating anxiety, another side-effect of progesterone could be to cause the blues. According to research (pdf) by Torbjörn Bäckström from the University of Umeå in Sweden, it seems to have the same effect on the brain as depressive drugs like alcohol and sleeping pills.

Most substances in the body, including hormones, get broken down into other substances, known as metabolites, before eventually being removed by the kidneys or the liver. When progesterone is broken down, its metabolites become active in the brain. And, it appears, they—and one in particular, allopregnanolone—bind to a system called the GABA-A receptor.

Poromaa explains that the GABA-A receptor is a little like the brain’s police force: it regulates, making sure there isn’t “too much excitement” going on. Drugs that bind to it cause it to step up the policing. Bäckström’s research suggests that metabolites of progesterone may be doing the same thing.

Isn’t it ironic?

If female hormones have such distinct effects, the next step is to wonder why the female body is designed in this way. But, Poromaa suggests, it’s more a result of evolutionary design meeting modern living. Progesterone’s effects may be particularly pronounced now because women are having far more periods, and far fewer children, than in the thousands of malnourished years before birth control.

Three hundred years ago women started menstruating around 17 or 18 because they were less healthy than today. Most women got pregnant almost immediately, and remained pregnant or breastfeeding for most of their reproductive lives, which ended around 40. The average woman might have had as few as 20 menstrual cycles in her life, Poromaa says. Progesterone levels are high during pregnancy, but it doesn’t trigger the same mood-altering mechanisms; it’s only at moderate levels, like those present after ovulation, or used for contraception, that progesterone has a depressive effect.

By contrast, modern women are eating better, using birth control, and menstruating earlier (the average age is 14). Their reproductive lives are also getting longer (now ending around 51), and they’re having fewer children. That means more periods, and so, more PMS.

There are some treatments for premenstrual dysphoric disorder (PMDD), a far more extreme version of PMS, suffered by 4% of women of reproductive age. But many are scientifically unproven and some are potentially dangerous.

Diet and vitamin supplements may help ease PMS. The ACOG suggests keeping blood sugar levels up with smaller, more frequent meals. Complex carbohydrates—like certain grains, as well as beans and lentils—could help with that, as they are broken down more gradually than sugar, bread or pasta. Calcium (found in yogurt and leafy green vegetables, or supplements) and magnesium might alleviate mood swings and physical symptoms like bloating from water retention. Cutting down on caffeine, alcohol, fat, sugar, and salt (so, all the classic comfort foods!) could also help to regulate blood sugar.

Meanwhile, many women dealing with PMS will probably continue to get through it like they always have: ideally with the understanding of their friends and families, and in the knowledge that it’s both real and, thankfully, transient.