Polycystic Ovary Syndrome May Originate in the Brain

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Polycystic ovary syndrome (PCOS), a condition that is a common cause of infertility and other female problems, may begin in the brain rather than the ovaries, researchers reported in a study published in the journal PNAS. The new research could change the way the disease is treated.

Globally, one in 10 women suffer from PCOS. The disorder can cause weight gain, large ovarian cysts, difficulty ovulating, acne, facial hair, depression, and painful and heavy periods. Over time, PCOS is linked to type 2 diabetes and cardiovascular disease. It’s responsible for 75 percent of anovulatory infertility cases, a condition where the woman doesn’t ovulate.

It can be a long time before a woman with PCOS receives an accurate diagnosis, adding to the frustration of the condition.

After diagnosis, treatments include taking the birth control pill or other hormonal medications. But these treatments only manage symptoms rather than addressing the cause.

Researchers have long known that the ovaries of women with PCOS produce extra testosterone. However, until this new study, they didn’t realize the extent which the brain is involved in this process.

In the current study, scientists at the University of New South Wales and the University of Sydney found that PCOS could not develop in mice that lacked receptors in their brains for male hormones such as testosterone—hormones known as androgens. On the other hand, PCOS can still develop when the androgen receptors in the ovaries of the mice are removed. This means the brain might play an important role in the development of the disease.

“For the first time we have a new direction of where we should be looking to try and develop treatments that will treat the cause of PCOS, the androgen excess in the ovary but also in the brain,” said lead researcher Kirsty Walters.

To reach their conclusions, the study authors evaluated four groups of mice: 1) a control group of mice without PCOS; 2) Mice missing androgen receptors in their bodies; 3) A group engineered without androgen receptors in their brains; 4) A final group missing androgen receptors in their ovaries.

The researchers administered a high dose of androgens to the rodents to see if this would cause the mice to develop PCOS.  As expected, the control group developed PCOS. However, PCOS was not detected in the mice missing androgen receptors in their bodies or brains.

The mice without androgen receptors in their ovaries developed PCOS, but at a lower rate compared with control animals. This indicates that the effect of androgens on the ovaries are not the only cause of PCOS.

The study authors point out in their paper that the data highlight the previously overlooked importance of androgen action outside the ovaries in the origins of PCOS. The study also showed that testosterone imbalances may be a cause rather than a consequence of PCOS.

Although this is a rodent study, reproductive systems in mice and humans are similar. The results are considered important because currently potential treatments for PCOS, which have not been highly effective, have focused on the ovaries. New treatments targeting the brain may have more success.

Source: Caldwell ASL, et al. Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome. PNAS, March 20, 2017. doi: 10.1073/pnas.1616467114