Past research has suggested that women with polycystic ovary syndrome are at greater risk for mental health problems, such as anxiety and depression. Now, a new study suggests this may be down to hormonal imbalances before birth that affect the brain.

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The greater mental health risk for women with PCOS may be explained by exposure to high testosterone levels before birth, according to researchers.

Principal investigator Dr. Elisabet Stener-Victorin, of the Department of Physiology and Pharmacology at the Karolinska Institutet in Sweden, and colleagues publish their findings in the Proceedings of the National Academy of Sciences.

Estimates suggest that as many as 5 million women of reproductive age in the US have polycystic ovary syndrome (PCOS) – a condition characterized by the growth of benign masses in one or both of the ovaries, known as ovarian cysts, as well as irregular periods and high blood levels of testosterone.

It is well established that female offspring of women with PCOS are more likely to develop the condition themselves. And it is not just the female offspring who are affected; the sons of women with PCOS tend to have a greater risk for obesity and diabetes, which are also complications of PCOS.

In addition, Dr. Stener-Victorin notes that 60% of women with PCOS have at least one mental health problem, such as depression, anxiety or an eating disorder, and they are also at greater risk for suicide.

Such risks have been attributed to increased exposure to male hormones, or androgens, through the mother’s blood in utero. However, the researchers note that the mechanisms underlying this association have been unclear.

For their study, Dr. Stener-Victorin and colleagues exposed a group of pregnant rats to high doses of testosterone, mimicking the conditions of pregnant women with PCOS.

Fast facts about PCOS
  • Symptoms of PCOS include acne, excess hair growth and weight gain
  • PCOS can affect girls as young as 11
  • Pregnant women with PCOS are at greater risk for preeclampsia, gestational diabetes, high blood pressure and preterm delivery.

Learn more about PCOS

The researchers assessed how the high testosterone levels affected the placenta of the pregnant mice, as well as fetal growth and adult health of both male and female offspring.

The team found that male and female offspring exposed to high doses of testosterone in utero late in their mother’s pregnancy were more likely to demonstrate anxiety-like behaviors in adulthood, compared with offspring that were not exposed to high doses of the hormone.

Further investigation revealed that the high testosterone doses had a significant effect on a brain region called the amygdala, involved in the regulation of emotion and behavior.

Specifically, the researchers found that testosterone interfered with the activity of a gene in the amygdala that regulates the androgen receptor. They also identified alterations in the receptors for a form of estrogen due to high testosterone doses, as well as changes in the genes that regulate serotonin and GABA – neurotransmitters involved in the control of anxious behavior.

However, when the team inhibited the receptors for androgen and estrogen in the offspring of PCOS rat models using two different drugs, they found this prevented them from developing anxiety-like behavior in adulthood.

Commenting on the importance of the findings, Dr. Stener-Victorin says:

Our results indicate a hitherto unknown biological mechanism that can help us understand why the daughters and sons of women with PCOS develop anxiety as adults.”

Medical News Today recently reported on a study suggesting diet and exercise may improve fertility for women with PCOS.