Genetic analysis suggests distinct subtypes of polycystic ovary syndrome

Results from NIH-funded study could lead to improvements in diagnosis and treatment.

What

Polycystic ovary syndrome (PCOS), an infertility disorder affecting at least 15% of reproductive-age women, may have at least two different subtypes, suggests a study funded by the National Institutes of Health. The findings could provide important information on the possible causes of PCOS and for developing more effective ways to treat the condition. The study appears in PLOS Medicine and was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases.

PCOS(link is external) is characterized by irregular or missing menstrual periods (due to lack of or infrequent ovulation), high levels of androgens (male hormones) and small cysts on the ovaries. Women with PCOS are also at higher risk of diabetes and heart disease.

The current study analyzed the genes of nearly 900 women who had irregular menstrual periods. Researchers categorized them according to their body mass index (BMI) and levels of glucose, insulin and reproductive hormones, including androgens. Their analysis revealed two PCOS subtypes, each associated with distinct groups of gene variants. The reproductive subtype, about 23%, had higher levels of luteinizing hormone (LH), a pituitary hormone that regulates the ovaries, and sex hormone binding globulin (SHBG), a protein that transports estrogen and androgens. This subtype also tended to have a lower BMI and lower insulin levels than the others.

The metabolic group, roughly 37%, had a higher BMI, higher glucose and insulin levels and lower levels of SHBG and LH. The remaining women had no clear combinations of traits but had a greater frequency of gene variants associated with PCOS, suggesting that this group may be distinct from the others. Understanding the genes underlying these subtypes may yield new ways to diagnose PCOS and develop personalized treatments.

The study was conducted by Andrea Dunaif, M.D., of the Mount Sinai Health System in New York City, and colleagues.

Who

Esther Eisenberg, M.D., a reproductive endocrinologist and medical officer in the NICHD Fertility and Infertility Branch, is available for interviews.

Article

Dapas, M, et al. Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. PLOS Medicine.2020.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD leads research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all. For more information, visit https://www.nichd.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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