NICHD PCOS Research Information

• Define the genetics of PCOS. A number of gene variants have been linked to PCOS and its associated conditions. Ongoing NICHD research projects aim to identify genetic variations that underlie the development of PCOS as well as individual responses to PCOS treatments. These projects include genome-wide association studies as well as studies focused on specific gene variations.
• Explore pathophysiological mechanisms of PCOS. PCOS is characterized by hyperandrogenism (high levels of androgens) and, in most cases, insulin resistance. NICHD is working to understand the cellular and molecular mechanisms of ovarian dysfunction in the context of these hormonal anomalies. Specifically, NICHD aims to characterize the roles of insulin, androgens, and other hormones in reproductive and metabolic dysfunction. The NICHD studies are using both animal models and human participants.
• Identify precursors or predictors of PCOS in adolescents. PCOS may be detectable in girls as early as, or even before, their first menstrual periods. Studies are examining early signs of PCOS in adolescents to better understand the relationships among obesity, high androgen levels, and PCOS. This knowledge could help scientists develop early interventions to manage or slow the development of PCOS.
• Develop new treatment strategies for PCOS. NICHD is evaluating the efficacy of both existing and new treatments for PCOS. These studies include pharmacological (drug) and non-pharmacological treatments. In vitro studies are examining the cellular and molecular mechanisms of pharmacological treatments.

Through its intramural and extramural organizational units, NICHD supports and conducts a broad range of research on PCOS that focuses on genetic, molecular, and cellular mechanisms underlying PCOS as well as studies to understand the ways that nutrition, metabolism, and circadian rhythms (sleep) affect PCOS, and how individual factors like genetics and the microbiome, regulate fertility and affect responses to treatment. Other research includes demographic and risk information related to PCOS.

Some recent findings from research supported and conducted by NICHD include the following. You can also learn more about recent research findings in the PCOS and Women’s Health fact sheet.

• PCOS and risk of adverse pregnancy outcomes. PCOS is known to affect the ability to become pregnant, but less is known about how PCOS affects pregnancy outcomes. Researchers analyzed the medical records of women with a history of PCOS who gave birth in Massachusetts between 2013 and 2017. The NICHD-funded study found that women with a history of PCOS were at greater risk of pregnancy complications related to cardiometabolic function, such as gestational diabetes and preeclampsia, as well as preterm birth than were those without PCOS. (PMID: 36149255)
• Using an animal model of PCOS to study bacteria and small molecules in the gut. Recent NICHD-supported research has focused on the importance of metabolic differences in the development of PCOS. Researchers used a mouse model of PCOS to investigate the roles of the gut microbiome and gut metabolites in the disease. The findings indicated that mouse models of PCOS had different levels of metabolites, called bile acids, compared to other mice. When PCOS-model mice and other mice were housed together, bile acid levels shifted before the researchers noted changes to the mouse microbiomes. These findings could be useful in developing of new PCOS therapies that target metabolites. (PMID: 34519532)
• Meta-analysis suggests reproductive and metabolic subtypes of PCOS. Researchers funded by NICHD compared the genomes of 893 people with PCOS (from previously published studies) to investigate whether different groups of symptoms were associated with different genetic changes, called variants. The study found that four variants were associated with a reproductive subtype, which had features such as atypical hormone levels. The study also found that one variant was significantly associated with a metabolic subtype, which had features like higher Body Mass Index, higher glucose and insulin levels, and lower levels of the hormones involved in the reproductive subtype. A separate analysis of 73 women with PCOS found that the subtypes tend to cluster in families. The results of this study could help researchers develop new ways to diagnose PCOS and develop personalized treatments. (PMID: 32574161 or please read the press release)
• A recent study from researchers in the NICHD’s intramural Division of Population Health Research found that children born to women with PCOS may be at higher risk for anxiety, attention-deficit/hyperactivity disorder, and behavioral problems, compared to children whose mothers do not have the infertility disorder. Check out the Science Update on these findings for more information.
• Intramural researchers are also collecting phenotypic data on children and adolescents with gynecologic conditions, including PCOS. Studies are also underway to understand androgen-receptor sensitivity and how differences in sensitivity may affect overall health. Visit the Pediatric and Adolescent Gynecology website for more information.

Learn more about NICHD-funded projects related to PCOS: https://reporter.nih.gov/search/PkK0ioUDiEixd7wrsFtvrQ/projects.  

• The NICHD-funded Consortia For Infertility and Reproductive Medicine (ConFIRM) Clinical Trial Program addresses important questions in male and female infertility and translates new discoveries into clinical practice.
• The Reproductive Genomics Program: Mouse Models of Infertility , previously funded by NICHD at the Jackson Laboratory, provides mutant models of infertility for research.
• The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]) is a national network of research-based centers, supported by NICHD’s extramural Fertility and Infertility Branch, that promotes interactions between basic and clinical scientists to improve reproductive health. Several of the centers focus on diseases and disorders of the female reproductive system, including PCOS.
  • The Ovarian Kaleidoscope Database , maintained through the NCTRI, provides information for researchers about the biological function, expression pattern, and regulation of genes expressed in the ovary, as well as other ovary-specific research information.