PCOS Research Activities and Advances

The Institute's research focuses on genetic, molecular, and cellular mechanisms underlying PCOS as well as studies to determine precursors or predictors of PCOS in adolescents. NICHD also supports and conducts studies on potential new treatments for PCOS, using animal models and human participants.

The Fertility & Infertility (FI) Branch is NICHD's principal entity for the support of research on PCOS. One of the long-term goals of the FI Branch is to find more effective treatments for the symptoms of PCOS as well as other conditions associated with the disorder. Treatments of interest include both pharmacological and non-pharmacological interventions. The FI Branch is also interested in how individual factors like genetics affect responses to treatment. Other research includes demographic and risk information related to PCOS. Some FI Branch–supported findings include:

• A New Animal Model to Study PCOS
  PCOS is a complex disease, and until recently, animal models of PCOS were not optimal, because they did not replicate all of the features seen in women with PCOS. NICHD-funded researchers showed that mice treated with the drug letrozole for 5 weeks at the time of puberty go on to develop both the reproductive and metabolic symptoms of PCOS. This new model could prove useful in studying the genetic mechanisms that contribute to PCOS in women and in developing new interventions to treat the disorder. (PMID: 26203175)
• Treatment for Anovulatory Infertility in PCOS
  The FI Branch's Reproductive Medicine Network conducted a clinical trial to compare the use of clomiphene citrate and letrozole to treat infertility in women with PCOS. The drugs work differently: Clomiphene changes the function of estrogen receptors, whereas letrozole inhibits the enzyme aromatase, which converts androgens to estrogens. The findings indicate that women with PCOS who took letrozole over five menstrual cycles were more likely to ovulate and had 44% more live births than did women who took clomiphene. Letrozole was also just as safe to mothers and babies as clomiphene was. (PMID: 25006718 or see the press release)
• Urine Levels of Gene Causing High Androgens Could Identify PCOS Women
  By comparing the genomes of thousands of women, researchers compiled a list of candidate genes that could cause PCOS. NICHD-funded researchers found that an unusual product of one of these candidate genes, called DENND1A.V2, alters the synthesis of androgens by the ovaries. Reducing the level of DENND1A.V2 in the steroid-producing cells of the ovaries, the thecal cells, in women with PCOS reduced the production of androgens; forcing overexpression of DENND1A.V2 in normal thecal cells caused them to make too much androgen, just like in PCOS. In addition, levels of DENND1A.V2 are high in the urine of women in PCOS, providing hope that a simple urine test could diagnose PCOS in the future.
  (PMID: 24706793 or see the press release)

The Division of Intramural Research (DIR) also conducts research to advance understanding of the causes of PCOS. For example, a recent finding from researchers in the Section on Genetics and Endocrinology found that a subgroup of women who were diagnosed with PCOS may actually have an adrenal gland disorder instead. Visit https://www.nichd.nih.gov/news/
releases/Pages/062716-PCOS-adrenal.aspx for more information.

• The Reproductive Medicine Network (RMN), founded in 1990, carries out large, multicenter clinical trials of diagnostic and therapeutic interventions for male and female infertility and reproductive diseases and disorders. The RMN, which is funded through the FI Branch, conducted several of the studies described above.
• The Reproductive Genomics Program: Mouse Models of Infertility  is an NICHD-funded program at the Jackson Laboratory that uses ENU mutagenesis to produce mouse models of infertility and includes mutagenesis of the mouse genome, phenotypic screening for infertility mutations, and regional mapping of each mutation to a chromosome. Breeding stock is available for scientists interested in using these models in their own research programs.
• 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 the FI Branch, that aims to promote interactions between basic and clinical scientists with the goal of improving 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 about the biological function, expression pattern, and regulation of genes expressed in the ovary. The database also contains information on gene sequences, chromosomal localization, and human and rodent mutation phenotypes as well as links to biomedical publications.