Notice of Special Interest: Optimizing Precision Treatment of Gynecologic, Reproductive and Obstetrical Outcomes in Adolescents and Adults with PCOS and Associated Comorbid Conditions (Clinical Trial Optional)
Notice Number:

Key Dates

Release Date:

September 1

First Available Due Date:
February 05, 2021
Expiration Date:
September 08, 2023

Related Announcements

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-200 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

Issued by

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)


The National Institute of Child Health and Human Development (NICHD) is issuing this Notice of Special Interest (NOSI) to announce the opportunity for investigators to apply for funding to optimize treatments of comorbid conditions in adolescents and reproductive age women with a diagnosis of Polycystic Ovary Syndrome (PCOS).

The goals of this initiative are to stimulate interdisciplinary scientific collaboration between gynecologists/reproductive endocrinologists/obstetricians and subspecialists in diverse medical fields, including cardiologists, endocrinologists, gastroenterologists, psychiatrists, mental health professionals, pulmonologists, among others, to: 1) advance individualized treatments consistent with gynecologic, reproductive and obstetrical needs and desires; 2) promote translational and clinical research to increase knowledge and understanding of interaction of various therapies on gynecologic, reproductive and obstetric outcomes; and 3) discover and develop novel safe and more effective therapies for adolescents and women with PCOS with underlying comorbid conditions. Ultimately, this research would advance precision therapeutics for adolescents and adults with PCOS who have concomitant medical conditions. 


Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in adolescent girls and women of reproductive age, with a prevalence of approximately 10% (~5 million women of childbearing age) in the US. PCOS is a genetically and phenotypically heterogeneous disorder with wide inter-individual variation in onset and presentation. Hyperandrogenism, a diagnostic criterion of PCOS, is linked to hyperlipidemia, a risk factor for cardiovascular disease, and approximately 40% of women with PCOS have insulin resistance independent of body weight, with concomitant increased risk of type 2 diabetes and cardiovascular disease.  Furthermore, prolonged episodes of anovulation and menstrual irregularity, related to chronic estrogenic stimulation of the endometrium, may ultimately lead to endometrial hyperplasia, a precursor of endometrial cancer. Within the last decade, evidence has shown that persons with PCOS have an increased incidence of anxiety and depression, as well as sleep disturbances. Thus, many persons with PCOS have one or more associated medical conditions that impair their quality of life and require additional medical treatment.

Treatment of concomitant medical conditions associated with PCOS may affect gynecologic, reproductive, and obstetrical outcomes in adolescents and reproductive age women with PCOS. For example, secondary analyses of data in studies of women using antidepressants have shown that antidepressant use is associated with longer time to pregnancy and increased first-trimester pregnancy loss, which may be dependent upon the type of antidepressant used. Additionally, controversy exists as to whether treatment of insulin resistance with metformin prior to and during pregnancy in women with PCOS is associated with lower incidence of miscarriage and preterm birth. Most therapeutic studies in persons with PCOS include heterogeneous populations of women that have one or more associated comorbid conditions which may affect the safety, efficacy, and outcomes being investigated. Although new diagnostic modalities are available to identify subpopulations of women with PCOS (i.e., ultrasound for non-alcoholic fatty liver disease (NALFD), new biomarkers for gestational diabetes), research on PCOS may not address distinct subpopulations.

Lifestyle modification, including diet and exercise, has been advocated as first-line treatment for most adolescents and adults with PCOS.  Nonetheless, pharmacologic treatment is often utilized to manage many of the PCOS-associated conditions since lifestyle modification is generally not sufficient to ameliorate chronic anovulation nor hyperandrogenism, nor the various presentations (i.e., irregular menses, hirsutism, infertility) and the associated “comorbid” conditions.  Many of the currently available medications to treat irregular menses or hirsutism interfere with conception or are contraindicated in pregnancy, thus limiting the utility and use in women with PCOS who desire to conceive. Moreover, preliminary data suggest that substantial weight loss immediately prior to conception may improve maternal outcomes but could have deleterious consequences such as increased early pregnancy loss.

Research Objectives

Studies using new approaches and alternative treatments that address the most optimal medications for co-occurring conditions such as gestational diabetes, metabolic syndrome, depression, disordered sleep, NALFD, dyslipidemia, among others, are needed to expand options for persons with PCOS. Additional knowledge gaps exist in how various therapies affect gynecologic, reproductive, and obstetrical sequelae of PCOS. Research addressing these knowledge gaps could yield safer and more effective treatments for various presentations of PCOS, leading to paradigm changes and scientific advances in individualized and precision therapy for adolescents and adults with PCOS.

Specific areas of interest include, but are not limited to, the following examples:

  • Studies to investigate effects of therapies of specific comorbid conditions on gynecologic, reproductive and/or obstetrical outcomes occurring in persons with PCOS.
  • Studies of the safety and efficacy of specific treatments addressing comorbid conditions (obesity, insulin resistance, anxiety, depression, sleep disorders, sleep disordered breathing, hyperandrogenism, endometrial hyperplasia, among others) that do not preclude pregnancy or breast-feeding in persons with PCOS.
  • Discovery of novel treatments of various components of metabolic syndrome in women with PCOS that have beneficial or non-deleterious impact on gynecologic, reproductive, obstetrical and perinatal outcomes.
  • Studies to identify pharmacologic treatments for anxiety and/or depression in adolescents and women with PCOS, including in the postpartum period, that do not interfere with fecundability, sexual function, obstetrical outcomes, and are safe in lactating women.
  • Studies investigating how treatments for PCOS affect the development of or risk for comorbid conditions, as well as studies investigating adjuvants used in conjunction with therapies to stimulate ovulation will not be considered responsive.

Application and Submission Information

This notice applies to due dates on or after June 5, 2019 and subsequent receipt dates through September 8, 2023. 

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

  • PA-20-183 Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
  • PA-20-200 NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-HD-20-026” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Although NICHD is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Esther Eisenberg, MD MPH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-6516

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