# Pathophysiology and therapeutic strategy for late reproductive aged women with PCOS

> **NIH NIH K23** · UNIVERSITY OF VIRGINIA · 2021 · $165,456

## Abstract

Project Summary
Polycystic ovary syndrome (PCOS) is a highly prevalent reproductive disorder characterized by
hyperandrogenism (HA) and oligo/anovulation. PCOS is also associated with metabolic syndrome,
obesity and insulin resistance. In young women with PCOS, several factors contribute to HA: a)
excess luteinizing hormone (LH) secretion, b) abnormal ovarian steroidogenesis, c) abnormal adrenal
steroidogenesis, and d) hyperinsulinemia/ insulin resistance. Of interest, HA (and menstrual function)
improves with age in PCOS. However, the relative contributions of the aforementioned HA-related
factors in young adult vs. late reproductive-aged women with PCOS are not known. Identifying the
most important predictor(s) of HA in older women with PCOS will be critically important for devising
the most relevant therapeutic strategies for older women with PCOS. While oral contraceptives
(OCs) that are effective in addressing HA and menstrual dysfunction, they are also associated with
adverse cardiovascular risks that may be further increased with age. Therefore, for older women with
PCOS, alternative therapies (e.g., metformin) could be preferable. In young women with PCOS,
metformin has been shown to be effective for treating menstrual dysfunction and biochemical HA.
However, the relative desirability of OC vs. metformin is not known in older PCOS women. We
propose to determine the relative contributions of four established predictors of HA (LH secretion,
ovarian response to recombinant human chorionic gonadotropin administration, adrenal response to
adrenocorticotropic hormone administration, and hyperinsulinemia) in older vs. young women with
PCOS in a physiological study (Aim 1). We will also determine the relative desirability (as determined
by quality of life assessments) of metformin vs. OCs in treating PCOS in women of late reproductive
age in a randomized cross-over study (Aim 2). Successful completion of these studies will provide 1)
a more complete and cohesive understanding of how the determinants of HA change with aging in
PCOS; and 2) critical insight into age-relevant therapeutic strategies for older reproductive aged
women with PCOS. The proposed studies in this K23 grant will be performed under the mentorship of
Christopher R. McCartney, M.D., who has made significant contributions to understanding the
pathophysiology of PCOS for the past 18 years. The research environment at my institution
(University of Virginia) is very collaborative and supportive. With a tremendous research support and
dedication from my mentor and my institution, I will continue to refine my research skills needed to
become an independent clinical investigator.

## Key facts

- **NIH application ID:** 10163692
- **Project number:** 5K23HD098319-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Su H. Kim
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,456
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163692

## Citation

> US National Institutes of Health, RePORTER application 10163692, Pathophysiology and therapeutic strategy for late reproductive aged women with PCOS (5K23HD098319-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163692. Licensed CC0.

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