# REPRODUCTIVE AGING IN NORMAL PREMENOPAUSAL WOMEN

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1994 · $181,378

## Abstract

The goal of this research proposal is to increase our understanding of
the effects of aging on the reproductive system of normal women.  While
women eventually experience complete loss of their reproductive potential
(menopause), this proposal focuses on women age 40-45 who have retained
regular ovulatory menstrual cycles.  These "older" women who have
retained menstrual function have lost 33-50% of their prior fertility
potential.  current demographic data indicates there is an increase in
the female population age 27-40 (baby boomers) who, as a group, tend to
defer marriage and childbearing.  Loss of reproductive efficiency with
age has become a pertinent clinical issue.  These proposed studies focus
on the hypothalamic-pituitary-ovarian axis as the probable sites of
reproductive aging.  We and others, have identified a monotropic FSH rise
as the initial hormonal change in older women.  We have two hypotheses
for the monotropic FSH rise:  1) it is a primary neuroendocrine change
that leads to follicular depletion, or 2) follicular depletion is the
primary change in reproductive aging which leads to a decrease in ovarian
feedback hormones.  In Section I we will explore in depth various aspects
of the monotropic FSH rise including investigation of possible changes
in other hormones (i.e. inhibin), FSH bioactivity, GnRH pulse patterns,
and control of the intercycle FSH rise.  The studies in Section I should
clarify the primary site of reproductive aging.  Since depletion of
ovarian follicles is the final common pathway of reproductive aging in
primate species, we hypothesize that women experience compromised
folliculogenesis prior to disruption of their cycles (indicative of
follicle depletion below a critical threshold).  In our ovarian studies
(Section II) we propose to monitor follicle development, perform
sonographic follicle aspirations, and study:  follicular fluid hormone
concentrations, granulosa cell function in tissue culture, and examine
the cytoskeleton (actin, tubulin) of oocytes.  Direct benefits are
anticipated from an increased understanding of aging effects on the
female reproductive system:  1) predictors can be developed, which, in
turn, would dictate specific therapies (or no therapy); 2) lead to
improved counseling regarding delayed childbearing, and 3) perhaps
interventions could be identified to delay the aging process.

## Key facts

- **NIH application ID:** 2197742
- **Project number:** 5R01HD018967-10
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** MICHAEL R SOULES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $181,378
- **Award type:** 5
- **Project period:** 1984-09-15 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197742

## Citation

> US National Institutes of Health, RePORTER application 2197742, REPRODUCTIVE AGING IN NORMAL PREMENOPAUSAL WOMEN (5R01HD018967-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197742. Licensed CC0.

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