# 11-Oxyandrogens and Aging: Health Implications

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $564,488

## Abstract

ABSTRACT
 The adrenal androgen precursors dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are known
to contribute to fetal development and adrenarche. The role of adrenal androgens following puberty and
throughout adulthood has been poorly understood. The adrenal glands are also the source of unique 11-
oxygenated metabolites of androstenedione (A4) and testosterone (T), collectively termed 11-oxyandrogens. Of
these, 11-ketotestosterone (11KT) and its 5α-reduced product, 11-ketodihydrotestosterone (11K-DHT), are
bioactive androgens, with potency equivalent to testosterone (T) and dihydrotestosterone (DHT), respectively.
These 11-oxyandrogens are central to the pathophysiology of several disorders of androgen excess, including
congenital adrenal hyperplasia, premature adrenarche, or castration-resistant prostate cancer. The role of 11-
oxyandrogens during physiological aging is unknown. The traditional androgens androstenedione (A4) and
testosterone (T), which also derive from the gonads, as well as the major adrenal androgen precursors, DHEA
and DHEAS, decline with aging. Intriguingly, we have recently found that the production of 11-oxyandrogens
remains sustained in aging individuals of both sexes. Moreover, our preliminary data suggest that 11KT is
associated inversely with bone degradation biomarkers, and directly with hemoglobin and hematocrit.
 The overall objectives of this application are: 1) to define the trends of circulating 11-oxyandrogens in
men and women throughout adulthood, with particular focus on aging; 2) to determine the implications of 11-
oxyandrogens on aging-related clinical outcomes, including bone, metabolic, and cardiovascular pathology; 3)
to define the bioactivity potential of 11-oxyandrogens. Three specific aims have been designed to address critical
gaps in our knowledge of adrenal androgen function throughout adulthood and aging. • In Aim 1, we will
characterize for the first time the longitudinal patterns of circulating 11-oxyandrogens in women, beginning with
reproductive stages, and following menopause. We will use mass spectrometry to quantify traditional sex-
steroids and 11-oxyandrogens in over 3,000 serum biospecimens from 569 women included in the Study of
Women Across the Nation (SWAN). • In Aim 2, we will test the working hypothesis that 11KT has direct
implications on bone and cardiovascular health. We will quantify an extensive set of steroids, including 11-
oxyandrogens, in over 2400 men and women, participants in the Dallas Heart Study (DSH). We will use the rich
datasets from both the SWAN and DHS, which include comprehensive health history and wellbeing survey
instruments (both studies), as well as laboratory and imaging evaluations of bone, metabolic, and cardiovascular
health (DHS). • In Aim 3, we will test the bioavailability of 11-oxyandrogens and their potential to be aromatized
to 11-oxyestrogens. Together, this work will reframe our understanding of bioactive androgens in human health
an...

## Key facts

- **NIH application ID:** 10778566
- **Project number:** 5R01AG080516-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Adina F Turcu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $564,488
- **Award type:** 5
- **Project period:** 2023-02-15 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778566

## Citation

> US National Institutes of Health, RePORTER application 10778566, 11-Oxyandrogens and Aging: Health Implications (5R01AG080516-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10778566. Licensed CC0.

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