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Androstenediol complements estrogenic bioactivity during the menopausal transition

Lasley, Bill L. PhD1; Chen, Jiangang PhD1; Stanczyk, Frank Z. PhD2; El Khoudary, Samar R. PhD, MPH3; Gee, Nancy A. BS1; Crawford, Sybil PhD4; McConnell, Daniel S. PhD5

doi: 10.1097/gme.0b013e31823df577
Original Articles

Objective The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids that have the potential to alter estrogen/androgen balance and explain the wide interwoman range of estrogen-related symptoms experienced during the MT.

Methods Annual serum samples from the Study of Women’s Health Across the Nation, which had previously been analyzed for immunoreactive estradiol (E2), testosterone, DHEAS, and sex hormone–binding globulin, were selected based on DHEAS concentration and analyzed for immunoreactive and bioactive estrogens and androgens, including immunoreactive androstenedione, dehydroepiandrosterone, and 5-androstene-3β,17β-diol (androstenediol [Adiol]).

Results A two-fold increase in circulating androstenedione and testosterone was found to rise in parallel with the rise in circulating DHEAS, whereas dehydroepiandrosterone and Adiol concentrations rose seven- to eight-fold. Circulating Adiol, which has both androgenic and estrogenic biological activity, was significantly associated (P < 0.02) with circulating estrogen bioactivity only when E2 concentrations were low and Adiol levels were high.

Conclusions The wide range of circulating levels of Adiol and its contribution to total circulating estrogenicity during the MT is consistent with the observed interwoman difference in symptoms at this time. Therefore, we conclude that Adiol contributes to circulating estrogenicity when E2 production falls at menopause and may contribute significantly to the endocrine changes experienced by midlife women.

Supplemental digital content is available in the text.Androstenediol contributes to circulating estrogenicity when estradiol production falls at menopause and may contribute significantly to the endocrine changes experienced by midlife women.

From the 1Center for Health and the Environment, University of California at Davis, Davis, CA; 2Department of Obstetrics and Gynecology and Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA; 3Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; 4Division of Preventive and Behavioral Medicine, University of Massachusetts, Worcester, MA; and 5Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.

Received August 18, 2011; revised and accepted October 18, 2011.

Funding/support: The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women’s Health (ORWH; Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495).

Financial disclosure/conflicts of interest: None reported.

The content of this article manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH.

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Address correspondence to: Daniel S. McConnell, PhD, The University of Michigan, 109 Observatory, SPH1 Rm 1867, Ann Arbor, MI. E-mail:

©2012The North American Menopause Society