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Circulating Bioactive Androgens in Midlife Women

Center for Health and the Environment (J.C., F.M.M., N.A.G., C.W., B.L.L.) and Department of Internal Medicine (S.E.K.-K.), University of California, Davis, Davis, California 95616; Department of Epidemiology (M.R.S., D.S.M.), School of Public Health, University of Michigan, Ann Arbor, Michigan 48104; and Department of Medicine/Geriatrics (G.A.G.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095

Address all correspondence and requests for reprints to: B. L. Lasley, Ph.D., University of California, Center for Health and the Environment, One Shields Avenue, Davis, California 95616. E-mail: bllasley{at}ucdavis.edu.

Context: It is important to characterize the biological activity of circulating androgenic steroid hormones during the menopausal transition because these appear to impact the metabolic and cardiovascular health risk factors of women.

Objective: The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum.

Design: This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study.

Setting: The study was conducted at a university laboratory.

Methods: A receptor-mediated luciferase expression bioassay based on HEK 293 cells that were stably cotransfected with plasmids containing the human androgen receptor and luciferase gene was developed. In 49 samples from menstruating women aged 42–52 yr, total testosterone (T) and SHBG concentrations were measured by immunoassay; free T concentrations were calculated from the total T and SHBG concentrations.

Results: Mean total T concentration of the sample was 1.15 nM (SD 0.46, range 0.57–3.86 nM). The mean bioactive androgen detected was 1.00 nM (SD 0.24, range 0.53–1.60 nM). Calculated free T (mean 0.0156 nM) was significantly lower than the levels of bioactive androgens measured by receptor-mediated bioassay. There was significant positive correlation between bioactive androgen levels and total T values in young women and polycystic ovarian disorder patients, whereas no correlation was found between the two values in middle-aged women.

Conclusions: An androgen receptor-mediated bioassay can provide additional information in the evaluation of total bioactive androgens in midlife women. Our data suggest that levels of circulating SHBG may have a significant impact on the levels of total circulating bioavailable androgens.

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