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: To develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum.

Design: Clinically relevant experimental study nested in a sample population of a longitudinal cohort study

Setting: University laboratory

Methods: A receptor-mediated luciferase expression bioassay based on HEK 293 cells which were stably cotransfected with plasmids containing the human androgen receptor (hAR) and luciferase gene was developed. In forty-nine samples from menstruating women aged 42-52 yr, total testosterone (T) and sex hormone binding globulin (SHBG) concentrations were measured by immunoassay; free T (FT) 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 FT (mean: 0.016 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 in polycystic ovarian disorder patients while no correlation was found between the two values in mid-aged women.

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