Serum testosterone bioassay evaluation in a large male cohort

Objective: To assess if a cell-based readout of androgen action in serum demonstrates a closer association with recognized classical parameters of androgen action in men than current measures of serum testosterone (T). Design: To develop, validate and utilize a mammalian cell-based assay to measure specifically bioactive T and determine if this measure is a physiologically relevant fraction of serum T. Measurements and participants: We have developed a specific serum T bioassay using human prostate cancer cells. A rapid 5-min exposure to 100% serum followed by serum withdrawal confers specificity of the assay to serum T and provides sufficient sensitivity to measure T in male serum samples. Matrix effects were experimentally discounted as a confounding issue. A total of 960 male serum samples from the Florey Adelaide Male Ageing Study (FAMAS) with previous comprehensive cohort data and serum measurements were utilized. Results: Bioassay T measurement in the 960 FAMAS serum samples returned a median of 10·7 nmol/l (1·7–45·4), and was most closely related to immunoassayed total T, but not immunoassayed bioavailable T or calculated free T. Immunoassayed total T demonstrated a positive association with isometric grip-strength (R2 = 0·127, P < 0·001), self-reported sexual desire (R2 = 0·113, P < 0·001) and erectile function (R2 = 0·085, P < 0·05) while bioassay T did not. Conclusions: While cellular bioassays offer a rapid and sensitive means of identifying the androgenic potential of complex environmental compounds, the utility of such assays in defining a clinically relevant fraction of serum T distinct from total T needs further investigation.Eleanor F. Need, Peter D. O’Loughlin, David T. Armstrong, Matthew T. Haren, Sean A. Martin, Wayne D. Tilley, the Florey Adelaide Male Aging Study, Gary A. Wittert and Grant Buchana