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Serum Androgen Bioactivity During 5-Dihydrotestosterone Treatment in Elderly Men

JUHA S. TAPANAINEN

PEKKA KUNELIUS

OLLI A. JäNNE^*,

From ^* Biomedicum Helsinki, Institute of Biomedicine, the Department of Clinical Chemistry, University of Helsinki, and Helsinki University Central Hospital, Helsinki; and the Department of Obstetrics and Gynecology and the Division of Urology, Department of Surgery, University of Oulu, Finland.

Correspondence to: Taneli Raivio, MD, PhD, Biomedicum Helsinki, Institute of Biomedicine/Physiology, PO Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland (e-mail: taneli.raivio{at}helsinki.fi).

The androgens used in the treatment of age-related androgen decline have different bioactivities that cannot be evaluated with conventional detection methods for serum steroids. We have recently developed a recombinant cell bioassay for the determination of androgen bioactivity in human serum that is based on androgen-specific interaction between the ligand-binding domain (LBD) and the N-terminal region of the androgen receptor (AR). In this work, we examined the effect of topically applied 5-dihydrotestosterone (DHT; 7.5-10 g of 2.5% DHT gel daily for 6 months) on circulating androgen bioactivity in 14 men (age range, 51-63 years) with symptoms of andropause and pretreatment serum testosterone less than 15 nM, or serum sex hormone-binding globulin concentration greater than 30 nM, or both. The mean (±SEM) pretreatment androgen bioactivity was 3.3 ± 0.3 nM testosterone equivalents, and the levels correlated with serum testosterone concentration (r = .55, P < .05). DHT gel treatment induced a sixfold increase (from 1.5 ± 0.1 nM to 9.0 ± 0.7 nM) in mean serum DHT level, whereas endogenous testosterone and estradiol levels measured with radioimmunoassays were suppressed by approximately 70% and approximately 50%, respectively (P < .0001). Concomitantly, serum androgen bioactivity increased by sevenfold (from 3.3 ± 0.3 to 23.6 ± 2.8 nM testosterone equivalents; P < .0001). We conclude that DHT gel therapy in elderly men significantly increases their circulating androgen bioactivity as measured with a mammalian cell bioassay. An androgen-specific bioassay such as ours may enable investigation of other androgens with different bioactivities, such as selective AR modulators.

     Key words: Androgen decline, bioassay, DHT

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