title: Serum androgen bioactivity during 5alpha-dihydrotestosterone treatment in elderly men.
abstract: 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 5alpha-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.
authors.affiliation: Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, Finland. taneli.raivio@helsinki.fi
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
authors.forename: Juha S
authors.initials: JS
authors.lastname: Tapanainen
authors.forename: Pekka
authors.initials: P
authors.lastname: Kunelius
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
mesh_terms: D000375:Aging / Q000097:blood*; D000728:Androgens / Q000097:blood*; D001681:Biological Assay; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology*; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000097:blood; D013997:Time Factors
chemical_list: D000728:Androgens; D006728:Hormones; D013196:Dihydrotestosterone; D013739:Testosterone