Biomedical subjects
Pekka Kunelius
Publications and source records attributed to Pekka Kunelius.
The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study.
The objective of the study was to investigate the effects of dihydrotestosterone (DHT) gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in this randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had nocturnal penile tumescence once per week or less, andropause symptoms, and a serum T level of 15 nmol/liter or less and/or a serum SHBG level greater than 30 nmol/liter. The mean age was 58 yr (range, 50-70 yr). Of these subjects, 114 men completed the study. DHT was administered transdermally for 6 months, and the dose varied from 125-250 mg/d. General well-being symptoms and sexual function were evaluated using a questionnaire, and prostate symptoms were evaluated using the International Prostate Symptoms Score, transrectal ultrasonography, and assay of serum prostate-specific antigen. Early morning erections improved transiently in the DHT group at 3 months of treatment (P < 0.003), and the ability to maintain erection improved in the DHT group compared with the placebo group (P < 0.04). No significant changes were observed in general well-being between the placebo and the DHT group. Serum concentrations of LH, FSH, E2, T, and SHBG decreased significantly during DHT treatment. Treatment with DHT did not affect liver function or the lipid profile. Hemoglobin concentrations increased from 146.0 +/- 8.2 to 154.8 +/- 11.4 g/liter, and hematocrit from 43.5 +/- 2.5% to 45.8 +/- 3.4% (P < 0.001). Prostate weight and prostate-specific antigen levels did not change during the treatment. No major adverse events were observed. Transdermal administration of DHT improves sexual function and may be a useful alternative for androgen replacement. As estrogens are thought to play a role in the pathogenesis of prostate hyperplasia, DHT may be beneficial, compared with aromatizing androgens, in the treatment of aging men.
Serum androgen bioactivity during 5alpha-dihydrotestosterone treatment in elderly men.
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.