A double-blind, placebo-controled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency

The efficacy and safety of androgen supplementation in older men remains co ntroversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furt hermore, the importance of aromatization and 5 alpha reduction in androgen actions among older men remains unclear. Dihydrotestosterone is the highest potency natural androgen with the additional features that it is neither a romatizable nor susceptible to potency amplification by 5a reduction. There fore, the effects of dihydrotestosterone may differ from those of T in olde r men. This study evaluated the efficacy and safety of 3 months treatment w ith transdermal dihydrotestosterone gel on muscle strength, mobility, and q uality of life in ambulant, community-dwelling men aged 60 yr or older. Eli gible men (plasma T :less than or equal to 15 nmol/liter) were randomized t o undergo daily dermal application of 70 mg dihydrotestosterone gel (n = 18 ) or vehicle (n = 19) and were studied before, monthly during, and 1 month after treatment. Among 33 (17 dihydrotestosterone, 16 placebo) men completi ng the study with a high degree of compliance, dihydrotestosterone had sign ificant effects on circulating hormones (increased dihydrotestosterone; dec reased total and free testosterone, LJ, and FSH; unchanged SHBG and estradi ol), lipid profiles (decreased total and low-density lipoprotein cholestero ls; unchanged high-density lipoprotein cholesterol and triglycerides), hema topoiesis (increased hemoglobin, hematocrit, and red cell counts), and body composition (decreased skinfold thickness and fat mass; unchanged lean mas s and waist to hip ratio). Muscle strength measured by isokinetic peak torq ue was increased in flexion of the dominant knee but not in knee extension or shoulder contraction, nor was there any significant change in gait, bala nce, or mobility tests, in cognitive function, or in quality of life scales . Dihydrotestosterone treatment had no adverse effects on prostate (unchang ed prostate volumes and prostate-specific antigen) and cardiovascular (no a dverse change in vascular reactivity or lipids) safety markers. We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstra tes expected androgenic effects, short-term safety, and limited improvement in lower limb muscle strength but no change in physical functioning or cog nitive function.