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Endocrine Care |
Department of Andrology (L.P.L., M.J., T.N.Z., A.J.C., D.J.H.), Concord Hospital and ANZAC Research Institute, Concord, New South Wales 2139, Australia; and Department of Cardiology (D.S.C.), Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW 2006, Australia
Address all correspondence and requests for reprints to: Prof D. J. Handelsman, ANZAC Research Institute, Concord, NSW 2139, Australia. E-mail: djh{at}med.usyd.edu.au
Abstract
The efficacy and safety of androgen supplementation in older men
remains controversial. Despite biochemical evidence of partial androgen
deficiency in older men, controlled studies using T demonstrate
equivocal benefits. Furthermore, the importance of aromatization and
5
reduction in androgen actions among older men remains unclear.
Dihydrotestosterone is the highest potency natural androgen with the
additional features that it is neither aromatizable nor susceptible to
potency amplification by 5 reduction. Therefore, the effects of
dihydrotestosterone may differ from those of T in older men. This study
evaluated the efficacy and safety of 3 months treatment with
transdermal dihydrotestosterone gel on muscle strength, mobility, and
quality of life in ambulant, community-dwelling men aged 60 yr or
older. Eligible men (plasma T 
15 nmol/liter) were randomized to
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 completing the study with a high degree of compliance,
dihydrotestosterone had significant effects on circulating hormones
(increased dihydrotestosterone; decreased total and free testosterone,
LH, and FSH; unchanged SHBG and estradiol), lipid profiles (decreased
total and low-density lipoprotein cholesterols; unchanged high-density
lipoprotein cholesterol and triglycerides), hematopoiesis (increased
hemoglobin, hematocrit, and red cell counts), and body composition
(decreased skinfold thickness and fat mass; unchanged lean mass and
waist to hip ratio). Muscle strength measured by isokinetic peak torque
was increased in flexion of the dominant knee but not in knee extension
or shoulder contraction, nor was there any significant change in gait,
balance, or mobility tests, in cognitive function, or in quality of
life scales. Dihydrotestosterone treatment had no adverse effects on
prostate (unchanged prostate volumes and prostate-specific antigen) and
cardiovascular (no adverse change in vascular reactivity or lipids)
safety markers. We conclude that 3 months treatment with transdermal
dihydrotestosterone gel demonstrates expected androgenic effects,
short-term safety, and limited improvement in lower limb muscle
strength but no change in physical functioning or cognitive
function.
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