Summary
Physicians are prescribing testosterone therapy increasingly for older men with low testosterone levels, but we still know very little about its benefits and harms. In this summary, we review several new studies on testosterone levels in older men.
There is growing interest in associations between testosterone levels, cognition, and mental health in older men. In a prospective U.S. study, researchers followed 574 men (mean age, 66) who did not have dementia at baseline. Multivariable analyses revealed that low baseline serum levels of free testosterone (but not total testosterone) were independently associated with increased risk for developing Alzheimer disease during 19 years of follow-up. In another study, U.S. Veterans Affairs researchers used computerized records to examine associations between testosterone levels and depression. During a 2-year follow-up, men with low baseline serum total testosterone levels (<200 ng/dL) were significantly more likely than men with higher levels to receive diagnoses of depression (22% vs. 7%). However, this study is limited by various indications for initial testosterone determinations (e.g., erectile dysfunction, osteoporosis) among the study cohort and by ascertainment of depression diagnoses from chart reviews.
Another area of interest is the relation between testosterone level and bone-mineral density. In a U.S. trial, 70 men (mean age, 71) with low serum testosterone levels (<350 ng/dL) were randomized to receive testosterone alone (200 mg intramuscularly every 2 weeks), IM testosterone plus oral finasteride (to mitigate adverse effects of testosterone on the prostate), or placebo. During 3 years, bone density increased significantly from baseline in both testosterone groups (e.g., by about 10% at the lumbar spine and by about 2.5% at the hip) but not in the placebo group. Prostate-specific antigen levels and prostate size increased more in the testosterone-only group than in the testosterone/finasteride group. However, dose reductions were required in a third of all testosterone recipients, because hematocrits increased to more than 52%.
How accurate are serum testosterone measurements? Researchers used liquid chromatography-tandem mass spectrometry (the reference standard) and 6 commercial assays to measure serum testosterone levels in 122 adult men. Compared with the reference standard, one assay averaged 99 ng/dL higher, and another assay averaged 90 ng/dL lower. Depending on the assay, 20% to 50% of measured values differed from the reference standard by more than 20%.Comment
These findings raise important questions. Should we measure total or free testosterone? How trustworthy are results from local laboratories? Do prospectively observed associations between testosterone levels and cognition or depression truly represent cause-and-effect? If so, would testosterone replacement therapy confer neuropsychiatric benefits? Even if testosterone therapy increases bone density, will fracture rates decrease? And, for any of these indications, will long-term benefits of testosterone therapy clearly outweigh harms?
The current flurry of interest in testosterone replacement therapy reminds us of the estrogen/progestin story before the Women's Health Initiative — lots of hype and intriguing observational studies, but few long-term outcome data. Accordingly, the Institute of Medicine has called for additional short-term trials to establish testosterone-therapy efficacy, followed by longer-term trials to establish safety, in a new report entitled Testosterone and Aging: Clinical Research Directions. (The executive summary is available free of charge.) Finally, a recent article in the New England Journal of Medicine provides a comprehensive overview of the risks engendered by testosterone-replacement therapy.
— Allan S. Brett, MDSource
Moffat SD et al. Free testosterone and risk for Alzheimer disease in older men. Neurology 2004 Jan 27; 62:188-93.
Shores MM et al. Increased incidence of diagnosed depressive illness in hypogonadal older men. Arch Gen Psychiatry 2004 Feb; 61:162-7.
Amory JK et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004 Feb; 89:503-10.
Wang C et al. Measurement of total serum testosterone in adult men: Comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 2004 Feb; 89:534-43.
Rhoden EL and Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004 Jan 29; 350:482-92.
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Journal Watch 3(3), 2004. © 2004 Massachusetts Medical Society
This is a part of article Testosterone in Older Men: Replay of the Estrogen Story? Taken from "Generic Propecia - Finasteride Archive" Information Blog
