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Testosterone in Older Men: More Clarity or More Confusion?

Results of three studies argue against wholesale use of this drug for anti-aging purposes.

Three new studies add to the literature — and perhaps to the confusion — about testosterone in older men.

To identify symptom-clusters associated with low testosterone levels in 3369 community-dwelling men (age range, 40–79), European researchers administered questionnaires and measured morning levels of total and free testosterone. Of 32 sexual, physical, and psychological symptoms considered as potentially related to hypogonadism, a cluster of three sexual symptoms — poor morning erection, low sexual desire, and erectile dysfunction — correlated most closely with low testosterone levels. In contrast, clusters of psychological and physical symptoms correlated poorly with low testosterone levels. The analysis suggested that late-onset hypogonadism is characterized by presence of the three sexual symptoms in men with total testosterone levels <317 ng/dL (11 nmol/L) and free testosterone levels <64 pg/mL (220 pmol/L).

Another study involved 1445 community-dwelling U.S. men (mean age, 61). In cross-sectional analyses, total testosterone and sex hormone–binding globulin levels were not associated with mobility limitation, subjective health, or any physical performance measures, whereas free testosterone was associated with subjective health and some (but not all) physical performance measures. During 7 years of follow-up, low free testosterone level at baseline was associated with subsequent decline in mobility but not in subjective health.

To study the effects of testosterone supplementation, U.S. researchers enrolled 209 men (age, 65) with limited mobility and with total testosterone levels of 100 to 350 ng/dL (3.5–12.1 nmol/L) or free testosterone levels <50 pg/mL (173 pmol/L). Men were randomized to receive either transdermal testosterone gel or placebo for 6 months, with testosterone doses adjusted to achieve serum levels of 500 ng/dL. Enrollment was halted early because significantly more adverse cardiovascular events occurred in the testosterone group than in the placebo group (23 vs. 5 events).

Comment: The first study summarized above suggests that sexual symptoms — and not vague physical and psychological symptoms — should be used if one wants to identify patients with late-onset hypogonadism. The second study shows correlations between free testosterone and some measures of physical performance; however, findings were mixed, and significant associations in observational studies do not necessarily indicate cause-and-effect. And the third study raises red flags about adverse effects of testosterone supplementation in older men. These studies — considered alongside other recent studies in which testosterone supplementation did not yield impressive results in frail older men (JW Gen Med Mar 9 2010) or in healthy older men (JW Gen Med Oct 18 2006) — argue against indiscriminate use of testosterone as an "anti-aging" drug. This conclusion is supported by a new practice guideline from the Endocrine Society (JW Gen Med Jul 15 2010).

— Allan S. Brett, MD

Published in Journal Watch General Medicine July 15, 2010

Citation(s):

Wu FCW et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010 Jul 8; 363:123. (http://dx.doi.org/10.1056/NEJMoa0911101)

• Medline abstract (Free)

Krasnoff JB et al. Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: The Framingham Offspring Study. J Clin Endocrinol Metab 2010 Jun; 95:2790. (http://dx.doi.org/10.1210/jc.2009-2680)

• Original article (Subscription may be required)
• Medline abstract (Free)

Basaria S et al. Adverse events associated with testosterone administration. N Engl J Med 2010 Jul 8; 363:109. (http://dx.doi.org/10.1056/NEJMoa1000485)

• Medline abstract (Free)

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