Testosterone Deficiency and What to Do About It

Male hypogonadism with low testosterone levels can negatively affect muscle mass and has been associated with the increased accumulation of visceral fat. Thus, in clinical practice it may be important to assess older men presenting with weight gain for testosterone deficiency.

The latest issue of the New England Journal of Medicine features two articles relevant to this issue.

In the first article, Frederick Wu and colleagues (for the EMAS group) surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers regarding general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples.

Symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly (inversely) related to the testosterone level. However, only the three sexual symptoms had a syndromic association with decreased testosterone levels diagnostic of hypogonadism.

Importantly, none of the non-sexual symptoms (decreased energy levels, depression, loss of strength, etc.) were specific enough to screen for or diagnose testosterone deficiency.

The authors conclude that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2/mL) and a free testosterone level of less than 220 pmol/L (64 pg/mL).

In the second article, Shehzad Basaria and colleagues from Boston University, examine the efficacy and safety of testosterone supplementation in older men (Testosterone in Older Men with Mobility Limitations (TOM) trial).

A total of 209 Community-dwelling men (mean age, 74 years) with limitations in mobility and low serum testosterone levels were randomly assigned to receive placebo or testosterone gel for 6 months. Not surprisingly, participants had a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity at the time of enrollment into the trial.

Just three years into the study, the data and safety monitoring board recommended that the trial be discontinued because there was a significantly higher rate of adverse cardiovascular events in the testosterone than in the placebo group.

During the course of the study, significantly more men in the testosterone group than in the placebo group had cardiac, respiratory, and dermatologic events.

Of particular concern to the data and safety monitoring board was the greater number of subjects with cardiovascular-related events (23 vs. 5) and atherosclerosis-related events (7 vs. 1).

On a positive note, the testosterone group did have significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load than the placebo group.

While the the study suggests that treating testosterone deficiency in older men with limitations in mobility and a high prevalence of chronic disease is not without risk, the authors raise some important caveats in interpreting this finding.

For one, the overall number of adverse events is rather small and there may have been some limitations with respect to the ascertainment of adverse events. Caution is also warranted in extrapolating these findings to other doses and formulations of testosterone or to other populations, particularly young men who have hypogonadism without cardiovascular disease or limitations in mobility.

I guess further studies will be needed to address the efficacy and safety of testosterone treatment for male hypogonadism. Clinicians will certainly have to carefully assess and discuss the risk/benefit ratio of testosterone substitution treatment with their patients.

Edmonton, Alberta

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Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F, Huhtaniemi IT, & the EMAS Group (2010). Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men. The New England journal of medicine PMID: 20554979

Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, Lebrasseur N, Fiore LD, & Bhasin S (2010). Adverse Events Associated with Testosterone Administration. The New England journal of medicine PMID: 20592293