Short-Term Testosterone Has Limited Effects in Aging Men

By Charles Bankhead
UTRECHT, Netherlands, Jan. 2 -- A daily dose of testosterone increased lean body mass, produced mixed metabolic effects, and had no effect on functional or cognitive status in older men, investigators here found.
Action Points --->
Explain to patients that testosterone supplementation improved lean body mass in older men but did not improve functional status or cognition.
Note that multiple studies of testosterone supplementation have yielded inconsistent results.
During six months of treatment, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group (P<0.001), Marielle H. Emmelot-Vonk, M.D., of the University of Utrecht, and colleagues reported in the Jan. 1 issue of the Journal of the American Medical Association.
Insulin sensitivity improved but HDL-cholesterol decreased and, by study end, the proportion of men meeting diagnostic criteria for metabolic syndrome trended higher in the testosterone group (47.8% versus 35.5%, odds ratio: 1.7, 95% CI: 0.97 to 2.8, P=0.07).
"The findings in this study do not support a net benefit on several indicators of health and functional and cognitive performance with six months of modest testosterone supplementation in healthy men with circulating testosterone levels in the lower range," the authors concluded.
The inconsistency of previous clinical trials of testosterone supplementation likely reflects differences in study design, the type and duration of treatment, and instruments employed to study aging, Dr. Emmelot-Vonk and colleagues stated.
Moreover, most studies had small sample sizes that limited power to detect differences in effects, and studies have had a limited scope, assessing only one or two aging-related outcomes, the authors continued.
The Institute of Medicine noted those limitations and other shortcomings in calling for more short-term, randomized, placebo-controlled clinical trials to examine the safety and efficacy of testosterone supplementation in aging men (National Academies Press, 2004).
So Dr. Emmelot-Vonk and colleagues conducted a blinded, randomized, placebo-controlled trial of testosterone supplementation in 237 healthy men ages 60 to 80. All study participants had testosterone levels <13.7 nmol/L and fell within the range of low-normal.
The men were randomized to 80 mg of testosterone twice daily for six months or a matching placebo regimen. All but 30 of the men completed the study.
Investigators examined the effects of testosterone supplementation on multiple outcomes: functional mobility (multiple tests), cognitive function (eight different tests), bone mineral density, body composition, metabolic risk factors, quality of life, and safety parameters.
Cognitive function and bone density did not change in the testosterone group relative to the placebo group.
Glucose, insulin, insulin sensitivity, and insulin resistance all improved significantly in the testosterone group compared with the placebo group (P=0.04 to P=0.007). However, HDL-cholesterol decreased from 1.2 mmol/L to 1.0 mmol/L in the testosterone group and remained unchanged in the placebo group (P<0.001).
The ratio of total cholesterol to HDL also was significantly higher in the men who received daily testosterone (P<0.001).
Quality-of-life measures did not differ between groups, and investigators found no evidence of a negative effect of testosterone in prostate safety.
Addressing limitations of the study, Dr. Emmelot-Vonk and co-authors acknowledged the brief period of follow-up, but they noted that other studies had demonstrated significant changes in outcomes within six months.
Additionally, they said, effects on supplementation should have been evident within six months for all but one of the endpoints chosen for the study (bone mineral density).
The testosterone dose used in the study was consistent with doses used in previous trials, they added. And, although testosterone levels in the blood did not increase among participants receiving the hormone, that was the experience in other studies as well.
"This study is, as far as we know, the largest study of testosterone supplementation with the most endpoints and a randomized, double-blind design," the investigators concluded. "Adherence was high and the dropout rate was low."
The study was supported by the Netherlands Organization for Health Research and Development and by Organon.
The authors reported no financial disclosures.
Primary source: JAMASource reference:Emmelot-Vonk MH, et al "Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men" JAMA 2008; 299: 39-52.