Testosterone produces substantial anabolic effects in young and middle-aged hypogonadal men (Bhasin et al 2001
). In contrast, the anabolic effects of testosterone replacement therapy in older men have been harder to demonstrate. Among the many published trials of testosterone in older men, some report strength gains and some do not. Only a few report strength gains that can be considered substantial in comparison to the benefits of resistance exercise training. In most cases, the studies reporting significant strength gains were performed in hypogonadal subjects and employed a higher dose of testosterone, for a longer duration.
In a recent report, Nair et al (2006)
describe treating a group of hypogonadal men for 24 months with a transdermal testosterone at a dose of 35 mg/week and finding no increase in strength. However, 35 mg/week is less than a replacement dose and resulted in only a 30% increase in the circulating testosterone concentration. Studies by Brill et al (2002)
, Clague et al (1999)
, Kenny et al (2001)
, and Snyder et al (1999)
also report small increases in strength. Brill et al treated older men for 1 month with 5 mg testosterone/day by patch and found an improvement in stair climb time, but no increase in strength. Clague et al treated men aged 60 or more with total T of 400 ng/dL or less were treated with 200 mg testosterone enanthate every two weeks by i.m. injection for 3 months and found no significant increase in strength. Kenny et al (2001)
treated hypogonadal and low-normal older men with 5 mg testosterone/day by patch for 1 year and found a 38% increase in strength with testosterone, but surprisingly also a 27% increase with placebo, with no significant difference between the two groups. Snyder et al (1999)
treated older hypogonadal and eugonadal men for 36 months with 6 mg testosterone/day by patch and found no increase in strength.
Several investigators have reported that testosterone caused moderate increases in strength; increases that are significant, but are still below than what can be obtained through resistance exercise training. Wang et al (2000)
treated younger and older men (aged 19–68) with total T of 300 ng/dL or less with a titrated dose of testosterone gel (equivalent of 5 to 10 mg per day) for 6 months found that the higher dose caused, a reduction in negative moods, a sizable increase in hematocrit (from 42 to 47), and modest increases in arm and leg strength. Sullivan et al (2005)
conducted a 3-month study of low- or high-intensity resistance exercise training in men aged 65 or more, who were not hypogonadal (total T = 480 ng/dL or less). Some subjects also received a weekly i.m. injection of 100 mg testosterone enanthate. The addition of testosterone produced a trend toward greater increases overall, but the effect of testosterone appears to be substantial in the low-intensity training group. Considering that few men in the community will perform high-intensity training on their own, these results may indicate usefulness for testosterone therapy.
Three studies have reported substantial strength gains following testosterone treatment and all have employed doses of testosterone that are somewhat higher than replacement doses. Ferrando et al (2002)
treated older hypogonadal and eugonadal men for 6 months with a biweekly injection of testosterone that was titrated to raises circulating testosterone into the normal range and resulted in an approximated doubling of circulating testosterone (from ~300 to ~600 ng/dL). Significant strength increases were observed, including a 15 kg increase in leg extension 1-RM strength. Page et al (2005)
treated a group of older, hypogonadal men for 36 months with biweekly i.m. injections of 200 mg testosterone enanthate and found significant improvements in hand grip strength. However, the study that best demonstrates the dose dependence is that of Bhasin et al (2005)
. Both older and younger men were first made hypogonadal with luprolide and then treated for 5 months with testosterone enanthate at doses ranging from 25 mg to 600 mg/week. Higher doses of testosterone produced large increases in strength, including an increase of 50 kg in leg press 1-RM strength in older men receiving a dose of 300 mg/week. The doses of 300 and 600 mg/week produced a high incidence of adverse effects and a dose of 125 mg/week was considered to be the best trade-off of beneficial and adverse effects.
The dose of testosterone also appears to be critical in determining whether increases in bone mineral density are observed. Snyder et al (1999)
treated older hypogonadal and eugonadal men for 36 months with 6 mg testosterone/day by patch and found that bone mineral density did not increase overall, but did do so in the group with the lowest pretreatment testosterone levels. However, Amory et al (2004)
treated older hypogonadal men for 36 months with biweekly i.m. injections of 200 mg testosterone enanthate and obtained substantial increases in bone mineral density, 3%–4% in the hip and a remarkable 10% in the lumbar spine.