Testosterone Replacement in Older Hypogonadal Men: A 12-Month Randomized Controlled Trial

Abstract

A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population.Fifteen hypogonadal men (mean age 68 Ϯ 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65 Ϯ 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone Ͻ60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory.Testosterone improved bilateral grip strength (P Ͻ 0.05 by ANOVA) and increased hemoglobin (P Ͻ 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean Ϯ SEM: Ϫ2.0 Ϯ 0.9 ng/dL vs. 0.8 Ϯ 0.7 ng/dL; P Ͻ 0.02). There were no significant changes in prostatespecific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit.Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks. (J Clin Endocrinol 82: [1661][1662][1663][1664][1665][1666][1667] 1997) A DECLINE in testicular function with a consequent decline in testosterone and bioavailable testosterone is recognized as a common occurrence in older men (1-5). Although there is great interindividual variability in testosterone and bioavailable testosterone (BT) levels with advancing age, half of healthy men between the ages of 50 -70 yr will have a BT level below the lowest level seen in healthy men who are 20 -40 yr of age (6).Studies have suggested that androgens have many important physiological actions including effects on sexual function, muscle, body composition, bone, bone marrow, prostate, and the central nervous system (7-11). However, data are sparse regarding the effects of the age-associated decline in testosterone secretion on these target systems.Few studies have assessed the role of testosterone replacement in older hypogonadal men and whether putative improvements in strength, body composition, and bone will occur without significant risks in this patient population. In a 6-month cross-over trial of testosterone, Tenover (12) found no change in muscle strength, an increase in hematocrit and prostate-specific antigen (PSA), a decrease in total cholesterol, and an increase in weight and lean body mass without changes in percent body fat. Morley et al. (13) found an increase in right-hand grip strength, an increase in hematocrit, and a d...

Endocrine and metabolic changes in human aging

“…In men, however, decreased testosterone causes an increase in leptin levels despite a decline in total fat mass (4). Testosterone replacement results in leptin levels decreasing (28). This suggests that elevated leptin levels play a role in the greater anorexia developed by males with aging.…”

“…Table 4 summarizes a number of studies demonstrating positive effects of testosterone replacement in men, similar to those seen with estrogen in women (25). In humans, testosterone increases muscle mass (26), muscle strength (27)(28)(29), bone mineral density (29,30), hemoglobin (28), and visuospatial cognitive function (31). Studies in the SAMP8 mouse, an animal model of Alzheimer disease (32), suggest that testosterone may play a role in the decline in memory and the overproduction of amyloid-6 protein seen in this species (14).…”

Androgens and male aging: current evidence of safety and efficacy

“…In most of these studies, the body weight change did not differ significantly. Testosterone therapy was associated with a greater improvement in grip strength than placebo [37,74,75]. A recent double-blind placebo-controlled study showed benefits of testosterone administration on skeletal muscle performance in elderly men with chronic heart failure [76], and another one found positive effects on the prevention of loss of muscle strength of the lower limbs [77].…”

Anorexia of ageing: a key component in the pathogenesis of both sarcopenia and cachexia

“…Hypertriglyceridemia blocks the ability of leptin to cross the blood–brain barrier 32. Male hypogonadism leads to an increase in leptin 33. The effects of ageing on ghrelin are controversial 34.…”