Androgen replacement in aging men

Serum testosterone and estradiol decline with advancing age in men, but the contribution of these changes to age-related bone loss remains unclear. Most studies show a closer relationship between bone density and serum estradiol than with serum testosterone. Nevertheless, hypogonadism is widely considered to be an important cause of male osteoporosis, occurring in up to 20% of men with vertebral fractures and 50% with hip fractures. Bone loss in hypogonadal men has been attributed to androgen and estrogen deficiency, low 1,25 dihydroxyvitamin D concentrations, malabsorption of calcium, and reduced circulating calcitonin. These abnormalities are corrected by testosterone replacement, which also decreases bone resorption and stimulates bone mineralization. Long-term testosterone replacement increases spine bone density by over 25%, although much of the improvement occurs in the first few years of treatment. There appears to be an inverse relationship between the basal serum testosterone and the increase in bone density observed with testosterone treatment, such that little change is seen in men with normal basal concentration. In contrast, an observational study in eugonadal men with vertebral fractures showed an increase in spine bone density of 5% after 6 months' treatment with testosterone, probably mediated by an increase in serum estradiol and a reduction in bone resorption. Although testosterone has beneficial effects on the skeleton, there may be adverse effects on the prostate and cardiovascular risk factors. Further studies are required to confirm the safety and efficacy of testosterone replacement in hypogonadal and eugonadal men with osteoporosis.