Hormonal changes in aging men: a therapeutic indication?

The rise in male life expectancy is paralleled by increased age-related clinical signs and symptoms such as muscle weakness, osteoporosis, benign prostatic hyperplasia, changes in body composition, fatigue, decreased sexual interest and activity, and increased prevalence of erectile dysfunction, all of which limit the quality of life. Many of these symptoms are similar to those of clinically well-defined hormone deficiencies, e.g. Kallman syndrome, Prader--Labhart--Willi syndrome or deficiencies due to treatment of pituitary tumors. Three male endocrine axes are characterized by age-related changes in concentrations of circulating hormones: (i) the hypothalamic--pituitary--testicular axis with lower serum levels of testosterone (T) and higher serum levels of luteinizing and follicle-stimulating hormone, (ii) the hypothalamic--pituitary--adrenal axis with its gradual decline in dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), (iii) the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis showing decreased hormone production concomitant with symptoms similar to those of GH-deficient adults. The beneficial effects of hormone replacement in nonelderly hormone-deficient individuals and in postmenopausal women raised hope that hormone substitution might prevent or even reverse some of the symptoms of male aging. However, this approach is hampered by the lack of individual age-related hormone reference values and reliable clinical read-out parameters. The findings so far do not support the need for widespread hormone replacement in elderly men. Larger long-term prospective studies are needed to identify clinically useful read-out parameters, and then demonstrate that hormone replacement can translate into functional parameters, thereby providing the individual benefit of treatment for aging men.