Effects of Age on Testicular Function and Consequences of Testosterone Treatment1

Abstract

Testosterone and gonadotropins. Several studies demonstrate that the serum testosterone concentration declines with increasing age. In one cross-sectional study of 83 healthy men, the free testosterone concentration declined by age 80 to approximately 40% of that at age 20, but because the serum concentration of sex hormone binding globulin (SHBG) increased during this age span, the serum concentration of total testosterone declined only to approximately 80% of that at age 20 (1). In another cross-sectional study of 71 healthy men, aged 26–90 yr, living in similar circumstances, the 33 younger men had a mean free testosterone concentration of 10.7 6 3.4 ng/dL (sd) and the 38 older men had a mean free testosterone concentration of 5.8 ng/dL (P , 0.01) (2). Total serum testosterone concentrations in the two groups were 659 6 201 ng/dL and 490 6 160 ng/dL, respectively (P , 0.01). In a third cross-sectional study in 810 healthy men mostly between 50 and 84 yr old, the serum bioavailable testosterone concentration declined by approximately 55– 60%, but the serum total testosterone concentration did not decline at all (3). In one longitudinal study, 39 healthy men whose mean serum total testosterone concentration was 633 6 22 ng/dL (se) when they enrolled in a study of aging in 1980 had a mean value of 464 6 33 ng/dL in 1994 (4). In another longitudinal study of 890 men, both total testosterone and the ratio of testosterone to SHBG decreased with age (Fig. 1) (5). The decline in testicular function appears to involve a combination of primary and secondary hypogonadism. A gradual increase in the serum concentration of LH indicates a degree of primary hypogonadism. In a cross-sectional study, the mean serum LH concentration in 33 men of an average age of 37 yr was 1.9 6 0.6 ng/mL and in 38 men of an average age of 71 yr was 2.2 6 0.6 ng/mL (2). In a longitudinal study, 39 men whose mean LH was 9.4 6 0.4 (se) mIU/mL when they enrolled in 1980 had a mean value of 13.7 6 1.3 mIU/mL in 1994 (4). However, the findings that LH secretory burst amplitude decreases with increasing age and that this decrease was the most prominent determinant of decreased testosterone secretion indicates a degree of secondary hypogonadism (6). This conclusion is supported by the failure of LH secretion to respond to drug-induced reduction of the serum testosterone concentration in old men as well as in young men (7).