The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men
Abstract
Serum androgens decline with age in normal men, despite normal or elevated
bioactive serum gonadotropins, suggesting that primary testicular
dysfunction occurs with aging. The authors further assessed the question
of age-related testicular dysfunction by evaluating whether raising serum
gonadotropins above the normal serum range for an extended time in healthy
elderly men might result in bringing their gonadal function to a level
similar to that found in young adult men. Five elderly (65 to 85 years
old) and five young adult men (26 to 33 years old) were given 50 mg of
clomiphene citrate (CC) twice a day for 8 weeks to stimulate gonadotropin
production. During that time, testosterone (T), non-sex hormone-binding
globulin bound T, and estradiol increased significantly in both age
groups, while serum inhibin increased significantly only in the young
adult men. The increases in serum androgens with CC administration were
significantly greater in the young adult men than in the elderly men.
These hormone changes occurred in the setting of serum gonadotropins that
increased significantly in both age groups, although there was a tendency
for the elderly men to have a smaller increase in luteinizing hormone.
Despite 8 weeks of stimulation of the pituitary-gonadal axis by CC
administration, the elderly men demonstrated significantly diminished
testicular responses compared with the young adult men. Sertoli cell
function, as determined by inhibin production, was more diminished in the
elderly men than was Leydig cell function. These data strengthen the
hypothesis that normal aging in men is accompanied by a decline in
testicular function.