The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men

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.