Comparative assessment in young and elderly men of the gonadotropin response to aromatase inhibition

Context: Aging in men is associated with a decline in serum testosterone ( T) levels. Objective: Our objective was to assess whether decreased T in aging might result from increased estradiol (E(2)) negative feedback on gonadotropin secretion. Design and Setting: We conducted a comparative intervention study (2004) in the Outpatient Endocrinology Clinic, Ghent University Hospital. Participants: Participants included healthy young and elderly men (n = 10 vs. 10). Interventions: We used placebo and letrozole (2.5 mg/d) for 28 d, separated by 2 wk washout. Main Outcome Measures: We assessed changes in serum levels of free E(2), LH, and FSH, free T, SHBG, and gonadotropins response to an iv 2.5-mu g GnRH bolus. Results: As assessed after 28 d of treatment, letrozole lowered E2 by 46% in the young men (P = 0.002) and 62% in the elderly men (P < 0.001). In both age groups, letrozole, but not placebo, significantly increased LH levels (339 and 323% in the young and the elderly, respectively) and T (146 and 99%, respectively) (P value of young vs. elderly was not significant). Under letrozole, peak LH response to GnRH was 152 and 52% increase from baseline in young and older men, respectively (P = 0.01). Conclusions: Aromatase inhibition markedly increased basal LH and T levels and the LH response to GnRH in both young and elderly men. The observation of similar to greater LH responses in the young compared with the elderly does not support the hypothesis that increased restraining of LH secretion by endogenous estrogens is instrumental in age-related decline of Leydig cell function.