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Submitted on May 3, 2005
Accepted on July 18, 2005
Department of Endocrinology, Ghent University Hospital, Belgium (G.T., H.D., P.C., J.M.K.), Department of Public Health, Ghent University, Ghent, Belgium (D.D.B.) and Internal Medicine Sub. Endocrinology Ospedale Putignano-Noci (Bari), Italy (V.A.G.)
* To whom correspondence should be addressed. E-mail: guy.tsjoen{at}ugent.be.
1. Context: Aging in men is associated with a decline in serum testosterone (T) levels.
2. Objective: To assess whether decreased T in aging might result from increased estradiol (E2) negative feedback on gonadotropin secretion.
3. Design: Comparative intervention study (2004)
4. Setting: Outpatient Endocrinology Clinic, Ghent University Hospital
5. Participants: Healthy young and elderly men (n = 10 vs. 10)
6. Interventions: placebo and letrozole (2.5 mg/day) 28 days, separated by 2 weeks washout.
7. Main Outcome Measures: Change of serum levels of (Free) E2, LH and FSH, (Free) T, SHBG and gonadotropins response to an i.v. 2.5 µg GnRH bolus.
8. Results: As assessed after 28 days of treatment letrozole lowered E2 by 46% in the young (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 young vs. elderly = NS). Under letrozole, peak LH response to GnRH was 152% and 52% increase from baseline in young and older men, respectively (P = 0.01).
9. 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.
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