Disparate Effect of Aromatization on the Central Regulation of GH Secretion by Estrogens in Men and Postmenopausal Women

Abstract

Estrogen receptor antagonism by tamoxifen inhibits GH secretion in both men and postmenopausal women, suggesting that estrogen, albeit at low concentration, stimulates GH secretion. However, systemic estrogen replacement in postmenopausal women does not enhance GH secretion. To clarify the role of estrogen in mediating GH secretion, we investigated the effect of estrogen deprivation by using aromatase inhibitors. Aim: To determine whether estrogens mediate GHecretion in men and postmenopausal women. Design: The effects of letrozole, an aromatase inhibitor, and tamoxifen were compared in an open-label crossover study. Eight men and 14 women received tamoxifen (20 mg/d) and letrozole (2.5 mg/d) for 2 weeks each. The primary endpoints were GH response to arginine stimulation and gonadal steroid levels. Results: In men, letrozole significantly (P,0.05) reduced the peak GH response to arginine (mean6 SEM; D 249.4% 6 18.1%). Tamoxifen also reduced the mean peak GH, but this did not reach statistical significance. In postmenopausal women, letrozole did not affect peak GH, whereas tamoxifen significantly (P , 0.05) reduced peak GH (D 247.3% 6 10%). In men, letrozole reduced circulating estradiol (from 43.1 6 2.8 to 12.7 6 1.3 pmol/L; P , 0.001), whereas in women estradiol was undetectable (,11 pmol/L) at baseline and throughout letrozole therapy.