Effects of suppression of follicle-stimulating hormone secretion on bone resorption markers in postmenopausal women

Context: It has recently been proposed that the increase in bone resorption after the menopause may not be due principally to estrogen deficiency but rather to the concomitant increase in circulating FSH levels. Objective: The objective of the study was to test whether suppression of FSH secretion in postmenopausal women reduces levels of bone resorption markers. Design: This was a prospective study. Setting: The study was conducted at a clinical research unit. Participants and Interventions: Postmenopausal women were treated with a GnRH agonist (leuprolide acetate, 7.5 mg im every 28 d; n = 21) or placebo injections (control; n = 20). Both groups received the aromatase inhibitor, letrozole, 2.5 mg/d, to eliminate variations in endogenous estrogen levels as a confounder. Main Outcome Measures: Serum FSH and bone resorption markers [serum C-terminal telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase 5b (TRAP5b)] at d 105 (3.5 months) of treatment as compared with baseline. Results: Compared with baseline, serum FSH levels did not change significantly in controls (+6%) but were reduced (-86%, into the premenopausal range) in the GnRH group. Due to the aromatase inhibitor-induced reduction in estrogen production, serum CTX and TRAP5b levels increased significantly in controls (+20 and +10%, respectively). In the GnRH group, suppression of FSH secretion did not reduce serum CTX or TRAP5b levels; rather, both markers also increased in these women (+34 and +15%, respectively; P = 0.161 and 0.266 for comparison of percent changes between groups). Conclusions: This direct interventional study demonstrates that FSH does not regulate bone resorption in postmenopausal women.