Effects of Recombinant Follicle-Stimulating Hormone on Bone Turnover Markers in Infertile Women Undergoing in Vitro Fertilization Procedure

Context: There is experimental but limited clinical evidence that FSH may have direct effects on bone. Objective: The aim of the study was to evaluate the effects of acute FSH stimulation on bone turnover in premenopausal women. Design and Setting: We conducted a prospective study at a referral center. Patients: Twenty-nine infertile women (age range, 30 – 40 yr) undergoing an in vitro fertilization procedure were included in the study. Interventions: Pharmacological suppression of endogenous gonadotropin and estradiol (E2) pro- duction by GnRH analog (leuprolide 1 mg/d sc) was followed by stimulation with recombinant FSH (rFSH; starting dose, 375 IU/d sc). Main Outcome Measures: We measured serum osteocalcin, C-telopeptides of type-1 collagen (-CTX), FSH, and E2 at the beginning of leuprolide administration (T0), at the beginning of rFSH administration (T1), and 3 d (T2) and 10 d (T3) after the first dose of rFSH. Results: At T1, the suppression of FSH and E2 secretion, as an effect of leuprolide administration, led to a significant increase in serum -CTX values vs. T0 (P 0.001). After the administration of rFSH, a rapid increase in serum FSH was observed, whereas serum E2 values increased more slowly. At T2, the increase in serum FSH values above our reference range for early follicular phase (with E2 in the reference range) did not induce any significant change in median serum -CTX values as compared to T1. At T3 (when both FSH and E2 were high), serum -CTX values decreased signif- icantly vs. T1 (P 0.001). Osteocalcin did not change significantly throughout the study period. Conclusions: Our model suggests that FSH does not acutely exert relevant direct effects on bone metabolism in premenopausal women.