Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial*

Objective To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. Design Prospective, double-blind, placebo-controlled, crossover trial. Setting Tertiary care research institution. Interventions Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 µ g of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen. Patients, Participants Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years. Main Outcome Measures We measured serum estradiol (E 2 ) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E 2 > 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P > 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. Results The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated. Conclusions Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.