Depot Pure GnRH Antagonist for Long-term Treatment of Ovarian Hyperthecosis Monitored by Multisteroid LCMS Profiling

Abstract

Ovarian hyperthecosis (OHT), severe hyperandrogenism after menopause in the absence of ovarian or adrenal tumors, is usually treated by surgical excision. We report a 58-year-old woman presenting with severe hyperandrogenism (serum testosterone 15.7-31.0 nmol/L, normal female <1.8 nmol/L) with menopausal gonadotropins and virilization but no adrenal or ovarian lesions. Multisteroid profiling by liquid chromatography mass spectrometry (LCMS) of adrenal and ovarian vein samples identified strong gradients in the left ovarian vein (10-to 30-fold vs peripheral blood in 17OHP4, 17 hydroxyprogesterone, 17 hydroxypregnenolone, androstenedione, testosterone, dehydroepiandrosterone) but the right ovarian vein could not be cannulated with the same findings in a second ovarian vein cannulation. OHT diagnosis was confirmed by an injection of a depot pure gonadotropin-releasing hormone (GnRH) antagonist (80 mg Degarelix, Ferring) producing a rapid (<24 hour) and complete suppression of ovarian steroidogenesis as well as serum luteinizing hormone and follicle-stimulating hormone lasting at least 8 weeks, with reduction in virilization but injection site reaction and flushing and vaginal spotting ameliorated by an estradiol patch. Serum testosterone remained suppressed at 313 days after the first dose despite recovery of menopausal gonadotropins by day 278 days. This illustrates use of multisteroid LCMS profiling for confirmation of the OHT diagnosis by ovarian and adrenal vein sampling and monitoring of treatment by peripheral blood sampling. Injection of a depot pure GnRH antagonist produced rapid and long-term complete suppression of ovarian steroidogenesis maintained over 10 months. Hence a depot pure GnRH antagonist can not only rapidly confirm the OHT diagnosis but also induce long-term remission of severe hyperandrogenism without surgery.