Ni Huajing, Schmidli Robert, Savkovic Sasha, Strasser Simone I, Hetherington Julie, Desai Reena, Handelsman David J
Department of Andrology, Concord Hospital, Sydney, Australia.
Department of Endocrinology, Canberra Hospital, Canberra, Australia.
J Endocr Soc. 2021 Nov 8;5(12):bvab167. doi: 10.1210/jendso/bvab167. eCollection 2021 Dec 1.
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 17OHP, 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.
卵巢泡膜细胞增生症（OHT）是指在无卵巢或肾上腺肿瘤的情况下，绝经后出现的严重高雄激素血症，通常采用手术切除治疗。我们报告了一名58岁女性，表现为严重高雄激素血症（血清睾酮15.7 - 31.0 nmol/L，正常女性<1.8 nmol/L），伴有绝经后促性腺激素及男性化表现，但无肾上腺或卵巢病变。通过液相色谱 - 质谱联用（LCMS）对肾上腺和卵巢静脉样本进行多类固醇分析，发现左卵巢静脉存在强烈梯度（17α-羟孕酮、17 - 羟孕酮、17 - 羟孕烯醇酮、雄烯二酮、睾酮、脱氢表雄酮与外周血相比为10至30倍），但在第二次卵巢静脉插管时无法插入右卵巢静脉，未得到相同结果。通过注射长效纯促性腺激素释放激素（GnRH）拮抗剂（80 mg地加瑞克，辉凌制药），快速（<24小时）且完全抑制卵巢类固醇生成以及血清黄体生成素和卵泡刺激素，持续至少8周，男性化表现减轻，同时通过雌二醇贴片改善注射部位反应、潮红和阴道点滴出血，从而确诊OHT。尽管在第278天时绝经后促性腺激素恢复，但首次给药后313天时血清睾酮仍被抑制。这说明了多类固醇LCMS分析在通过卵巢和肾上腺静脉采样确诊OHT以及通过外周血采样监测治疗中的应用。注射长效纯GnRH拮抗剂可快速且长期完全抑制卵巢类固醇生成，并维持超过10个月。因此，长效纯GnRH拮抗剂不仅可以快速确诊OHT，还能在不进行手术的情况下诱导严重高雄激素血症的长期缓解。
