Pascale M M, Pugeat M, Roberts M, Rousset H, Déchaud H, Dutrieux-Berger N, Tourniaire J
Hospices Civils de Lyon, France.
Clin Endocrinol (Oxf). 1994 Nov;41(5):571-6. doi: 10.1111/j.1365-2265.1994.tb01820.x.
Recent studies have suggested that androgen secretion by ovarian virilizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion in women with such tumours.
A single i.m. injection of D-Trp-6-GnRH (GnRHa), 3.75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroepiandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non-classical 21-hydroxylase deficiency were screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 50 mg twice daily for 3 weeks, starting 1 week before GnRHa administration.
Testosterone, androstenedione (A), DHEAS, 17-hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa.
In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning, exploratory laparotomy was undertaken. A Sertoli-Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hilus cell tumour and two hyperthecoses in the four post-menopausal patients. After bilateral ovariectomy and hysterectomy in the post-menopausal woman and after unilateral ovariectomy in the premenopausal women, androgen levels were normalized.
In virilized women, the findings of increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarian androgen-secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonadotrophin stimulation.
近期研究表明，卵巢男性化肿瘤分泌雄激素可能依赖促性腺激素。本研究旨在探讨给予促性腺激素释放激素（GnRH）激动剂对患有此类肿瘤女性雄激素分泌的抑制作用。
对5例因男性化临床症状前来就诊、血浆睾酮（T）水平高于7 nmol/l但硫酸脱氢表雄酮（DHEAS）水平正常的非亲属患者，单次肌内注射3.75 mg的D-色氨酸-6-促性腺激素释放激素（GnRHa）。通过地塞米松抑制试验、促肾上腺皮质激素（ACTH）刺激试验及肾上腺CT扫描筛查肾上腺肿瘤或非经典21-羟化酶缺乏症，所有患者均排除此类疾病。1例绝经前患者在GnRHa给药前1周开始，每日2次服用50 mg醋酸环丙孕酮，共3周。
通过对GnRHa给药前及给药3周后采集的血样进行放射免疫分析，测定血浆睾酮、雄烯二酮（A）、DHEAS、17-羟孕酮（OHP）、促黄体生成素（LH）和促卵泡生成素（FSH）的浓度。
每位患者中，GnRHa均抑制了促性腺激素水平，并将T和A降至正常对照女性的范围。鉴于这些结果，且由于盆腔超声和CT扫描无法准确定位卵巢雄激素分泌肿瘤，遂进行了剖腹探查术。绝经前患者发现了支持细胞-间质细胞瘤，4例绝经后患者分别发现了颗粒细胞瘤、门细胞瘤和2例卵泡膜细胞增生症。绝经后女性进行双侧卵巢切除术和子宫切除术后，以及绝经前女性进行单侧卵巢切除术后，雄激素水平恢复正常。
在男性化女性中，血清睾酮升高而促性腺激素水平正常，且GnRHa抑制促性腺激素可使睾酮水平恢复正常，这表明各种卵巢雄激素分泌肿瘤以及卵泡膜细胞增生症并非自主性的，而是明显依赖于持续的促性腺激素刺激。
