Steingold K, De Ziegler D, Cedars M, Meldrum D R, Lu J K, Judd H L, Chang R J
Department of Obstetrics and Gynecology, University of California School of Medicine, Los Angeles 90024.
J Clin Endocrinol Metab. 1987 Oct;65(4):773-8. doi: 10.1210/jcem-65-4-773.
Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.
此前，我们报道，对多囊卵巢疾病（PCO）患者短期给予高效促性腺激素释放激素激动剂（GnRHa）1个月，可完全抑制卵巢类固醇生成，而对肾上腺类固醇生成无明显影响。这项新研究旨在评估长期给予GnRHa对PCO患者激素分泌模式和临床反应的影响。8例PCO患者和10例患有子宫内膜异位症的排卵正常女性，每天皮下注射[D-组氨酸6-（亚胺苄基）]、脯氨酸9-乙酯]GnRH（GnRHa；100微克），持续6个月。将她们的结果与8例接受双侧卵巢切除术的女性的激素值进行比较。对GnRHa的反应是，PCO患者和排卵正常女性在1个月时血清LH升高，之后逐渐降至基线。在两组中，整个治疗期间FSH分泌均受到抑制。血清雌二醇、雌酮、孕酮、17-羟孕酮、雄烯二酮和睾酮水平在1个月时显著下降至卵巢切除术后女性的水平，此后一直保持较低水平。相比之下，血清孕烯醇酮和17-羟孕烯醇酮受到部分抑制，脱氢表雄酮、硫酸脱氢表雄酮和皮质醇水平未发生变化。临床上，3例PCO患者的增生性子宫内膜组织学转变为非活动模式，另外2例PCO患者中，1例增生性子宫内膜变为非活动，另1例未发生变化。所有排卵正常女性的增生性子宫内膜组织学均发生消退。在GnRHa给药的第一个月，所有研究对象均出现阴道出血，之后除1例PCO患者外，所有患者均闭经。所有排卵正常女性和8例PCO患者中的4例出现潮热。所有PCO患者均表示皮肤油腻感主观减轻，5例患者毛发生长减少。我们得出结论，对于绝经前女性：1）长期给予GnRHa可导致卵巢类固醇分泌明显完全持续抑制；2）肾上腺类固醇分泌不受直接或间接影响；3）其应用可能有助于治疗PCO女性的子宫内膜增生和卵巢雄激素过多。
