de Ziegler D, Steingold K, Cedars M, Lu J K, Meldrum D R, Judd H L, Chang R J
Department of Obstetrics and Gynecology, University of California School of Medicine, Los Angeles 90024.
J Clin Endocrinol Metab. 1989 Jun;68(6):1111-7. doi: 10.1210/jcem-68-6-1111.
Persistent suppression of gonadotropin and ovarian steroid production can be achieved in women with polycystic ovarian disease (PCO) by daily administration of a long-acting GnRH agonist (GnRHa). This study was designed to determine the patterns of recovery of clinical responses and hormonal secretion after chronic GnRHa administration in women with PCO. Six women with PCO were treated with daily sc injections of [D-His6(imBzl),Pro9-NEt]GnRHa (100 micrograms) for 6 months. Blood samples were obtained at the time of and three times weakly for 90 days after discontinuation of agonist therapy. In five women who did not ovulate, the suppressed serum FSH levels rose to pretreatment values within 10 days. In contrast, a gradual and progressive increase in serum LH (as measured by bioassay and immunoassay) was apparent by day 18. The LH increase coincided with progressive increases in serum estrone (E1), androstenedione, and testosterone. Serum estradiol (E2) began to rise on day 28. All hormones returned to their pretreatment baseline values within the 90-day recovery interval, with the exception of E2. Trend analysis of the slopes of recovery revealed that the incremental secretion patterns of E1, E2, androstenedione, and testosterone differed significantly from that of FSH, but not from those of bioactive or immunoactive LH. Serum progesterone, dehydroepiandrosterone sulfate, and cortisol did not change after withdrawal of GnRHa. One woman ovulated spontaneously on day 52 before which her hormone secretion patterns were indistinguishable from those of the other women. In summary, 1) during recovery after discontinuation of chronic GnRH agonist therapy the patterns of FSH and LH release suggested resumption of endogenous GnRH action on the pituitary with greater release of FSH than LH, a pattern that would be expected in the absence of ovarian steroid influence; 2) the lack of early estrogen production despite the increase in serum FSH concentrations suggests inadequate FSH secretion, abnormal ovarian responsiveness to FSH, or impaired FSH bioactivity; 3) androgen secretion was provoked by the increase in LH secretion; 4) per unit LH measured by bioassay, greater ovarian androgen secretion was stimulated in PCO than ovulatory women; and 5) the likelihood of spontaneous ovulation during recovery was minimal.
通过每日给予长效促性腺激素释放激素激动剂（GnRHa），可使多囊卵巢疾病（PCO）女性的促性腺激素和卵巢甾体激素分泌持续受到抑制。本研究旨在确定PCO女性长期应用GnRHa后临床反应和激素分泌的恢复模式。6例PCO女性每日皮下注射[D-组氨酸6（亚胺苄基），脯氨酸9-乙酯]GnRHa（100微克），共6个月。在停用激动剂治疗时及停药后90天内每周采集3次血样。5例未排卵女性，其被抑制的血清促卵泡激素（FSH）水平在10天内升至治疗前水平。相比之下，到第18天时，血清促黄体生成素（LH，通过生物测定法和免疫测定法测量）呈逐渐进行性升高。LH升高与血清雌酮（E1）、雄烯二酮和睾酮的逐渐升高同时出现。血清雌二醇（E2）在第28天开始升高。除E2外，所有激素在90天的恢复间隔内均恢复至治疗前基线水平。对恢复斜率的趋势分析显示，E1、E2、雄烯二酮和睾酮的递增分泌模式与FSH显著不同，但与生物活性或免疫活性LH的模式无差异。停用GnRHa后，血清孕酮、硫酸脱氢表雄酮和皮质醇无变化。1例女性在第52天自发排卵，在此之前其激素分泌模式与其他女性无法区分。总之，1）在停用慢性GnRHa治疗后的恢复过程中，FSH和LH的释放模式提示内源性GnRH对垂体的作用恢复，FSH释放量大于LH，这是在无卵巢甾体激素影响时预期会出现的模式；2）尽管血清FSH浓度升高，但早期雌激素分泌缺乏提示FSH分泌不足、卵巢对FSH反应异常或FSH生物活性受损；3）LH分泌增加引发雄激素分泌；4）以生物测定法测量，每单位LH刺激PCO女性的卵巢雄激素分泌量多于排卵女性；5）恢复过程中自发排卵的可能性极小。
