Filicori M, Flamigni C, Cognigni G, Dellai P, Arnone R, Falbo A, Capelli M
Reproductive Medicine Unit, University of Bologna, Italy.
J Clin Endocrinol Metab. 1993 Jul;77(1):130-3. doi: 10.1210/jcem.77.1.8325935.
Different depot GnRH analogs (GnRH-A) are currently used for the reversible suppression of the pituitary-ovarian axis in several reproductive and neoplastic disorders in women. In spite of anecdotal reports of incomplete suppression by some depot GnRH-A, this issue has never been systematically investigated in adult women. Thus, we elected to study 40 normally cycling women with male-related infertility or benign reproductive disorders; each group of 10 subjects received a different GnRH-A for 3 months: buserelin (group B; 300 micrograms, sc, every 12 h, as a control), goserelin (group G; 3.6 mg, sc, every 28 days), leuprorelin (group L; 3.75 mg, im, every 28 days), and triptorelin (group T; 3.75 mg, im, every 28 days). Depot GnRH-A was administered by one of the investigators. GnRH tests (100 micrograms, iv) were performed before treatment (cycle day 7; test A) and on treatment days 57 (i.e. 1 day after the third depot GnRH-A; test B) and 84 (i.e. 28 days after the third depot GnRH-A; test C). Immunoreactive (i) LH levels were measured with an ultrasensitive immunochemiluminometric assay. Profound suppression of the iLH response to the GnRH test occurred in all subjects during treatment. Conversely, FSH levels in the third month of treatment tended to be higher in the depot GnRH-A groups than in group B, and this difference achieved statistical significance (P < 0.05) in groups G and L during test C. In GnRH test B, while the mean estradiol (E2) level was less than 75 pmol/L (< 20 pg/mL) in all group B subjects, individual E2 levels were greater than 75 pmol/L in five patients receiving depot GnRH-A (two in group G, one in L, and two in T). Finally, individual E2 levels during test C were greater than 75 pmol/L in only two patients of group G, who also reported vaginal spotting. Thus, we conclude that in adult women, 1) iLH was profoundly suppressed in the third month of administration of all GnRH-A tested; 2) FSH suppression with depot GnRH-A was less marked than that with high-dose short-acting sc buserelin; and 3) signs of an incomplete block of ovarian function can be present in the third month of depot GnRH-A administration, particularly when goserelin is employed.
目前，不同的长效促性腺激素释放激素类似物（GnRH-A）被用于可逆性抑制女性垂体-卵巢轴，以治疗多种生殖系统疾病和肿瘤疾病。尽管有一些关于某些长效GnRH-A抑制不完全的传闻报道，但该问题从未在成年女性中进行过系统研究。因此，我们选择研究40名月经周期正常、患有男性相关不孕症或良性生殖系统疾病的女性；每组10名受试者接受不同的GnRH-A治疗3个月：布舍瑞林（B组；300微克，皮下注射，每12小时一次，作为对照）、戈舍瑞林（G组；3.6毫克，皮下注射，每28天一次）、亮丙瑞林（L组；3.75毫克，肌肉注射，每28天一次）和曲普瑞林（T组；3.75毫克，肌肉注射，每28天一次）。长效GnRH-A由一名研究人员进行给药。在治疗前（月经周期第7天；测试A）以及治疗第57天（即第三次长效GnRH-A注射后1天；测试B）和第84天（即第三次长效GnRH-A注射后28天；测试C）进行GnRH试验（静脉注射100微克）。采用超灵敏免疫化学发光分析法测定免疫反应性（i）促黄体生成素（LH）水平。在治疗期间，所有受试者的iLH对GnRH试验的反应均受到显著抑制。相反，在治疗的第三个月，长效GnRH-A组的促卵泡生成素（FSH）水平往往高于B组，在测试C期间，G组和L组的这种差异具有统计学意义（P<0.05）。在GnRH试验B中，B组所有受试者的平均雌二醇（E2）水平均低于75皮摩尔/升（<20皮克/毫升），而在接受长效GnRH-A治疗的5名患者中，其个体E2水平高于75皮摩尔/升（G组2名、L组1名、T组2名）。最后，在测试C期间，仅G组的2名患者个体E2水平高于75皮摩尔/升，这两名患者还出现了阴道点滴出血。因此，我们得出结论，在成年女性中，1）在所有测试的GnRH-A给药的第三个月，iLH受到显著抑制；2）长效GnRH-A对FSH的抑制作用不如高剂量短效皮下注射布舍瑞林明显；3）在长效GnRH-A给药的第三个月，可能会出现卵巢功能未完全阻断的迹象，尤其是使用戈舍瑞林时。
