Blumenfeld Z
Reproductive Endocrinology, Department of Obstetrics and Gynecology, Rambam Medical Centre, Technion, Faculty of Medicine, Haifa, Israel.
Minerva Endocrinol. 2007 Mar;32(1):23-34.
Decreased secretion of pituitary gonadotropins, by decreasing gonadal function, may possibly protect against the sterilizing effects of chemotherapy. Although previous claims that primordial germ cells fare better than germ cells that are part of an active cell cycle have been made, this hypothesis has not been seriously tested clinically until recently. The only prospective randomized study performed to date found that gonadotropin releasing hormone agonistic analogue (GnRH-a) protected the ovary against cyclophosphamide-induced damage in Rhesus monkeys by significantly decreasing the number of follicles lost during the chemotherapeutic insult. We have administered a monthly depot i.m. injection of GnRH-a to more than 125 young patients exposed to gonadotoxic chemotherapy for malignant or nonmalignant diseases, after informed consent, starting before chemotherapy for up to 6 months, in parallel and until the end of chemotherapeutic treatment. Less than 7% developed irreversible hypergonadotropic amenorrhea. The remainder (>93%) resumed cyclic ovarian function, of which 32 patients spontaneously conceived 46 times. These patients were compared to a control group of over 125 patients of comparable age (15-40 years), who were similarly treated with chemotherapy but without the GnRH-a adjuvant. The 2 groups were similar in age, diagnosis, and the ratio of HD to non-Hodgkin lymphoma patients. The 2 groups also received similar doses of radiotherapy exposure and the proportion of radio-plus chemotherapy-treated patients was similar. The cumulative doses of each chemotherapeutic agent and the mean or median radiotherapy exposure did not differ between the groups. Our and others' results support the effectiveness of GnRH-a administration also to patients receiving cyclophosphamide pulses for systemic lupus erythematosus and other autoimmune diseases. Possible explanations for the beneficial effect of the GnRH-a on minimizing the gonadotoxic effect of chemotherapy are discussed. Multi-center prospective, randomized studies are awaited to substantiate the in vivo effect of GnRH-a as an unequivocal means of minimizing follicular apoptosis.
垂体促性腺激素分泌减少，通过降低性腺功能，可能有助于预防化疗的绝育作用。尽管此前有人声称原始生殖细胞比处于活跃细胞周期的生殖细胞表现更好，但这一假设直到最近才得到临床的认真检验。迄今为止进行的唯一一项前瞻性随机研究发现，促性腺激素释放激素激动剂类似物（GnRH-a）通过显著减少化疗损伤期间丢失的卵泡数量，保护恒河猴卵巢免受环磷酰胺诱导的损伤。我们在获得知情同意后，于化疗前开始，每月皮下注射一次GnRH-a，共治疗了125多名因恶性或非恶性疾病接受性腺毒性化疗的年轻患者，持续6个月，直至化疗结束。不到7%的患者出现不可逆的高促性腺激素性闭经。其余患者（>93%）恢复了周期性卵巢功能，其中32名患者自然受孕46次。将这些患者与125多名年龄相仿（15 - 40岁）的对照组患者进行比较，对照组患者同样接受化疗，但未使用GnRH-a辅助治疗。两组在年龄、诊断以及霍奇金淋巴瘤与非霍奇金淋巴瘤患者的比例方面相似。两组接受的放疗剂量也相似，接受放疗加化疗的患者比例也相似。各化疗药物的累积剂量以及放疗平均或中位数暴露量在两组之间无差异。我们和其他人的结果支持GnRH-a对接受环磷酰胺脉冲治疗的系统性红斑狼疮和其他自身免疫性疾病患者也有效。文中讨论了GnRH-a在最小化化疗性腺毒性作用方面有益效果的可能解释。期待多中心前瞻性随机研究来证实GnRH-a作为最小化卵泡凋亡明确手段的体内效果。
