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GnRH-a对年轻女性生育力和卵巢功能的保护作用以及化疗所致性腺毒性的最小化

Preservation of fertility and ovarian function and minimization of chemotherapy-induced gonadotoxicity in young women by GnRH-a.

作者信息

Blumenfeld Z, Eckman A

机构信息

Department of Obstetrics and Gynecology, Technion-Faculty of Medicine, Rambam Medical Center, Haifa 31096, Israel.

出版信息

J Natl Cancer Inst Monogr. 2005(34):40-3. doi: 10.1093/jncimonographs/lgi015.

Abstract

Improved long-term survival in young women with lymphoma and leukemia has increased attention to the preservation of their future fertility. We have attempted to minimize the gonadotoxic effect of chemotherapy by cotreatment with a GnRH agonist analog, inducing a temporary prepubertal milieu. Our prospective clinical case series includes 92 women with lymphoma, aged 15-40 years, 10 with leukemia and 18 undergoing chemotherapeutic treatments for nonmalignant autoimmune diseases. Depot D-TRP6-GnRH-a was injected monthly from before the initiation of chemotherapy until its conclusion, for up to 6 months. We used 82 similarly treated patients with lymphoma not given GnRH-a as a comparison group. All but five of the surviving evaluable patients with GnRH-a/chemotherapy cotreatment resumed spontaneous ovulation and menses or conceived, whereas 53% of the patients in the comparison group experienced premature ovarian failure (P<.01). Mechanisms to explain this apparent chemoprotective effect are discussed, and the work of other investigators in this area is reviewed.

摘要

淋巴瘤和白血病年轻女性长期生存率的提高,使得人们愈发关注保留她们未来生育能力的问题。我们试图通过与促性腺激素释放激素(GnRH)激动剂类似物联合治疗来尽量减少化疗对性腺的毒性作用,从而诱导出一个暂时的青春期前环境。我们的前瞻性临床病例系列包括92名年龄在15至40岁之间的淋巴瘤女性、10名白血病女性以及18名因非恶性自身免疫性疾病接受化疗的女性。从化疗开始前直至结束,每月注射长效D-色氨酸6-促性腺激素释放激素类似物(Depot D-TRP6-GnRH-a),最长持续6个月。我们将82名同样接受治疗但未使用GnRH-a的淋巴瘤患者作为对照组。在接受GnRH-a/化疗联合治疗且存活的可评估患者中,除5人外,其余均恢复了自然排卵和月经或成功受孕,而对照组中53%的患者出现了卵巢早衰(P<0.01)。本文讨论了解释这种明显化学保护作用的机制,并回顾了该领域其他研究者的工作。

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