Ana S Cvetanovic, Matteo Lambertini, Kevin Punie, Gorana G Matovina Brko, Nikola D Zivkovic, Maja J Popovic, Marijana M Milovic Kovacevic, Lazar S Popovic
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Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. 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引用次数: 0
摘要
肿瘤不孕症是一个极其重要的话题,由于越来越多的证据表明,保留生育力并不会影响癌症患者的治疗效果,反而会大大有助于保护患者的生活质量,因此对这一话题的讨论也越来越多。化疗的影响从微乎其微到卵巢完全萎缩不等。关于单克隆抗体和靶向疗法对卵巢和生育能力的影响,目前只有有限的数据。通过在化疗期间使用促性腺激素释放激素激动剂(GnRHa)来暂时抑制卵巢功能,可降低化疗的性腺毒性效应,从而减少卵巢早衰(POI)的发生几率。目前,化疗期间同时服用 GnRH 类似物是唯一公认的保留卵巢功能的药物治疗方法。值得注意的是,大多数关于化疗期间使用促黄体生成素释放激素激动剂预防卵巢功能早衰的随机研究都是针对乳腺癌妇女进行的,而针对血液系统恶性肿瘤患者的研究则少得多。此外,大多数关于乳腺癌的随机对照试验都显示,无论激素受体状态如何,治疗引起的 POI 风险都会降低。此外,对血液恶性肿瘤的研究也得出了阴性结果;然而,由于存在许多局限性,必须谨慎解读这些研究结果。美国临床肿瘤学会(American Society of Clinical Oncology)和《ESMO 临床实践指南》(ESMO Clinical Practice Guidelines)建议将精子、卵细胞和胚胎冷冻保存作为标准实践,只有在经证实的生育力保存方法不可行时才向患者提供 GnRHa。在这篇手稿中,我们通过临床前和临床数据,对癌症患者化疗期间使用 GnRHa 抑制卵巢的应用进行了全面的文献综述,并对该领域未来的研究前景进行了展望。
Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.
Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.
期刊介绍:
Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.