Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs.
化疗是癌症的主要治疗手段之一。然而，其使用可能引发多种副作用，包括对女性患者的生殖毒性作用。卵巢储备功能抑制与雌激素缺乏会导致癌症患者生活质量下降，并常引发不孕及过早绝经。传统烷化剂类细胞抑制药物在此方面毒性尤为显著，它们可导致卵巢卵泡及其内含细胞DNA损伤，同时可能诱发氧化应激或干扰多种信号通路。通过体外实验、动物模型及少量临床研究，学界已探讨了多种药物在传统化疗过程中对卵巢储备功能的保护作用。本文综述了特定激素（抗苗勒管激素、胃饥饿素、黄体生成素、褪黑素）、调控凋亡通路活性与基因表达因子（C1P、S1P、微小RNA），以及若干天然化合物（槲皮素、雷帕霉素、白藜芦醇）与合成制剂（硼替佐米、右雷佐生、戈舍瑞林、促性腺激素释放激素类似物、伊马替尼、二甲双胍、他莫昔芬）在预防常用细胞抑制药物所致生殖毒性方面的潜在保护效应。该研究方向为保护及改善癌症患者卵巢储备功能提供了前景广阔的策略，但仍需通过严谨设计的临床试验，以明确评估这些药物对接受卵巢毒性抗癌药物治疗女性患者激素功能及生育能力的改善作用。
Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms
肿瘤(癌症)患者之家