Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

Simple Summary: Though chemotherapy is generally known to be effective in the fight against cancer, its application is associated with a number of side effects, including toxic impacts on the ovaries. The most ovotoxic cytostatic chemotherapeutics are the classical alkylating compounds, particularly cyclophosphamide. Thus, it is of utmost importance to find effective means to protect ovaries against the negative influence of chemotherapeutic agents. This review paper presents the results of the current research work on the hitherto proposed agents potentially protecting the functions and state of ovaries exposed to chemotherapy. A large body of promising results have been reported, but as presented, it is necessary to undertake thorough and comprehensive studies aimed at providing an explicit evaluation of the efficacy of selected ovoprotecting agents and their possible clinical use in the future. Abstract: 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.