Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

Survivorship issues are an area of crucial importance to be addressed as early as possible by all health care providers dealing with cancer patients. In women diagnosed during their reproductive years, the possible occurrence of chemotherapy-induced premature ovarian insufficiency (POI) is of particular concern being associated with important menopause-related symptoms, psychosocial issues as well as infertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy has been studied to reduce the gonadotoxic impact of chemotherapy thus diminishing the chance of developing POI. Despite more than 30 years of research in both preclinical and clinical settings, the performance of this strategy has remained highly debated until recently. In particular, the potential mechanisms of action for the protective effects of GnRHa during chemotherapy are still not clearly identified. Nevertheless, important novel research efforts in the field have better elucidated the role of this option that is now endorsed for clinical use by several guidelines. This manuscript aims at providing an extensive overview of the literature on the use of temporary ovarian suppression with GnRHa during chemotherapy in cancer patients by addressing its biological rationale, the available preclinical and clinical evidence as well as the still existing grey zones in this field that future research efforts should address.