Use of gnrh agonists for prevention of chemotherapy-induced gonadotoxicity
The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial [1, 2]. Ovarian suppression to prevent oocyte loss during chemotherapy was proposed based upon the observation that non-cycling cells appear more resistant to cytotoxicity and that pre-pubertal girls resume menstruation after cancer treatment more often then post-pubertal girls [3]. Studies in rats and primates provide some support for the use of GnRHa for ovarian protection [4, 5]. Studies in humans that suggest benefit, however, have been predominantly observational with historic controls. The efficacy of GnRHa to protect the ovary during chemotherapy has yet to be proven in adequate randomized control trials; however, use of this treatment strategy with the goal of preventing premature ovarian failure is becoming more common. The 2006 American Society of Clinical Oncologists consensus statement on fertility preservation recommendations for cancer patients emphasized the need for safety and effectiveness data and recommended that patients considering the option of GnRHa enroll in clinical trials [6]. Several randomized trials are in progress, both for patients utilizing gonadotoxic agents for cancer and for rheumatologic conditions; however, the results of these trials have yet to be published. This chapter summarizes the current evidence and debate for and against the use of GnRHa during chemotherapy. Natural GnRH and ovarian steroidogenesis Natural human GnRH is released from the hypothalamus in a pulsatile fashion to stimulate gonadotropin release from the pituitary gland.
