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Hormonal Suppression for Fertility Preservation in Males and Females

M Meistrich, Dept. Experimental Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, United States
G Shetty, Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, 77030, United States

Correspondence: Gunapala Shetty, Email: sgunapal{at}mdanderson.org

Abstract

Methods to restore fertility of men and women sterilized by medical treatments and environmental toxicant exposures are under investigation. Rendering spermatogenesis and ovarian follicular development kinetically quiescent by suppression of gonadotropins has been proposed to protect them from damage by cytotoxic therapy. Although the method fails to protect the fertility of male mice and monkeys, gonadotropin and testosterone suppression in rats before or after cytotoxic therapy does enhance the recovery of spermatogenesis. However the mechanism involves not the induction of quiescence but rather the reversal, by suppression of testosterone, of a block in differentiation of surviving spermatogonia caused by damage to the somatic environment. In men, only one of eight clinical trials was successful in protecting or restoring spermatogenesis after cytotoxic therapy. In females, protection of primordial follicles in several species from damage from cytotoxic agents using GnRH analogues has been claimed; however only two studies in mice appear convincing. The protection cannot involve induction of quiescence in the already dormant primordial follicle but may involve direct effects of GnRH analogues or indirect effects of gonadotropin suppression on the whole ovary. Although numerous studies in female patients undergoing chemotherapy indicate that GnRH analogues might be protective of ovarian function, none of the studies showing protection were prospective randomized clinical trials and thus are inconclusive. Considering interspecies differences and similarities in the gonadal sensitivity to cytotoxic agents and hormones, mechanistic studies are needed to identify the specific beneficial effects of hormonal suppression in select animal models that may be applicable to human.