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This chapter discusses the current knowledge of hormonal suppression as a means to preserve or restore fertility in males. The seminiferous tubules contain the germ cells, which consist of stem and differentiating spermatogonia, spermatocytes, spermatids and sperm and the sertoli cells, which support and regulate germ cell differentiation. The eventual recovery of sperm production depends on the survival of the spermatogonial stem cells and their ability to differentiate after exposure to cytotoxic agents. Several studies support the conclusion that gonadotropin suppression does not protect spermatogenesis in mice from damage. Seven clinical trials have been performed in attempts to demonstrate protection of spermatogenesis in humans by hormone suppression treatment before and during cytotoxic therapy, but six indicated no protection. One contribution to the difference in the stimulation of recovery by hormone suppression after cytotoxic treatment may be the interspecies differences in the block in differentiation of spermatogonia.