Effects of chemotherapy and radiotherapy on spermatogenesis in humans

Treatment of cancer with chemo- or radiotherapy causes reduction of sperm counts often to azoospermic levels that may persist for several years or be permanent. The time course of declines in sperm count can be predicted by the sensitivity of germ cells, with differentiating spermatogonia being most sensitive, and the known kinetics of recovery. Recovery from oligo- or azoospermia is more variable and depends on whether there is killing of stem cells and alteration of the somatic environment that normally supports differentiation of stem cells. Of the cytotoxic therapeutic agents, radiation and most alkylating drugs are the most potent at producing long-term azoospermia. Most of the newer biologic targeted therapies, except those used to target radioisotopes or toxins to cells, seem to have only modest effects, mostly on the endocrine aspects of the male reproductive system; however, their effects when used in combination with cytotoxic agents have not been well studied.