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This chapter reviews the empiric therapies available today for male infertility and discusses their mode of action. It reviews published literature on outcomes available and analyzes the evidence for use and dosing recommendations. With the exception of low-dose vitamin supplementation and aromatase inhibitors, empiric therapy is seldom recommended in the treatment of the infertile male. Gonadotropin-releasing hormone (GnRH) stimulates the synthesis and release of the gonadotropic hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), in the anterior pituitary. Treatment of hypogonadotropic hypogonadism with exogenous gonadotropins or GnRH has produced good results compared with treatment of other male infertility problems. Exogenous testosterone therapy can produce azoospermia or severe oligospermia through the inhibition of gonadotropin secretion. Glutathione therapy has been used in various pathologic conditions in which reactive oxygen species are thought to play a pathogenic role. Administration of high-dose antioxidants has a potential beneficial effect on male fertility.