Many medications cause alterations in all categories of male infertility. Cimetidine, now an over-the-counter heartburn medication, suppresses the hypothalamic-pituitary-gonadal (HPG) axis in a reversible manner. Genitourinary infections in the male are an uncommon but potentially treatable source of infertility. Chlamydia trachomatis has long been studied as a putative disrupter of male fertility. Clomiphene citrate has been used since the early 1990s to stimulate spermatogenesis in the man with nonobstructive azoospermia. Kallmann syndrome is a rare subset of hypogonadotropic hypogonadism (HH) associated with other midline defects including anosmia. Another endocrine disorder, hyperprolactinemia, is also responsible for male infertility. Prolactin inhibits luteinizing hormone (LH) action on Leydig cells. Although the incidence of a prolactin-secreting pituitary adenoma is low, it is the most common functional pituitary tumor. Macroadenomas have warranted a referral to a neurosurgeon for transphenoidal or, more recently, endoscopic removal.

This chapter focuses on the genetic basis of male infertility. The male specific Y (MSY) is a chromosomal material that bridges the two polar pseudoautosomal regions and is unique in the human genome. A karyotype and Y-chromosomal microdeletion assay should be obtained as complementary tests in all non-obstructive azoospermia (NOA) and severely oligospermic men prior to intracytoplasmic sperm injection (ICSI) and the use of testicular sperm. Prognosis and planning are optimized with any informative result. Steroidogenic acute regulatory (StAR) protein is the rate-limiting step for androgen biosynthesis in particular and all steroids in general. The hypothalamic-pituitary-gonadal (HPG) axis controls human sexual maturation and spermatogenesis. The hypothalamus secretes gonadotropin- releasing hormone (GnRH) which regulates the production of Folliclestimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary gonadotropes. Kallmann syndrome results from the failure of the GnRH-releasing neurons to migrate to the olfactory lobe during development.