Pre-testicular causes of male infertility

Doctors group the causes of male infertility by where the problem lies. Pre-testicular causes sit before the testes, in the hormone signals that drive them. Testicular causes lie in the testes themselves, and post-testicular causes lie in the tubes that carry sperm away.

The chain of command runs from the hypothalamus to the pituitary gland (a small gland beneath the brain) and then to the testes. The hypothalamus releases gonadotrophin-releasing hormone (GnRH, the hormone that starts the cascade), so the pituitary sends out LH and FSH. If those signals fall, the testes are under-stimulated rather than primarily damaged, and testosterone and sperm production fall. This is hypogonadotrophic hypogonadism: hypogonadism means the testes make too little testosterone or too few sperm, and hypogonadotrophic means the cause is low LH and FSH.

Hyperprolactinaemia means too much prolactin, a hormone from the pituitary gland that normally stimulates milk production. Certain drugs or prolactin-secreting pituitary tumours can raise it. In men, excess prolactin inhibits the pulsatile (burst-like) release of GnRH, so LH, FSH and testosterone fall.

Kallmann syndrome pairs hypogonadotrophic hypogonadism with anosmia, a reduced or absent sense of smell. The neurons that make GnRH begin in the developing nose and migrate into the brain before birth. In Kallmann syndrome that migration is incomplete, so too little GnRH reaches the pituitary and puberty is delayed or may not happen.

Anabolic steroids supply androgen (male sex hormone) from outside. The brain detects plenty and reduces its own signals by negative feedback (the normal brake that testosterone puts on the hypothalamus and pituitary), so GnRH, LH and FSH fall and the testes are under-stimulated. Pituitary disease can also cut the LH and FSH signal, so testosterone and sperm production fall even though the testes themselves are healthy.