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Causes of primary hypogonadism in males

INTRODUCTION

Hypogonadism in a man refers to a decrease in one or both of the two major functions of the testes: sperm production and testosterone production. These abnormalities usually result from disease of the testes (primary hypogonadism) or disease of the pituitary or hypothalamus (secondary hypogonadism). In occasional cases, however, a defect in the ability to respond to testosterone is the cause of hypogonadism. (See "Diagnosis and treatment of disorders of the androgen receptor" and "Steroid 5-alpha-reductase 2 deficiency".)

The distinction between primary and secondary hypogonadism is made by measurement of the serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH):

  • The patient has primary hypogonadism if the serum testosterone concentration and the sperm count are below normal and the serum LH and FSH concentrations are above normal.
  • The patient has secondary hypogonadism if the serum testosterone concentration and the sperm count are subnormal and the serum LH and FSH concentrations are normal or reduced.

Primary hypogonadism differs from secondary hypogonadism in two ways:

  • Primary hypogonadism is more likely to be associated with a decrease in sperm production than in testosterone production. Although many testicular diseases damage both the seminiferous tubules and the Leydig cells, they usually damage the seminiferous tubules to a greater degree. As a consequence, the sperm count may be low, and the serum FSH concentration normal or high, yet the serum testosterone concentration remains normal (see above). In contrast, in secondary hypogonadism, there is a proportionate reduction in testosterone and sperm production.
  • Primary hypogonadism is more likely to be associated with gynecomastia, presumably due to the stimulatory effect of the supranormal serum FSH and LH concentrations on testicular aromatase activity. This results in increased conversion of testosterone to estradiol and enhanced testicular secretion of estradiol relative to testosterone.
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