Classification and Epidemiology of Hypogonadism

Abstract

Male hypogonadism (HG) is the functional incompetence of the male gonads to produce male sex hormones and to carry out spermatogenesis. The definition of HG relies on the measurement of serum total testosterone (tT) concentrations. A recent consensus has proposed tT concentrations of about 12 nmol/L (346 ng/dL) as the lower limit of normal and 8 nmol/L (231 ng/dL) as the unequivocally low value that deserves replacement therapy. For tT values between these limits, calculation of free T (fT) may be helpful.

The most common classification is based on the topographic localization of the cause of HG at different levels of the hypothalamic-pituitary-testicular (HPT) axis. Accordingly, the cause of HG may be of hypothalamic, pituitary, or testicular origin. HG of hypothalamic or pituitary origin is referred to as “secondary,” “central,” or hypogonadotropic HG, whereas HG induced by testicular disorders is referred to as “primary” or hypergonadotropic. Certain disorders may impair the whole HPT axis and result in combined HG. Moreover, HG may be classified depending on the testicular compartment being affected, as selective, affecting either Leydig cell function or spermatogenesis, or total, affecting both. Alternatively, HG is classified according to the age at onset, as the clinical sequelae of HG can be variable in different ages. HG at early fetal life usually results in disorders of sex development, whereas onset at the end of fetal life results in mild disorders, as maldescended testes and micropenis. HG in childhood may remain undetected, until delayed puberty is suspected with persistence of sexual infantilism and appearance of eunuchoidal proportions. HG in adulthood may also be insidious, since nonspecific symptoms usually precede sexual symptoms. Finally, late-onset HG (LOH) observed among several aging men is characterized by partial T deficiency and gradual onset.

The prevalence of HG in the community is variable, as the studies that contain such data have used different age ranges or T thresholds, and is estimated to be around 6–12% among 30–70-year-old men, with a progressive increase with age. The majority of cases concerns LOH, whereas overt HG due to organic disorders is much less common. The incidence of congenital hypogonadotropic HG is 1:10,000, while that of Klinefelter syndrome, the most common chromosomal abnormality in humans, is 1 in 650 newborn males.