Primary testicular dysfunction is a major contributor to abnormal pubertal development in males with Prader-Willi...

Recent studies challenge the assumption that hypogonadism in Prader-Willi syndrome (PWS) is due only to hypothalamic dysfunction.

The aims of the study were to characterize sexual development and reproductive hormones in PWS males and investigate the etiology of hypogonadism.

Physical examination and blood sampling were performed on 37 PWS males, ages 4 months to 32 yr.

All had a history of undescended testes; age at orchiopexy ranged from 2 months to 6 yr. Pubertal signs were variable, but none achieved full genital development. Anti-Mullerian hormone (AMH) levels in PWS boys were near the lower limits of normal, decreasing from 44.4 +/- 17.8 ng/ml (mean +/- sd) in young children to 5.9 +/- 4.7 ng/ml in adolescents, similar to normal males. In contrast, inhibin B was consistently low (27.1 +/- 36.1 pg/ml) or undetectable in all age groups. In adult males, FSH levels were high (20.3 +/- 18.3 IU/liter), LH levels were normal (4.2 +/- 4.3 IU/liter), and testosterone levels were low (1.87 +/- 1.17 ng/ml). Only two adults had severe hypogonadotropic hypogonadism with undetectable levels of LH and FSH and high AMH levels (34.9 and 36.7 ng/ml), unlike the other nine adults with AMH levels 2.6 +/- 2.1 ng/ml. Androstenedione (1.06 +/- 0.30 ng/ml) and DHEAS (281.1 +/- 143.6 microg/dl) in adult PWS were normal.

Pubertal development in PWS is characterized by normal adrenarche, variable hypothalamic dysfunction, and hypogonadism due to a unique testicular defect. Primary testicular dysfunction is a major component of hypogonadism in PWS.