Context: The pathophysiology of hypogonadism in boys with Prader-Willi Syndrome( PWS) remains uncertain. Several reports described hypogonadotropic hypogonadism, some reported primary gonadal failure, and others a combination of both. Objectives: The aim of the study was to evaluate gonadal function over time in boys with PWS and the effect of GH treatment. Measurements: We made a longitudinal assessment of inhibin B, FSH, testosterone, and LH levels in prepubertal boys and male adolescents with PWS. Patients and Methods: We studied 68 boys participating in the Dutch PWS Cohort study. Serum inhibin B, FSH, LH, and testosterone levels were compared with reference values. Results: Boys with PWS had normal inhibin B levels between 6 months and 10 yr of age, but after onset of puberty, inhibin B levels declined to less than the 5th percentile, and FSH levels increased to more than the 95th percentile. Two years after the onset of puberty and in young adults, inhibin B levels were significantly lower (P = 0.008 and P < 0.0001), and FSH levels were significantly higher (P = 0.034 and P < 0.0001) than at onset of puberty. Testosterone levels increased but remained below the 5th percentile, and LH levels increased but not above the 95th percentile. Age showed a significant correlation with inhibin B levels (r = -0.31; P = 0.001) after 9 yr of age. GH treatment had no significant effect on inhibin B levels. Conclusion: Our study indicates that the majority of male patients with PWS have primary testicular failure, which becomes apparent after onset of puberty. Hypogonadotropic hypogonadism did not appear to be the main reason of hypogonadism in most boys. Copyright,
Journal of Clinical Endocrinology and Metabolism
Department of Pediatrics

Siemensma, E., De Lind Van Wijngaarden, R., Otten, B., de Jong, F., & Hokken-Koelega, A. (2012). Testicular failure in boys with Prader-Willi syndrome: Longitudinal studies of reproductive hormones. Journal of Clinical Endocrinology and Metabolism, 97(3). doi:10.1210/jc.2011-1954