Primary ovarian dysfunction contributes to the hypogonadism in women with Prader-Willi Syndrome.

Background/aims: To investigate the etiology of hypogonadism in women with Prader-Willi Syndrome (PWS).

Methods: Ten women aged 23 +/- 5.5 years with PWS and 10 age- and BMI-matched controls were included. Blood samples were drawn and abdominal ultrasounds were performed on days 2-4 of spontaneous cycles or at random from amenorrheic women. Anti-Mullerian hormone (AMH), inhibin B (INB), gonadotropins, sex steroids, TSH, prolactin, ovarian volume and antral follicle count (AFC) in PWS women were compared with results from controls and the reference ranges.

Results: Compared to controls, PWS women had lower INB (mean +/- SD = 17.6 +/- 12.8 pg/ml vs. 110.6 +/- 54.5; p = 0.0002) and AMH levels (1.18 +/- 0.86 ng/ml vs. 3.53 +/- 2.42; p = 0.01). INB levels were exceptionally low in all PWS women, but individual AMH levels overlapped with the levels in the controls. Ovarian volume (mean +/- SD = 3.7 +/- 2.3 ml vs. 30.5 +/- 28.8; p = 0.03) and AFC (6.4 +/- 6.9 vs. 14.0 +/- 8.2; p = 0.01) were lower in the PWS group compared to the controls. Three PWS patients had abnormally high follicle-stimulating hormone levels, while only 1 had hypogonadotropic hypogonadism.

Conclusions: Our results suggest a unique follicular stage-specific insult in women with PWS. Thus, primary ovarian dysfunction is a major component of hypogonadism in PWS.