Spectrum of Hypogonadism and Its Management in Adolescents With Prader-Willi Syndrome: A Retrospective Cohort Study...

Adult data indicate that hypogonadism is underdiagnosed and undertreated in Prader-Willi Syndrome (PWS).

We aimed to describe the spectrum of pubertal development, and the diagnosis and treatment of hypogonadism in paediatric/adolescent patients with PWS.

A retrospective cohort study of patients with PWS aged 6-18 years seen at an Australian tertiary paediatric centre between 1 January 1990 and 31 May 2025 (n = 65).

Spontaneous puberty onset was achieved in 63% females aged ≥ 8 years and 68% males aged ≥ 9 years with onset at a median age of 10.3 [8.9-12.5] years in females and 12.3 [11.9-14.3] years in males. By last visit, hypogonadism was diagnosed in 77% of females (95% central aetiology, 5% unknown) and 88% of males (73% central aetiology, 27% primary/mixed) at a median age of 14.1 [13.1-15.8] years in females and 15.3 [14.1-15.6] years in males. Pubertal hormone replacement therapy was initiated in 80% females and 60% males, with no significant change in proportion of patients with behavioural/psychiatric issues post treatment. Median femoral neck bone mineral density showed age-adjusted z-score of -1.5 [-2.2 to -0.8] and height-adjusted of -0.9 [-1.6 to 0.3].

Despite approximately two-thirds of adolescents with PWS entering puberty spontaneously, the majority demonstrated hypogonadism before transitioning to adult care, emphasising the need for ongoing pubertal assessment in this population. Aetiology is predominantly central hypogonadism, but there can also be a component of primary hypogonadism. Longitudinal controlled studies are required to determine optimal detection of hypogonadism and timing of pubertal hormone replacement in PWS.