Endocrine Abstracts

Background: Males with congenital or acquired hypogonadotropic hypogonadism (HH) or other central disorders of the hypothalamic-pituitary-gonadal (HPG) axis experience absent or delayed puberty due to gonadotropin deficiency (GD). This condition disrupts key developmental windows, including mini-puberty and adolescent puberty, resulting in underdeveloped testes, impaired fertility potential, and significant psychosocial burden. Standard testosterone therapy, while effective for virilisation, does not stimulate testicular growth or spermatogenesis, making it insufficient for long-term reproductive outcomes.

The PinG Study: The PinG study is an NIHR-funded, UK multicentre, open-label, randomised controlled trial to evaluate efficacy of gonadotropin regimens for pubertal induction in males aged 12–35 years with GD. Participants are stratified into partial (maximal testes volume ≥4mL) or severe (<4mL) disease. All arms receive gonadotropins, and treatment duration ranges from 18 to 24 months, with follow-up continuing until the conclusion of therapy. PinG aims to determine whether combination gonadotropin therapy offers superior outcomes to hCG alone in partial GD, and whether rFSH pre-treatment benefits those with severe GD. This trial builds on findings from our meta-analysis of over 100 studies, which confirmed the efficacy of gonadotropins in promoting testicular development and spermatogenesis in young males. The primary outcome is the proportion of participants achieving spermatogenesis. Secondary outcome measures include hormonal biomarkers, testicular volume, time to spermatogenesis and maximum sperm concentration, quality of life and pathogenic genetic variant identification via whole genome sequencing. The trial design reflects current clinical practice but adds structured monitoring and broader outcome assessments. A nested qualitative study will be conducted to deepen understanding of the lived experience of GD. Participants will take part in two semi-structured interviews: one before starting treatment to explore the impact of delayed puberty on self-esteem, relationships, diagnosis, and expectations; and one after treatment to explore individual’s perceptions of change in physical and psychological wellbeing. This component aims to capture patient priorities and inform patient-centred care. Study has initial approvals: NIHR CPMS 58941.

Conclusion: By informing optimal pubertal induction strategies, PinG has potential to improve quality of life and also reproductive outcomes for males with GD and contribute to the standardisation of gonadotropin-based pubertal induction in adolescence.