Peer-reviewed article
Current perspectives on the pharmacologic treatment of boys and adolescents with congenital hypogonadotropic hypogonadism.
Rodolfo A Rey, Romina P Grinspon ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical review of pharmacological treatments for congenital hypogonadotropic hypogonadism, a rare endocrine disorder affecting testicular development in boys and adolescents. The review examines testosterone, gonadotropins, GnRH, and kisspeptin therapies across different developmental stages. While the document addresses child health, it focuses on clinical management of a specific medical condition rather than broader child well-being outcomes.
Key points
- Testosterone therapy promotes secondary sexual characteristics and virilization but does not induce testicular maturation or spermatogenesis
- Gonadotropin therapy more directly promotes testicular growth and spermatogenesis compared to testosterone alone
- Early gonadotropin treatment in infancy can reproduce features of physiological mini-puberty, though long-term reproductive benefits remain uncertain
- Pulsatile GnRH is physiologically attractive but limited by availability and treatment complexity
- Treatment should be individualized based on developmental stage, testicular phenotype, and patient preferences
Limitations
This is a clinical literature review focused on pharmacological mechanisms and treatment approaches for a rare endocrine disorder. It does not evaluate population-level child well-being outcomes, programme effectiveness, or provide data on the prevalence or broader developmental impact of the condition on affected children.
Abstract
INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) in boys and adolescents requires age- and developmentally appropriate treatment to address androgen deficiency, testicular maturation, pubertal development, and ultimately fertility. The dynamic physiology of the hypothalamic-pituitary-testicular axis necessitates therapeutic strategies that differ substantially between infancy and adolescence. AREAS COVERED: This review examines current pharmacological approaches to CHH across childhood and adolescence, focusing on testosterone, dihydrotestosterone, gonadotropins, pulsatile gonadotropin-releasing hormone (GnRH), and emerging kisspeptin-based therapies. Literature search was made in Pubmed for the period 1990-2026. EXPERT OPINION: Testosterone remains the standard approach for inducing secondary sexual characteristics and effectively promotes virilization, growth, bone accrual, and psychosocial well-being, but does not induce testicular maturation or spermatogenesis. Gonadotropin therapy, particularly sequential follicle-stimulating hormone followed by luteinizing hormone or human chorionic gonadotropin, more directly promotes Sertoli-cell maturation, testicular growth, and spermatogenesis. Early gonadotropin treatment in infancy can reproduce several features of physiological mini-puberty, although its long-term reproductive benefits remain uncertain. Pulsatile GnRH is physiologically attractive but limited by availability and treatment complexity, whereas kisspeptin remains investigational. Treatment should be individualized according to developmental stage, testicular phenotype, therapeutic goals, anticipated fertility, treatment burden, and patient preferences. Major unmet needs include pediatric-specific formulations, optimized regimens, comparative trials, biomarkers of treatment response, and long-term reproductive outcomes.