Current perspectives on the pharmacologic treatment of boys and adolescents with congenital hypogonadotropic hypogonadism.

Authors

Rodolfo A Rey, Romina P Grinspon

Published in

Expert opinion on pharmacotherapy. Sep 27, 2026. Epub Sep 27, 2026.

Abstract

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.
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.
Testosterone remains the standard approach for 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.

PMID:
42802581
Bibliographic data and abstract were imported from PubMed on 28 Sep 2026.

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