Combined gonadotropin therapy to replace mini‐puberty in male infants with congenital hypogonadotropic hypogonadism

Abstract

Infants born with severe central disorders of the hypothalamic‐pituitary‐gonadal axis leading to gonadotropin deficiency not only lack pubertal development in adolescence, but also lack infantile mini‐puberty. This period of mini‐puberty, where infants have gonadotropin and sex steroid concentrations up into the adult range, is vital for future reproductive capacity, particularly in boys. At present, there is no consensus on the diagnosis or management of infants with gonadotropin deficiency due to congenital hypogonadotropic hypogonadism or multiple pituitary hormone deficiency. Case series suggest that gonadotropin treatment in male infants with absent mini‐puberty is effective in promoting both testicular descent in those with undescended testes and also facilitating increased penile size. Moreover, replacement with follicle‐stimulating hormone increases the testicular Sertoli cell population, measurable as an increase in testicular volume and inhibin B, thus hypothetically increasing the capacity for spermatogenesis in adult life for these patients. However, long‐term follow‐up data is limited for both outcomes pertaining to fertility and nonreproductive sequelae, including neurodevelopment and psychological well‐being. The use of international registries for patients with gonadotropin deficiency is a key element in the collection of high‐quality, geographically widespread data to inform best‐practice management from birth to adulthood.