Gonadotropins in mini-puberty: pathophysiological and therapeutic implications for male congenital hypogonadism

Background: Mini-puberty is a transient but critical postnatal activation of the hypotha‐ lamic–pituitary–gonadal axis, essential for male gonadal maturation, penile and testicu‐ lar growth, and future reproductive potential: this physiological hormonal surge is ab‐ sent or blunted in congenital hypogonadotropic hypogonadism (CHH), often manifest‐ ing as micropenis, cryptorchidism, and impaired Sertoli cell proliferation. Objective: The aim of this review is to summarize current evidence on the impact of early go‐ nadotropin therapy in male infants with CHH. Methods: We conducted a comprehen‐ sive literature review using PubMed, including studies reporting on male infants with confirmed or suspected CHH receiving gonadotropin therapy. Keywords included “mini-puberty and hypogonadism”, “gonadotropins and infancy,” and “gonadotropin therapy in CHH.” Eligible studies reported biochemical outcomes (luteinizing hormone, follicle-stimulating hormone, testosterone, inhibin B, anti-Müllerian hormone) and clini‐ cal measures (penile length, testicular volume, testicular descent). Data extraction fo‐ cused on endocrine responses, genital growth, and safety. Results: Twelve studies including 95 infants were analyzed. Early gonadotropin therapy effectively restored post‐ natal hormonal levels, with consistent increases in testosterone, inhibin B, and anti-Müllerian hormone. Clinically, treatment induced significant penile growth, increased testicular volume and partial or complete testicular descent in the majority of cases. Both continuous infusion and intermittent injection regimens were effective, though hormone kinetics and growth responses varied. No serious adverse events were reported, and therapy was generally well tolerated. Conclusions: Early gonadotropin therapy during mini-puberty represents a safe and effective intervention to replicate the physiological postnatal hormonal surge in male infants with CHH. Prospective longitudinal studies are warranted to evaluate sustained effects on puberty, fertility, and adult reproductive function.