{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:12:07Z","timestamp":1790611927292,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Mini-puberty is a transient but critical postnatal activation of the hypothalamic\u2013pituitary\u2013gonadal axis, essential for male gonadal maturation, penile and testicular growth, and future reproductive potential: this physiological hormonal surge is absent or blunted in congenital hypogonadotropic hypogonadism (CHH), often manifesting as micropenis, cryptorchidism, and impaired Sertoli cell proliferation. Objective: The aim of this review is to summarize current evidence on the impact of early gonadotropin therapy in male infants with CHH. Methods: We conducted a comprehensive literature review using PubMed, including studies reporting on male infants with confirmed or suspected CHH receiving gonadotropin therapy. Keywords included \u201cmini-puberty and hypogonadism\u201d, \u201cgonadotropins and infancy,\u201d and \u201cgonadotropin therapy in CHH.\u201d Eligible studies reported biochemical outcomes (luteinizing hormone, follicle-stimulating hormone, testosterone, inhibin B, anti-M\u00fcllerian hormone) and clinical measures (penile length, testicular volume, testicular descent). Data extraction focused on endocrine responses, genital growth, and safety. Results: Twelve studies including 95 infants were analyzed. Early gonadotropin therapy effectively restored postnatal hormonal levels, with consistent increases in testosterone, inhibin B, and anti-M\u00fcllerian 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.<\/jats:p>","DOI":"10.3390\/children13010133","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T16:21:13Z","timestamp":1768494073000},"page":"133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gonadotropins in Mini-Puberty: Pathophysiological and Therapeutic Implications for Male Congenital Hypogonadism"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8591-0964","authenticated-orcid":false,"given":"Ignazio","family":"Cammisa","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-7779","authenticated-orcid":false,"given":"Donato","family":"Rigante","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clelia","family":"Cipolla","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1210\/endrev\/bnae003","article-title":"Mini-puberty, physiological and disordered: Consequences, and potential for therapeutic replacement","volume":"45","author":"Rohayem","year":"2024","journal-title":"Endocr. 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