{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:28:27Z","timestamp":1793654907796,"version":"4.5.1"},"reference-count":330,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ESPE Research Unit"},{"name":"NIHR Academic Clinical Fellowship"},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003514","name":"Stockholm City Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second\u2014termed \u201cmini-puberty\u201d\u2014in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and\/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic \u201cmini-puberty\u201d in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications.<\/jats:p>","DOI":"10.1210\/endrev\/bnae003","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T15:28:39Z","timestamp":1706023719000},"page":"460-492","source":"Crossref","is-referenced-by-count":118,"title":["Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement"],"prefix":"10.1210","volume":"45","author":[{"given":"Julia","family":"Rohayem","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Children\u2019s Hospital of Eastern Switzerland , 9006 St. Gallen , Switzerland"},{"name":"University of Muenster, 48149 Muenster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-6846","authenticated-orcid":false,"given":"Emma C","family":"Alexander","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London , London EC1M 6BQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Heger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Children's Hospital Auf der Bult , 30173 Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0405-3401","authenticated-orcid":false,"given":"Anna","family":"Nordenstr\u00f6m","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska University Hospital , 17176 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-903X","authenticated-orcid":false,"given":"Sasha R","family":"Howard","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London , London EC1M 6BQ , UK"},{"name":"Department of Paediatric Endocrinology, Royal London Children's Hospital, Barts Health NHS Trust , London E1 1FR , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"issue":"4","key":"2024071216315219600_bnae003-B1","first-page":"808","article-title":"The ontogenesis of human foetal hormones. 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