{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:28:09Z","timestamp":1785338889201,"version":"3.55.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Isolated Premature Thelarche (PT) is a common clinical issue in pediatric endocrinology. Because its early presentation resembles that of Central Precocious Puberty (CPP), which requires intervention, its management is highly controversial, caught between \u201cactive intervention\u201d and \u201cwatchful waiting.\u201d This leads to inconsistent clinical practices and significant anxiety for affected families. This review aims to move beyond this traditional dichotomy by conducting an in-depth analysis of the natural history, pathophysiological mechanisms, diagnostic criteria, and progression risks of PT. We propose a new paradigm for a tiered, individualized management approach based on risk stratification, providing a clear, evidence-based pathway for clinical decision-making. Through a comprehensive review of recent clinical studies, reviews, and expert consensus, this paper analyzes the theoretical basis and evidence supporting a \u201cwatchful waiting\u201d strategy. It defines the rigorous initial evaluation and dynamic monitoring protocols required for its implementation and clarifies the quantitative indicators for transitioning from \u201cobservation\u201d to \u201cactive intervention.\u201d For children with typical PT\u2014characterized by a normal growth rate, no significant bone age advancement, a prepubertal pelvic ultrasound, and a very low basal luteinizing hormone level\u2014\u201dwatchful waiting\u201d or \u201cactive surveillance\u201d is a safe, effective, and preferred management strategy. This is an active medical monitoring process, not passive waiting. \u201cActive intervention\u201d (i.e., Gonadotropin-Releasing Hormone agonist therapy) should be strictly limited to the few \u201cprogressive\u201d cases that show sustained pubertal progression, growth acceleration, and significant bone age advancement during follow-up, and are confirmed as CPP by a Gonadotropin-Releasing Hormone stimulation test. The risk-stratified management pathway proposed herein aims to effectively address the clinical dilemma, avoid over-treatment, and achieve individualized, precise management for children with PT.<\/jats:p>","DOI":"10.3389\/fendo.2025.1705194","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T05:40:47Z","timestamp":1769406047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Management strategies for isolated premature thelarche: a risk-stratified clinical pathway favoring \u201cwatchful waiting\u201d"],"prefix":"10.3389","volume":"16","author":[{"given":"Yan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, First Affiliated Hospital, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chongqing Traditional Chinese Medicine Hospital, The First Affiliated Hospital of Chongqing University of Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinna","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Encephalopathy, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Chongqing Traditional Chinese Medicine Hospital, The First Affiliated Hospital of Chongqing University of Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2174\/1573396320666230726110658","article-title":"Premature thelarche: an updated review","volume":"20","author":"Leung","year":"2024","journal-title":"Curr Pediatr Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s12887-019-1426-6","article-title":"The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China","volume":"19","author":"Zhang","year":"2019","journal-title":"BMC Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e2015665","DOI":"10.1001\/jamanetworkopen.2020.15665","article-title":"Trends in the incidence of central precocious puberty and normal variant puberty among children in Denmark, 1998 to 2017","volume":"3","author":"Brauner","year":"2020","journal-title":"JAMA Netw Open"},{"key":"B4","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.bpobgyn.2017.11.004","article-title":"Disorders of puberty","volume":"48","author":"Sultan","year":"2018","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-3732","article-title":"Evaluation and referral of children with signs of early puberty","volume":"137","author":"Kaplowitz","year":"2016","journal-title":"Pediatrics"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2017-0247","article-title":"Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche","volume":"31","author":"Cicek","year":"2018","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1590\/2359-3997000000144","article-title":"Central precocious puberty: revisiting the diagnosis and therapeutic management","volume":"60","author":"Brito","year":"2016","journal-title":"Arch Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1159\/000512764","article-title":"For premature thelarche and premature adrenarche, the case for waiting before testing","volume":"93","author":"Kaplowitz","year":"2020","journal-title":"Horm Res Paediatr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ecl.2024.01.002","article-title":"Females with breast development before three years of age","volume":"53","author":"Kaplowitz","year":"2024","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.galenos.2020.2019.0202","article-title":"Girls with Premature Thelarche Younger than 3 Years of Age May Have Stimulated Luteinizing Hormone Greater than 10 IU\/L","volume":"12","author":"Seymen","year":"2020","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2017.1318374","article-title":"No association between estrogen receptor gene polymorphisms and premature thelarche in girls","volume":"33","author":"Lee","year":"2017","journal-title":"Gynecol. Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e202410501","DOI":"10.5546\/aap.2024-10501.eng","article-title":"Endocrine disruptors as risk factors for idiopathic premature thelarche in girls: A case-control study","volume":"123","author":"Palmieri","year":"2025","journal-title":"Arch Argent Pediatr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002047","article-title":"Premature thelarche and the PURA syndrome","volume":"129","author":"Rezkalla","year":"2017","journal-title":"Obstet. Gynecol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1487884","article-title":"Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome","volume":"15","author":"Giannopoulou","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2017-0243","article-title":"Ultrasonographic assessment of pubertal breast development in obese children: compliance with the clinic","volume":"31","author":"Yuce","year":"2018","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B16","doi-asserted-by":"publisher","first-page":"37","DOI":"10.5114\/pedm.2020.103112","article-title":"Uterine and ovarian parameters in healthy North Indian girls from 5 to 16 years by ultrasonography","volume":"27","author":"Dixit","year":"2021","journal-title":"Pediatr Endocrinol Diabetes Metab"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0092","DOI":"10.1097\/MD.0000000000010092","article-title":"Observational study pelvic ultrasound a useful tool in the diagnosis and differentiation of precocious puberty in Chinese girls","volume":"97","author":"Wen","year":"2018","journal-title":"Med (Baltimore)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2346072.036","article-title":"The utilization of basal luteinizing hormone in combination with the basal luteinizing hormone and follicle-stimulating hormone ratio as a diagnostic tool for central precocious puberty in girls","volume":"28","author":"Chotipakornkul","year":"2023","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B19","article-title":"Management of premature breast or pubic hair development in young girls","volume":"67","author":"Brauner","year":"2017","journal-title":"Rev Prat"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad081","article-title":"Approach to the patient: central precocious puberty","volume":"108","author":"Kilberg","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1518764","article-title":"Early warning value of multiple serum indicators combined with ultrasound detection in girls with central precocious puberty","volume":"16","author":"Song","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e2021480","DOI":"10.23750\/abm.v92i5.12295","article-title":"The role of pelvic ultrasound for the diagnosis and management of central precocious puberty: An update","volume":"92","author":"Talarico","year":"2021","journal-title":"Acta BioMed"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-021-02947-z","article-title":"Triptorelin stimulated luteinizing hormone concentrations for diagnosing central precocious puberty: study of diagnostic accuracy","volume":"75","author":"Vukovic","year":"2022","journal-title":"Endocrine"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-021-04022-1","article-title":"Diagnosis and management of precocious sexual maturation: an updated review","volume":"180","author":"Cheuiche","year":"2021","journal-title":"Eur J Pediatr"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e2023222","DOI":"10.23750\/abm.v94i6.15316","article-title":"Long-term health consequences of central precocious\/early puberty (CPP) and treatment with Gn-RH analogue: a short update","volume":"94","author":"Soliman","year":"2023","journal-title":"Acta BioMed"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.3390\/ijerph14091044","article-title":"The effect of bisphenol A on puberty: A critical review of the medical literature","volume":"14","author":"Leonardi","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3126309","article-title":"Serum kisspeptin and AMH levels are good references for precocious puberty progression","volume":"2020","author":"Xue","year":"2020","journal-title":"Int J Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2016-0217","article-title":"AMH levels in girls with various pubertal problems","volume":"30","author":"Savas-Erdeve","year":"2017","journal-title":"J Pediatr Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1705194\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:10:58Z","timestamp":1771924258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1705194\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":28,"alternative-id":["10.3389\/fendo.2025.1705194"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1705194","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"article-number":"1705194"}}