{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:07:48Z","timestamp":1793210868142,"version":"4.5.0"},"reference-count":234,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100005709","name":"Endocrine Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005709","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Central precocious puberty (CPP), which is traditionally defined as the development of secondary sexual characteristics before age 8 years in girls and age 9 years in boys, results from the premature activation of the hypothalamic\u2013pituitary\u2013gonadal (HPG) axis. CPP can be associated with short adult stature, adverse psychosocial outcomes, and increased cardiometabolic and cancer risks in adulthood. Gonadotropin-releasing hormone (GnRH) agonists can effectively suppress premature activation of the HPG axis and have the potential to increase adult height as well as improve psychosocial and long-term health outcomes among patients with CPP. However, as secular trends have continued to shift toward earlier age of pubertal onset, some subpopulations of children with CPP, as it is currently defined, may not require the same extent of diagnostic evaluation and treatment.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n Develop evidence-based recommendations related to the diagnosis and treatment of CPP.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to address 10 clinical questions related to the diagnosis and treatment of CPP. Systematic reviews of health-related benefits and harms were conducted for each clinical question. The guideline development panel (GDP) also used the GRADE evidence-to-decision (EtD) framework to address stakeholder values and preferences, costs and required resources, cost-effectiveness, acceptability, feasibility, and potential impacts on health equity.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In girls with thelarche (Tanner stage B2) between ages 7.0 and 8.0 years, the GDP suggests watchful waiting via periodic physical examinations (every 4-6 months) rather than immediately performing evaluation with laboratory testing or radiologic imaging. In addition, the GDP suggests that all girls with breast development (ie, Tanner stage B2) before age 7 years should first be observed for 4 to 6 months to differentiate unsustained or slowly progressive puberty vs rapidly progressive puberty. These recommendations are largely based on evidence that girls with slowly progressive puberty attain a normal adult height without treatment. When hormonal evaluation is performed to confirm central (GnRH-dependent) activation as the cause of precocious puberty, the GDP suggests starting the evaluation with ultrasensitive basal luteinizing hormone (LH) concentration rather than routine GnRH\/GnRH agonist (GnRHa) stimulation testing for all patients. While brain magnetic resonance imaging has been a traditional part of CPP evaluation, the GDP suggests that it should not be routinely performed in girls ages 6.0 to 8.0 years and boys ages 8.0 to 9.0 years without central nervous system (eg, neuro-ophthalmologic) symptoms, largely based on a low prevalence of pathologic intracranial findings in these age groups. The GDP suggests against routine genetic testing for patients with CPP, although they judged that genetic testing (eg, MKRN3 sequencing) should be considered for patients with familial CPP through a shared decision-making process. The GDP suggests GnRHa treatment for many children with CPP, although available evidence suggests that some patient subgroups (eg, older girls with slowly progressive CPP) may be less likely to receive a net benefit with this treatment. Rather than always starting GnRHa treatment with a monthly injectable formulation, the GDP suggests that treatment should be initiated with the formulation (such as a longer-acting formulation) that is anticipated to be used long-term. The GDP suggests against routine addition of growth hormone therapy to increase adult height. They also suggest against the routine biochemical testing (eg, LH, sex steroids) to monitor pubertal suppression while receiving GnRHa, instead reserving biochemical testing to confirm clinically suspected treatment failure. Finally, the GDP suggests against routinely continuing GnRHa treatment beyond chronologic age 10.0 to 11.0 years (girls) or 11.0 to 12.0 years (boys) and\/or bone age 11.0 to 12.0 years (girls) or 12.0 to 13.0 years (boys).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n These clinical recommendations were developed to address important uncertainties in the diagnosis and treatment of children with CPP. They are based on the best available scientific evidence regarding clinical outcomes judged to be most important to patients and families. The GDP's overarching goal was to suggest diagnostic and therapeutic strategies that will most likely provide net clinical benefits while simultaneously considering important contextual factors such as cost and feasibility. The guideline-development process highlighted important knowledge gaps and the substantial need for additional research.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/clinem\/dgag168","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:34:33Z","timestamp":1776166473000},"page":"2101-2144","source":"Crossref","is-referenced-by-count":18,"title":["Central precocious puberty: an Endocrine Society clinical practice guideline"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-693X","authenticated-orcid":false,"given":"Ana Claudia","family":"Latronico","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Clinical Hospital, S\u00e3o Paulo Medical School, University of S\u00e3o Paulo , S\u00e3o Paulo 05403 900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2811-1322","authenticated-orcid":false,"given":"Stephanie A","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Boston Children's Hospital , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6308-1635","authenticated-orcid":false,"given":"Morgan","family":"Alonzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Children's Hospital Colorado , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-0276","authenticated-orcid":false,"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Research Institute La Princesa, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u03ccn (CIBEROBN), Instituto de Salud Carlos III and IMDEA, Food Institute, CEIUAM+CSI , Madrid E-28009 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-5412","authenticated-orcid":false,"given":"Ana Pinheiro Machado","family":"Canton","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Clinical Hospital, S\u00e3o Paulo Medical School, University of S\u00e3o Paulo , S\u00e3o Paulo 05403 900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-6767","authenticated-orcid":false,"given":"Jean-Claude","family":"Carel","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Department, Robert-Debr\u00e9 Hospital, Paris Cit\u00e9 University , Paris 75019 ,","place":["France"]},{"name":"Inserm U1141 NeuroDiderot, Paris City University , Paris F-75006, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0958-5845","authenticated-orcid":false,"given":"Fernando","family":"Cassorla","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Materno Infantil, Universidad de Chile , Santiago 8320000 ,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0851-6998","authenticated-orcid":false,"given":"Evangelia","family":"Charmandari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, National and Kapodistrian University of Athens Medical School , Athens 11527 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6135-7474","authenticated-orcid":false,"given":"Erica A","family":"Eugster","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology\/Diabetology, Riley Hospital for Children at IU Health, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6343-4768","authenticated-orcid":false,"given":"Anna","family":"Grandone","sequence":"additional","affiliation":[{"name":"Department of Woman, Child, General and Specialized Surgery, University of Campania L. 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