{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:06:05Z","timestamp":1789657565856,"version":"4.0.1"},"reference-count":54,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Letrozole, a third-generation aromatase inhibitor, has been increasingly investigated as an off-label treatment to improve growth outcomes in pediatric boys, whereas its use in girls has remained limited because of concerns regarding safety and efficacy, given the critical role of estrogens in female physiology. This gender gap has delayed research on letrozole in girls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically evaluate the clinical efficacy, growth outcomes, and safety profile of letrozole in girls with peripheral precocious puberty (PPP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Acquisition<\/jats:title>\n                    <jats:p>PubMed\/MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to May 2026, following PRISMA 2020 guidelines (PROSPERO: CRD420261423918). Eligible studies evaluated letrozole monotherapy in girls aged \u226418 years. Risk of bias was assessed using Joanna Briggs Institute checklists and the Murad tool. Data were synthesized narratively according to the Synthesis Without Meta-analysis (SWiM) guideline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Synthesis<\/jats:title>\n                    <jats:p>Twenty-two observational studies encompassing 151 female patients were included. Twenty-one studies evaluated letrozole for PPP, predominantly McCune\u2013Albright syndrome, where treatment effectively slowed pubertal progression, reduced bone age advancement, and improved predicted adult height. One exploratory study evaluated girls with short stature without pubertal disorders. Transition to central precocious puberty occurred during follow-up in 41.3% of patients. Safety was favorable (adverse events: 3.3%), with no clinically significant hyperandrogenism or hepatotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Letrozole demonstrates meaningful clinical benefits in girls with PPP, particularly regarding pubertal control and predicted adult height, accompanied by a favorable safety profile. Well-designed prospective studies are needed to establish optimal dosing, long-term safety, and final adult height outcomes in the female pediatric population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag372","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:34:20Z","timestamp":1788867260000},"source":"Crossref","is-referenced-by-count":0,"title":["Letrozole in pediatric females for peripheral precocious puberty: a systematic review of efficacy and safety"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0582-934X","authenticated-orcid":false,"given":"Carlotta","family":"Tartarini","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of Florence , 50134 Florence ,","place":["Italy"]},{"name":"Auxo-endocrinology Unit, Meyer Children's Hospital IRCCS , 50139 Florence 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