{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:40:28Z","timestamp":1787719228040,"version":"build-2784847793"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Takeda Pharmaceuticals Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: As the first approved GnRH agonist, leuprorelin is distinguished by its broad application in managing central precocious puberty (CPP). Despite the extensive use of leuprorelin in CPP management, uncertainties still persist regarding its long-term efficacy and safety. We conducted a systematic review and meta-analysis to assess the long-term efficacy and safety of leuprorelin treatment in children with CPP. Methods: We conducted electronic searches in PubMed, Embase, and the Cochrane Library up until 15 November 2023. All relevant studies concerning leuprorelin treatment in children with CPP were included. Results: The final adult height of children with CPP eventually reached the target height, with a significant difference of MD: 1.75 cm (95% CI: 0.46\u20133.03). The MD in BMI standard deviation score between baseline and post-leuprorelin treatment was \u22120.03 (95% CI: \u22120.28\u20130.22). For the onset of menstrual puberty, the MD between children with CPP who received leuprorelin treatment and those who did not was 0.73 years latency (95% CI: \u22120.74\u20132.20) without significant difference. The timing of menstrual puberty of the leuprorelin-treated group was 15.83 months (95% CI: 11.62\u201320.03) after the discontinuation of leuprorelin treatment. The proportion of menstrual regularity was 85% (95% CI: 75\u201391%), and the average incidence rate of polycystic ovary syndrome (PCOS) was 8% (95% CI: 3\u201322%) for children with CPP that treated with leuprorelin. Conclusions: Leuprorelin treatment does not affect BMI or the onset of menstrual puberty in the long term, but has positive effects on adult height for children with CPP. Moreover, no severe adverse events related to leuprorelin treatment were observed.<\/jats:p>","DOI":"10.3390\/children12060712","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:07:58Z","timestamp":1748592478000},"page":"712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-Term Efficacy and Safety of Leuprorelin Treatment in Children with Central Precocious Puberty: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Ling","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-4817","authenticated-orcid":false,"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1056\/NEJMcp0800459","article-title":"Clinical practice. Precocious puberty","volume":"358","author":"Carel","year":"2008","journal-title":"New Engl. J. Med."},{"key":"ref_2","unstructured":"Subspecialty Group of Endocrinology, Heredity and Metabolism, Society of Pediatrics, Chinese Medical Association, and Editorial Board of Chinese Journal of Pediatrics (2015). Consensus on the diagnosis and treatment of central precocious puberty (2015). Chin. J. Pediatr., 53, 412\u2013418."},{"key":"ref_3","unstructured":"Subspecialty Group of Endocrinology, Heredity and Metabolism, Society of Pediatrics, Chinese Medical Association, and Editorial Board of Chinese Journal of Pediatrics (2022). Expert consensus on the diagnosis and treatment of central precocious puberty (2022). Chin. J. Pediatr., 61, 16\u201322."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/S2352-4642(23)00237-7","article-title":"Central precocious puberty: A review of diagnosis, treatment, and outcomes","volume":"7","author":"Zevin","year":"2023","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S2213-8587(15)00380-0","article-title":"Causes, diagnosis, and treatment of central precocious puberty","volume":"4","author":"Latronico","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1210\/jc.2005-1693","article-title":"Final height in girls with central idiopathic precocious puberty treated with gonadotropin-releasing hormone analog and oxandrolone","volume":"91","author":"Vottero","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/cen.14410","article-title":"Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis","volume":"94","author":"Luo","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1159\/000501336","article-title":"Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium","volume":"91","author":"Fuqua","year":"2019","journal-title":"Horm. Res. Paediatr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Higgins, J.P., and Green, S. (2008). Cochrane Handbook for Systematic Reviews of Interventions, Wiley-Blackwell.","DOI":"10.1002\/9780470712184"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., G\u00f8tzsche, P.C., Ioannidis, J.P., Clarke, M., Devereaux, P.J., Kleijnen, J., and Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ, 151.","DOI":"10.7326\/0003-4819-151-4-200908180-00136"},{"key":"ref_11","first-page":"1","article-title":"The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses","volume":"2","author":"Peterson","year":"2011","journal-title":"Ott. Ott. Hosp. Res. Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1210\/jc.2004-1863","article-title":"Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: Evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty","volume":"90","author":"Tanaka","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"398639","DOI":"10.1186\/1687-9856-2010-398639","article-title":"Leuprolide acetate 1-month depot for central precocious puberty: Hormonal suppression and recovery","volume":"2010","author":"Neely","year":"2010","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jpag.2014.09.002","article-title":"Use of a Gonadotropin-releasing Hormone Analog to Treat Idiopathic Central Precocious Puberty Is Not Associated with Changes in Bone Structure in Postmenarchal Adolescents","volume":"28","author":"Iannetta","year":"2015","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1210\/jcem.87.2.8202","article-title":"Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy","volume":"87","author":"Boot","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1515\/jpem-2021-0142","article-title":"Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)","volume":"34","author":"Ramos","year":"2021","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1515\/jpem.2011.006","article-title":"Outcome of gonadotropin-releasing analog treatment for children with central precocious puberty: 15-year experience in southern Thailand","volume":"24","author":"Jaruratanasirikul","year":"2011","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.6065\/apem.2040220.110","article-title":"Clinical findings influencing time to menarche post gonadotropin-releasing hormone agonist therapy in central precocious puberty","volume":"26","author":"Wu","year":"2021","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Kim, S.Y., and Kim, M. (2022). Can Body Mass Index Affect Height Growth at Menarche among Girls Receiving Treatment for Early Puberty? A Retrospective Study in Korean Girls. Children, 9.","DOI":"10.3390\/children9010110"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.6065\/apem.2244210.105","article-title":"Comparison of the effect of gonadotropin-releasing hormone agonist dosage in girls with central precocious puberty","volume":"28","author":"Jang","year":"2023","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_22","first-page":"361","article-title":"Effect of gonadotropin-releasing hormone analog treatment on final height in girls aged 6-10 years with central precocious and early puberty","volume":"55","author":"Onat","year":"2020","journal-title":"Turk. Pediatri. Arsivi"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1687-9856-2011-7","article-title":"Efficacy of Leuprolide Acetate 1-Month Depot for Central Precocious Puberty (CPP): Growth Outcomes During a Prospective, Longitudinal Study","volume":"2011","author":"Lee","year":"2011","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lee, H.S., Yoon, J.S., Park, K.J., and Hwang, J.S. (2018). Increased final adult height by gonadotropin-releasing hormone agonist in girls with idiopathic central precocious puberty. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201906"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"24","DOI":"10.6065\/apem.2020.25.1.24","article-title":"Relationship between final adult height and birth weight after gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty","volume":"25","author":"Cho","year":"2020","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lin, Y.C., Lin, C.Y., Chee, S.Y., Yen, H.R., Tsai, F.J., Chen, C.Y., and Wang, C.H. (2017). Improved final predicted height with the injection of leuprolide in children with earlier puberty: A retrospective cohort study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185080"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1590\/2359-3997000000101","article-title":"Evaluation of central precocious puberty treatment with GnRH analogue at the Triangulo Mineiro Federal University (UFTM)","volume":"59","author":"Borges","year":"2015","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_28","unstructured":"WHO (2023). Polycystic Ovary Syndrome, WHO."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Popovic, J., Geffner, M.E., Rogol, A.D., Silverman, L.A., Kaplowitz, P.B., Mauras, N., Zeitler, P., Eugster, E.A., and Klein, K.O. (2022). Gonadotropin-releasing hormone analog therapies for children with central precocious puberty in the United States. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.968485"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1530\/EJE-15-0590","article-title":"Management of endocrine disease: Long-term outcomes of the treatment of central precocious puberty","volume":"174","author":"Guaraldi","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"168","DOI":"10.6065\/apem.2346168.084","article-title":"2022 Clinical practice guidelines for central precocious puberty of Korean children and adolescents","volume":"28","author":"Kim","year":"2023","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_32","first-page":"33","article-title":"A Critical Appraisal of the Effect of Gonadotropin-Releasing Hormon Analog Treatment on Adult Height of Girls with Central Precocious Puberty","volume":"9","author":"Bereket","year":"2017","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chung, L.Y., Kang, E., Nam, H.K., Rhie, Y.J., and Lee, K.H. (2021). Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center. J. Korean Med. Sci., 36.","DOI":"10.3346\/jkms.2021.36.e219"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2165\/11202230-000000000-00000","article-title":"Triptorelin embonate (6-month formulation)","volume":"70","author":"Keating","year":"2010","journal-title":"Drugs"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/6\/712\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:43:50Z","timestamp":1760031830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/6\/712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["children12060712"],"URL":"https:\/\/doi.org\/10.3390\/children12060712","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]}}}