促性腺激素释放激素类似物在中枢性性早熟 治疗中的临床应用与研究回顾
Clinical Application and Research Review of Gonadotropin-Releasing Hormone Analogues in the Treatment of Central Precocious Puberty
DOI: 10.12677/acm.2026.1631007, PDF,   
作者: 刘晓璇, 马兆慧：济宁医学院临床医学院，山东 济宁；张艳红*：济宁医学院附属医院内分泌与遗传代谢科，山东 济宁
关键词: 促性腺激素释放激素类似物；中枢性性早熟；生长激素；青春期；Gonadotropin-Releasing Hormone Analogues； Central Precocious Puberty； Growth Hormone； Puberty
摘要: 青春期是从儿童期至成年期的过渡时期，儿童青春期的身高增长对成人终身高至关重要。中枢性性早熟(CPP)患者由于下丘脑–垂体–性腺轴(HPGA)功能提前启动、促性腺激素释放激素增加，导致性腺发育并分泌性激素，从而促进内、外生殖器发育及第二性征的出现，这一过程会限制其生长潜力，导致其成人终身高往往未能达到理想水平。目前，促性腺激素释放激素类似物(GnRHa)是治疗CPP的常用药物，已被证实具有可靠的干预疗效；此外，GnRHa联合重组人生长激素(rhGH)治疗也被广泛应用，多数患儿在系统干预后能有效抑制性腺的早期发育。本文旨在详细探讨GnRHa在提高CPP患儿身高方面的临床疗效，为个体化治疗提供更多理论依据。
Abstract: Adolescence is the transition period from childhood to adulthood, and the height growth of children during adolescence is crucial for adult lifelong height. Patients with central precocious puberty (CPP) often fail to achieve ideal levels of adult lifelong height due to the early activation of hypothalamic-pituitary-gonadal axis (HPGA) function and the increase of gonadotropin-releasing hormone, which leads to gonadal development and secretion of sex hormones, thus promoting the development of internal and external genitalia and the emergence of secondary sexual characteristics. Gonadotropin-releasing hormone analogue (GnRHa) is commonly used in the treatment of CPP, and has been proven to have reliable intervention effects. In addition, GnRHa combined with recombinant human growth hormone (rhGH) is widely used, and most children can effectively inhibit early gonadal development after systematic intervention. The purpose of this article is to thoroughly discuss the clinical efficacy of GnRHa in improving the height of children with CPP, providing more theoretical evidence for personalized treatment.
文章引用：刘晓璇, 马兆慧, 张艳红. 促性腺激素释放激素类似物在中枢性性早熟 治疗中的临床应用与研究回顾[J]. 临床医学进展, 2026, 16(3): 2145-2152. https://doi.org/10.12677/acm.2026.1631007

参考文献

[1] 中华医学会儿科学分会内分泌遗传代谢学组, 中华儿科杂志编辑委员会. 中枢性性早熟诊断与治疗专家共识(2022) [J]. 中华儿科杂志, 2023, 61(1): 16-22.
[2] Maione, L., Bouvattier, C. and Kaiser, U.B. (2021) Central Precocious Puberty: Recent Advances in Understanding the Aetiology and in the Clinical Approach. Clinical Endocrinology, 95, 542-555. [Google Scholar] [CrossRef] [PubMed]
[3] 邱世超, 汪治华, 宋娜, 等. 女童中枢性性早熟诊断模型构建、评分卡设计及外部验证[J]. 中国当代儿科杂志, 2024, 26(12): 1267-1274.
[4] Lahlou, N., Carel, J.-C., Chaussain, J.-L. and Roger, M. (2000) Pharmacokinetics and Pharmacodynamics of GnRH Agonists: Clinical Implications in Pediatrics. Journal of Pediatric Endocrinology and Metabolism, 13, 723-737. [Google Scholar] [CrossRef] [PubMed]
[5] Popovic, J., Geffner, M.E., Rogol, A.D., Silverman, L.A., Kaplowitz, P.B., Mauras, N., et al. (2022) Gonadotropin-Releasing Hormone Analog Therapies for Children with Central Precocious Puberty in the United States. Frontiers in Pediatrics, 10, Article ID: 968485. [Google Scholar] [CrossRef] [PubMed]
[6] Soliman, A.T., Alaaraj, N., De Sanctis, V., et al. (2023) Long-Term Health Consequences of Central Precocious/Early Puberty (CPP) and Treatment with GN-RH Analogue: A Short Update. Acta Biomedica, 94, e2023222.
[7] Fu, J., Zhang, J., Chen, R., et al. (2020) Response to Letter to the Editor from Fu: “Long-Term Outcomes of Treatments for Central Precocious Puberty or Early and Fast Puberty in Chinese Girls”. The Journal of Clinical Endocrinology & Metabolism, 105, e3844-e3845. [Google Scholar] [CrossRef] [PubMed]
[8] Partsch, C.-J., Heger, S., Sippell, W.G. and German Decapeptyl Study Group, (2000) Treatment of Central Precocious Puberty: Lessons from a 15 Years Prospective Trial. Journal of Pediatric Endocrinology and Metabolism, 13, 747-758. [Google Scholar] [CrossRef] [PubMed]
[9] Franzini, I.A., Yamamoto, F.M., Bolfi, F., Antonini, S.R. and Nunes-Nogueira, V.S. (2018) GnRH Analog Is Ineffective in Increasing Adult Height in Girls with Puberty Onset after 7 Years of Age: A Systematic Review and Meta-Analysis. European Journal of Endocrinology, 179, 381-390. [Google Scholar] [CrossRef] [PubMed]
[10] Vuralli, D., Gonc, N.E., Ozon, Z.A., Kandemir, N. and Alikasifoglu, A. (2021) Which Parameters Predict the Beneficial Effect of GnRHa Treatment on Height in Girls with Central Precocious Puberty? Clinical Endocrinology, 94, 804-810. [Google Scholar] [CrossRef] [PubMed]
[11] Park, H.K., Choo, M.S. and Shim, Y.S. (2020) Adult Height after Gonadotropin‐Releasing Hormone Agonist Treatment in Girls with Early Puberty: A Meta‐Analysis. Clinical Endocrinology, 93, 135-145. [Google Scholar] [CrossRef] [PubMed]
[12] Ying, Y., Tang, J., Chen, W., Cai, Z. and Niu, W.T. (2017) GnRH Agonist Treatment for Idiopathic Central Precocious Puberty Can Improve Final Adult Height in Chinese Girls. Oncotarget, 8, 109061-109067. [Google Scholar] [CrossRef] [PubMed]
[13] Alaaraj, N., Soliman, A.T., De Sanctis, V., et al. (2022) Growth, Bone Maturation and Ovarian Size in Girls with Early and Fast Puberty (EFP) and Effects of Three Years Treatment with GnRH Analogue (GnRHa). Acta Biomedica, 92, e2021333.
[14] Cheuiche, A.V., da Silveira, L.G., Lucena, I.R.S., Puñales, M., Costenaro, F., Kopacek, C., et al. (2025) Doppler Assessment of the Uterine Arteries Is a Valuable Adjunct Tool for the Evaluation of Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls with Central Precocious Puberty. Neuroendocrinology, 115, 520-529. [Google Scholar] [CrossRef] [PubMed]
[15] Shim, Y.S., Lim, K.I., Lee, H.S. and Hwang, J.S. (2020) Long-Term Outcomes after Gonadotropin-Releasing Hormone Agonist Treatment in Boys with Central Precocious Puberty. PLOS ONE, 15, e0243212. [Google Scholar] [CrossRef] [PubMed]
[16] Wit, J.M. (2021) Should Skeletal Maturation Be Manipulated for Extra Height Gain? Frontiers in Endocrinology, 12, Article ID: 812196. [Google Scholar] [CrossRef] [PubMed]
[17] Klein, K.O., Dragnic, S., Soliman, A.M. and Bacher, P. (2018) Predictors of Bone Maturation, Growth Rate and Adult Height in Children with Central Precocious Puberty Treated with Depot Leuprolide Acetate. Journal of Pediatric Endocrinology and Metabolism, 31, 655-663. [Google Scholar] [CrossRef] [PubMed]
[18] 袁意, 余丽蓉, 吴限. 醋酸曲普瑞林联合重组人生长激素对大骨龄中枢性性早熟女童生长发育的影响[J]. 中国临床药理学杂志, 2023, 39(24): 3547-3551.
[19] Cho, A.Y., Shim, Y.S., Lee, H.S. and Hwang, J.S. (2023) Effect of Gonadotropin-Releasing Hormone Agonist Monotherapy and Combination Therapy with Growth Hormone on Final Adult Height in Girls with Central Precocious Puberty. Scientific Reports, 13, Article No. 1264. [Google Scholar] [CrossRef] [PubMed]
[20] Shi, Y., Ma, Z., Yang, X., Ying, Y., Luo, X. and Hou, L. (2022) Gonadotropin-Releasing Hormone Analogue and Recombinant Human Growth Hormone Treatment for Idiopathic Central Precocious Puberty in Girls. Frontiers in Endocrinology, 13, Article ID: 1085385. [Google Scholar] [CrossRef] [PubMed]
[21] 卢蓉, 郝莉霞, 刘庆, 等. 不同方案治疗中枢性性早熟女童的效果及对体重指数和身高的影响[J]. 中国性科学, 2021, 30(7): 134-137.
[22] 臧亚勤, 徐亮, 沈耀红. 曲普瑞林联合重组人生长激素治疗中枢性性早熟女童的效果观察[J]. 解放军医药杂志, 2022, 34(1): 53-56.
[23] 宋建, 崔北勇, 诸宏伟. 曲普瑞林联合重组人生长激素治疗女童中枢性性早熟的临床疗效观察[J]. 中华全科医学, 2023, 21(9): 1544-1546, 1551.
[24] Gyon, Y., Yun, Y.J., Kim, Y. and Han, H. (2015) Age at Menarche and near Final Height after Treatment with Gonadotropin-Releasing Hormone Agonist Alone or Combined with Growth Hormone in Korean Girls with Central Precocious Puberty. Clinical Pediatric Endocrinology, 24, 175-183. [Google Scholar] [CrossRef] [PubMed]
[25] Liu, S., Liu, Q., Cheng, X., Luo, Y. and Wen, Y. (2016) Effects and Safety of Combination Therapy with Gonadotropin-Releasing Hormone Analogue and Growth Hormone in Girls with Idiopathic Central Precocious Puberty: A Meta-Analysis. Journal of Endocrinological Investigation, 39, 1167-1178. [Google Scholar] [CrossRef] [PubMed]
[26] Song, W., Zhao, F., Liang, S., Li, G. and Xue, J. (2018) Is a Combination of a GnRH Agonist and Recombinant Growth Hormone an Effective Treatment to Increase the Final Adult Height of Girls with Precocious or Early Puberty? International Journal of Endocrinology, 2018, Article ID: 1708650. [Google Scholar] [CrossRef] [PubMed]
[27] 马晓宇, 倪继红, 杨露露, 等. GnRHa治疗对特发性中枢性性早熟和快速进展型早发育儿童的远期影响[J]. 中华内分泌代谢杂志, 2020, 36(1): 58-62.
[28] Galip, N., Ankay, N. and Bundak, R. (2023) Vasculitis-Like Palpable Purpuric Rash Induced by Decapeptyl in a Pediatric Patient Diagnosed Central Precocious Puberty. Journal of Clinical Research in Pediatric Endocrinology, 15, 307-311. [Google Scholar] [CrossRef] [PubMed]
[29] Metbulut, A.P., Adıgüzel, K.T., İslamoğlu, C., Boyraz, M. and Mısırlıoğlu, E.D. (2021) Evaluation of Hypersensitivity Reactions with Leuprolide Acetate and Triptorelin Acetate in Children. Indian Journal of Endocrinology and Metabolism, 25, 527-531. [Google Scholar] [CrossRef] [PubMed]
[30] Omar, A.A., Nyaga, G. and Mungai, L.N.W. (2020) Pseudotumor Cerebri in Patient on Leuprolide Acetate for Central Precocious Puberty. International Journal of Pediatric Endocrinology, 2020, Article No. 22. [Google Scholar] [CrossRef] [PubMed]
[31] Palma, L., Gaudino, R., Cavarzere, P. and Antoniazzi, F. (2018) Does the Risk of Arterial Hypertension Increase in the Course of Triptorelin Treatment? Journal of Pediatric Endocrinology and Metabolism, 33, 449-452. [Google Scholar] [CrossRef] [PubMed]
[32] Tal, R. and Seifer, D.B. (2017) Ovarian Reserve Testing: A User’s Guide. American Journal of Obstetrics and Gynecology, 217, 129-140. [Google Scholar] [CrossRef] [PubMed]
[33] Chen, W.J., Li, H.F. and Zhou, B.B. (2016) Advances in Evaluation and Treatment of Ovarian Reserve. The Journal of Practical Medicine, 32, 19-22.
[34] Xu, Y., Han, C.Y., Park, M.J. and Gye, M.C. (2022) Increased Testicular Insulin-Like Growth Factor 1 Is Associated with Gonadal Activation by Recombinant Growth Hormone in Immature Rats. Reproductive Biology and Endocrinology, 20, Article No. 72. [Google Scholar] [CrossRef] [PubMed]
[35] 邱世超, 高婷, 高飞飞, 等. 血清LH、IGF-ⅠSDS、IGFbp3诊断女童快速进展型中枢性性早熟的价值研究[J]. 中国妇幼健康研究, 2024, 35(11): 7-12.
[36] 尹鹏, 倪卫东, 赵义勇, 等. 血清AMH、基础LH联合诊断女童中枢性性早熟的临床价值及二者与盆腔超声表现的关系分析[J]. 中国计划生育和妇产科, 2024, 16(2): 101-105.
[37] Tao, Y., Si, C., Li, H., Han, J., Hou, H. and Yang, M. (2020) Effect of Gonadotropin-Releasing Hormone Analog on Ovarian Reserve in Children with Central Precocious Puberty. Annals of Palliative Medicine, 9, 53-62. [Google Scholar] [CrossRef] [PubMed]
[38] Orszulak, D., Niziński, K., Bil, A., Gawlik, A., Ziora, K. and Drosdzol-Cop, A. (2024) The Effect of Gonadoliberin Analog Treatment in Precocious Puberty on Polycystic Ovarian Syndrome Prevalence in Adulthood. Frontiers in Endocrinology, 15, Article ID: 1314752. [Google Scholar] [CrossRef] [PubMed]
[39] Faienza, M.F., Brunetti, G., Acquafredda, A., Delvecchio, M., Lonero, A., Gaeta, A., et al. (2017) Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues. Hormone Research in Paediatrics, 87, 162-169. [Google Scholar] [CrossRef] [PubMed]
[40] Karavani, G., Chill, H.H., Schachter-Safrai, N., Lomnitz, G., Gillis, D. and Bauman, D. (2021) Gonadotropin Releasing Hormone Analogue Treatment of Central Precocious Puberty Is Not Associated with Altered Prevalence of Polycystic Ovary Syndrome: A Single Center Cohort Study. Clinical Diabetes and Endocrinology, 7, Article No. 14. [Google Scholar] [CrossRef] [PubMed]
[41] Buyukyilmaz, G., Koca, S.B., Adiguzel, K.T., Gurbuz, F. and Boyraz, M. (2023) Body Mass Index Evolution and Ovarian Function in Adolescent Girls Who Received GnRH Agonist Treatment for Central Precocious Puberty or Early and Fast Puberty. Journal of Pediatric Endocrinology and Metabolism, 36, 1044-1051. [Google Scholar] [CrossRef] [PubMed]
[42] van der Sluis, I.M., Boot, A.M., Krenning, E.P., Drop, S.L.S. and de Muinck Keizer-Schrama, S.M.P.F. (2002) 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. The Journal of Clinical Endocrinology & Metabolism, 87, 506-512. [Google Scholar] [CrossRef] [PubMed]
[43] Zhao, Q.H., Liu, J. and Xu, H.J. (2021) A Comparative Study of the Efficacy of Different Doses of Gonadotropin-Releasing Hormone Agonists in the Treatment of Precocious Puberty in Children. World Clinical Drugs, 42, 422-427.
[44] 李建英, 蒙娇阳, 李瑞凤. 不同剂量醋酸曲普瑞林对特发性中枢性性早熟患儿性激素及骨代谢的影响[J]. 河北医药, 2023, 45(17): 2624-2627.
[45] Loochi, S.A., Demol, S., Nagelberg, N., Lebenthal, Y., Phillip, M. and Yackobovitch-Gavan, M. (2021) Gonadotropin Releasing Hormone Analogue Therapy in Girls with Idiopathic Precocious Puberty/Early-Fast Puberty: Dynamics in Adiposity Indices, Eating Habits and Quality of Life. Journal of Pediatric Endocrinology and Metabolism, 34, 373-383. [Google Scholar] [CrossRef] [PubMed]
[46] 蒋颖, 顾威. 性早熟患儿促性腺激素释放激素类似物治疗中甲状腺功能的变化[J]. 山东医药, 2021, 61(14): 54-57.
[47] 陈梅芳. 促性腺激素释放激素类似物在儿童中枢性性早熟治疗中的效果及安全性[J]. 临床合理用药, 2024, 17(10): 105-108.
[48] Wojniusz, S., Callens, N., Sütterlin, S., Andersson, S., De Schepper, J., Gies, I., et al. (2016) Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty. Frontiers in Psychology, 7, Article ID: 1053. [Google Scholar] [CrossRef] [PubMed]
[49] Yu, R., Yang, S. and Hwang, I.T. (2019) Psychological Effects of Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Central Precocious Puberty. Journal of Pediatric Endocrinology and Metabolism, 32, 1071-1075. [Google Scholar] [CrossRef] [PubMed]
[50] Xie, L., Yang, Y., Xiong, X., Yang, L., Wu, X. and Zhang, D. (2023) A Clinical Study of Girls with Idiopathic Central Precocious Puberty and Psychological Behavior Problems. Clinical Pediatrics, 62, 914-918. [Google Scholar] [CrossRef] [PubMed]

为你推荐