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Do GnRH Analogues Cause Weight Gain in Girls Diagnosed with Central Precocious Puberty?

Year 2023, Volume: 20 Issue: 1, 105 - 110, 27.04.2023
https://doi.org/10.35440/hutfd.1190733

Abstract

Background: Gonadotropin-releasing hormone analogues (GnRHa) have been widely used in the treatment of patients with central precocious puberty (CPP) for many years. In previous studies regarding the effects of GnRHa therapy on body mass index (BMI), conflicting results have been obtained. In this study, it was aimed to evaluate the effects of GnRHa therapy on BMI in girls diagnosed with CPP.
Material and method: In the study, a total of 145 female patients, who were treated and followed up due to CPP between September 2016 and June 2021, were included. In the retrospective review of medical records of the patients, age at admission, height, weight, BMI and standard deviation scores (SDS), bone age, Tanner stage, serum follicle-stimulating hormone (FSH) levels, luteinizing hormone (LH) levels, estradiol (E2) levels and the peak LH level in the GnRH stimulation test in the beginning and after the first year of treatment were evaluated.
Results: The mean age of 145 patients with central precocious puberty in the beginning of treatment was 7.27±0.97 years, and the mean bone age was 9.12±1.10 years. In the beginning of treatment, 118 (81.38%) of the patients were at a normal weight or underweight, and 27 (18.62%) patients were overweight or obese. 109 (75.17%) of the patients were in Tanner stage 2, 30 (20.69%) patients were in Tanner stage 3, and 6 (4.14%) patients were in Tanner stage 4. While the mean BMI-SDS of all patients was 0.11±0.99 before the treatment, it increased significantly (p<0.01) in the first year of treatment and was found as 0.35 ± 0.95. While the mean BMI-SDS of patients who were at a normal weight or underweight was -0.21± 0.78 before the treatment, it was found as 0.09±0.84 after the treatment (p < 0.01). The initial BMI-SDS of overweight or obese patients was 1.53±0.40, and it was found as 1.48±0.49 after the treatment (p=0.41).
Conclusion: In our study, it was shown that GnRHa therapy used in the treatment of central precocious puberty increased the BMI-SDS in patients who were at a normal weight or underweight, but it did not cause any change in patients who were overweight or obese.

References

  • 1. Carel JC, Leger J, Clinical practice. Precocious puberty. N Engl J Med 2008; 358(22):2366-77.
  • 2. Carel JC, Eugster EA, A. Rogol, Ghizzoni L, Palmert MR, Antoniazzi F, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009; 123(4):e752-62.
  • 3. De Kroon MLA , Renders CM, van Wouwe JP, van Buuren V, Hirasing RA. The Terneuzen Birth Cohort: BMI change between 2 and 6 years is most predictive of adult cardiometabolic risk. PLoS One 2010; 5 (11); e13966.
  • 4. Barker DJP, Osmond C, Forsén TJ, Kajantie E, Eriksson JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005; 353(17):1802-9.
  • 5. Pasquino AM, Pucarelli I, Accardo F, Demiraj V, Segni M, Di Nardo R. Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: impact on adult height, body mass index, bone mineral content, and reproductive function. J Clin Endocrinol Metab 2008; 93(1):190–5.
  • 6. Heger S, Partsch CJ, Sippell WG. Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function. J Clin Endocrinol Metab 1999; 84:4583–90.
  • 7. Oostdijk W, Rikken B, Schreuder S, Otten B , Odink R , Rouwe C, et al. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch. Dis. Child 1996; 75(4):292-7.
  • 8. Paterson WF, McNeill E, Young D, Donaldson MDC. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin. Endocrinol 2004; 61(5):626-34.
  • 9. Palmert MR, Mansfield MJ, Crowley Jr WF, Crigler Jr JF, Crawford JD, Boepple PA. Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty. J Clin Endocrinol Metab 1999; 84:4480–8.
  • 10. Neyzi O, Bundak R, Gökçay G, Günöz H, Furman A, Darendeliler F, et al. Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children. J Clin Res Pediatr Endocrinol 2015; 7:280–293.
  • 11. Demir K, Özen S, Konakçı E, Aydın M, Darendeliler F. A Comprehensive Online Calculator for Pediatric Endocrinologists: ÇEDD Çözüm/TPEDS Metrics. J Clin Res Pediatr Endocrinol 2017; 9:182–184.
  • 12. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44:291–303.
  • 13. Milner GR, Levick RK, Kay R. Assessment of bone age: a comparison of the Greulich and Pyle, and the Tanner and Whitehouse methods. Clin Radiol 1986; 37: 119–21.
  • 14. Resende EAMR, Lara BHJ, Reis JD, Ferreira BP, Pereira GA, Borges MF. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endocrinol Metab 2007; 92:1424– 9. doi: 10.1210/jc.2006-1569.
  • 15. 17-Lee HS, Park HK, Ko JH, Kim YJ, Hwang JS. Utility of Basal luteinizing hormone levels for detecting central precocious puberty in girls. Horm Metab Res 2012; 44: 851-4.
  • 16. Xiaoping L, Yan L, Ling H, Wei W, Yanqin Y, Feng Y. Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis. Clin Endocrinol 2021; 94(5): 786–796.
  • 17. Feuillan PP, Jones JV, Barnes K, Oerter-Klein K, Cutler Jr GB. Reproductive axis after discontinuation of gonadotropinreleasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty. J Clin Endocrinol Metab 1999; 84(1):44-9.
  • 18. Chiumello G, Brambilla P, Guarneri MP, Russo G, Manzoni P, Sgaramella P. Precocious puberty and body composition: effects of GnRH analog treatment. J Pediatr Endocrinol Metabol 2000;13 Suppl 1:791–4.
  • 19. Paterson WF, McNeill E, Young D, Donaldson MD. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol 2004; 61(5):626-34.
  • 20. Carel JC, Roger M, Ispas S, Tondu F, Lahlou N, Blumberg J, et al. Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty. J Clin Endocrinol Metab 1999; 84(6):1973-8.
  • 21. Lee SJ, Yang EM, Seo JY, Kim CJ. Effects of gonadotropinreleasing hormone agonist therapy on body mass index and height in girls with central precocious puberty. Chonnam Med J 2012; 48:27–31.
  • 22. Wolters B, Lass N, Reinehr T. Treatment with Gonadotropin-Releasing Hormone Analogues: Different Impact on Body Weight in Normal-Weight and Overweight Children. Horm Res Paediatr 2012; 78:304–311 DOI: 10.1159/000346145.
  • 23. Messaaoui A, Massa G, Tenoutasse S, Heinrichs C. [Treatment of central precocious puberty with Gonadotropin-Releasing Hormone agonist (triptorelin) in girls: breast development, skeletal maturation, height and weight evolution during and after treatment]. Rev Med Brux 2005; 26(1):27-32. 24. Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Segni M, Rosano M, et al. Reduction of baseline body mass index under gonadotropinsuppressive therapy in girls with idiopathic precocious puberty. Eur J Endocrinol 2004; 150(4):533-7.
  • 25. Paterson WF, McNeill E, Young D, Donaldson MDC. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol 2004; 61(5):626-34.
  • 26. Alessandri SB, Pereira Fde A, Villela RA, Antonini SR, Elias PC, Martinelli Jr CE, et al. Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist. Clinics (Sao Paulo) 2012; 67(6):591–6.
  • 27. Cassio A, Bal MO, Orsini LF, Balsamo A, Sansavini S, Gennari M, et al. Reproductive outcome in patients treated and not treated for idiopathic early puberty: long-term results of a randomized trial in adults. J Pediatr 2006; 149:532–6.
  • 28. Lazar L, Lebenthal Y, Yackobovitch-Gavan M, Shalitin S, de Vries L, Phillip M, et al. Treated and untreated women with idiopathic precocious puberty: BMI evolution, metabolic outcome, and general health between third and fifth decades. J Clin Endocrinol Metab 2015; 100(4):1445–51. doi:10.1210/jc.2014-3748.
  • 29. Magiakou MA, Manousaki D, Papadaki M, Hadjidakis D, Levidou G, Vakaki M, et al. The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study. J. Clin. Endocrinol. Metab 2010; 95(1):109-17.doi: 10.1210/jc.2009-0793.
  • 30. Klein KO, Barnes KM, Jones JV, Feuillan PP, Cutler Jr GB. Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. J. Clin. Endocrinol. Metab 2001; 86, 4711–4716.
  • 31. Pich J, Bibiloni MDM, Pons A, Tur JA. Weight self-regulation process in adolescence: the relationship between control weight attitudes, behaviors, and body weight status. Front. Nutr 2015; 2:14. doi: 10.3389/fnut.2015.00014.
  • 32. Vuralli D, Ozon A, Gonc EN, Alikasifoglu A, Kandemir N. Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty. J Pediatr Endokrinol Metab 2020 Ocak 28;33(1):99-105.

Santral Puberte Prekoks Tanısı Konulan Kız Çocuklarında GnRH Analogları Kilo Artışı Yapar mı?

Year 2023, Volume: 20 Issue: 1, 105 - 110, 27.04.2023
https://doi.org/10.35440/hutfd.1190733

Abstract

Amaç: Gonadotropin-releasing hormone analogları (GnRHa), uzun yıllardır santral puberte prekokslu (SPP) hastaların tedavisinde yaygın olarak kullanılmaktadır. Önceki çalışmalarda GnRHa tedavisinin vücut kitle indeksi (VKİ) üzerindeki etkileri ile ilişkili çelişkili sonuçlar mevcuttur.Bu çalışmada SPP tanısı konulan kız çocuklarında GnRHa tedavisinin VKİ üzerindeki etkisinin değerlendirilmesi amaçlanmıştır.
Materyal ve metod: Çalışmaya Eylül 2016 – Haziran 2021 tarihleri arasında SPP nedeniyle izlenen ve tedavi edilen toplam 145 kız hasta alındı. Olguların geriye dönük dosya kayıtlarında; başvuru anındaki yaşı, başlangıç ve tedavinin birinci yılındaki boy, kilo, VKİ ve standart deviasyon skorları (SDS), kemik yaşı, Tanner evresi, serum folikül uyarıcı hormon (FSH), lüteinizan hormon (LH), östradiol (E2) seviyeleri ve GnRH stimülasyon testi sırasındaki pik LH seviyesi değerlendirildi.
Bulgular: Santral puberte prekoks saptanan 145 hastanın tedavi başlangıcındaki yaş ortalaması 7.27±0.97 yıl, ortalama kemik yaşı 9.12±1.10 yıl idi. Tedavi başlangıcında 118 (% 81.38) hasta normal veya düşük kilolu, 27 (% 18.62) hasta ise kilolu yada obezdi. 109 (%75.17) olgu tanner evre 2, 30 olgu (% 20.69) tanner evre 3 ve 6 olgu (% 4.14) ise tanner evre 4’te idi. Tüm hastaların tedavi öncesi ortalama VKİ-SDS’si 0,11±0,99 iken, tedavinin birinci yılında 0.35 ± 0.95 olarak bulundu ve anlamlı ölçüde artış saptandı (p<0.01). Normal veya düşük kilolu hastaların tedavi öncesi ortalama VKİ-SDS’si -0.21± 0.78 iken, tedavi sonrası 0.09±0.84 saptandı (p < 0.01). Kilolu veya obez hastaların başlangıç VKİ-SDS’si 1.53±0.40 iken, tedavi sonrası 1.48±0.49 saptandı (p=0.41).
Sonuç: Çalışmamızda santral puberte prekoks tedavisinde kullanılan GnRHa tedavisinin zayıf ve normal kilolu olgularda VKİ-SDS’sini artırdığı, fazla kilolu veya obez grupta ise değişikliğe yol açmadığı gösterilmiştir.

References

  • 1. Carel JC, Leger J, Clinical practice. Precocious puberty. N Engl J Med 2008; 358(22):2366-77.
  • 2. Carel JC, Eugster EA, A. Rogol, Ghizzoni L, Palmert MR, Antoniazzi F, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009; 123(4):e752-62.
  • 3. De Kroon MLA , Renders CM, van Wouwe JP, van Buuren V, Hirasing RA. The Terneuzen Birth Cohort: BMI change between 2 and 6 years is most predictive of adult cardiometabolic risk. PLoS One 2010; 5 (11); e13966.
  • 4. Barker DJP, Osmond C, Forsén TJ, Kajantie E, Eriksson JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005; 353(17):1802-9.
  • 5. Pasquino AM, Pucarelli I, Accardo F, Demiraj V, Segni M, Di Nardo R. Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: impact on adult height, body mass index, bone mineral content, and reproductive function. J Clin Endocrinol Metab 2008; 93(1):190–5.
  • 6. Heger S, Partsch CJ, Sippell WG. Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function. J Clin Endocrinol Metab 1999; 84:4583–90.
  • 7. Oostdijk W, Rikken B, Schreuder S, Otten B , Odink R , Rouwe C, et al. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch. Dis. Child 1996; 75(4):292-7.
  • 8. Paterson WF, McNeill E, Young D, Donaldson MDC. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin. Endocrinol 2004; 61(5):626-34.
  • 9. Palmert MR, Mansfield MJ, Crowley Jr WF, Crigler Jr JF, Crawford JD, Boepple PA. Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty. J Clin Endocrinol Metab 1999; 84:4480–8.
  • 10. Neyzi O, Bundak R, Gökçay G, Günöz H, Furman A, Darendeliler F, et al. Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children. J Clin Res Pediatr Endocrinol 2015; 7:280–293.
  • 11. Demir K, Özen S, Konakçı E, Aydın M, Darendeliler F. A Comprehensive Online Calculator for Pediatric Endocrinologists: ÇEDD Çözüm/TPEDS Metrics. J Clin Res Pediatr Endocrinol 2017; 9:182–184.
  • 12. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44:291–303.
  • 13. Milner GR, Levick RK, Kay R. Assessment of bone age: a comparison of the Greulich and Pyle, and the Tanner and Whitehouse methods. Clin Radiol 1986; 37: 119–21.
  • 14. Resende EAMR, Lara BHJ, Reis JD, Ferreira BP, Pereira GA, Borges MF. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endocrinol Metab 2007; 92:1424– 9. doi: 10.1210/jc.2006-1569.
  • 15. 17-Lee HS, Park HK, Ko JH, Kim YJ, Hwang JS. Utility of Basal luteinizing hormone levels for detecting central precocious puberty in girls. Horm Metab Res 2012; 44: 851-4.
  • 16. Xiaoping L, Yan L, Ling H, Wei W, Yanqin Y, Feng Y. Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis. Clin Endocrinol 2021; 94(5): 786–796.
  • 17. Feuillan PP, Jones JV, Barnes K, Oerter-Klein K, Cutler Jr GB. Reproductive axis after discontinuation of gonadotropinreleasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty. J Clin Endocrinol Metab 1999; 84(1):44-9.
  • 18. Chiumello G, Brambilla P, Guarneri MP, Russo G, Manzoni P, Sgaramella P. Precocious puberty and body composition: effects of GnRH analog treatment. J Pediatr Endocrinol Metabol 2000;13 Suppl 1:791–4.
  • 19. Paterson WF, McNeill E, Young D, Donaldson MD. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol 2004; 61(5):626-34.
  • 20. Carel JC, Roger M, Ispas S, Tondu F, Lahlou N, Blumberg J, et al. Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty. J Clin Endocrinol Metab 1999; 84(6):1973-8.
  • 21. Lee SJ, Yang EM, Seo JY, Kim CJ. Effects of gonadotropinreleasing hormone agonist therapy on body mass index and height in girls with central precocious puberty. Chonnam Med J 2012; 48:27–31.
  • 22. Wolters B, Lass N, Reinehr T. Treatment with Gonadotropin-Releasing Hormone Analogues: Different Impact on Body Weight in Normal-Weight and Overweight Children. Horm Res Paediatr 2012; 78:304–311 DOI: 10.1159/000346145.
  • 23. Messaaoui A, Massa G, Tenoutasse S, Heinrichs C. [Treatment of central precocious puberty with Gonadotropin-Releasing Hormone agonist (triptorelin) in girls: breast development, skeletal maturation, height and weight evolution during and after treatment]. Rev Med Brux 2005; 26(1):27-32. 24. Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Segni M, Rosano M, et al. Reduction of baseline body mass index under gonadotropinsuppressive therapy in girls with idiopathic precocious puberty. Eur J Endocrinol 2004; 150(4):533-7.
  • 25. Paterson WF, McNeill E, Young D, Donaldson MDC. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol 2004; 61(5):626-34.
  • 26. Alessandri SB, Pereira Fde A, Villela RA, Antonini SR, Elias PC, Martinelli Jr CE, et al. Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist. Clinics (Sao Paulo) 2012; 67(6):591–6.
  • 27. Cassio A, Bal MO, Orsini LF, Balsamo A, Sansavini S, Gennari M, et al. Reproductive outcome in patients treated and not treated for idiopathic early puberty: long-term results of a randomized trial in adults. J Pediatr 2006; 149:532–6.
  • 28. Lazar L, Lebenthal Y, Yackobovitch-Gavan M, Shalitin S, de Vries L, Phillip M, et al. Treated and untreated women with idiopathic precocious puberty: BMI evolution, metabolic outcome, and general health between third and fifth decades. J Clin Endocrinol Metab 2015; 100(4):1445–51. doi:10.1210/jc.2014-3748.
  • 29. Magiakou MA, Manousaki D, Papadaki M, Hadjidakis D, Levidou G, Vakaki M, et al. The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study. J. Clin. Endocrinol. Metab 2010; 95(1):109-17.doi: 10.1210/jc.2009-0793.
  • 30. Klein KO, Barnes KM, Jones JV, Feuillan PP, Cutler Jr GB. Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. J. Clin. Endocrinol. Metab 2001; 86, 4711–4716.
  • 31. Pich J, Bibiloni MDM, Pons A, Tur JA. Weight self-regulation process in adolescence: the relationship between control weight attitudes, behaviors, and body weight status. Front. Nutr 2015; 2:14. doi: 10.3389/fnut.2015.00014.
  • 32. Vuralli D, Ozon A, Gonc EN, Alikasifoglu A, Kandemir N. Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty. J Pediatr Endokrinol Metab 2020 Ocak 28;33(1):99-105.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Ruken Yıldırım 0000-0002-9558-3856

Edip Unal 0000-0002-9809-0977

Early Pub Date April 27, 2023
Publication Date April 27, 2023
Submission Date October 17, 2022
Acceptance Date February 27, 2023
Published in Issue Year 2023 Volume: 20 Issue: 1

Cite

Vancouver Yıldırım R, Unal E. Santral Puberte Prekoks Tanısı Konulan Kız Çocuklarında GnRH Analogları Kilo Artışı Yapar mı?. Harran Üniversitesi Tıp Fakültesi Dergisi. 2023;20(1):105-10.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty