LEUPROLİDE ASETAT TEDAVİSİ ALAN SANTRAL PUBERTE PREKOKS TANILI KIZ HASTALARDA UZUN DÖNEM SONUÇLAR

Yıl 2020, , 369 - 375, 20.12.2020

Esra Özmen Prof. Dr. Sibel Tulgar Kınık

https://doi.org/10.37696/nkmj.714085

Öz

Amaç: Santral puberte prekoks (SPP), hipotalamo-hipofizer-gonadal (HHG) aksın erken aktivasyonuna bağlı olarak sekonder seks karakterlerinin kızlarda sekiz, erkeklerde dokuz yaşından önce görülmesidir. Bu çalışmada amaç; SPP tanısıyla leuprolide asetat tedavisi alan kız olguların tedavi bitiminden sonraki uzun dönem pubertal verilerini ve boy kazanımlarını araştırmaktır.
Materyal ve Metot: Aralık 2002– Haziran 2013 tarihleri arasında SPP nedeniyle izlenen ve tedavi edilen toplam 70 kız olgu çalışmaya dahil edildi. Olguların dosya bilgilerinden anamnez, fizik muayene bulguları, anne-baba boyları, laboratuar ve radyolojik tetkikleri, tedavi öncesi ve tedavi bitimindeki boy, kilo, vücut kitle indeksi, hedef boy (MPH=midparenteral height) kaydedildi. Tedavinin başlangıcında ki tahmini erişkin boy (TEB) hesaplandı. Tedavinin kesilmesinden sonra olgular yeniden değerlendirildiğinde adet başlama yaşı ve düzeni, final boyları, VKİ kaydedildi.
Bulgular: Leuprolide asetat tedavisi gören 70 hastada TEB 157.7±7.4 cm, MPH 158.3±4.5 cm, final boy 161.3±6.7 cm bulundu. Hastaların final boy uzunlukları ile başvuru anındaki boy yaşı, MPH değeri, başvuru anındaki ve tedavi bitimindeki boy uzunluğu arasında pozitif yönde bir ilişki saptandı ve istatistiksel olarak anlamlı kabul edildi (sırasıyla r=0.443, p<0.001, r=0.502, p<0.001, r=0.462, p<0.001 r=0.610, p<0.001). Hastaların %2.9’unda (n=2) adet düzensizliği tespit edildi. Olguların tedavi öncesi ve tedavi sonrası relatif VKİ’ları arasında fark saptanmadı.
Sonuç: Leuprolide asetat tedavisinin HHG aksının baskılanması, pubertal bulguların ilerlemesinin durdurulması, menarşın geciktirilmesi ve final boyun korunmasında etkili olduğu gösterildi. Tedavinin adet düzensizliği, obeziteyi arttırıcı yönde yan etkilerinin olmadığı saptandı.

Anahtar Kelimeler

Adet düzeni, Final boy, Leuprolide asetat, Obezite, Puberte prekoks

Destekleyen Kurum

Başkent Üniversitesi - ANKARA

Proje Numarası

Proje No: KA 14/334

LONG-TERM RESULTS IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY AFTER LEUPROLIDE ACETATE TREATMENT

Öz

Aim: Central precocious
puberty (CPP) commonly refers to the development of pubertal sex
characteristics as a consequence of the premature activation of the hypothalamic-
pituitary-gonadal (HPG) axis before the age of eight years in girls and nine
years in boys. This study’s aim is to research the female patinet`s long term
lenght gains who received leuprolide acetate with a diagnose of CPP.

Material
and Methods: Between December 2002 and June 2013, a total
of 70 female patients who has been monitored of central precocious puberty
included in the study. From the files of the cases; anamnesis, physical
examination, height of mother and father, midparenteral height (MPH) laboratory
and radiological findings and weight, height and body mass index (BMI) before
and after treatment recorded.

Results: In
70 patients diagnosed as CPP and given leuprolide acetate treatment average for
21.73±8.45 months, predicted adult height(PAH) 157.7±7.4 cm, MPH 158.3±4.5 cm,
final height found as 161.3±6.7 cm. There was a statiscally significant
positive correlation  between final
height and height age, MPH value, height on admission and after treatment (r=0.443,
p<0.001, r=0.502, p<0.001, r=0.462, p<0.001 r=0.610, p<0.001 in
order). %2.9 of the patients have irregular menstruel periods. There was
statistically significant relation of BMI between before and after the
treatment.

Conclusion: It
is shown that Leuprolide acetat therapy is efficient in suppressing HHG axis,
preventing the advancement of pubertal findings, prolonging the menarch and
preserving the final height. The treatment showed no adverse effects on
increasing obesity and menstrual irregularity.

Anahtar Kelimeler

menstruration, Leuprolide acetate, Obesity, Precocious puberty

Proje Numarası

Proje No: KA 14/334

Kaynakça

• 1. Carel JC, Léger J. Precocious puberty. N Engl J Med. 2008;358(22):2366-77.
• 2. Lebrethon MC, Bourguignon JP. Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr. 2000;12:394-399.
• 3. Sorensen K, Mouritsen A, Aksglaede L, Hagen CP, Mogensen SS, Juul A. Recent secular trends in pubertal timing: implications for evaluation and diagnosis of precocious puberty. Horm Res Paediatr. 2012;77(3):137-45.
• 4. Crowley WF Jr, Comite F, Vale W, Rivier J, Loriaux DL, Cutler GB Jr. Therapeutic use of pituitary desensitization with a long-acting lhrh agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab. 1981;52(2):370-2.
• 5. Partsch CJ, Sippell WG. Treatment of central precocious puberty. Best Pract Res Clin Endocrinol Metab. 2002;16:165-189.
• 6. Partsch CJ, Hümmelink R, Lorenzen F, Sippell WG. The significance and characteristics of the LHRH test in diagnosing precocious puberty development in girls: the stimulated LH/FSH quotient differentiates between central precocious puberty and prematüre thelarche. Monatsschr Kinderheilkd. 1989;137(5):284-8.
• 7. Parker KL, Baas-Bailon RG, Lee PA. Depot leuprolide acetate dosage for sexual precocity. J Clin Endocrinol Metab. 1991;71:50-52.
• 8. Gunoz H, Bundak R, Furman A, Darendeliler F, Saka N. Z-score reference values for height in Turkish children aged 6 to 18 years. J Clin Res Pediatr Endocrinol. 2014;6(1):28-33.
• 9. Tanner JM, Goldstein H, WhitehouseRH. Standards for children’s height at ages 2–9 years allowing for height of parents. Arch Dis Child. 1970;45:755–762.
• 10. Bundak R, Furman A, Gunoz H, Darendeliler F, Bas F, Olcay N. Body mass index references for Turkish children. Acta Pediatrica. 2006;95:194-198.
• 11. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. Stanford, CA: 1959, Stanford University Press.
• 12. Zachmann M, Sobradillo B, Frank M, Frisch H, Prader A. Bayley-Pinneau, Roche-Wainer-Thissen, and Tanner height predictions in normal children and in patients with various pathologic conditions. J Pediatr. 1978;93(5):749-55.
• 13. 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.
• 14. Antoniazzi F, Zamboni G, Bertoldo F, Lauriola S, Mengarda F, Pietrobelli A, et al. Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation. J Clin Endocrinol Metab. 2003;88(3):1096-1010.
• 15. Lee PA, Neely EK, Fuqua J, Yang D, Larsen LM, Mattia-Goldberg C, et al. Efficacy of Leuprolide Acetate 1 Month Depot for Central Precocious Puberty (CPP): Growth Outcomes During a Prospective, Longuitudinal Study. Int J Pediatr Endocrinol. 2011;2011(1):7.
• 16. 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 (Oxf). 2004;61(5):626-34.
• 17. 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 reproduetive funetion. J Clin Endocrinol Metab. 1999;84(12):4583-90.
• 18. Jaruratanasirikul S, Thaiwong M. Outcome of gonadotropin releasing analog treatment for children with centralprecocious puberty:15-year experience in southern Thailand. J Pediatr Endocrinol Metab. 2011;24:519-23.
• 19. Allali S, Lemaire P, Couto-Silva AC, Prété G, Trivin C, Brauner R. Predicting the adult height of girls with central precocious puberty. Med Sci Monit. 2011;17:41-8.
• 20. Wheeler MD, Styne DM. Diagnosis and management of precocious puberty. Pediatr Clin North Am. 1990; 37:1255-71.
• 21. Lee SJ, Yang EM, Seo JY, Kim CJ. Effects of gonadotropin-releasing hormone agonist therapy on body mass index and height in girls with central precocious puberty. Chonnam Med J. 2012;48:27-31.
• 22. Nield LS, Cakan N, Kamat D. A practical approach to precocious puberty. Clin Pediatr (Phila). 2007;46 (4):299-306.
• 23. Heger S, Sippell WG, Partsch CJ. Gonadotropin-releasing hormone analogue treatment for precocious puberty. Twenty years of experience. Endocr Dev. 2005;8:94-125.
• 24. Brito VN, Latronico AC, Arnhold IJ, Mendonca BB. A single luteinizing hormone determination 2 hours after depot leuprolide is useful for therapy monitoring of gonadotropin-dependent precocious puberty in girls. J Clin Endocrinol Metab. 2004;89(9):4338-42.
• 25. Tanaka T, Hibi I, Kato K, Saito S, Shimizu N, Suwa S, et al. A dose fınding study of a süper long-acting luteinizing hormone-releasing hormone analog (leuprolide acetate depot, TAP-144-SR) in the treatment of central precocious puberty. The TAP-144-SR CPP Study Group. Endocrinol Jpn. 1991;38(4):369-76.
• 26. Carel JC, Lahlou N, Guazzarotti L, Joubert-Collin M, Roger M, Colle M, et al. Treatment of central precocious puberty with depot leuprorelin. French Leuprorelin Trial Group. Eur J Endocrinol. 1995;132(6):699-704.
• 27. Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL. Overweight prevalence and trends for children and adolescents. The National Health and Nutrition Examination Surveys, 1963 to 1991. Arch Pediatr Adolesc Med. 1995;149:1085-91.
• 28. Styne DM. Childhood and adolescent obesity: prevalence and significance. Pediatr Clin North Am. 2001;48: 823-54.
• 29. Hermann-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, et al. Secondary sexual characteristics and menses in young girls seen in Office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997;99: 505-12.
• 30. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relationto increased body mass index and race.Pediatrics. 2001;108:347-53.
• 31. Traggiai C, Perucchin PP, Zerbini K, Gastaldi R, De Biasio P, Lorini R. Outcome after depot gonadotrophin-releasing hormone agonist treatment for central precocious puberty: effects on body mass index and final height. Eur J Endocrinol. 2005;153(3):463-4.
• 32. Brito VN, Latronico AC, Cukier P, Teles MG, Silveira LF, Arnhold IJ, et al. Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropinreleasing hormone analogs. J Clin Endocrinol Metab. 2008;93(7):2662-9.
• 33. Poomthavorn P, Suphasit R, Mahachoklertwattana P. Adult height, body mass index and time of menarche of girls with idiopathic central precocious puberty after gonadotropin-releasing hormone analogue treatment. J Pediatr Endocrinol Metab. 2011;27: 524-8.
• 34. Kim EY. Long-term effects of gonadotropin-releasing hormone analogs in girls with central precocious puberty. Korean J Pediatr. 2015;58(1):1-7.
• 35. Lazar L, Kauli R, Bruchis C, Nordenberg J, Galatzer A, Pertzelan A. Early polycystic ovary-like syndrome in girls with central precocious puberty and exaggerated adrenal response. Eur J Endocrinol. 1995;133(4):403-6.
• 36. Bridges NA, Cooke A, Healy MJ, Hindmarsh PC, Brook CG. Ovaries in sexual precocity. Clin Endocrinol (Oxf). 1995;42:135-40.