EFFECT OF IRON OVERLOAD AND IRON CHELATORS ON ANTI-MÜLLERIAN HORMONE LEVEL IN EGYPTIAN FEMALE PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i4.16711Abstract
Objective: This work aims to determine the effect of iron overload on serum anti-müllerian hormone (AMH) levels in females subjected to transfusion-dependent β-thalassemia by measuring serum ferritin and to investigate the effects of iron chelation therapy including oral deferiprone and subcutaneous deferoxamine in the management of transfusion-related iron overload together with reproductive function.
Methods: 90 female patients with thalassemia major (TM), thalassemia intermedia (TI) and thalassemia minor (T minor) were selected to investigate AMH by ELISA and ferritin by IRMA.
Results: Serum AMH level was lower in female patients with transfusion dependent β-thalassemia than in T minor also, Ferritin was 25 fold more in TM compared to T minor (3088.0±2497.6 ng/ml vs. 120.3±36.2 ng/ml). There was significant negative correlation of AMH with ferritin in TM (r =-0.949; P<0.001*), in TI (r =-0.378; P =0.039*) and in T minor (r =-0.754; P<0.001*). The iron chelator, deferoxamine had significantly higher ferritin and lower AMH in TM and TI than deferiprone.
Conclusion: the results demonstrated that females with TM and TI were found to have lower serum AMH levels than T minor and inversely related to the serum ferritin levels in all thalassemic groups. Also, it demonstrated that deferiprone was more efficient than deferoxamine in removing excess iron and reduced the deleterious effect of excess iron to the reproductive system, which leads to fertility preservation of female patients with transfusion–dependent β-thalassemia.
Keywords: Anti-müllerian hormone, Ferritin, Iron overload, β-thalassemia, Deferoxamine, Deferiprone.
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References
Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis 2010;5:11.
Matin S, Jahromi MG, Karemizadeh Z, Haghpanah S, De Sanctis V, Soliman A, et al. The frequency of adrenal insufficiency in adolescents and young adults with thalassemia major versus thalassemia intermedia in Iran. Mediterr J Hematol Infect Dis 2015;7(1):e2015005.
Weatherall D. 2003 William Allan Award Address. The Thalassemias: The role of molecular genetics in an evolving global health problem. Am J Hum Genet 2004;74:385-92.
World Bank. Report of a Joint WHO-March of Dimes Meeting; 2006.
El-Beshlawy A, Kaddah N, Moustafa A, Mouktar G, Youssry I. Screening for beta-thalassaemia carriers in Egypt: Significance of the osmotic fragility test. East Mediterr Health J 2007;13:780-6.
Grow K, Vashist M, Abrol P, Sharma S, Yadav R. Beta thalassemia in India: Current status and the challenges ahead. Int J Pharm Pharm Sci 2014;6(4):28-33.
Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med 2005;353(11):1135-46.
Di Matteo R, Liuzza F, Pezzillo F, Gerardino L, Maccauro G. Subtrochanteric femoral fracture in a 26-year-old woman affected by β-talassemia major due to minor trauma: Analysis of bone modification causing the complication. Clin Ter 2007;158(5):425-9.
Muncie HL Jr, Campbell J. Alpha and beta thalassemia. Am Fam Physician 2009;80(4):339-44.
Musallam KM, Rivella S, Vichinsky E, Rachmilewitz EA. Non-transfusion-dependent thalassemias. Haematologica 2013;98:833-44.
De Domenico I, Ward DM, Kaplan J. Specific iron chelators determine the route of ferritin degradation. Blood 2009;114:4546-51.
Grady RW, Berdoukas VA, Rachmielewitz EA. Optimizing chelation therapy: Combining deferiprone and desferrioxamine. 42nd Annual Meeting of the American Society of Hematology. San Francisco; 2000.
Origa R, Bina P, Agus A, Crobu G, Defraia E, Dessì C, et al. Combined therapy with deferiprone and desferrioxamine in thalassemia major. Haematologica 2005;90:1309-14.
Brittenham GM. Iron-chelating therapy for transfusional iron overload. N Engl J Med 2011;364(2):146-56.
Galanello R. A thalassemic child becomes adult. Rev Clin Exp Hematol 2003;7(1):4-21.
Telfer P, Coen PG, Christou S, Hadjigavriel M, Kolnakou A, Pangalou E, et al. Survival of medically treated thalassemia patients in Cyprus. Trends and risk factors over the period 1980-2004. Haematologica 2006;91:1187-92.
Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008;10:42.
Cunningham MJ. Update on thalassemia: Clinical care and complications. Pediatr Clin North Am 2008;55:447-60, ix.
Bajoria R, Chatterjee R. Current perspectives of fertility and pregnancy in thalassemia. Hemoglobin 2009;33 Suppl 1:S131-5.
Origa R, Piga A, Quarta G, Forni GL, Longo F, Melpignano A, et al. Pregnancy and beta-thalassemia: An Italian multicenter experience. Haematologica 2010;95:376-81.
Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Müllerian hormone expression pattern in the human ovary: Potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004;10:77-83.
Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: Relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab 2003;88:5957-62.
Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-Müllerian hormone: A new marker for ovarian function. Reproduction 2006;131(1):1-9.
WHO Growth Reference; 2007. Available from: http://www.who.int/growthref/en/.
Melchiori L, Gardenghi S, Rivella S. Beta-thalassemia: HiJAKing ineffective erythropoiesis and iron overload. Adv Hematol 2010;2010:938640.
Porter JB, Davis BA. Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. Best Pract Res Clin Haematol 2002;15:329-68.
Pemde HK, Chandra J, Gupta D, Singh V, Sharma R, Dutta AK. Physical growth in children with transfusion-dependent thalassemia. Pediatr Health Med Ther 2011;2:13-9.
Li CK, Luk CW, Ling SC, Chik KW, Yuen HL, Li CK, et al. Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: Retrospective study. Hong Kong Med J 2002;8:255-60.
Salih KM, Al-Mosawy WF. Evaluation some consequences of thalassemia major in splenectomized and non-splenectomized Iraqi patients. Int J Pharm Pharm Sci 2013;5 Suppl 4:385-8.
Fahim FM, Saad K, Askar EA, Eldin EN, Thabet AF. Growth parameters and vitamin D status in children with thalassemia major in upper Egypt. Int J Hematol Oncol Stem Cell Res 2013;7:10-4.
Hashemi A, Ghilian R, Golestan M, Akhavan GM, Zare Z, Dehghani MA. The study of growth in thalassemic patients and its correlation with serum ferritin level. Iran J Pediatr Hematol Oncol 2011;1(4):147-51.
Vogiatzi MG, Macklin EA, Trachtenberg FL, Fung EB, Cheung AM, Vichinsky E, et al. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol 2009;146:546-56.
Hamed EA, ElMelegy NT. Renal functions in pediatric patients with beta-thalassemia major: Relation to chelation therapy: Original prospective study. Ital J Pediatr 2010;36:39.
Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, Te Velde ER, Broekmans FJ. Anti-müllerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab 2006;91:4057-63.
de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC. Antimüllerian hormone serum levels: A putative marker for ovarian aging. Fertil Steril 2002;77(2):357-62.
Lee TH, Liu CH, Huang CC, Hsieh KC, Lin PM, Lee MS. Impact of female age and male infertility on ovarian reserve markers to predict outcome of assisted reproduction technology cycles. Reprod Biol Endocrinol 2009;7:100.
Singer ST, Vichinsky EP, Gildengorin G, van Disseldorp J, Rosen M, Cedars MI. Reproductive capacity in iron overloaded women with thalassemia major. Blood 2011;118(10):2878-81.
Chang HH, Chen MJ, Lu MY, Chern JP, Lu CY, Yang YL, et al. Iron overload is associated with low anti-müllerian hormone in women with transfusion-dependent ß-thalassaemia. BJOG 2011;118:825-31.
Prabhu R, Prabhu V, Prabhu RS. Iron overload in beta thalassemia - A review. J Bio Sci Technol 2009;1(1):20-31.
El Beshlawy A. The Egyptian experience with oral iron chelators. Hematology 2005;10 Suppl 1:174-5.
El-Beshlawy A, Manz C, Naja M, Eltagui M, Tarabishi C, Youssry I, et al. Iron chelation in thalassemia: Combined or monotherapy? The Egyptian experience. Ann Hematol 2008;87(7):545-50.
Peng CT, Chow KC, Chen JH, Chiang YP, Lin TY, Tsai CH. Safety monitoring of cardiac and hepatic systems in beta-thalassemia patients with chelating treatment in Taiwan. Eur J Haematol 2003;70:392-7.
Pennell DJ, Berdoukas V, Karagiorga M, Ladis V, Piga A, Aessopos A, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006;107(9):3738-44.
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