Tsilionis Vasileios, Moustakli Efthalia, Dafopoulos Stefanos, Zikopoulos Athanasios, Sotiriou Sotirios, Zachariou Athanasios, Dafopoulos Konstantinos
Department of Obstetrics and Gynecology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.
Laboratory of Medical Genetics, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
Metabolites. 2024 Dec 20;14(12):717. doi: 10.3390/metabo14120717.
Thalassemia is an autosomal recessive hereditary chronic hemolytic anemia characterized by a partial or complete deficiency in the synthesis of alpha- or beta-globin chains, which are essential components of adult hemoglobin. Mutations in the globin genes lead to the production of unstable globin chains that precipitate within cells, causing hemolysis. This shortens the lifespan of mature red blood cells (RBCs) and results in the premature destruction of RBC precursors in the bone marrow. Regular red blood cell transfusions are the standard treatment for thalassemia. However, these transfusions can lead to increased iron overload, which can impair vital systems such as the liver, heart, ovaries, and endocrine system. Focusing on female reproductive endocrinology, recurrent blood transfusions can cause iron accumulation in the pituitary and hypothalamus, leading to hypogonadotropic hypogonadism (HH), the most common endocrinopathy in these patients, affecting 40-91% of women. Recurrent transfusions and the resulting iron overload can also lead to oxidative stress and ovarian damage in patients with beta-thalassemia major (BTM). Despite advancements in iron chelation therapy, hypothalamic-pituitary damage associated with HH contributes to subfertility and sexual dysfunction, often with little to no recovery. In women exposed to gonadotoxic drugs, particularly those with BTM, anti-Mullerian hormone (AMH)-a marker of ovarian reserve-is frequently used to assess ovarian damage. This review aims to explore the pathophysiology of β-thalassemia and its major clinical manifestations, with a focus on endocrine complications and their impact on ovarian reserve. It also investigates how metabolomics can provide insights into the disease's metabolic alterations and inform current and emerging therapeutic strategies to mitigate complications and optimize patient outcomes, potentially leading to more effective and personalized treatments.
地中海贫血是一种常染色体隐性遗传性慢性溶血性贫血，其特征是α或β珠蛋白链的合成部分或完全缺陷，而α或β珠蛋白链是成人血红蛋白的重要组成部分。珠蛋白基因突变导致产生不稳定的珠蛋白链，这些链在细胞内沉淀，引起溶血。这缩短了成熟红细胞（RBC）的寿命，并导致骨髓中RBC前体的过早破坏。定期红细胞输血是地中海贫血的标准治疗方法。然而，这些输血会导致铁过载增加，这会损害肝脏、心脏、卵巢和内分泌系统等重要系统。专注于女性生殖内分泌学，反复输血会导致垂体和下丘脑铁蓄积，导致低促性腺激素性性腺功能减退（HH），这是这些患者中最常见的内分泌病，影响40-91%的女性。反复输血及由此导致的铁过载也会导致重型β地中海贫血（BTM）患者出现氧化应激和卵巢损伤。尽管铁螯合疗法取得了进展，但与HH相关的下丘脑-垂体损伤会导致生育力低下和性功能障碍，通常几乎无法恢复。在接触性腺毒性药物的女性中，尤其是患有BTM的女性，抗苗勒管激素（AMH）——一种卵巢储备标志物——经常被用于评估卵巢损伤。本综述旨在探讨β地中海贫血的病理生理学及其主要临床表现，重点关注内分泌并发症及其对卵巢储备的影响。它还研究了代谢组学如何能够深入了解该疾病的代谢改变，并为当前和新兴的治疗策略提供信息，以减轻并发症并优化患者预后，从而可能带来更有效和个性化的治疗方法。
