Reproductive Endocrine Stability Despite Persistent Hypogonadism in Well-Chelated Adult Women with Transfusion-Dependent β-Thalassemia

Background: Endocrine complications remain a major cause of long-term morbidity in patients with transfusion-dependent β-thalassemia (TDT), with hypogonadism being the most frequently reported abnormality. Although iron overload is central to disease pathophysiology, its relationship with reproductive endocrine function in well-chelated adult women remains unclear. Methods: This retrospective longitudinal study evaluated endocrine function in 15 adult women with transfusion-dependent β-thalassemia major over a two-year follow-up period at a tertiary care center. Age, hormonal profiles, ovarian reserve markers, and clinical reproductive characteristics were assessed at baseline and follow-up. An age-matched control group of 22 healthy women was included. Endocrine and biochemical evaluation comprised gonadotropins (follicle-stimulating hormone and luteinizing hormone), estradiol, thyroid-stimulating hormone, prolactin, anti-Müllerian hormone, hemoglobin, serum iron, total iron-binding capacity, vitamin B12, folate, 25-hydroxyvitamin D, and cardiac and hepatic MRI T2* assessment of iron burden. Results: Hypogonadism was clinically prevalent, while other endocrine axes largely remained within reference ranges during follow-up. No newly emerging overt endocrine disorders were identified. Reproductive hormone levels showed no significant temporal changes and were comparable to those of healthy controls. AMH levels demonstrated marked interindividual variability and did not consistently correlate with systemic or imaging-based iron indices. Conclusions: In well-chelated adult women with transfusion-dependent β-thalassemia, reproductive endocrine parameters appear biochemically stable over short-term follow-up, yet clinically relevant hypogonadism persists. AMH variability may reflect subtle ovarian reserve impairment not captured by conventional gonadotropin measurements, supporting the need for longitudinal, phenotype-oriented endocrine surveillance.