Gonadotropin–Testosterone Axis and Semen Response after Correction of Chronic Anaemia in β-Thalassaemia, Sickle Cell Disease, and Iron-Deficiency Anaemia: A Structured Review

Abstract

Background: Male reproductive dysfunction is increasingly relevant in chronic anaemias as survival into adulthood has improved in β-thalassaemia and sickle cell disease, while iron-deficiency anaemia remains globally common. Impaired fertility arises through hypoxia, oxidative stress, gonadal axis dysfunction, iron overload, and treatment-related gonadotoxicity. The key clinical question is whether correcting anaemia improves semen quality and gonadal function. Objectives: To review PubMed-indexed human studies on the effect of correcting β-thalassaemia, sickle cell disease, and iron-deficiency anaemia on semen parameters, gonadal-axis markers, and fertility outcomes; to distinguish reversible from persistent reproductive injury; and to derive a practical diagnostic framework. Methods: A structured PubMed-only review (search date: 2026-04-26) combined disease terms with fertility-related keywords. Only human male studies reporting fertility-relevant outcomes were included. No meta-analysis was performed. Quality was assessed using NIH and Joanna Briggs Institute checklists. Results: Fifteen original studies met inclusion criteria; four directly evaluated anaemia correction. Transfusion in β-thalassaemia and sickle cell disease increased haemoglobin, testosterone, gonadotropins, and sperm count within 7 days. Intravenous iron in iron-deficiency anaemia similarly improved hormonal and semen variables. Persistent injury — sperm DNA fragmentation, pituitary iron deposition, compensated hypogonadism, and transplant-related gonadotoxicity — coexisted with reversible changes. No study demonstrated conception or live-birth benefit. Conclusions: Anaemia correction improves male reproductive physiology, but evidence is limited by small uncontrolled studies. Correction should precede infertility labelling and prompt repeat endocrine and semen assessment. Durable fertility in β-thalassaemia and sickle cell disease requires managing iron toxicity, vaso-occlusive damage, and treatment-related gonadotoxicity.