Gonadotropin–Testosterone Axis and Semen Response after Correction of Chronic Anaemia in β-Thalassaemia, Sickle Cell Disease, and Iron-Deficiency Anaemia: A Structured Review
Ashraf T. Soliman
*
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar and Department of Pediatrics, Alexandria University, Alexandria, Egypt.
Fawzia Alyafei
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Nada Alaaraj
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Noor Hamed
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Shayma Ahmed
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Ahmed Elawwa
Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
*Author to whom correspondence should be addressed.
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.
Keywords: β-thalassaemia, sickle cell disease, iron-deficiency anaemia, male infertility, gonadotropins, testosterone, semen analysis, hypogonadism, iron overload, sperm DNA fragmentation, haematologic optimisation