Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia

Objective: To determine the prevalence and risk factors of hypogonadotropic hypogonadism in transfusion-dependent patients with thalassemia. Patients and Methods: The authors examined 29 patients with thalassemia major aged 15 years or older. Luteinizing hormone-releasing hormone tests were performed and beta-thalassemia mutations were analyzed by direct sequencing. Results: The prevalence of hypogonadotropic hypogonadism was 72%. Failure of puberty was observed in 5 of 11 (45%) boys and 7 of 18 (39%) girls. Arrested puberty was noted in two boys (18%) and five girls (28%). Ten girls (56%) did not menstruate, two (11%) had regular menstrual cycles, one (6%) had irregular menstrual cycles, and five (28%) developed secondary amenorrhea. Twenty-one and eight patients had the beta(0)/beta(0) and beta(0)/beta(+) hematologic phenotypes, respectively. beta(0)-thalassemia mutation alleles involved IVS II-654 (CT), codons 41/42 (-TCTT), codons 27/28 (+C), and codons 17 (A-T). beta(+)-thalassemia mutations alleles were -28 (A-G) and HbE (codons 26(GAG-AAG)). Hematologic phenotype (odds ratio, 28.50; P = 0.002) was the only risk factor identified in the logistic regression analysis. Conclusions: In patients with thalassemia major, genetic differences may influence their susceptibility to hypogonadotropic hypogonadism, possibly as a result of differences in the amounts of blood transfused and/or their vulnerability to free radical damage. The hematologic phenotype is a main determinant of the severity of thalassemia major; hence, it may influence the need for and frequency of blood transfusion and the patient's iron-overload status.