Sexual Maturation in β-Thalassemia Major Patients in Assiut University Hospital

Thalassemia refers to a group of inherited diseases characterized by decreased or absent synthesis of normal globin chains . The direct consequence is an imbalance of the alpha and beta globin chain synthesis that results in anemia from ineffective erythropoiesis and hemolysis.

The term thalassemia major refers to the severe form that is often associated with life-long transfusion dependent anemia.

Hypogonadism is the most frequently reported endocrine complication, affecting 70-80% of thalassemia major patients. Hypogonadism is likely to be caused by iron deposits in the gonads, pituitary gland or both.

Hypogonadotropic hypogonadism resulting from iron deposition in the pituitary gonadotrope is more commonly found than gonadal iron deposition in ovaries or testes occurs.

Iron deposition in the anterior pituitary gland can be demonstrated beginning in the first decade of life, but clinical manifestations are usually not evident until the onset of puberty. At the earlier stage, only a diminished gonadotropin reserve with intact gonadotropin pulse was observed .

The direct effect of iron, in particular that of NTBI(non-transferrin-bound iron) on the ovaries and testes is currently unknown. The ovarian reserve is preserved in the majority of female thalassemia patients, even in women with amenorrhea. In males, histological examination of testicular tissues from autopsies demonstrated testicular interstitial fibrosis with small, heavily pigmented, undifferentiated seminiferous tubules and an absence of Leydig cells .

There are three main clinical presentations of the HPG(hypothalamic pituitary gonadal axis)axis derangement in thalassemia major, including delayed puberty, arrested puberty and hypogonadism. Delayed puberty is defined as the absence of any pubertal signs by 14 years in boys and 13 years in girls . Arrested puberty is defined as the absence of further pubertal progression for more than 1 year after puberty has started.

Chelation therapy with desferoxamine before the age of puberty has helped patients to attain normal sexual maturation in some studies but not in others. In a study of 40 patients with transfusion-dependent thalassemia major, 90% of 19 patients who began treatment with desferoxamine before the age of 10 had normal sexual development compared with only 38% of those treated after the age of 10. In contrast, another study reported no difference in the frequency of pubertal maturation when iron chelation therapy was started at the age of 10 or earlier. Serum ferritin levels were still higher than normal in previous studies.

After a period of 5-7 years, 50% of hypogonadal males achieved normal testosterone levels and 32% of amenorrheic women became pregnant, either spontaneously or using in vitro fertilization . With modern medications, iron-induced hypogonadism may be reversible with intensive iron chelation regimens.