ß-Thalassemia Major Patients Receiving Chelation Therapy Clinical Trial
Official title:
Assessment of Sexual Maturation in β-Thalassemia Major Patients Receiving Iron Chelation Therapy in Assiut University Hospital
cross sectional study to asses sexual maturation in β-Thalassemia Major patients receiving Iron Chelation Therapy in assuit University Hospital and maintenance of 2ry sexual characters and reproduction
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.
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