β-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek population

Abstract

beta-thalassemia (beta-thal) is characterized by disturbances of the reproductive system. The aim of the present study was: 1) to assess the hypothalamic- pituitary-gonadal axis in patients with beta-thal in relation to their phenotype and 2) to determine prognostic features of current gonadal status. We studied 135 patients (67 males and 68 females) with beta-thal through history, physical examination, spermiograms and GnRH test. These patients were divided into beta-thal major (51 males and 62 females) and beta-thal intermedia phenotypes (16 males and 6 females). Male patients with beta-thal major were subdivided into three groups a) eugonadal (35%, Tanner's stage V, normal testicular volume, normal spermiograms, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanner's stage II-V, low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin values and abnormal response to GnRH test) and c) patients with HH of early onset (41%, Tanner's stage I, small testicular volume, abnormal spermiograms, abnormal basal and stimulated hormone values). Female patients with beta-thal major were subdivided into: a) eugonadal (32%, Tanner's stage V, regular menstruation, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (34%, Tanner's stage II-V, secondary amenorrhea, subnormal basal and stimulated gonadotrophin values) and c) patients with HH of early onset (34%, Tanner's stage I, primary amenorrhea, subnormal basal and stimulated hormone values). Patients with beta-thal intermedia were subdivided into eugonadal (75% of males, 33% of females) and hypogonadal (25% of males, 67% of females). Current gonadal status could not be predicted by means of transfusion or chelation parameters. In conclusion, beta-thal patients could be eugonadal or develop early or late onset HH. trade mark-thal intermedia patients have a more favorable profile than beta-thal major individuals. Current gonadal status of beta-thal patients cannot be predicted by means of history, clinical or laboratory parameters.

Endocrine and Bone Complications inβ-Thalassemia Intermedia: Current Understanding and Treatment

“…Delayed puberty and hypogonadism are the most common endocrine common complications in β -TI and are attributed to iron-mediated damage leading to dysregulation of the hypothalamic-pituitary axis [ 9 , 25 , 26 , 28 – 30 ]. Delayed puberty is defined as no puberty in girls by 13 years and in boys by 14 years.…”

“…Hypogonadism is defined as absence of testicular development in boys and breast development in girls by 16 years. Hypogonadic hypogonadism is the most frequent and often undertreated endocrine complication of β -TI, seen in 24% of patients, affecting females more than males [ 9 , 25 , 30 ]. It has been shown to be correlated with early onset of transfusion therapy and serum ferritin levels of approximately 2000 ng/mL in TM patients [ 31 ] and high LIC [ 21 ], increasing age [ 25 ] and HU treatment [ 9 ] in β -TI patients.…”

Reproductive capacity in iron overloaded women with thalassemia major

“…Reproductive capacity in TM women cannot be well predicted by means of age, menstrual status, or transfusion and chelation parameters. 1,9 Yet, as overall survival continues to improve, 10,11 attainment of reproductive capacity is crucial for many patients, a concern often brought up to the hematologist.…”

Ghrelin and leptin levels in relation to puberty and reproductive function in patients with beta-thalassemia

“…Gradual increase of iron deposition in different organs could be responsible for tissue damage and a number of complications including impaired growth and puberty delay in these patients. [2][3][4][5] Pubertal development and fertility are determined proved the protocol of this study, which is in accordance with the internationally accepted principles as found in the European Community guidelines (EEC Directive of 1986; 86/609/EEC) and the US guidelines (NIH publication #85-23, revised in 1985). Ninetyeight homozygote beta-thalassemic patients, aged 18-23 years attending the special clinic participated in this study.…”