Hypogonadism in βthalassemic adolescents: A characteristic pituitary-gonadal impairment. The ineffectiveness of long-term iron chelation therapy

The pituitary-gonadal function was studied in 18 βthalassemic female adolescents, 8 with delayed puberty and 10 with primary amenorrhea, treated with repeated transfusions and long-term iron chelation therapy by subcutaneous infusion. A 100 μg gonadotropin-releasing hormone (GnRH) test, a double-bolus GnRH test after estradiol administration in non-responders, a 400 μg thyrotropin-releasing hormone (TRH) test and a 'high dose' human menopausal gonadotropin (hMG) test were performed. LH and FSH peak levels were significantly lower in thalassemic patients than in controls, both in the 100 μg GnRH test (LH was 4.3 ± 0.7 mIU/ml vs 40.8 ± 6.0 mIU/ml and FSH 3.3 ± 0.5 mIU/ml vs 9.6 ± 1.1 mIU/ml, respectively) and in the double-bolus GnRH test (LH was 2.3 ± 0.2 mIU/ml vs 59.0 ± 4.9 mIU/ml and FSH 1.8 ± 0.3 mIU/ml vs 14.0 ± 1.0 mIU/ml). The mean prolactin response to the TRH test was 27.8 ± 3.2 ng/ml. After the 'high dose' hMG test 12 out of 14 admitted patients showed a poor response, lower than 250 μg/ml. Our data suggest that the hypogonadotropic condition of the thalassemic adolescents is due to pituitary hyporesponsiveness to GnRH and that most of these patients also have an impairment of ovarian function. Both conditions are a consequence of iron deposits in glands. Moreover, there is evidence that pituitary-gonadal function cannot be preserved by long-term iron chelation therapy.