PROSPECTIVE-STUDY OF THE HYPOTHALAMIC-PITUITARY AXIS IN THALASSEMIC PATIENTS WHO DEVELOPED SECONDARY AMENORRHEA

OBJECTIVE We aimed to prospectively evaluate during 10 years the GnRH- gonadotrophin secretory dynamics in a cohort of 15 menstruating girls with beta-thalassaemia major lo determine whether they sustained progr essive damage to this axis. DESIGN Patients were characterized by 12-h our gonadotrophin profiles (by sampling blood at 15-minute intervals) and assessment of gonadotrophin responses to 100 mug GnRH bolus (by sa mpling blood at 20-minute intervals for 1 hour and at 2 hours) sequent ially during the follicular and luteal phases of their menstrual cycle s, 12-14 months and 5-6 years after the onset of secondary amenorrhoea . SUBJECTS We studied 15 post-menarcheal thalassaemia girls and five a ge-matched control subjects who were the healthy siblings of the patie nts. MEASUREMENTS FSH and LH assays were determined using commercial R IA systems and double antibody techniques. Pulse detection used the Pu lsar technique of Merriam and Wachter. RESULTS We demonstrated that du ring their amenorrhoeic period, all thalassaemia patients had gonadotr ophin pulse abnormalities and low-normal GnRH-stimulated gonadotrophin levels indicating that they had GnRH-gonadotrophin secretory insuffic iency. During the subsequent 10 years there was progressive deteriorat ion of hypothalamic-pituitary function in all patients; 66% became apu lsatile and all had marked reduction in their GnRH-stimulated gonadotr ophin levels. CONCLUSIONS Our investigation suggests that thalassaemia patients with secondary amenorrhoea had severe and progressive damage to their hypothalamic pituitary axes despite intensive chelation ther apy.