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Prospective study of the hypothalamic-pituitary axis in thalassaemic patients who developed secondary amenorrhoea
R Chatterjee1, M Katz, T F Cox
1Department of Obstetrics and Gynaecology, University College and Middlesex Hospital Medical School, London, UK.
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 to determine whether they sustained progressive damage to this axis.
Design:
Patients were characterized by 12-hour gonadotrophin profiles (by sampling blood at 15-minute intervals) and assessment of gonadotrophin responses to 100 micrograms GnRH bolus (by sampling blood at 20-minute intervals for 1 hour and at 2 hours) sequentially during the follicular and luteal phases of their menstrual cycles, 12-14 months and 5-6 years after the onset of secondary amenorrhoea.
Subjects:
We studied 15 post-menarcheal thalassaemic girls and five age-matched control subjects who were the healthy siblings of the patients.
Measurements:
FSH and LH assays were determined using commercial RIA systems and double antibody techniques. Pulse detection used the Pulsar technique of Merriam and Wachter.
Results:
We demonstrated that during their amenorrhoeic period, all thalassaemic patients had gonadotrophin pulse abnormalities and low-normal GnRH-stimulated gonadotrophin levels indicating that they had GnRH-gonadotrophin secretory insufficiency. During the subsequent 10 years there was progressive deterioration of hypothalamic-pituitary function in all patients; 66% became apulsatile and all had marked reduction in their GnRH-stimulated gonadotrophin levels.
Conclusions:
Our investigation suggests that thalassaemic patients with secondary amenorrhoea had severe and progressive damage to their hypothalamic-pituitary axes despite intensive chelation therapy.