Prospective study of the hypothalamic-pituitary axis in thalassaemic patients who developed secondary amenorrhoea.

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.