TRANSDERMAL ESTRADIOL SUBSTITUTION THERAPY FOR FEMALE HYPOGONADISM IN THALASSEMIA MAJOR

The efficacy and metabolic effects of estradiol (E2) administered by a transdermal therapeutic system (TTS) in the replacement therapy of hypogonadism, was evaluated in five women (aged 17-22.1 years) with β-thalassemia major and hypogonadism. Two sizes of TTS (5 and 10 cm2) were used in this study delivering, respectively, 25 and 50 μg E2 daily for 3 1 1/2 days. The systems were applied to the skin and were changed twice weekly for 3 weeks a month. Using this sequence, the lower dose of 25 μg E2 TTS was administered in all patients for 6-12 months. In addition, two of the patients were given 50 μg E2 transdermally in combination with an oral progestogen for 4 months. The administration of 25 μg E2 TTS resulted in breast development in all cases. The vaginal cells reached pubertal maturity. Uterine size, measured by pelvic ultrasound, progressively increased but no withdrawal bleeding occurred. In the two patients receiving 50 μg E2 TTS and oral progestogen, breast tissue and uterine size further progressed and withdrawal bleeding occurred. Plasma estradiol levels rose during E2 TTS administration in every patient. The patches were well tolerated and no systemic side effects were reported. No adverse metabolic effects were observed, except for an increased sensitivity to the aggregating agents in two cases.