PHARMACOKINETICS OF SEX STEROIDS IN PATIENTS WITH BETA-THALASSEMIA MAJOR

Aims-To assess the pharmacokinetics of oral, intramuscular, or transde rmal hormone replacement in patients with thalassaemia major. Methods- Oral (testosterone undecanoate 40 mg) and intramuscular (testosterone propionate 15 mg, phenylpropionate 30 mg, isocaproate 30 mg and decano ate 50 mg) testosterone and transdermal (17beta oestradiol 25 ug and 5 0 mug) oestradiol were evaluated in 21 male (16-29 years) and 11 femal e (19-26 years) patients with beta thalassaemia major and various form s of hypogonadism. Results-In male patients given oral testosterone, p eak testosterone concentrations were observed either two to four hours or seven hours after administration; intramuscular testosterone produ ced peak values seven days after injection. Transdermal 17beta oestrad iol given to female patients produced a biphasic pattern with an initi al peak concentration occurring at 36 hours and a secondary rise at 84 hours. Conclusions-The results indicate that oral androgens should be given twice daily in cases of hypogonadism, and where growth is incom plete, lower than recommended doses. If intramuscular testosterone is used, smaller doses of 10-25 mg should be given every one to two weeks . Transdermal administration of 25-50 mug 17beta oestradiol generally produces a plasma E2 value in the early to mid-follicular phase range (100-300 pmol/l). This is appropriate in adults but excessive for prep ubertal girls. Diffuse iron infiltration of tissues does not seem to i nterfere with the absorption of androgens and oestrogens from the gut, muscle, or skin.