The effects of sex-steroid administration on the pituitary-thyroid axis in transsexuals

Objective: Estrogen and androgen administration modulate the pituitary-thyroid axis through alterations in thyroid hormone-binding globulin (TBG) metabolism, but the effects of sex steroids on extrathyroidal thyroxine (T-4) to triiodothyronine (T-3) conversion in humans are unknown. Design and methods: We studied 36 male-to-female and 14 female-to-male euthyroid transsexuals at baseline and after 4 months of hormonal treatment. Male-to-female transsexuals were treated with cyproterone acetate (CA) 100 mg/dayalone (n= 10) or in combination with either oral ethinyl estradiol (or-EE) 100 mu g/day (n = 14) or transdermal 17 beta-estradiol (td-E) 100 mu g twice a week (n = 12). Female-to-male transsexuals were treated with i.m. testosterone 2 50 mg twice a week. A t-test was used to test for differences within groups and ANOVA with post hoc analysis to test for differences between the groups. Results: Or-EE increased TRG (100 +/- 12%, P < 0.001) and testosterone decreased TBG (-14 +/- 4%, P = 0.01), but free T-4 did not change. Td-E and CA did not affect TBG concentrations. TSH was not different between groups at baseline or after treatment. CA decreased T-3/T-4 ratios (- 9 +/- 3%, P = 0.04), suggesting that T-4 to T-3 conversion was lower. Testosterone increased T-3/T-4 ratios (30 +/- 9%, P = 0.02), which probably reflects higher T-4 to T-3 conversion. Conclusion: Oral but not transdermal estradiol increases TBG, whereas testosterone lowers TBG. Testosterone increases T-3/T-4 ratios. Estradiol does not affect T-3/T-4 ratios, irrespective of the route of administration.