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 (T4) to triiodothyronine (T3) 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/day alone (n=10) or in combination with either oral ethinyl estradiol (or-EE) 100 μg/day (n=14) or transdermal 17β-estradiol (td-E) 100 μg twice a week (n=12). Female-to-male transsexuals were treated with i.m. testosterone 250 mg twice a week. A t-test was used to test for differences within groups and ANOVAwith post hoc analysis to test for differences between the groups. Results: Or-EE increased TBG (100 ± 12%, P<.001) and testosterone decreased TBG (−14 ± 4%, P =0.01), but free T4 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 T3/T4 ratios (−9 ± 3%, P=0.04), suggesting that T4 to T3 conversion was lower. Testosterone increased T3/T4 ratios (30 ± 9%, P=0.02), which probably reflects higher T4 to T3 conversion. Conclusion: Oral but not transdermal estradiol increases TBG, whereas testosterone lowers TBG. Testosterone increases T3/T4 ratios. Estradiol does not affect T3/T4 ratios, irrespective of the route of administration.