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

¹ Department of Endocrinology and Metabolism and ² Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands and ³ The Institute of Endocrinology, Reproduction and Metabolism, University Hospital Vrije Universiteit, 1007 MB Amsterdam, The Netherlands

(Correspondence should be addressed to P H Bisschop; Email: p.h.bisschop{at}amc.uva.nl)

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 17ß-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.

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				A. Mueller, F. Kiesewetter, H. Binder, M. W. Beckmann, and R. Dittrich Long-Term Administration of Testosterone Undecanoate Every 3 Months for Testosterone Supplementation in Female-to-Male Transsexuals J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3470 - 3475. [Abstract] [Full Text] [PDF]