Background: Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism.

Design: A prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 Male-to-Female Transsexuals (MFT) and 47 Female-to-Male Transsexuals (FMT). The subjects were studied at baseline, and one year and two years after starting cross-sex hormone treatment.

Results: The baseline levels of uric acid were higher in the MFT group. Compared to baseline, uric acid levels had fallen significantly after one year of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT. After two years of cross-sex hormone therapy, the FEUA had increased in MFT (p=0.001) and fallen in FMT (p=0.004). In MFT, the levels of uric acid at two years were lower in those who had received higher doses of estrogens (p=0.03) and the FEUA was higher (p=0.04). The FEUA at two years was associated with both the estrogen dose (p=0.02) and the serum levels of estradiol-17 beta (p=0.03). In MFT, a correlation was found after two years of therapy between the HOMA-IR and the serum uric acid (r=0.59; p=0.01).

Conclusions. Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.