Differential effects of cross-sex hormonal treatment on plasma asymmetric dimethylarginine (ADMA) in healthy male-to-female and female-to-male transsexuals

ObjectiveSex hormone administration affects plasma levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). We investigated the effects of cross-sex hormone treatment (CHT) on plasma ADMA concentration in an open-label study in 40 male-to-female (M–F) and 14 female-to-male (F–M) transsexuals.Methods: M–F received (1) cyproterone acetate (CA) 50 mg bid (n = 10), (2) CA 50 mg bid + ethinyl estradiol (EE) 50 μg bid (n = 15), or (3) CA 50 mg bid + transdermal estradiol (tE2) patches daily delivering 100 μg 17β-estradiol (n = 15). F–M received 250 mg mixed testosterone esters intramuscularly every 2 weeks (n = 14).Results: All M–F treatment arms showed a decrease in plasma ADMA concentration after 16 weeks of CHT (mean percentage change from pre-treatment (95% confidence interval)): −26.2% (−30.9 to −21.5%) for EE + CA, −8.9% (−13.4 to −4.3%) for tE2 + CA, and −11.3% (−17.4 to −5.2%) for CA. Testosterone administration to females increased ADMA by 9.4% (2.6 to 16.3%). The change in the EE + CA treated group was still significant after 52 weeks of CHT. In M–F and F–M, CHT had opposite effects on concentrations of other plasma amino acids as well, with EE + CA treatment causing a decrease and testosterone administration resulting in an increase.Conclusion: Administration of anti-androgens alone or combined with estrogens to males decreases and testosterone administration to females increases the plasma ADMA concentration, possibly reflecting a general effect of sex hormones on amino acid metabolism.