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

OBJECTIVE

Sex 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) 50mg bid (n=10), (2) CA 50mg bid+ethinyl estradiol (EE) 50 microg bid (n=15), or (3) CA 50mg bid+transdermal estradiol (tE(2)) patches daily delivering 100 microg 17beta-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 tE(2)+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.