Influence of sex hormones on plasma endothelin levels.

OBJECTIVE

To determine whether a sex-associated difference in endothelin levels exists and to assess whether this difference is mediated by sex hormones.

DESIGN

Initial survey in healthy persons, followed by a nonrandomized intervention.

SETTING

A university teaching hospital.

PATIENTS: Twenty-three healthy men, 29 healthy women, 20 pregnant women, and 12 male-to-female and 13 female-to-male transsexual patients.

MEASUREMENTS: Plasma levels of endothelin were first assessed in healthy men, healthy women, and pregnant women; subsequently, endothelin levels were determined in male-to-female and female-to-male transsexual patients both before and during cross-gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethynylestradiol and cyproterone acetate to men.

RESULTS

Endothelin levels were higher in men than in women (5.9 +/- 1.2 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). Endothelin levels were lower in pregnant women than in age- and sex-matched nonpregnant controls (2.19 +/- 0.73 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). In 12 male-to-female transsexuals treated with estradiol and the progestational agent cyproterone acetate, endothelin levels decreased from 8.1 +/- 3.0 to 5.1 +/- 2.0 pg/mL (P < 0.01). In 13 female-to-male transsexuals treated with testosterone, endothelin levels increased from 6.2 +/- 1.1 to 7.8 +/- 1.2 pg/mL (P < 0.01).

CONCLUSION

Sex hormones may modulate plasma endothelin levels, with male hormones raising levels and female hormones lowering them. This finding may be important in explaining sex-associated differences in susceptibility to atherosclerotic cardiovascular disease.