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.