Gender-related differences in erythrocyte glutathione peroxidase activity in healthy subjects

OBJECTIVE The antioxidant property of oestrogens may partly explain the gender differences in atherosclerotic heart disease and a reduction in the incidence of coronary heart disease, as well as mortality from cardiovascular disease in women undergoing postmenopausal oestrogen therapy. In the present study, we tested the hypothesis that the antioxidant glutathione peroxidase (GSH-Px) erythrocyte activity is gender related and is correlated with oestradiol serum levels. PATIENTS One hundred and fifty healthy women (90 premenopausal; 60 postmenopausal) and 150 age-matched healthy men were recruited during routine health screening. DESIGN AND MEASUREMENTS Serum was analysed for oestradiol (E 2), progesterone and testosterone concentrations, and erythrocytes for GSH-Px enzyme activity. Thirty of the 60 postmenopausal women were treated with transdermal therapy for 30 days with 8-mg E 2 patches (nominal daily dose 100 mug), while the remaining 30 acted as controls. RESULTS Erythrocyte GSH-Px activity was significantly higher in premenopausal than in postmenopausal women ( P = 0.0014), and higher in premenopausal women than in age-matched men ( P = 0.025). By contrast, no significant differences were observed between postmenopausal women and the age-matched male population. In postmenopausal women, E 2 replacement therapy induced a significant increase in erythrocyte GSH-Px activity ( P < 0.001). GSH-Px positively correlated with serum E 2 levels in both premenopausal (r = 0.26, P = 0.011) and postmenopausal women treated with oestrogen replacement therapy ( r = 0.42, P = 0.022). No significant correlations in the female population were found between GSH-Px erythrocyte activity and the other sex steroid hormones examined (r(2) ≤ 0.10, P ≥ 0.45). No statistically significant correlations were found between GSH-Px and E 2, progesterone and testosterone in the male population (r(2) ≤ 0.15, P ≥ 0.30). CONCLUSIONS Our findings support the hypothesis that oestrogens are responsible for the sex-related differences in glutathione peroxidase activity. The hypothesis generated from the present study can be tested directly in experimental models involving specific bone marrow cells by analysis of specific glutathione peroxidase transcriptional changes.