Objective:
The atheroprotective action of estrogen is mediated by estrogen receptors (esr) 1 and 2, expressed in atherosclerotic lesions. the effects of hormone replacement therapy (hrt) and esr1 pvuii genotypes on atherosclerosis have not previously been studied prospectively in postmenopausal women.
Methods:
We investigated the effect of hrt on the progression of atherosclerosis in a 5-year follow-up study of 88 postmenopausal women aged 45-71 years at baseline allocated into three groups based on the use of hrt. the hrt-evp group (n=26) used sequential estradiol valerate (ev) plus progestin (p), the hrt-ev group ev alone (n=32), and a control group (n=30) was without hrt. the atherosclerosis severity score (as) of the abdominal aorta and carotid arteries were determined by sonography and the esr1 pvuii genotypes (p/p, p/p and p/p) by pcr.
Results:
Hrt, time and esr1 pvuii genotype had a statistically significant or borderline significant main effect on as during 5-year follow-up (p=0.004, p<0.001 and p=0.090, respectively), when analyzed by repeated measures analysis of variance. there was a significant genotype-by-treatment (hrt-evp and control groups) interaction for as (p=0.034). in response to hrt-evp, subjects with p/p, compared with those with p/p and p/p genotypes, had a less increase in as (1.61+/-1.14 vs. 1.71+/-1.27 vs. 2.43+/-1.27). baseline as as covariate in similar model does not change the significant interaction effect between hrt-evp and control groups (p=0.036). but this effect was not found between hrt-ev and control groups.
Conclusions:
Our results suggest that the effect of hrt-evp in postmenopausal women on progression of as may be determined in part by the genotype of esr1 pvuii.