The effect of hormone replacement therapy on atherosclerotic severity in relation to ESR1 genotype in postmenopausal women.
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.
Koivu
Tommi A
TA
Laboratory of Atherosclerosis Genetics, Center for Laboratory Medicine, University Hospital of Tampere, Finland.
Fan
Yue-Mei
YM
Mattila
Kari M
KM
Dastidar
Prasun
P
Jokela
Hannu
H
Nikkari
Seppo T
ST
Kunnas
Tarja
T
Punnonen
Reijo
R
Lehtimäki
Terho
T
D000368:Aged; D000704:Analysis of Variance; D001161:Arteriosclerosis / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000235:genetics*; D013997:Time Factors
D011960:Receptors, Estrogen