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Estrogens modulate lipid metabolism and the increased risk of atherosclerosis in postmenopausal women is at least partly due to the reduction of estrogen production after menopause. We studied the effect of menopause on the contents of long-chain fatty acids, free cholesterol (FC) and cholesterol ester (CE) in uterine artery wall.The uterine artery intima samples were obtained in connection with surgery of 21 postmenopausal and 51 premenopausal women. The amount of FC, CE and phospholipid fatty acids were measured by gas chromatography after extraction and fractionation and these lipid values were related to menopausal status, age and serum total and low-density lipoprotein (LDL) cholesterol levels.Premenopausal females had significantly less intimal FC (161 +/- 50 vs. 407 +/- 276 microg/100 mg wet weight, P = 0.003) and CE (19 +/- 34 vs. 305 +/- 348 microg/100 mg wet weight, P = 0.050) and smaller proportion of linoleic acid out of all phospholipid fatty acids (4.2 vs. 7.2%, P = 0.002) than postmenopausal women after adjustment with age. The content of CE (r = 0.34, P = 0.025) and the FC-to-CE ratio (r = -0.45, P = 0.002) correlated with age in premenopausal but not in postmenopausal women. Moreover, the intimal content of CE correlated with the percentage of intimal phospholipid linoleic acid in postmenopausal women (r = 0.79, P = 0.020). The same was true for FC (r = 0.73, P0.001).These results indicate that CE and FC accumulation into the wall of uterine artery depends on menopausal status, independently of age, and that the phospholipid long-chain fatty acid composition differs significantly between premenopausal and postmenopausal women. This suggests that estrogens may be involved in the regulation of artery wall lipid composition.

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.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.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, P0.001 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.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.

aDepartment of Obstetrics and Gynecology, University Hospital of Tampere, Tampere, Finland bDepartment of Clinical Chemistry, University Hospital of Tampere, Tampere, Finland CDepartment of Diagnostic Radiology, University Hospital of Tampere, Tampere, Finland dDepartment of Pathology, University Hospital of Tampere, Tampere, Finland eDepartment of Public Health/Biometry Unit, University of Tampere, Tampere, Finland

Objectives : The aim of the study was to obtain information on the possible relationship between impaired ovarian function and risk factors for cardiovascular disease. Material and methods : Serum lipid levels, plasma fibrinolytic potential and histological and biochemical changes in the intima of the uterine artery were investigated in premenopausal women with irregular menstrual cycles, and the results were compared with those from regularly menstruating women. In addition, the same parameters were studied in postmenopausal women on hormone replacement therapy (HRT) and in postmenopausal women who had never used HRT. In total 64 patients undergoing hysterectomy for benign reasons were included the study. Results : Plasma fibrinogen concentration was significantly higher in irregularly menstruating women as compared with women with regular cycles. In women with irregular cycles thickened or sclerotic arterial intima was a significantly more common finding as compared with regularly menstruating women. A significant positive correlation was observed between plasma fibrinogen concentration and intimal esterified cholesterol content in women with thickened or sclerotic uterine artery. Conclusions : These data suggest an important role for normal ovarian function in the prevention of atherosclerosis.

The incidence of atherosclerotic plaques in the aorta and in the carotid and iliac arteries was investigated using high resolution B-mode ultrasonography in 40 postmenopausal women using sequentially combined oestradiol valerate 2 mg--levonorgestrel 0.25 mg replacement therapy. In addition, serum lipid, lipoprotein and apolipoprotein levels were measured. Similar studies were performed for 40 postmenopausal women using oestradiol valerate alone and for 40 women who had never used hormone replacement therapy (HRT). Ultrasonographically observed atherosclerotic plaques were less common (P = 0.011) in oestradiol valerate--levonorgestrel users than in women without HRT. More than three atherosclerotic plaques were observed in 62% of the women without HRT but only in 30% of the women using combined therapy (P = 0.003). The total number of plaques did not differ between the two hormone using groups. The mean serum triglyceride, total cholesterol and apolipoprotein B levels were lowest in oestradiol valerate--levonorgestrel users when compared with those of women with oestradiol valerate monotherapy and those of women without HRT. Combined oestradiol valerate--levonorgestrel replacement therapy, like oestradiol valerate monotherapy, prevents the progression of atherosclerosis in postmenopausal women. The lipid patterns were not adversely affected by the addition of the androgenic levonorgestrel.

The material consisted of 32 patients, 12 of whom were selected for control. All were cases approaching the menopause and had been subject to oophorectomia bilateralis and hysterectomia for myomas. All 20 investigation patients received estradiol valerianate orally 4 mg/day for 6 mth. During the course the serum estradiol level increased 5–6-fold from the postmenopausal levels. No significant changes occurred in the serum triglycerides and total cholesterol, whereas in the control group the triglycerides decreased. The proportional concentration of β-lipoproteins decreased. There was also a slight decrease in the pre-β-lipoproteins. The proportional concentration of β-lipoproteins increased, as also serum high density lipoprotein (HDL) cholesterol. In the liver enzymes no changes occurred. Blood pressure increased in one patient. There were no other complications.

The series comprises 70 women with climacteric symptoms; 14 of them were oophorectomized. The first group of patients received 4 mg of oestriol succinate per day or a placebo in a double-blind experiment. In the second part of the study oophorectomized women were given 8 mg of oestriol succinate per day or 16 mg/day divided into two doses. Serum total cholesterol, HDL-cholesterol and serum triglycerides were estimated before drug treatment and after drug administration for three and six months. Administration of 4–16 mg/day of oestriol succinate was without effect on serum total cholesterol. A significant increase of 25–30% in HDL-cholesterol was observed following administration of oestriol succinate (8 mg or 16 mg divided into two doses) with a rising tendency in total triglyceride value.