The EWA (Estrogen in Women with Atherosclerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins

Abstract

Abstract. Os I, Hofstad AE, Brekke M, Abdelnoor M, Nesheim BI, Jacobsen AF, Birkeland K, Larsen A, Midtbù K, Westheim A (Ullevaal University Hospital and Aker University Hospital, Oslo, Norway). The EWA (Estrogen in Women with Atherosclerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. J Intern Med 2000; 247: 433±441.Objectives. To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. Setting. In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examinerblind. Subjects. Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease.Interventions. The women were randomized to HRT, i.e. transdermal application of continuous 17-b oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. Main outcomes. Effects on lipids and lipoproteins. Results. After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. Conclusions. In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

Transforming growth factor (TGF)‐β1 inversely related to vascular cell adhesion molecule‐1 in postmenopausal women with coronary artery disease. A possible mechanism for the putative cardioprotective role of TGF‐β1?

“…The study population has previously been described in detail [17]. All women ( n =118) participating in the study had CHD verified with coronary angiography.…”

“…Exclusion criteria were no previous treatment with HRT, age over 71 years, previous severe cerebrovascular episode, increased risk of pulmonary embolism/deep vein thrombosis, serious psychological problems, abuse of drugs or alcohol, and gynaecological or breast cancer. The women were randomized to HRT ( n =60) or to a control group ( n =58), and followed with clinical examination and blood sampling for after 3 and 12 months [17]. The study was approved by the Regional Ethical Committee [17].…”

“…The women were randomized to HRT ( n =60) or to a control group ( n =58), and followed with clinical examination and blood sampling for after 3 and 12 months [17]. The study was approved by the Regional Ethical Committee [17].…”

“…Previously, in the EWA (Estrogen in Women with Atherosclerosis) study [17], we investigated the effects of hormone replacement therapy (HRT) on levels of active TGF‐β 1 [18] as well as on soluble adhesion molecules [19]. The purpose of the present investigation was to look at a possible relationship between circulating active TGF‐β 1 and adhesion molecules in postmenopausal women with angiographically verified CHD, and also to elucidate whether TGF‐β 1 levels were related to the number of affected coronary vessels.…”

Complexities of oestrogen in stroke

“…A total of 118 women were treated with placebo or oestrogen alone, followed by tri-monthly progestin. Three months of oestrogen alone decreased triacylglycerol (triglyceride) levels, but no differences were observed at 12 months, indicating benefits of acute treatment or that progestin nullified the effect [140]. However, opposite effects were reported in women (aged 75 years or older) when treated with conjugated oestrogen+tri-monthly medroxyprogesterone.…”