Menopause Live - IMS Updates

Date of release: 17 October, 2011

Postmenopausal hormone therapy and coronary artery atherosclerosis

A recent study raised once again the issue of potential effects of postmenopausal hormone therapy (HT) on the development of coronary artery atherosclerosis [1]. The study group included 654 postmenopausal women undergoing coronary angiography for the evaluation of suspected ischemia. Timing and type of menopause, use of hormone therapy (HT), and quantitative angiographic evaluations were obtained at baseline, and the women were followed for a median period of 6 years for cardiovascular (CVD) events. Ever-users of HT had a significantly lower prevalence of obstructive coronary artery disease (CAD) compared with never-users (age-adjusted odds ratio 0.41; 95% confidence interval (CI) 0.28–0.60). Women with natural menopause initiating HT before age 55 years had lower CAD severity compared with never-users (age-adjusted β [SE] = -6.23 [1.50], p < 0.0001), whereas those initiating HT at age 55 years or more, actually very few in number, did not differ statistically from never-users. HT use remained a significant predictor of obstructive CAD when adjusted for a ‘healthy user’ model (odds ratio 0.44; 95% CI 0.30-0.73; p = 0.002). An association between HT and fewer CVD events was observed only in the natural menopause group (hazard ratio 0.60; 95% CI 0.41–0.88; p = 0.009) but became non-significant when adjusted for the presence or severity of obstructive CAD. Using the quantitative measurements of the timing and type of menopause and HT use, earlier initiation of HT was associated with less angiographic CAD in women with natural but not surgical menopause. The data suggest that the effect of HT use on reduced cardiovascular event rates is mediated by the presence or absence of angiographic obstructive atherosclerosis.


Many studies in the late 1980s and early 1990s addressed the issue of the beneficial effects of HT on coronary atherosclerosis. Interestingly, the most prestigious journals in ObGyn, Cardiology and Internal Medicine were happy at that time to publish studies on HT and CAD. Some studies examined the results of coronary arteriograms in this respect. Sullivan summarized these data as follows: ‘Four cross-sectional studies that used coronary arteriography to determine the extent of coronary atherosclerosis have provided some of the most convincing evidence that estrogen replacement reduces cardiovascular risk in postmenopausal women. One study of outcome in women undergoing coronary arteriography at baseline has found that the greatest improvement in total mortality occurred in women with significant coronary stenosis’ [2]. But the Heart and Estrogen/progestin Replacement Study and, later on, the Women’s Health Initiative (WHI) study changed the understanding of the association between the development of atherosclerosis and postmenopausal HT. The ERA trial, a secondary prevention study that compared coronary angiographies at baseline with those after 3 years of HT, concluded early in the year 2000 that ‘estrogen does not appear to provide a cardiovascular benefit in postmenopausal women with established coronary heart disease’ [3]. Since then, there were very few invasive studies still looking into the interaction of HT with the extent of coronary artery stenosis. The WISE study (the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation study) assessed coronary angiograms in postmenopausal women with suspected ischemia [4]. Their age range was 36–86 years (mean age at menopause 44 years), and only about a quarter had ≥ 70% stenosis in one or more major epicardial coronary arteries at baseline. Women were recruited during 1998–2002, then followed for a median period of 6 years and clinical endpoints were recorded. The investigators found that, while HT use was associated with reduced CAD, there was no independent relationship of lifetime estrogen exposure to angiographic CAD or major adverse cardiovascular events. The new analysis from the WISE study [1] brings additional information related to timing of hormone use. Women with natural menopause initiating HT before age 55 years had lower CAD severity compared with never-users. Interestingly, the same results were obtained from the WHI estrogen-alone arm (10-year follow-up period), where less coronary calcifications were detected by fast coronary CT scans in hormone users aged 50–59 at baseline who were compared to women in the placebo arm [5]. Thus, the cardioprotective effects of HT in the early postmenopause seem realistic and well substantiated by good-quality clinical data.


Amos Pines
Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Shufelt CL, Johnson BD, Berga SL, et al. Timing of hormone therapy, type of menopause, and coronary disease in women: data from the National Heart, Lung, and Blood Institute-sponsored Womens Ischemia Syndrome Evaluation. Menopause 2011;18:943-50.

  2. Sullivan JM. Coronary arteriography in estrogen-treated postmenopausal women. Prog Cardiovasc Dis 1995;38:211-22.

  3. Herrington DM, Reboussin DM, Brosnihan KB, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med 2000;343:5229.

  4. Merz CN, Johnson BD, Berga SL, et al. Total estrogen time and obstructive coronary disease in women: insights from the NHLBI-sponsored Womens Ischemia Syndrome Evaluation (WISE). J Womens Health (Larchmt) 2009;18:1315-22.

  5. Manson JE, Allison MA, Rossouw JE, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007;356:2591-602.