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Purpose: The recent Women's Health Initiative (WHI) results have demonstrated that combined estrogen plus progestin imparts a small but significant increase in cardiovascular risk and breast cancer among asymptomatic women. However, the effect and potential benefit of unopposed estrogen is not as clear. We sought to evaluate the progression of subclinical atherosclerosis in postmenopausal women using no hormone replacement therapy (HRT), combined therapy, and estrogen alone in an observational study.

Methods: Postmenopausal women without symptoms or known coronary heart disease (CHD) were evaluated at our center for follow-up of coronary calcification. Patients were physician referred and underwent two consecutive electron beam tomography scans at least 1 year apart. All women fitting the study criteria were asked to participate, and those who consented were included. Demographic data, risk factors for CHD, HRT, and other medication use were collected by interview.

Results: The study included 177 asymptomatic women. Calcium progression was 14.6% ± 21% in women taking any hormone therapy (n = 97). Annual calcium progression rates in nonusers (n = 80) was 22.3% ± 32%. Relative to the nonuser group, HRT treatment inhibited the progression of atherosclerosis by 35% (p = 0.01). This effect was independent of age, risk, cardiovascular factors, statin use, or baseline CAC score. Thirty-five of the 97 women (36%) were taking estrogen plus progestin, with an annual increase in calcium scores of 24% ± 23%, similar to the non-HRT women (22%). Those women taking estrogen replacement only (n =62) was 63% lower (9% ± 22%).

Conclusions: This is an observational study, and the results are in accordance with the recently published WHI study, demonstrating no benefit of estrogen plus progestin compared with no therapy. However, women taking unopposed estrogen demonstrated a significant slowing of subclinical atherosclerosis compared with non-HRT and estrogen plus progestin.