Lower Doses of Estrogen Inhibit Atherosclerosis

Abstract & Commentary

By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: This study provides an experimental basis for the assumption that low-dose CEE may be as effective as the traditional dose in inhibiting coronary atherosclerosis progression in early postmenopausal subjects.

Source: Appt S, et al. Low dose estrogens inhibit coronary artery atherosclerosis in postmenopausal monkeys. Maturitas. 2006;55:187-194.

Clarkson and colleagues report the results of a lower-dose estrogen trial in a monkey model of coronary atherosclerosis. The animals were fed an atherogenic diet for 10 months, calculated to induce atherosclerosis comparable to that observed in early postmenopausal women. After oophorectomy, the animals were randomized to treatment for two years with a dose of conjugated equine estrogens equivalent to 0.3 mg per day in women or placebo. This dose had no effect on circulating lipid levels, nevertheless the treated animals had an average 52% reduction in coronary atherosclerosis. This degree of protection was similar to studies in this model using a dose of conjugated estrogens equivalent to 0.625 mg per day.1


One response to the publications from the Women's Health Initiative has been a scientific and clinical effort to assess and use lower doses of estrogen. Half of the standard dose of conjugated equine estrogens has been demonstrated to effectively treat menopausal symptoms and to prevent bone loss. It is reasonable to ask whether symptoms and bone are especially sensitive to the effects of estrogen, and whether lower doses of estrogen will beneficially impact other target tissues. The cardiovascular system is of obvious concern because it was already apparent that lower doses of estrogen do have a lesser effect on circulating lipids and lipoproteins.

As we move to the use of lower doses, keep in mind that there exists a considerable group of women who metabolize and clear estrogen at a greater rate, requiring a higher dose to achieve the desired effects. I have argued in past issues of OB/GYN Clinical Alertthat the only objective assessment of adequacy of dose can be found in the measurement of bone density. Women who are losing bone despite estrogen therapy, adequate calcium and vitamin D intake, and the absence of other causes of bone loss require an adjustment of the estrogen dose.


  1. Lobo RA, et al. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism. Fertil Steril. 2001;76:13-24.
  2. Lindsay R, et al. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA. 2002;287:2668-2676.