By: Thomas Pickering, MD, DPhil, FRCP, Director of Integrative and Behavioral Cardiology Program
of the Cardiovascular Institute at Mount Sinai School of Medicine, New York.

Estrogen can be given in two ways as hormone replacement therapy in post-menopausal women: as pills (oral administration) or a skin patch (transdermal administration). A study of 200 hypertensive, post-menopausal Italian women examined the effects of a patch containing natural estrogen (17-estradiol), which was changed twice a week and taken in conjunction with a pill of progestin (norethisterone 2.5 mgs) taken for 12 days of each 28-day cycle. Half of the women (100) were given the estrogen/progestin combination, while the other half got placebo. The study lasted 18 months and evaluated changes of blood pressure, lipids, blood sugar and the size of the heart (measured by echocardiography).

There was no noticeable effect of the hormones on blood pressure, although the women in both groups were given blood pressure lowering medication as needed. The estrogen replacement lowered the blood levels of total cholesterol (from 241 to 225 mg/dl), LDL cholesterol (from 166 to 138 mg/dl), triglycerides (from 135 to 104 mg/dl), glucose (from  95 to 83 mg/dl), and fibrinogen (from 368 to 345 mg/dl). HDL cholesterol did not change. The echocardiogram showed a greater reduction in the size of the heart (left ventricular mass) in the women treated with estrogen.

Doctor’s comments

These results suggest that the estrogen skin patch, given in combination with progestin pills, has a good effect on cardiovascular risk factors. One interesting finding was that HDL cholesterol was not affected; other studies using estrogen taken as pills (typically Premarin, which is not the natural estrogen, but one derived from horse estrogen) have shown an increase of HDL. The reason for this may be that HDL is made in the liver, and when estrogen is taken by mouth, it is absorbed from the intestines, and then passes through the liver in much higher concentration than when it is absorbed through the skin. Another difference between the effects of estrogen depending on how it is administered is that the skin patch estrogen in this study lowered triglycerides, whereas the oral estrogen raises them. The authors suggested that treatment with estrogen could be individualized women who have a low HDL might do better when given oral estrogen, while the patch might be better for women with high triglycerides.

Other benefits that were observed were a reduction of blood sugar (glucose) and fibrinogen. Fibrinogen is a protein that is part of the blood-clotting machinery, and high levels are a risk factor for heart disease. The reduction in the size of the heart is also potentially a good thing. Since the blood pressure was the same in the women given estrogen as in those given placebo, lower blood pressure is unlikely to be the explanation, so there may be a direct effect of estrogen on the heart.

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