HRT may not ease heart disease in diabetic women

Since diabetes robs women of the so-called "estrogen advantage" that protects them from heart disease as they approach and enter meno-pause, most physicians recommend hormone replacement therapy (HRT) in an effort to even out the playing field.

As estrogen production wanes with the advent of menopause, the risk of myocardial infarction triples for diabetic women compared to the general population and the risk of stroke leaps fivefold.

Now a growing body of evidence suggests that estrogen and progestin replacement therapy may not be magic bullets against heart disease as earlier studies indicated — leaving diabetic women even further behind in the race against heart disease as other evidence of postmenopausal problems unique to diabetic women.

In what the National Institutes of Health have called "surprising results," the HERS (Heart and Estrogen/Progestin Replacement Study) reported more than a year ago that estrogen plus progestin in postmenopausal women with heart disease did not prevent further heart attacks or death from coronary heart disease. Additionally, the hormone replacement regimen increased the risk of deep vein thrombosis and pulmonary embolism.

However, HRT did have positive effects on lipoproteins, reduced LDL cholesterol by 11%, and increased HDL cholesterol by 10%.

Yet most doctors continue to highly recommend HRT for diabetic women who do not have other contraindications for some of its other well-documented benefits and as a way of "hedging their bets," says one endocrinologist. So what does the HERS mixed bag of answers mean?

"It means it’s still an open question," says James H. O’Keefe Jr., MD, a cardiologist and director of preventive care at the Mid-America Heart Institute in Kansas City, MO. "It means we don’t have any real answers now." He is an advocate of tight control and weight loss as any diabetic’s strongest defense against complications. However, he recommends that clinicians explore the benefits and risks of HRT with every perimenopausal patient with diabetes.

Further unhappy news for diabetic women has emerged in other studies:

• A study published in the British Journal of Endocrinological Metabolism last July says neither unopposed transdermal estradiol nor a combined estradiol-progestin had any beneficial effect on insulin sensitivity, as some earlier studies suggested.

• And worst of all, National Health and Nutrition Examination I data published earlier this year show that while the U.S. death rate from heart disease is declining in the general population, the death rate among diabetic women climbed by 23% from 1971 to 1993, while among nondiabetic women, it fell by 27%.

Barbara Klein, MD, an ophthalmologist at the University of Wisconsin in Madison who has studied hormone-related events in diabetic women that evolved from a diabetic retinopathy study, says more study is needed to sort out the conflicts in results. She says since nobody seems to have a firm grip on the reasons HRT does or does not work to help diabetic women avoid cardiovascular disease, "Caution is the word here."

She notes that many women with diabetes slip through the cracks of counseling on the benefits of hormone replacement or even of taking birth control pills until they are in the optimum health to promote healthy pregnancies.

HRT still has positive effects in women with diabetes, says Andrea Baccarelli, MD, an endo crinologist at the Mayo Clinic in Rochester, MN. "It’s very individualized." She recommends HRT to all her menopausal diabetic patients if there are no contraindications.

"As diabetic women approach menopause, they should be screened intensely for all risk factors and all risks taken into account," she says.

Since hyperlidipemia is a major factor in coronary artery disease and since the beneficial effects of HRT seem to be supported by the HERS study, "I think there is more need for a diabetic woman to take HRT than in other women. I encourage it," Baccarrelli says.

Clinicians suggest a wide range of steps to reduce the risk of cardiovascular disease in diabetic women. Of course at the top of the list are good diet and exercise.

And there is some interesting new evidence to substantiate them. Three Harvard studies show dramatic benefits for diabetic women for therapies that range from walking to following a whole grain diet and using vitamins C and E.

Gleaning data from the Nurses’ Health Study, Frank Hu, MD, PhD, assistant professor of medicine at Harvard University Medical School in Boston, found some intriguing results:

Walking. Women who walked at a normal pace for at least one hour a week were 28% less likely to develop Type 2 diabetes. Those who walked at a brisk pace (more than 2.3 miles per hour) reduced their risk of developing Type 2 diabetes by 59%.

Whole grains. Switching from highly refined grains to whole grains lowered women’s risk of developing Type 2 diabetes by 31%.

Vitamins C and E. In as yet unpublished results, diabetic women who regularly took an unspecified amount of vitamins C and E in supplement form reduced their risk of congenital heart disease (CHD) by 53%, probably due to the antioxidant properties of the two vitamins. Intake of vitamins C and E from food were less likely associated with lower risk of CHD.

Hu recommends clinicians help their patients find a way around the barriers to physical activity and better dietary habits. "They’ll tell you they don’t have the time to take a walk or to fix brown rice instead of instant, so help them find simple cumulative effects — like climbing stairs, parking farther away from the entrance to a building, or even talking a walk while the brown rice is cooking!"

Walking is by far Hu’s physical activity of choice: "It’s easy, safe, cheap, and even for obese diabetic patients, it’s extremely practical."

Other clinicians recommend that women can reduce their cardiovascular risks by using metformin and losing even a moderate amount of weight. Some recommend 24-hour silent angina screening to determine if a woman is unaware of chest pain because diabetic neuropathy is reducing her sensitivity to the pain.

[Contact James O’Keefe at (816) 931-7714, Barbara Klein at (608) 263-0276, Andrea Baccarrelli at (507) 284-2511, and Frank Hu at (617) 432-0113.]