HRT May Cut Risk of Type 2 Diabetes by 35% Still overshadowed by rise in adverse events.

From Center For Clinical Age Management, Inc.

Menopause
HRT May Cut Risk of Type 2 Diabetes by 35% Still overshadowed by rise in adverse events.
By OB/GYN News: Miriam E. Tucker
Mar 2, 2003, 7:03pm

NEW YORK — Hormone replacement therapy has been shown to prevent the development of type 2 diabetes in a large, randomized, double-blind, placebo-controlled trial of postmenopausal women with coronary heart disease.

But it may not matter much.

The findings come from the 2,029 of 2,763 postmenopausal women with coronary heart disease in the Heart and Estrogen/Progestin Replacement Study (HERS) who did not have diabetes at baseline. Over a mean follow-up of 4.1 years, the cumulative incidence of diabetes was 6.2% in those assigned to HRT, compared with 9.5% in those assigned to placebo, for a 35% reduction in risk in the HRT arm (Ann. Intern. Med. 138[1]:1-9, 2003).

HERS data published last summer showed that HRT use did not reduce the risk of cardiovascular events and was associated with increased risks for venous thromboembolism and biliary tract surgery (JAMA 288[1]:49-66, 2002). Two months later, the Women's Health Initiative demonstrated that HRT was associated with pulmonary embolism, deep vein thrombosis, stroke, breast cancer, and cardiovascular disease in initially healthy postmenopausal women (JAMA 288[3]:321-33, 2002).

Thus, “I don't think we can conclude [the diabetes finding] is good news. [HRT] has a modest effect on glucose, but what effect it has on the patient otherwise I think is suspect,” HERS coinvestigator Dr. Elizabeth Barrett-Connor said at a conference sponsored by the American Diabetes Association.

She did note, however, that the new finding may give an extra boost to women who choose to use HRT to treat severe menopausal symptoms despite these risks. “Some women will tell you life isn't worth living without estrogen,” noted Dr. Barrett-Connor, professor and chief of the division of epidemiology at the University of California, San Diego.

Still, extreme caution is essential in using HRT in women with diabetes or impaired glucose tolerance, since it raises the risk of problems for which those patients are already more vulnerable, such as venous thromboembolism and pulmonary embolism. If the decision is made to use HRT, “use as little as you can for as short a time as you can get away with,” she advised.

Compared with women assigned to HRT, those on placebo were at higher risk for developing diabetes among the 1,181 women who were normoglycemic at baseline as well as the 218 who entered the trial with impaired fasting glucose. The results were not changed after adjustment for a wide variety of potential confounders such as body mass index, hypertension, dyslipidemia, or cardiovascular medication use.

The risk reduction was due almost entirely to the fact that women in the HRT group maintained lower fasting glucose levels than did women on placebo, said Dr. Alka M. Kanaya of the University of California, San Francisco, and her associates.

Although several previous observational trials had suggested a link between both unopposed estrogen and combined estrogen/progestin and improved glucose tolerance, only one other randomized placebo-controlled trial had evaluated the association before HERS.

In that 3-year trial of 788 women, the Postmenopausal Estrogen/Progestin Interventions (PEPI) study, women taking 0.625 mg/day of estrogen—with or without a progestational agent—had mean fasting insulin levels 16% lower and mean fasting glucose values 2.2 mg/dL lower than those taking placebo (Diabetes Care 21[10]:1589-95, 1998).

However, their mean 2-hour postprandial glucose values were 6.4 mg/dL higher. This finding is of concern, because some data suggest that high peak glucose levels may represent a greater cardiovascular risk than does fasting glucose.

Transdermal HRT could turn out to be a safer alternative to current oral HRT therapies for women with diabetes or glucose intolerance, but the data are conflicting. Transdermal estrogen produces less of an increase in triglycerides, with no discernible effect on glucose or on vascular reactivity. It also carries a lower risk of gallstones. On the other hand, it may not be as effective as oral HRT in alleviating menopausal symptoms. Data are insufficient to draw firm conclusions, she said.