Hormone Therapy Raises CHD Risk in Women With Metabolic Syndrome

Fran Lowry

October 12, 2010

October 12, 2010 (Chicago, Illinois) — Hormone therapy (HT) increased the risk for coronary heart disease (CHD) in women who had metabolic syndrome at the time they started HT, but had no effect on CHD risk in women without metabolic syndrome, according to new research reported here at the North American Menopause Society (NAMS) 21st Annual Meeting.

The finding will help clinicians refine their decisions about which patients to put on HT and may lead to greater safety and an improved risk–benefit ratio for the controversial treatment, said Robert A. Wild, MD, PhD, from Oklahoma University Health Sciences Center in Oklahoma City.

Most of the research about hormones and CHD risk before the randomized controlled Women's Health Initiative (WHI) study was observational in nature and suggested HT was protective. As a result, the unexpected finding from the WHI that HT actually increased events caused a great deal of controversy and consternation, Dr. Wild said.

He and his team hypothesized that part of the reason for the difference might be a result of the presence or absence at baseline of the metabolic syndrome.

In this case-control cohort study, the researchers identified 359 women with incident CHD (nonfatal myocardial infarction or fatal CHD) during the estrogen-plus-progestin or estrogen-alone parts of the WHI study and matched them with 817 control patients who did not develop CHD.

The researchers then looked at how many of the women had metabolic syndrome at baseline.

Metabolic syndrome was defined as the presence of 3 of the following National Cholesterol Education Programs Adult Treatment Panel III criteria: waist circumference larger than 35 inches; triglycerides higher than 150 mg/dL; HDL-cholesterol lower than 50 mg/dL; blood pressure 130/85 mm Hg or higher; and fasting glucose of 100 mg/dL or higher.

The study found that women with metabolic syndrome had a 29% increased risk of having a CHD event if they took hormones, but the risk was not increased if they did not take hormones.

Table. Pooled Results* From Estrogen-Plus-Progestin and Estrogen-Only Groups

With Metabolic Syndrome Control Patients CHD Odds Ratio (95% Confidence Interval)
Placebo 185 87 1.0 referrent
HT 172 135 1.72 (1.20 - 2.47)
Without metabolic syndrome      
 Placebo 217 67 1.0 referrent
 HT 243 70 0.98(0.66 - 1.48)

*After adjustment for baseline history of myocardial infarction, smoking, age, education, and lipid-lowering medication.

"The findings are in keeping with current recommendations," Dr. Wild told Medscape Medical News in an interview. "You need to know somebody's baseline risk, and determining if they have the metabolic syndrome is easy to do in your office."

The study results have enhanced his ability to counsel patients, he added. "I am an ob/gyn, but I also practice preventive cardiology, so I am always trying to assess the potential baseline risk. I'm not sure that an average gynecologist does. We know that people with metabolic syndrome are at greater cardiovascular risk, and it may well be that way even in the early part of their menopause transition, so you kind of tend to want to shy away from giving HT or use it in a different risk–benefit equation. Hormone choices are complex."

The results of this study are very helpful for patients and physicians, commented Margery L.S. Gass, MD, executive director of NAMS and a consultant at the Cleveland Clinic in Ohio.

"I think this truly adds something to our knowledge and will help us in decision making. If women already have some significant cardiovascular risk factors, they could be harmed instead of benefited, and the metabolic syndrome perhaps should be considered as a cardiac risk factor," she said. "A fair number of women will have metabolic syndrome, especially these days with our obesity epidemic, so hormones may not be in their best interest, and they should only consider them if they are severely incapacitated by their symptoms."

Steven R. Goldstein, MD, newly elected NAMS president and professor of obstetrics and gynecology at New York University Langone Medical Center in New York City, told Medscape Medical News that the data from this study were significant but not surprising.

"You have to individualize therapy. Even before this paper came out, if a woman came into my office weighing 190 pounds, with high blood pressure, central adiposity, and a strong family history of diabetes, she's just a bad thing waiting to happen. But another woman who weighs 107 pounds, exercises every day, has normal cholesterol, and no risk for diabetes, intuitively I say as a clinician that, although it's not a 100% guarantee, this woman is the kind of patient who should do better on exogenous hormone medication."

He continued: "It's nice to know that if you are basically healthy you have less risk with [HT] than if you have metabolic syndrome. That's huge. Everybody's not the same."

Dr. Wild, Dr. Gass, and Dr. Goldstein have disclosed no relevant financial relationships.

North American Menopause Society 21st Annual Meeting: Abstract 3. Presented October 8, 2010.

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