Cardiovascular disease (heart attack and stroke) is the leading cause of death in women. In fact, it kills nine times more women than breast cancer.  Estrogen’s effect in preventing cardiovascular disease is the subject of intense debate.  Conflicting studies in the last few years have shown that the use of hormone replacement therapy (HRT) seems to result in either a 20 –30% reduction in heart disease or no reduction at all.  However, the most recent studies are showing that estrogen’s effect in reducing cardiovascular disease is not as significant as had been previously believed.

Why the difference in studies?

Observational Studies

Until recently most of our information on the benefits and risks of hormone replacement therapy (HRT) came from observational studies consisting of a group of people who are observed for a long time.  Researchers do not assign either a drug or a placebo;  they simply monitor selected health patterns of the participants and analyze the results.  The "granddaddy" (or in this case "grandmommy") of them all is the ongoing Harvard Nurses’ Health Study,  which has been following 120,000 nurses since 1976.  The participants, my mother is one of them,  fill out questionnaires every two years about their lifestyle and health.   

The use of such a large number of people in the Nurses' Health Study gives weight to its conclusions.  However, these studies have limitations because the researchers can’t randomly assign a control group (a group getting no treatment).  This particular study has been criticized for its "healthy women bias"--nurses tend to be more educated, wealthier, and have healthy life-styles, all of which have been associated with a lower incidence of cardiovascular disease.  The most current results (August 2000) of the Nurses' Health Study showed that HRT caused a 9% reduction in cardiovascular disease;  however, greater results were obtained with lifestyle choices--a 16% reduction with diet improvements and a 13% reduction with decreased smoking.

Controlled Studies

These studies are expensive to conduct and are usually much smaller and shorter, but they are considered the "gold standard" of studies.  In the best of these studies, people are chosen at random and neither the patients nor the researchers know who has been assigned the drug or placebo. 

Two of these controlled studies have cast doubt on the degree of estrogen’s beneficial effect in reducing cardiovascular disease.  In 1998, the HERS study looked at 2000 women who already had cardiovascular disease and concluded that HRT did nothing to reduce the incidence of deaths in those who already had the disease.  Many researchers thought that the addition of progestin (medroxyprogesterone/Provera) in this study may have prevented any benefit.  In August 2000, the results of a three-year study of 300 women (some of whom did not take a progestin) showed that even estrogen alone did not slow the progression of cardiovascular disease.  The most recent study, the Women's Health Initiative (July 2002), has also questioned HRT's benefit to the heart.  It now appears that your decision to take HRT should not be based on heart benefits.

The conflicting results between the observational and controlled studies might be explained by the fact that estrogen has mixed effects on the cardiovascular system:

Estrogen’s Heart Benefits

Oral estrogen has been shown to have a very positive effect on cholesterol--increasing HDL ("good" cholesterol) and decreasing LDL ("bad" cholesterol). It is uncertain whether estrogen patches and creams will provide the same amount of cholesterol benefit because they are metabolized by the body differently. 

Estrogen’s Heart Risks

Estrogen may promote clotting, which is a factor in both heart attacks and stroke. It will also raise the levels of a substance called C-reactive protein, which is associated with increased inflammation in the arteries and may be a major risk for heart disease.  Ask your primary care provider to perform this inexpensive blood test on your next visit.

So what should you do?

From what we know now,  for those women who already have a an established case of heart disease, HRT offers no benefit; for those women at risk of developing heart disease,  HRT should not be the primary preventative measure.  Diet, smoking cessation, and exercise have been shown to be more effective as primary measures.  Medication may be added to control high blood pressure and cholesterol when lifestyle changes are ineffective.

Progesterone Benefits

HRT should not be considered as a primary treatment for high cholesterol.  There has been recent interest in the use of micronized progesterone (often referred to as natural progesterone) as the progesterone compound of choice for those women with high cholesterol who are taking HRT.  A major study has shown natural progesterone to be superior to the synthetic medroxyprogesterone ( Provera) because it does not reduce estrogen’s cholesterol benefit.  (Note: Progesterone compounds are needed to offset estrogen’s negative effect on the uterus.)  

What are you needs?

Additions/Alternative to HRT-

Lifestyle Changes

 

Diet, exercise, and smoking cessation should be the cornerstone of any therapy to prevent cardiovascular disease.  These lifestyle changes have a more significant effect on cardiovascular health than HRT--with little risk of side effects.  Lifestyle changes also have a profound effect on almost every other disease state that HRT helps. 

 

Supplements

 

Antioxidants are the most studied supplements in preventing cardiovascular disease.  Although currently subject to debate, vitamin E and coenzyme-Q10 seem to be the most beneficial.  However, instead of the "supplement du jour" for heart health, it is usually best to try to eat a wide variety of fruits and vegetables (5-7 servings a day) before adding supplements.

 

Prescription drugs

 

Estrogen has a beneficial effect on cholesterol levels but prescription cholesterol-lowering agents are much more effective.  Estrogen is not effective in controlling high blood pressure, so prescription medication may be needed.  Again, lifestyle changes may prevent the need for both of these types of medications.

Benefit to Risk

The benefit to risk ratio of HRT and cardiovascular disease is a subject of much debate. Yet, there is little debate about the benefits of lifestyle changes, so these and other risk factors such as high blood pressure, high cholesterol and diabetes should be addressed first.

The current statistical consensus on the use HRT for cardiovascular disease for those women with no increased risk of breast cancer:

The risks probably outweigh the benefits:

~for those women who do not already have cardiovascular disease but are at an increased risk.  For now, risk of cardiovascular disease should probably not be the primary reason for taking HRT.  If you are taking estrogen for some other purpose such as osteoporosis, the long term use of HRT may possibly be beneficial for your heart.

 

No evidence of benefit:

~for those women who already have cardiovascular disease. However,  if you already have cardiovascular disease and have been on HRT for more than a year, it may better  to continue until newer studies clarify the benefit of long term use.

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