Estrogen & Hormones: Estrogen & Heart Disease

If you’re a 40-something woman, you probably have given hormone replacement therapy (HRT) at least a passing thought. As you get closer to menopause age (the average age for menopause is 51.4 years), you’ll be giving more serious consideration to questions about HRT. When you reach menopause, will HRT be right for you?

A familiar favorite

As recently as 10 years ago, virtually every woman at menopause automatically got a prescription for estrogen or estrogen combined with progestin, another female hormone. Hormone replacement therapy was standard treatment to relieve hot flashes, vaginal dryness, insomnia and other menopausal symptoms.

Estrogen and the cardiovascular system

Scientists are still learning about the actions of estrogen in the body. Studies have shown that estrogen affects almost every tissue or organ system, including the heart and blood vessels. Estrogen’s known effects on the cardiovascular system include a mix of positive and negative:

  • Increases HDL cholesterol (the good kind)
  • Decreases LDL cholesterol (the bad kind)
  • Promotes blood clot formation, and also causes some changes that have the opposite effect.
  • Relaxes, smooths and dilates blood vessels so blood flow increases
  • Soaks up free radicals, naturally occurring particles in the blood that can damage the arteries and other tissues.

Estrogen probably affects the cardiovascular system in other ways that are as yet undiscovered. New research continues to give scientists and physicians more information – and raise more questions about this important and controversial hormone.

Over the years, evidence was accumulating that suggested estrogen also helped protect women against heart disease. With heart disease is the number one killer among women over age 65, this is an important issue. Women develop heart disease 10 years later than men, but by age 65, their risk is equal to that of men.

The accepted thinking was that the drop in estrogen levels associated with menopause accounted for this jump in heart disease risk in women. When estrogen levels decline, levels of LDL cholesterol (the harmful kind) increase, and levels of HDL cholesterol (the positive kind) decrease, leading to the build up of fat and cholesterol in the arteries that contributes to heart attack and stroke. It made sense that replacing estrogen through HRT would potentially improve heart health. This thinking contributed to a huge rise in the number of women being prescribed estrogen.

Rethinking old ideas

Recent studies on the long-term use of HRT are changing that way of thinking. With scientific data potentially linking HRT to higher risks of heart attack, stroke and other serious health problems, many women are reconsidering HRT.

The buzz about estrogen started in the late 1990s when a report from the Heart and Estrogen-Progestin Replacement Study (HERS) was published in the Journal of the American Medical Association (JAMA). This study of more than 2,700 women with existing coronary heart disease was designed to test whether estrogen plus progestin would prevent a second heart attack.

During the first year of HRT, women in the study had a 50 percent increase in heart attack and stroke. But, after two years of treatment, women on HRT actually had less heart disease and fewer heart attacks and strokes compared with women not taking HRT.

The study left many unanswered questions, leading researchers to take another look at these same women. They published their results in 2002. This time around, after nearly three more years of followup, the researchers concluded that there was no lasting decrease in heart disease or heart attack/stroke risk from HRT, and HRT increased the risk of blood clots.

Evidence adding up

Meanwhile, an even larger study, the Women’s Health Initiative (WHI), was raising more questions about the potential risks associated with HRT. Involving more than 160,000 women, WHI is the world’s largest clinical trial of health interventions for midlife women, studying the effects HRT, diet changes and calcium and vitamin D supplements on heart disease, osteoporotic fractures and breast and colorectal cancer risk.

In 2002, scientists at the National Institutes of Health (NIH) National Heart, Lung and Blood Institute halted the arm of the WHI study in which women were taking combination estrogen and progestin. Early data from this group of women showed that HRT significantly increased the risk of breast cancer, heart attack, stroke and blood clots in the legs and lungs.

Then, in 2004, the NIH stopped the estrogen-only study arm, in which women who had undergone hysterectomy were taking estrogen. Data showed that estrogen increased their risk of blood clots and stroke and did not reduce the risk of heart attack. (Estrogen’s effect on breast cancer risk was unclear.)

A change in recommendations

These studies were the first large-scale trials that looked for cause and effect with heart disease and HRT. HRT does offer some benefits, such as preventing osteoporosis and reducing the risk of colon cancer. But the data on heart-related risks from these studies were very compelling. As a result, the American Heart Association and the U.S. Food and Drug Administration developed new guidelines for the use of HRT:

  1. HRT should not be used for prevention of heart attack or stroke.
  2. Use of HRT for other problems such as preventing osteoporosis should be carefully considered and the risks weighed against the benefits. Women who have existing coronary artery disease should consider other options.
  3. HRT may be used short-term to treat menopausal symptoms.
  4. Long-term use is discouraged because the risk for heart attack, stroke and breast cancer increases the longer HRT is used.

The bottom line, say physicians at the Miller Family Heart & Vascular Institute at Cleveland Clinic: weigh the benefits of HRT against the risks and discuss the whole subject of HRT with your physician to be able to make an informed decision.

Additional Information

For more information about HRT and your heart, call the Miller Family Heart & Vascular Institute Resource and Information Center Nurse at 216.445.9288 or toll-free 866.289.6911.

To make an appointment with a Preventive Cardiology specialist, call 216.444.9353, or toll-free 800.223.2273, ext. 49353. Preventive Cardiology can assess your heart and circulatory system health and help you set up a plan to reduce your risk for heart attack and stroke if needed.

To discuss hormone replacement therapy with a Cleveland Clinic expert, call 216.444.4HER to schedule an appointment with a gynecologist or nurse practitioner.


  • Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280(7):605-13
  • Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, Hsia J, Hulley S, Herd A, Khan S, Newby LK, Waters D, Vittinghoff E, Wenger N; HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288(1):49-57
  • Manson J, Hsia J, Johnson K et al. Estrogen plus progestin and risk of coronary heart disease. New Engl J of Med 2003; 349:523-534.
  • U.S. Department of Health and Human Services and the National Institutes of Health. Facts on Menopausal Hormone Therapy, June 2005.
  • Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomies. JAMA 2004; 291:1701-12.
  • The American Heart Association
  • Heart Truth for Women, NHLBI