How do my body's natural hormones affect my risk of heart disease?
Women tend to develop heart disease 10 to 15 years later in life than men. This delay is thought to be largely due to the protective effects of estrogen. Estrogen alters the levels of cholesterol and fat in your blood,2 changes the way your blood forms clots,3 affects how well your blood flows though the body and how the blood vessels respond,4, 5 and has an impact on many factors related to the build up of fatty plaques in the arteries. All of these processes influence the development of heart disease.6
When a woman goes through menopause, her body stops producing estrogen and these protective effects are lost. At around the same age the risk of heart disease in women begins to increase. It was therefore thought that replacing the lost estrogen might help prevent heart disease.
Can hormone therapy be used to prevent heart disease?
No. Hormone therapy, either estrogen alone or combined with progestin, does not prevent you from having a heart attack or dying of heart disease.7, 8 In the past, some doctors prescribed hormone therapy in an attempt to lower heart risk, but current guidelines state that hormone therapy should not be used to treat or prevent heart disease in women.9 Early studies that compared women who chose to take hormone therapy with those who didn't showed that hormone therapy users had a lower risk of heart disease.1, 10, 11 However, when more tightly controlled experiments randomly assigned women to hormone therapy or a dummy pill, the results were not positive.
The Women's Health Initiative study of more than 16,000 healthy postmenopausal women found that a combination of estrogen and progestin provided no protection from heart attack, stroke or heart disease.7 In fact, hormone therapy users had a slightly higher risk of heart disease, blood clots and stroke.12 The trial was stopped early because women taking hormone therapy also began to show an increased risk of breast cancer. The Women's Health Initiative also found that estrogen alone had no effect on the risk of heart disease or breast cancer, but increased the risk of stroke and blood clots.13 Overall, researchers decided that while the risk of harm is small from using hormone therapy to prevent heart disease, it still outweighs any potential benefits.
Most studies of hormone therapy have only looked at one type of estrogen plus progesterone pill called Prempro, and one type of estrogen alone pill called Premarin. It is not known whether other forms of hormone therapy have the same effects. Some research has shown that when hormones are imbedded in a patch and absorbed through the skin, they affect the body differently.12
Why was there a flip-flop on hormone therapy recommendations?
Initial trials in animals and humans looked very promising. Both the estrogen and estrogen plus progestin treatment plans seemed to reduce the risk of heart disease in women who chose to try hormone therapy. But studies that compare women who choose a particular treatment with those who don't cannot fully eliminate the possibility that other differences may explain the lower risk of heart disease. The women taking hormone therapy were younger, healthier, and at a lower risk for heart disease to begin with.14 Women who took hormone therapy had access to better healthcare,15 and were better off financially than those who were not using hormone therapy.
All of these factors may have affected the results of the initial studies. When researchers do their number crunching, they use mathematical equations to adjust for these factors, but this is not a foolproof method. The gold standard test for medical treatments is the randomized controlled trial where women are randomly assigned to the treatment or a dummy pill. The two groups of women are evenly matched in terms of age, education, health, etc., minimizing the chances that these other factors will affect the results. When randomized controlled trials of hormone therapy were conducted, such as the Women's Health Initiative, the results showed that hormone therapy does not prevent heart disease.
Do the heart risks of hormone therapy change with age?
Most women studied in the large hormone trials were older, and many started hormones more than 10 years after menopause began. Could the lack of a heart benefit be because many of these women had already developed clogged arteries, and heart disease could have been prevented if the hormones were started earlier?
A 2007 analysis of the Women's Health Initiative suggests that this might be the case. In this study, the sooner after menopause a woman started taking hormone therapy, the lower her risk of developing heart disease.16 For women who started taking hormone therapy between ages 50 and 59, the risks of developing heart disease or of dying from any cause were actually slightly lower than women taking a dummy pill. However, there were so few younger women in the study that the results could have been due to chance. One other study showed that estrogen replacement in younger women reduced the burden of coronary artery calcium, a measure of hardening of the arteries.17
The possibility that hormone therapy can reduce heart risk in younger women, particularly if it is taken in the first 5 years after menopause, is being explored in trials such as the Kronos Early Estrogen Prevention (KEEPS) Study and the Early versus Late Intervention with Estradiol (ELITE) study.
For now, hormone therapy should not be taken to prevent heart disease even among very young postmenopausal women. However, the results of studies like the Women's Health Initiative should reassure younger women who want to take HT for menopausal symptoms that they need not be scared off by the possible heart risks.
Should I use hormone therapy if I already have heart disease?
No. If you have been diagnosed with heart disease or have had a heart attack, stroke, or blood clots, you should not take hormone therapy. Hormone therapy, either estrogen-only or combination, does not reduce the risk of additional heart problems for women who already have heart disease. Combination hormone therapy increases the risk of heart attack in the first year of therapy, as well as increasing the risk of blood clots and stroke.18-22
What alternatives to hormone therapy are being studied?
Currently, researchers are looking into a group of drugs called Selective Estrogen-Receptor Modulators (SERMs), which have also been called "designer estrogens." They are compounds that have beneficial effects on bone density like estrogen, but without estrogen's negative effects on the breast or lining of the uterus. The hope is that these new compounds will provide the benefits of replacement estrogen without the negative side effects, such as cancer and heart problems. So far, most studies of SERMs have found that they do not increase heart disease risk but, like hormone therapy, increase the risk of stroke and blood clots.
The most-studied of the four FDA-approved SERMS is raloxifene (Evista), used to prevent and treat postmenopausal osteoporosis (thinning of the bones) and to prevent breast cancer in women at high risk. In the RUTH trial, over 10,000 women with heart disease or multiple risk factors received raloxifene or a dummy pill once a day for more than 5 years. Raloxifene cut the risk of breast cancer and spine fractures, and did not increase the risk of heart attack, hospitalization for heart disease, or dying of heart disease. However, women taking raloxifene had a slightly higher risk of dying of a stroke or having blood clots in the leg veins, which can move to other parts of the body.23
Current guidelines state that, like hormone therapy, SERMs should not be used for the prevention or treatment of heart disease in women.9