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What is the Women's Health Initiative?
The Women's Health Initiative (WHI) was a large, randomized preventive clinical trial funded by the federal government to determine if hormones prevent heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. The trial involved women who used estrogen and medroxyprogesterone acetate (synthetic progestin) each day. This was one of the most commonly prescribed hormone therapy in the United States for women who have a uterus. There was also an estrogen-only group, a placebo (sugar pill) group, and a lifestyle and diet group. This study was done on women between the ages of 50-79, with the majority of the women being 60-69 years old in the group using the hormone therapy.
What are the main findings in the study on estrogen plus progestin?
When compared to women taking a placebo, the study showed:
- The number of women who were diagnosed with breast cancer was slightly higher in women taking estrogen plus progestin.
- The number of women who developed heart attacks, strokes, or blood clots in the lungs and legs was higher in women taking estrogen plus progestin.
- The number of women who had hip and other fractures or colorectal cancer was lower in women taking estrogen plus progestin.
- There were no differences in the number of women who had endometrial cancer (cancer of the lining of the uterus) or in the number of total deaths.
- There was no observed increase in the risk of breast cancer in women taking estrogen alone versus those taking a placebo. In fact, there was a slight decrease.
These findings highlight the importance of having your mammograms and keeping your scheduled appointments.
What are the conclusions from these findings?
- The estrogen plus progestin combination studied in the WHI does not prevent heart disease in older, postmenopausal women several years post menopause.
- For women taking estrogen plus progestin, the risks (increased breast cancer, heart attack, stroke, and blood clots in the lungs and legs) outweigh the benefits (fewer hip fractures and colon cancer) for women who do not have other reasons besides prevention to take hormone therapy. However, this study should not be applied to younger women or symptomatic women.
Increased health risks
What are the increased risks for women taking estrogen plus progestin?
For every 10,000 women taking estrogen plus progestin pills:
- 38 developed breast cancer each year, compared to 30 breast cancers for every 10,000 women taking a placebo each year.
- 37 developed a heart attack, compared to 30 out of every 10,000 taking a placebo.
- 29 had a stroke each year, compared to 21 out of every 10,000 women taking a placebo.
- 34 had blood clots in the lungs or legs, compared to 16 out of every 10,000 women taking a placebo.
What risks are lower for women taking estrogen plus progestin?
Estrogen plus progestin showed a decrease in total cholesterol, low density-lipoprotein (LDL -bad cholesterol), triglycerides, and an increase in high density- lipoprotein (HDL-good cholesterol)
For every 10,000 women taking estrogen plus progestin pills:
- 10 had a hip fracture each year, compared to 15 out of every 10,000 women taking a placebo.
- 10 developed colon cancer each year, compared to 16 out of every 10,000 women taking a placebo.
How many women were affected?
Only 2.5 percent of the women in this study showed these effects. This means that over the course of one year, for every 10,000 women taking estrogen plus progestin, we would expect:
- Seven more women with heart attacks (as opposed to those who are only taking the placebo)
- Eight more women with strokes
- Eight more women with breast cancer
- 18 more women with blood clots
- Six fewer colorectal cancers
- Five fewer hip fractures
- Fewer fractures in the bones
When did the increased risk of breast cancer become apparent for women taking estrogen plus progestin compared to women taking a placebo?
There was no difference in the development of breast cancer during the first 4 years among women taking estrogen plus progestin, compared to those taking a placebo. After that time, the numbers began to increase. After an average of 5.2 years, there was an increased risk of breast cancer in women taking estrogen plus progestin compared to those taking placebos.
Is there an increased risk of breast cancer in women taking estrogen alone?
There is no evidence of an increased risk of breast cancer in women who are taking estrogen alone, compared to those taking a placebo, even after several years; there was actually a decreased risk of being diagnosed with breast cancer.
What about the risk of ovarian cancer and hormone use?
The WHI did not find any increased risk in ovarian cancer at 5 years.
What are breast specialists saying about the WHI results?
If you are healthy and taking hormones only to prevent hot flashes and other symptoms, HT may make sense to you. Discuss your goals for therapy carefully with your doctor. Taking HT is a decision that each woman needs to make. Breast experts also note that taking estrogen with progestin increases breast tissue density, which makes it harder to read mammograms accurately. When women stop taking the hormones, the dense white tissue on the mammogram goes away within a few weeks.
What do heart experts say about the WHI? Will taking the combined hormones damage my heart?
The studies show that the combination of estrogen plus progestin fails to protect the heart and blood vessels in older women, when initiated >10 years post menopause. However, they do not show damage in the heart from taking this combination. There are likely some women who could take hormones safely and benefit, particularly women closer to the age of menopause. However, you should definitely stop hormone therapy if you have had a heart attack, stroke, or stroke-like symptoms, or if you have developed a vein clot. You also probably should stop oral hormone therapy if you need to be immobilized because of a broken bone or a need for major surgery, because of blood clotting concerns.
A study recently published in BMJ followed 1006 women aged 45-58 for 10 years, who were recently postmenopausal (average time since menopause was 7 months) or had perimenopausal symptoms. 502 were assigned to receive hormone replacement therapy and the other 504 were assigned placebo. After 10 years of follow-up, women receiving hormone replacement therapy early after menopauses had a significantly reduced risk of mortality, heart failure, and myocardial infarction.
What is the biggest danger of taking these hormones together, with regard to my heart and blood vessels?
There is an increase in vein clotting early in the course of therapy. In the first one to two years of this combination therapy, clotting in veins is the major risk of hormone therapy. Clotting in veins is different from clotting in arteries that go to the heart.
Quality of life
What did WHI report in improvement on quality of life issues such as sense of well-being, better sleep, improved sexual function, skin improvement, and enhanced dental health?
The WHI did not factor these issues into the results of its recommendations.
Are there recommendations about other hormone alternatives, such as lower-dose estrogens, micronized progesterone, and natural hormones?
We cannot make specific recommendations about other hormone medications, such as different estrogens or progestins. We also cannot make recommendations about hormones women take in lower dosages or in different ways, such as patches instead of pills. This includes compounded "natural" products. Without scientific trial data, one cannot assume that alternative estrogen plus progestin treatments have the same risks or are any safer than those studied in WHI.
I am taking prescription hormones, what should I do?
Do not panic or abruptly discontinue your hormones. We recommend that you talk with your health care provider about your individual health risk profile and the hormones you are currently taking. Stopping abruptly may cause a recurrence of menopausal symptoms (even if you did not have them before going on hormones). It is also possible that benefits could exceed risks for you or that there are alternative lifestyle changes or medications that you can take to lower your health risks if needed.
How much of a difference can lifestyle changes make?
You should try to change your lifestyle to become healthier, if at all possible. Exercise is the secret to good health. A healthy diet also can go far toward preserving your good health. Don't smoke, and if you do smoke, quit. There are several good clinical studies that show that controlling high blood pressure and normalizing your cholesterol levels lead to robust benefits for your heart and blood vessels. Those are the most important things you can do for your health before you need medications. Observational data suggests that exercise can actually reduce the risk of breast cancer. Some studies show that if you are a postmenopausal woman who exercises aerobically four hours a week, you can decrease your breast cancer risk by 15 to 20 percent. If you only exercise one hour a week, you can decrease your risk by seven percent. The benefits were even greater in premenopausal women who exercise. The bottom line is that exercise is important for preventing breast cancer as well as preventing strokes, heart attacks, and clots. Eat a healthy diet, including calcium, every day, and eat less saturated fat (solid at room temperature) and more olive and fish oils. Avoiding alcohol can help you reduce your risk of breast cancer and prevent hot flashes. Avoiding drinks with caffeine also can help you prevent hot flashes. Exercising regularly and having a normal Body mass index (BMI) 18-24.9 kn/m2 may help decrease your hot flashes.
Are there other drugs that can protect my heart and blood vessels from disease?
We know that in a large trial of women with osteoporosis, there were fewer breast cancer cases in women on Raloxifene but no heart disease benefit. Another trial evaluated men and women who had heart or blood vessel disease or diabetes plus a risk factor to learn the effects of a drug called angiotensin enzyme converting inhibitor. Ask your doctor about all of the options for your heart, including lifestyle options. Statins have been shown to lower cholesterol and to decrease heart events in both men and women who have heart disease.
What can I do if I want to keep taking the hormones for bone protection?
You have to look closely at your personal history and risk factors. If you have a high risk of osteoporosis or colon cancer, for example, you might choose to continue taking estrogen and progestin pills to prevent a broken hip and colon cancer. We still don't know the safest preparation that will give us these protective effects, however. You should also explore with your doctor alternative medicines that could also protect your bones such as the bisphosphonate family of drugs, known as Fosamax® or Actonel®. Miacalcin®, which helps protect the backbone, usually is used by women who can't take bisphosphonates. Raloxifene is a different type of drug that appears to decrease stimulation to the breast and reduce the risk of spine fracture. Don't forget that your body needs calcium and Vitamin D during and after menopause. You'll probably need to supplement your diet with calcium, and as you age, you'll need Vitamin D to aid with absorption. If you have had severe bone loss, magnesium supplements may help you absorb calcium better. It is best to get calcium in your diet.
- North American Menopause Society. Menonotes Accessed 8/2/2013.
- Women’s Health Initiative WHI In dbGAP Accessed 8/2/2013.
- Schierbeck, L. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012; 34:e6409
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 7/5/2013...#2780