Hormone Therapy: The Risks & Benefits
By Elizabeth Santoro, RN, MPH & Jae Hong Lee, MD, MPH
In the past few years, many women have stopped taking hormone replacement therapy because of growing evidence that the risks outweigh the benefits for most women. However, millions still struggle with the decision: should I go on, should I stay on, or should I go off?
For decades, women were told that hormone therapy was like a fountain of youth that would protect them against many of the diseases and symptoms of aging that increase after menopause. Since estrogen alone was known to increase the risk of uterine cancer, doctors usually prescribed a combination of estrogen and progestin, unless a woman had a hysterectomy and therefore was at no risk of uterine cancer.
In addition to its proven effectiveness for decreasing hot flashes, night sweats, and vaginal dryness, hormone therapy was thought to decrease osteoporosis, prevent heart disease, improve memory and concentration, reduce wrinkles, and improve mood. Women were encouraged to start hormone therapy before menopause started and to continue to take it for years, if not decades, in order to improve their health and their quality of life.
The latest study which has revealed that the risks of hormone therapy outweigh the benefits is known as the Women’s Health Initiative, and it was funded by the National Institutes of Health (NIH). The study included 8,506 women taking estrogen plus progestin, 10,739 taking estrogen alone, and 8,102 in a placebo group. In July 2002, the estrogen and progestin part of the study was stopped for ethical reasons when it was determined that the women taking combination hormones were more likely to develop breast cancer, stroke, and blood clots, and at least as likely to develop heart disease, compared to women taking placebo. A year after the study was stopped in 2002, an article was published indicating that estrogen plus progestin also increases the risks of dementia. In 2004, the part of the study that evaluated estrogen alone was also stopped for ethical reasons, when the results indicated that estrogen alone increases the risks of blood clot and stroke.
To emphasize that lost hormones don’t necessarily need to be replaced, the term “hormone replacement therapy” has been changed to “hormone therapy.” Doctors now advise women to use hormone therapy only for severe symptoms of menopause that reduce the quality of life, such as severe hot flashes, night sweats, insomnia, and vaginal dryness. They are also urged to take hormones at the lowest dose that is effective and for the shortest possible period of time.
When is it Safe for Women to Use Hormone Therapy?
Although the studies evaluated PremPro and premarin, the FDA assumes that other similar products would have the same risks and benefits. The FDA has developed guidelines for when hormone replacement therapy is effective. The recommendations are listed below.· Hormone therapy is effective for short term use for the relief of moderate to severe postmenopausal symptoms such as hot flashes
· Hormone therapy is an effective treatment for moderate to severe vulvar and vaginal atrophy, but topical agents should be considered first
· Hormone therapy is effective for reducing the risk of osteoporosis, but other drugs, diet, and exercise are as well. For that reason, it should only be considered for women at significant risk for osteoporosis and for those women who cannot take other medications that prevent osteoporosis.
· Hormone therapy should be taken at the lowest dose and for the shortest duration that is needed to achieve the desired treatment outcome
Available at: www.fda.gov/womens/menopauseWhat Are the Risks and Benefits of Hormone Therapy?
The most recent information about hormone therapy comes from three major trials that were part of the NIH-sponsored Women’s Health Initiative (WHI): the estrogen plus progestin trial, the Women’s Health Initiative Memory Study, and the estrogen-alone trial. Each study was stopped early for ethical reasons when it became clear that women taking hormones were more likely to be harmed than helped. The main findings of each study are summarized below, followed by a more detailed discussion, including the age of the women in the studies.Estrogen plus Progestin Trial (stopped in July 2002)
· Hormones increased risk for breast cancer, heart disease, stroke, and blood clots
· Hormones decreased risk for fractured hip and colon cancerWomen’s Health Initiative Memory Study (stopped in May 2003)
· Women taking hormones had twice the risk for developing dementia
· Hormones provided no protection against mild cognitive impairment/memory lossEstrogen-alone Trial (stopped in February 2004)
· Estrogen increased risk for stroke
· Estrogen decreased risk for hip fracture
· No positive or negative effect on breast cancerTimeline of the Studies with their Findings
July 2002: Estrogen Plus Progestin Trial
This study of combination hormones recently reached a major conclusion: the risks of combination hormone therapy outweigh the benefits. The results were so compelling that women in the study were asked to stop taking their hormone pills and the clinical trial was ended early after approximately five years.
This part of the Women’s Health Initiative study enrolled approximately 16,600 women. The women of ages 50-79 were randomly assigned to two groups: 8,506 received estrogen plus progestin and 8,102 were given placebo. In order to be eligible for the study, each participant had to have an intact uterus.
The study found that women taking combination hormone therapy pills had an increased risk of experiencing heart attacks, strokes, blood clots, and breast cancer compared to women taking placebo. On the plus side, fewer women on combination hormone therapy had colorectal cancer and hip fractures. The results of this study do not apply to women without a uterus (who have had a hysterectomy) who take estrogen but not progestin.
Compared to women taking placebo, within 5 years the women who received estrogen and progestin experienced:
-- 41% more strokes
-- 29% more heart attacks
-- twice as many blood clots
-- 22% more heart disease of all types
-- 26% more breast cancer
-- 37% fewer cases of colorectal cancer
-- one-third fewer hip fractures
-- 24% fewer bone fractures of any type
-- no difference in the overall death rate
It's important to note that only 2.5% of the women in the study experienced health problems. So, while the percentage increase in some diseases was rather large, the risk for most patients remained relatively small. That does not mean these risks are not important.
To provide a better sense of the additional risks that come with combination hormone therapy, the study data can be summarized more simply. Compared to a group of 10,000 women taking placebo, 10,000 women taking combination hormone therapy will experience:
-- 7 more heart attacks
-- 8 more strokes
-- 8 more cases of breast cancer
-- 18 more blood clots
-- 6 fewer cases of colorectal cancer
-- 5 fewer hip fractures
Since the long-term risks of taking HRT outweigh the benefits, some women may consider combination hormone therapy for short-term use to treat severe symptoms of menopause such as debilitating "hot flashes." However, even short-term use (less than one year) increases some risks; for example, the increase in heart disease comes primarily from the first year of hormone use.
The decision to stop the study shocked the medical community, because the study had been scheduled to continue through 2005. The study was stopped because the number of women taking the hormones who had developed invasive breast cancer was above the danger threshold that had been set before the study was started. Since the women taking hormones also experienced other serious health problems, it was decided that the risks of hormone treatment outweighed the benefits. However, the women who had taken estrogen plus progestin will continue to be studied to evaluate the long-term effects.May 2003: The Women’s Health Initiative Memory Study
Doctors had claimed that hormones would improve memory, so it was shocking when studies indicated that instead of helping, hormone therapy may double the risk of Alzheimer’s disease and other dementias. The Women’s Health Initiative Memory Study (WHIMS) found that out of 4,532 women, 61 were diagnosed with probable dementia. Of that group, 40 women had received estrogen plus progestin while 21 women were in the placebo group. In addition, estrogen plus progestin did not prevent memory loss.
The women in this study were approximately 25 percent of the 16,000 Women’s Health Initiative (WHI). The 4,532 women enrolled in WHIMS were age 65 or older when they started taking hormones in the study, postmenopausal, considered free of dementia at the beginning of the study, and recruited from 39 clinical centers. The NIH-sponsored study was stopped early, after almost four years.
It is unclear if the results of the study would be similar for younger postmenopausal women, since the women in the study were at least 15 years older than the average newly menopausal woman. Doctors, patients, and hormone therapy companies are hoping that women who start hormones at the time they are starting menopause may do better. In addition, the risk of a woman developing dementia was low, even if she took hormone therapy: based on this study, only 45 out of 10,000 women taking hormones would develop probable dementia each year for the first five years. This would be more than the 22 out of 10,000 women not taking hormones that would have developed probable dementia per year for the same five years.
Nonetheless, this adds to the growing evidence that the risks of hormone therapy outweigh the benefits. Overall, recent research strongly suggests that hormones should not be used as a prevention strategy to fight the diseases of old age, such as heart disease and Alzheimer’s disease, or the symptoms of old age, such as memory loss.
February 2004: The Estrogen-alone Trial
More bad news from the NIH-sponsored Women’s Health Initiative (WHI) study caused the estrogen-alone trial to be stopped early. The main reasons were that estrogen did not prevent or delay heart disease and it significantly increased the risk of stroke. This part of the study was stopped almost two years after stopping the “combination” (estrogen plus progestin) study and a few months after the WHIMS trial was halted.
The decision to stop the estrogen-alone trial one year early came after women had taken the hormone for nearly seven years. This multi-center trial enrolled 11,000 healthy postmenopausal women ages 50-79 who also had a hysterectomy. During the course of the study, an independent advisory committee reviewed the data and monitored the safety of the women in the study. When it became clear that estrogen alone was not as safe as expected, they were torn between two options: stop the study or continue with the study after sending a letter to the participants explaining the risk of stroke in addition to several other findings. The NIH decided to stop the trial, but to continue to study the women who had received the hormones. Their rationale was that after almost seven years, estrogen-alone had not shown the expected benefits at preventing or delaying heart disease. In addition, the risk of stroke was similar to that found in women taking estrogen plus progestin -- and that study had been stopped early.
Stopping the trial was important for safeguarding the health of women in the study who were taking hormones. Since this was a group of healthy women, the increased risk of stroke was deemed unacceptable by the NIH. In addition, the hormones had no effect on heart disease or breast cancer. Although the women taking hormones were less likely to have hip fractures, that did not make up for the increased risks.
Key Points to Remember about Hormone Therapy
The bottom line is that hormone therapy does not improve health or prevent diseases of old age such as heart disease and Alzheimer’s disease. Instead, hormones can have the opposite effect and therefore increase a likelihood of developing one of these diseases, as well as stroke, breast cancer, and blood clots. Nonetheless, hormone therapy does have benefits for some women. It can be used effectively to treat severe short-term symptoms of menopause, such as hot flashes and insomnia, and also for moderate to severe cases of vulvar and vaginal atrophy. Hormone therapy is also recommended to treat severe postmenopausal osteoporosis when non-estrogen medications or other strategies are unsuccessful or impossible. A decision to use any combination of estrogen and progestin should be discussed with a physician who is expert on the topic, and specific criteria for the indication, dose, and duration of these hormones must be met prior to their prescription and administration.
