Aug. 7, 2003 -- Combined hormone replacement therapy (HRT) using estrogen plus progestin may not only increase a woman's risk of breast cancer, but it may also make her more likely to die from the disease.
A British study shows for the first time that HRT users are more likely to die of breast cancer than women who have never used HRT, and the breast cancer risks associated with combined estrogen-progestin hormone therapy are up to four times greater than those associated with estrogen-only HRT.
The study, published in the Aug. 9 edition of The Lancet, involved about 1 million women between the ages of 50 and 64 and also confirms previous studies that found HRT slightly raises the risk of breast cancer in postmenopausal women.
Half of the women were HRT users. A total of 9,364 breast cancers were reported after an average of 2.6 years, and 637 deaths were reported after an average of 4.1 years.
Researchers found the risk of breast cancer increased the longer a woman used HRT, but this effect wore off within a few years after stopping HRT. Women who had used HRT at the start of the study had an almost 70% higher risk of developing breast cancer and a 22% higher risk of dying from it than women who never used HRT. Past users of HRT did not have an increased risk of the disease or death from it.
The study showed that current use of combination HRT was associated with a higher risk of breast cancer than estrogen-only HRT. The longer HRT was used, the greater the risk. Also, the increased risk varied on the type of estrogen and progestin as well as whether the women took the hormones continuously or periodically.
Researchers estimate that for every 1,000 postmenopausal women who take HRT for 10 years, use of estrogen-only HRT will cause an extra five breast cancer cases and combined HRT will cause an extra 19 cases.
"Combined estrogen-progesterone HRT is usually prescribed for women who still have a uterus, to avoid the increased risk of cancer of the uterus caused by estrogen-only therapy," says researcher Valerie Beral, professor at Cancer Research UK, in a news release.
"Since our results show a substantially greater increase in breast cancer with combined HRT, women need to weigh the increased risk of breast cancer caused by the addition of progestin against the lowered risk of uterine cancer," says Beral. "Comparing the risks is by no means simple, and women may well want to discuss options with their doctor."
In an editorial the accompanies the study, Chris van Wheel and colleagues from the University of Nijmegen, Netherlands, say these findings are in line with two recent studies published in The Journal of the American Medical Association that found a higher risk of advanced or invasive breast cancers in combination HRT users.
"The problem is in those women who are already, often for a long time, taking HRT -- estimated at between 20% and 50% of all women 45-70 years of age in the western population," they write. "This group should discontinue HRT use as soon as possible.
"Discontinuing HRT should be suggested in as supportive a way as possible, because no one will benefit from panic or over-reaction: general practitioners need to use the opportunities arising from their regular contacts with patients taking HRT to discuss treatment-related risks, to give advice about stopping, and to offer alternative support."
Sorting Out the Risks and Benefits of HRT
To help women make sense of the confusion surrounding HRT, WebMD consulted an expert, JoAnn V. Pinkerton, MD, director of the Mid-life Health Center at the University of Virginia in Charlottesville and chairwoman of the professional education committee of the North American Menopause Society.
Q. Who should be concerned about these and other recent studies on hormone replacement therapy?
A. I think there are two main groups of women who are most concerned with HRT issues.
First, there are the women with significant menopausal symptoms, such as hot flashes, and are considering going on HRT.
The second group of women are those who have been on HRT for a long time, have read the recent information on HRT, decided to transition off HRT, and now have not fared well in terms of having significant menopausal symptoms.
Q. For women thinking of starting HRT for relief of menopausal symptoms, what are some alternative options to consider?
A. About 25% of menopausal women have significant symptoms, and about 15% of those have moderate to severe symptoms, enough that they affect the woman's quality of life. That usually means more than 10 hot flashes a day, waking up several times during the night with night sweats, difficulty concentrating, and possibly vaginal dryness and pain during intercourse.
For people with milder symptoms, we first try lifestyle changes, including:
- Wearing lighter, layered clothing
- Using fans and air conditioning
- Avoiding hot flash triggers, such as spicy food or wine
- Learning relaxation techniques or paced breathing
For people with more frequent hot flashes, we may try over-the-counter remedies with the understanding that we have limited data on their safety and effectiveness, such as:
- Black cohosh
- Soy products
- Phytoestrogens (plant-based estrogen-like substances), such as red clover
What we know from studies is that these over-the-counter products work about as well as a placebo or sometimes a little bit worse.
Q. What's left for women with more severe symptoms that aren't relieved by alternative methods?
A. These women will need some type of medical intervention, and without a doubt hormone replacement therapy is the most effective. It works 95% to 98% of the time, and it works with both mild as well as the more intense or severe hot flashes.
For women who don't want to go on hormones or those for whom HRT is not recommended, such as those with a history of breast cancer, we are trying low-dose antidepressants. These drugs are showing an effectiveness at relieving hot flashes of between 30%-60%, and we can get effective treatment in that range at lower doses than are needed to treat depression, so hopefully there are fewer side effects.
Q. How do you discuss the risks and benefits of HRT with women who need relief from menopausal symptoms?
A. First, we identify the reasons she is considering treatment with HRT, such as the severity of her symptoms, bone density, risk of breast cancer, cholesterol levels, and personal ideas about hormones.
Then, we go through our current understanding of the risk and benefits of hormone replacement therapy, largely based on the results of the WHI study but also other data. For example, we discuss:
- The increase in heart events, breast cancer, and gallstones
- The decreases in hip factures and colon cancers found with HRT
- The study that found that women who were 65 and older when they started hormones had an increase in dementia
- The fact that HRT tends to make the breast denser and harder to spot breast cancers through mammograms, which increases the likelihood that a woman on HRT might have an abnormal mammogram. This could lead to unnecessary testing, such as a breast biopsy.
Q. How do you explain the increase in breast cancer risk associated with HRT use shown by the WHI study?
A. The number I use with my patients is that an extra eight out of 10,000 women using estrogen-plus-progestin HRT developed breast cancer per year -- that translates to 0.08 per 100. Then, we actually calculate their individual statistical risk and show them that the risk of breast cancer is actually higher from their own statistical chance and that the increase from hormones for most women is a small increase.
My advice is to look at the absolute increased risk seen with HRT and to interpret it in terms of the particular woman and her own risks and benefits. Eight additional cases per 10,000 women is a very small number, but it's very significant to those eight women. It's also very important for women who are at risk for breast cancer to know that they are increasing their chance of breast cancer with long-term use of HRT.
Q. How has your discussion about the risks and benefits of HRT for women entering menopause changed?
A. The biggest difference is that before the WHI study, we felt hormones would treat the symptoms, decrease their chances of heart disease and hip fracture without increasing the risk for breast cancer, and potentially decrease the chance of Alzheimer's disease.
Now, when women come in we're primarily focusing on relief of menopausal symptoms and educating them that we don't think that we're preventing heart disease or Alzheimer's and that we are slightly increasing their chance of breast cancer.
Q. What about older women who are already on HRT? What are their concerns?
A. For women in the 55- to 60-year age group, they are most concerned about their risk for breast cancer. We identify their statistical chance of having breast cancer and then talk about the potential added risk from long-term use of HRT, look at their bone density, and for most women who have been on HRT for more than five years, we either lower the dose or taper them off.
For women in their late to mid-60s, they are most concerned about the potential increase in dementia.
Q. What about the women who went off HRT due to the news from the WHI study?
A. What's happened since July 2002 is that many women elected to wean down their dose of HRT or stop it abruptly, and we are now seeing these women back in the office.
Many have made the transition successfully, and many are miserable and really miss their hormones. For those women, we look at the risks and the benefits, and many of them choose to go on a low dose of hormone replacement therapy to improve their quality of life.
Q. If a woman is using HRT, what are some issues she should discuss with her doctor?
A. Here are some questions I'd recommend:
- How long have I been on hormones?
- Why did I start to use hormones?
- Why am I continuing to use hormones?
- What are my risk and benefits to continuing them?
Each of these issues should be discussed at each visit.
Q. If a woman decides to stop taking hormones, are there other issues she should consider?
A. One issue many women are not aware of is that when women go off hormones, they usually begin having symptoms, such as hot flashes, that begin two weeks later and peak at about eight weeks after they stopped taking hormones. But these symptoms then start to calm back down. A three-month trial is usually long enough for women to get a sense of whether stopping HRT is something they can handle.