For decades, women have used hormone replacement therapy (HRT, also known as postmenopausal hormone therapy) because of its ability to relieve menopausal symptoms such as hot flashes. Many doctors and their patients believed HRT had other positive health benefits as well. However, recent studies have called some of these beliefs into question.
The purpose of this document is to discuss what is known about how hormone replacement therapy (HRT) can affect a woman’s risk of getting certain cancers. It does not discuss in detail the possible effects of HRT on other diseases such as osteoporosis (bone thinning), heart disease, and dementia.
This is not meant to be a policy statement of the American Cancer Society -- it is a summary of medical articles on the subject. Women are encouraged to discuss this information with their doctor. A woman and her doctor may decide that hormones are or are not needed for a period of time for her menopausal symptoms.
Background
Menopause is the period in a woman's life when her ovaries stop releasing egg cells and begin to make smaller amounts of the 2 main female hormones, estrogen and progesterone. Eventually, this results in the end of menstrual periods. Women who have their ovaries removed by surgery (oophorectomy) or whose ovaries stop functioning for other reasons also go through menopause, although not as gradually.
Lowered hormone levels cause the symptoms that are often associated with menopause -- hot flashes, dryness and thinning of vaginal tissues, and mood swings. Low estrogen levels also increase a woman's risk of other health problems, such as osteoporosis.
Estrogen replacement therapy (ERT) raises estrogen levels in the body by giving women synthetic versions of this hormone.
Combined hormone replacement therapy (HRT) uses both estrogen and progestin (progesterone-like hormone). Combined HRT (also known as combined hormone therapy) can be given 2 ways.
- Continuous HRT involves giving the same dose of estrogen and progestin each day.
- Sequential (cyclical) HRT uses differing amounts of the hormones during a month-long period to mimic natural menstrual cycles.
ERT and combined HRT are sometimes prescribed to relieve menopausal symptoms and are believed by some to lower a woman's risk of certain other health problems related to low estrogen levels.
Both ERT and combined HRT may be delivered as a systemic therapy. This means that the hormones are given as pills or as a patch, so that the hormones are absorbed through the skin and reach all parts of the body through the bloodstream. Alternatively, hormone treatments may be applied topically, that is, to specific areas rather than system-wide. In this case, smaller amounts of hormones are placed within the reproductive tract as creams or as rings of materials that slowly release the hormones to nearby body tissues.
Endometrial (Uterine) Cancer
ERT: The use of systemic estrogen alone (ERT) increases a woman's risk for developing endometrial cancer (cancer of the lining of the uterus). Prolonged use of vaginal creams or rings containing estrogen may also increase estrogen levels in the body. Therefore, it is important to discuss potential risks and follow up with your doctor if you use these medications.
To avoid raising this risk, estrogen is almost never prescribed alone to women who have gone through menopause and who still have a uterus.
Combined HRT: For women who still have their uterus, studies show that replacing both estrogen and progestin (combined HRT) may provide the benefits of estrogen replacement without increasing the risk of endometrial cancer.
One recent study showed that about 1 in 9 women treated with estrogen alone for 3 years developed a type of precancerous change in their endometrium called atypical hyperplasia. Women treated with both types of hormones did not develop this change any more often than women not taking any hormones.
The Women’s Health Initiative, a large, randomized, controlled trial of women getting either continuous combined HRT or a placebo (an inactive substance used for comparison, also known as a "sugar pill"), also found that combined HRT did not increase endometrial cancer risk. However, more of the women getting HRT had abnormal vaginal bleeding (a possible sign of endometrial cancer) that required further testing.
Although the addition of progestin seems to help protect against the increased risk of endometrial cancer, one study suggests that, at least for sequential HRT, some of this protection may be lost after more than 5 years of therapy.
The risk of endometrial cancer decreases within a short period of time after ERT or HRT is discontinued.
A woman who has had her uterus completely removed (total hysterectomy) is not in danger of developing endometrial cancer, regardless of whether she takes ERT or HRT.
Breast Cancer
Combined HRT: Results from the Women’s Health Initiative (WHI) showed that daily use of combined HRT (estrogen and progesterone) increased a woman’s chances of developing breast cancer by about 25% if she took it for several years. Women who took this combined HRT also had a higher risk of having breast cancer detected at a more advanced stage and were more likely to have abnormal results on mammograms.
(The study also found that combined HRT increased the risk of developing heart disease, stroke, and blood clots in the legs that can travel to the lungs. It did not have a beneficial effect on mental function or on preventing Alzheimer’s disease. Women taking this combination of hormones did have lower risks for osteoporosis and colon cancer, however.)
Although many experts have recommended that women stop taking combination hormone treatment, others have disagreed. They point out that the WHI study only looked at continuous HRT (a combination pill), not the sequential kind where a woman takes estrogen for several weeks followed by several days of progesterone.
However, at least 2 recent population studies (by Beral and Li) have found the type of combination HRT did not appear to make a difference.
But not all of the questions surrounding combined HRT and breast cancer risk have been answered. Most of the increased risk of breast cancer from combined HRT is thought to be due to the progestin. Doctors are now looking at whether the dose of progestin can be decreased to lower the risk of breast cancer while still protecting the endometrium.
Women who no longer have a uterus (due to hysterectomy) should receive ERT instead of combined HRT. These women do not need progestin to protect against uterine cancer and may be increasing their risk of breast cancer by taking combined HRT.
The risk of HRT applies only to current and recent users. A woman's breast cancer risk decreases soon after stopping HRT and appears to return to that of the general population within 5 years of stopping.
ERT: In a separate part of the WHI, women taking only estrogens, who had had a hysterectomy, and whose ovaries were either removed or had stopped functioning, did not have an increased risk of breast cancer and may have had a slightly decreased risk. (However, other effects, such as an increased risk of stroke, probably outweighed any benefits.)
The British "Million Women Study," although not as scientifically strong as the WHI study, reported a slightly increased risk of breast cancer among women who took ERT. The increase in this study was small enough that it may have been due to chance.
Ovarian Cancer
Ovarian cancer is relatively rare, so it is hard to study whether something increases a woman’s risk for it. Even when the risk is found to be increased, a woman’s overall risk is still likely to be low. For example, a woman is much more likely to be affected by a 50% increase in her risk for breast cancer than by a 50% increase in her risk for ovarian cancer, because her risk for ovarian cancer is much lower to begin with.
ERT: One recent study showed that women who take only estrogen, particularly for more than 10 years, have a higher risk for ovarian cancer. The risk increased with longer ERT use.
Combined HRT: In the same study, women who took estrogen and progesterone therapy, whether continuous or sequentially (that is, estrogen for several weeks, followed by several days of progesterone), did not have a higher risk for ovarian cancer, unless they previously took estrogen alone for a period of time without any progesterone.
Recently, the Women’s Health Initiative study found that continuous combined HRT may increase the risk of ovarian cancer slightly, but this finding may have been due to chance because of the small number of women who developed ovarian cancer during the study.
Colon Cancer
Combined HRT: The Women’s Health Initiative study found that combined HRT reduced the risk of colorectal cancer by about 40%. However, women who were taking HRT were more likely to have colorectal cancer diagnosed at an advanced stage than were women who were not taking HRT. Of course, these results must be weighed along with the effects of HRT on the risk of other types of cancer, as well as its effects on noncancerous conditions.
ERT: In the estrogen-only arm of the WHI, estrogen replacement therapy did not seem to have an effect on the risk of colorectal cancer.
Conclusions
The decision to use hormone replacement therapy (ERT or HRT) after menopause should be made by each woman and her doctor after weighing the possible risks and benefits. Factors to consider include the risk of breast, endometrial, and ovarian cancer; the risks of other serious conditions affected by ERT or HRT not discussed here, such as heart disease, stroke, and dementia; and the availability of other medications that may treat menopausal symptoms or osteoporosis. Other considerations include the severity of menopausal symptoms and the type and dose of the hormones the doctor recommends.
If a woman and her doctor decide that ERT or HRT is appropriate to treat specific menopausal symptoms or health problems, it should be prescribed at the lowest dose that is effective in her case and for as short a time as possible. Other treatments for these symptoms and conditions should also be considered.
It is important that any woman taking ERT or HRT be checked yearly by her doctor for any signs of cancer.
All women should report any abnormal or excessive postmenopausal vaginal bleeding to their doctor without delay -- it may be a sign of endometrial cancer.
Women should follow ACS guidelines for cancer early detection, especially those for breast cancer.
The addition of progestin to estrogen (combined HRT) reduces but does not eliminate the risk for endometrial cancer. If you are using estrogen-containing vaginal cream or rings, consult with your doctor regarding follow-up and the possible need for progestin treatment.
For women who have had a total hysterectomy (removal of the uterus), the addition of progestin is unnecessary because the risk of endometrial cancer has been removed. The addition of progestin does not protect against breast cancer, and in fact probably raises the risk further, so ERT is a better option.
In recent years, several over-the-counter "natural" products have been marketed to help with menopausal symptoms, including certain vitamins, soy-based products, and herbal products such as black cohosh and red clover. These products are considered dietary supplements (as opposed to drugs) and have not been evaluated by the US Food and Drug Administration (FDA) for their safety or effectiveness. Studies are now being done to help determine if these products are effective or if they are any safer than the hormone replacement therapy drugs now in use.
Additional Resources
National Organizations and Web Sites*
Food and Drug Administration (FDA)
Telephone: 1-888-463-6332
Internet Addresses
Home Page: www.fda.gov
Menopause & Hormones Page: www.fda.gov/womens/menopause/
National Cancer Institute
Telephone: 1-800-4-CANCER (1-800-422-6237)
Internet Addresses
Home Page: www.cancer.gov
Menopausal Hormone Use Page: www.cancer.gov/clinicaltrials/digest-postmenopausal-hormone-use
National Institutes of Health
Telephone: 1-301-496-4000
Internet Addresses
Home Page: www.nih.gov
Menopausal Hormone Therapy Information Page:
www.nih.gov/PHTindex.htm
National Women’s Health Information Center
Telephone: 1-800-994-WOMAN (1-800-994-9662)
Internet Addresses
Home Page: www.4women.gov
Menopause & Hormone Therapy Page:
www.4women.gov/Menopause/
*Inclusion on this list does not imply endorsement by the American Cancer Society.
References
Anderson GL, Judd HL, Kaunitz AM, Barad DH, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: The Women’s Health Initiative randomized trial. JAMA 290(13):1739-1748, 2003.
Beral V, Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-427, 2003.
Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. JAMA. 289: 3243-3253, 2003.
Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, Hubbell FA, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Eng J Med. 350(10): 991-1004, 2004.
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Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 283(4): 485-491, 2000.
Weiderpass E, Adami HO, Baron JA, Magnusson C, Bergstrom R, Lindgren A, Correia N, Persson I. Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst 91(13):1131-1137, 1999.
Weiderpass E, Baron JA, Adami HO, Magnusson C, Lindgren A, Bergstrom R, Correia N, Persson I. Low-potency estrogen and risk of endometrial cancer: a case-control study. Lancet 353(9167):1824-1828, 1999.
Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA 291(14):1701-1712, 2004.
Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321-333, 2002.
Revised: 10/07/04
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