For decades, women have used hormone replacement therapy (HRT, also known as post-menopausal hormone therapy or PHT) to ease symptoms of menopause, such as hot flashes. Many doctors and their patients believed HRT had other health benefits, too. But recent research studies have led doctors to question some of these beliefs.

Here we will discuss what is known about how hormone replacement therapy (HRT) can affect a woman's risk of getting certain cancers. We will not go into 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 published medical studies on the subject. Women who are thinking about using HRT are should talk with their doctors about the information covered here. Woman should also understand the risks and benefits of HRT and the follow-up they will need to have with their doctors if HRT is used. Based on this information, a woman and her doctor may decide that hormones are or are not needed for a period of time to help with symptoms of menopause.

Menopause, symptoms, and hormone replacement therapy

Menopause is the time in a woman's life when her ovaries stop releasing eggs and start making smaller amounts of the 2 main female hormones, estrogen and progesterone. Over time, this results in the end of menstrual periods. Women who have their ovaries removed by surgery (oophorectomy) or whose ovaries stop working for other reasons also go through menopause, too, but much more suddenly.

Lowered hormone levels cause the symptoms that are often linked to menopause -- hot flashes and night sweats, for instance. These symptoms tend to start early and fade away at some point, whether or not they are treated. Other symptoms, like dryness and thinning of vaginal tissues can start later and may worsen over time. Low estrogen levels also increase a woman's risk of other health problems, such as osteoporosis.

Types of hormone replacement therapy

The term hormone replacement therapy (HRT) is used to mean estrogen and progestin, or estrogen alone, given to a woman whose levels of these hormones are low due to menopause.

Estrogen replacement therapy

Estrogen replacement therapy (ERT) is used to raise estrogen levels in the body. CEE (conjugated equine estrogens) forms of ERT (such as Premarin^®) are most common and have been used for the longest time.

Combined hormone replacement therapy

Combined hormone replacement therapy uses both estrogen and progestin (progesterone-like hormone). Combined HRT can be given 2 ways:

• Continuous HRT involves giving the same dose of estrogen and progestin each day.

• Sequential (cyclical) HRT uses different amounts of the hormones during the month so that it is more like the natural menstrual cycle.

ERT and combined HRT are sometimes used to relieve symptoms of menopause. Some doctors believe hormone therapy can also lower a woman's risk of some other health problems linked to low estrogen levels.

How hormone replacement therapy is given

Both ERT and combined HRT may be given as a systemic therapy. This means that the hormones are given as pills or as a patch. They are absorbed through the digestive system, the mucous membranes, or the skin and reach all parts of the body through the bloodstream.

As another option, hormone treatments may be used topically. This means they mainly reach nearby areas rather than the whole body. Hormones that are placed in the vagina can enter the bloodstream, but the amount that gets in depends on the type of hormone and the dose. Dry or thinned vaginal tissues respond to very small doses of estrogen. These smaller doses are placed inside the vagina in the form of creams, rings, or tablets that slowly release hormones to the vagina and nearby tissues. Even though tiny amounts of hormone may enter the blood, most of it stays in the vaginal tissues. This is considered topical use.

HRT and endometrial (uterine) cancer risk

ERT

Using systemic estrogen (ERT) by itself increases a woman's risk of developing endometrial cancer (cancer of the lining of the uterus). Long-term use of vaginal creams, rings, or tablets containing estrogen may also increase estrogen levels in the body. The risk continues to be increased even after ERT is no longer used.

For these reasons, estrogen alone is almost never given 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 combined HRT (progestin and estrogen) may help menopause symptoms without increasing the risk of endometrial cancer.

One study showed that about 1 in 9 women treated with estrogen alone for 3 years developed a type of pre-cancerous 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 (WHI), 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. But more of the women getting HRT had abnormal vaginal bleeding (a possible sign of endometrial cancer) that needed further testing.

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. But because the only reason for giving progestin is to protect the endometrium, a woman without a uterus would most likely be given ERT alone.

HRT and breast cancer risk

Combined HRT

Results from the Women's Health Initiative (WHI) have shown that daily use of combined HRT increases a woman's chance of developing breast cancer by about 5% to 6% with each year of use. Out of 10,000 women who took combined HRT for a year, this would add up to about 8 more cases of breast cancer than in those who took no hormones. The longer HRT was used, the more the risk increased.

In this study, women who took 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.

A follow-up study from the WHI released in early 2008 looked at the women about 2 years after they had stopped taking HRT. The researchers found that found that women who had taken HRT continued to have a higher risk of breast cancer than women who had not taken HRT.

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 take ERT instead of combined HRT. These women do not need progestin to protect against uterine cancer and are 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 is thought to decrease after stopping HRT and return to that of the general population (the usual risk) within 5 years of stopping.

ERT

A separate part of the WHI looked at women who had had a hysterectomy, and whose ovaries were either removed or had stopped working. Those who were taking only estrogens did not have an increased risk of breast cancer.

The British "Million Women Study," and many other studies like this, reported a very slight increase in breast cancer risk (about 1% to 3% increase per each year of use) among women who took ERT.

HRT and ovarian cancer risk

Ovarian cancer is so rare that it is hard to study whether something increases a woman's risk for it. Even when the relative risk (or probability) is found to be increased, a woman's absolute 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. To put this another way, in a group of 100 women with a 12% risk of breast cancer and a 2% risk of ovarian cancer, you would expect about 2 cases of ovarian cancer and 12 breast cancers. A 50% risk increase in both cancers would mean there would be 18 women with breast cancer but only 3 with ovarian. So each woman's absolute risk of ovarian cancer would still be much lower than her risk of breast cancer.

ERT

Studies have shown that women who take ERT have higher risk for ovarian cancer compared to women who take no hormones after menopause. The risk of ovarian cancer increases the longer a woman uses ERT, particularly among those who have used ERT for more than 10 years.

Combined HRT

It's still not known if HRT increases the risk of ovarian cancer. In one recent study, women who took estrogen and progestin (either together or in cycles) did not have a higher risk for ovarian cancer unless they had previously taken estrogen without progestin.

The WHI 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.

HRT and colon cancer risk

Combined HRT

The WHI study found that combined HRT reduced the risk of colorectal cancer by about 40%. This effect seemed to fade when the women were checked a little more than 2 years after the HRT was stopped. This reduction has also been found in other studies like this. 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 non-cancerous conditions.

ERT

In the WHI group that took estrogen only, estrogen replacement therapy did not seem to have any effect on the risk of colorectal cancer.

Conclusions

The decision to use hormone replacement therapy (ERT or combined HRT) after menopause should be made by each woman and her doctor after weighing the possible risks and benefits. Factors to think about include

• the risk of breast, endometrial, and ovarian cancer

• the risks of other serious conditions affected by ERT or combined HRT not covered here, such as heart disease, stroke, and serious blood clots (DVT or deep vein thrombosis)

• other medicines that may be used to treat menopausal symptoms or osteoporosis.

Other factors to consider include how severe the woman's menopausal symptoms are and the type and dose of the hormones the doctor recommends.

If a woman and her doctor decide that ERT or combined HRT is the best treatment for certain symptoms of menopause or health problems, it is usually best to use it at the lowest dose that works for her 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 combined HRT be checked yearly by her doctor for any signs of cancer.

All women should report any vaginal bleeding that happens after menopause to their doctors right away -- it may be a sign of endometrial cancer.

Women should follow the American Cancer Society guidelines for cancer early detection, especially those for breast cancer. These guidelines are in Breast Cancer: Early Detection. To get these guidelines, please call 1-800-ACS-2345 (1-800-227-2345) or visit our Web site at www.cancer.org.

Adding progestin to estrogen (combined HRT) reduces the risk of endometrial cancer, but may not eliminate it entirely. If you are using vaginal cream, rings, or tablets containing estrogen talk to your doctor about follow-up and the possible need for progestin treatment.

For women who have had a total hysterectomy (removal of the uterus), progestin does not need to be added because there is no risk of endometrial cancer. Adding progestin does not protect against breast cancer and, in fact, raises the risk further, so ERT is a better option.

In recent years, many over-the-counter "natural" products have been marketed to help with menopausal symptoms. These include 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 Food and Drug Administration (FDA) for their safety or effectiveness. Some of the products have been tested, mostly in small clinical trials, but many of the tests had problems with the way they were done that could affect their outcomes. Well-controlled scientific studies are needed to help find out if these products work and if they are any safer than the hormone replacement therapy drugs now in use. You can learn more from reading How to Know What Is Safe: Choosing and Using Dietary Supplements. This is available on our Web site at www.cancer.org, or call us at 1-800-ACS-2345 (1-800-227-2345).

Additional resources

National organizations and Web sites*

Food and Drug Administration (FDA)
Toll-free number: 1-888-463-6332
Web site: www.fda.gov
Menopause & Hormone Replacement Page: www.fda.gov/womens/healthinformation/menopause.html

National Cancer Institute
Toll-free number: 1-800-422-6237 (1-800-4-CANCER)
Web site: www.cancer.gov
Menopausal Hormone Use Page: www.cancer.gov/clinicaltrials/digest-postmenopausal-hormone-use

National Institutes of Health
Telephone number: 1-301-496-4000
Web site: www.nih.gov
Menopausal Hormone Therapy Information Page: www.nih.gov/PHTindex.htm

National Women's Health Information Center
Toll-free number: 1-800-994-9662 (1-800-994-WOMAN)
Web site: www.womenshealth.gov
Menopause & Hormone Therapy Page: www.4women.gov/Menopause/

*Inclusion on this list does not imply endorsement by the American Cancer Society.

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Last Medical Review: 08/13/2008
Last Revised: 08/13/2008