Menopausal Hormone Therapy
and Cancer Risk

For decades, women have used hormone therapy to ease symptoms of menopause, such as hot flashes and sweating. This is called menopausal hormone therapy, and you may see it abbreviated as HT or MHT. You may also hear it described as hormone replacement therapy (HRT), postmenopausal hormone therapy (PHT), or postmenopausal hormones (PMH).

In the past, many doctors and their patients believed HT had other health benefits besides helping menopause symptoms. But several well-conducted studies have led doctors to conclude that the risks of HT may outweigh the benefits for most women. Still, each woman may have different concerns that should be discussed with her doctor.

Here we will discuss what is known about how HT can affect a woman’s risk of getting certain cancers. We will not go into the possible effects of HT on other diseases like osteoporosis (bone thinning), stroke, heart disease, blood clots, and dementia.

This is not meant to be a policy statement of the American Cancer Society – it’s a summary of published medical studies on the subject. Women who are thinking about using HT should talk with their doctors about the information covered here. Women should also understand the risks and benefits of HT and the follow-up they will need if HT is used. Based on this information, a woman and her doctor may decide that hormones are or are not needed for a short time to help with symptoms of menopause. As the menopausal change winds down, most of the symptoms taper off. At that time, it’s a good idea to stop HT because the risks tend to climb even higher.

Menopause, symptoms, and hormone therapy

Menopause is the time span 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, these hormone changes cause menstrual periods to stop. Women who have their ovaries removed by surgery (oophorectomy) or whose ovaries stop working for other reasons go through menopause, too, but much more suddenly.

Changing hormone levels cause the symptoms that are often linked to menopause – hot flashes and night sweats, for instance. These symptoms tend to fade away at some point, whether or not they are treated. Other symptoms, like dryness and thinning of vaginal tissues can start after menopause, and may get worse over time. Low estrogen levels are normal after “the change,” and can also increase the risk of other health problems like osteoporosis.

Types of hormone therapy

The most commonly prescribed hormones are estrogen and progestin used together, but HT can also refer to estrogen alone. It is important to know which type of HT you are talking about when looking at the risks. In this discussion, we will use estrogen therapy (ET) to mean estrogen alone, and estrogen progestin therapy (EPT), often called combined HT, to mean estrogen and progestin together.

ET and EPT 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.

Both types of HT are discussed in detail, along with the possible risks of each. Note that there are other types of hormones prescribed by doctors during menopause, but we don’t yet have enough data to discuss their potential risks.

The word “bio-identical” is sometimes used by sellers to describe hormones that contain estrogens or progestins with the same chemical structure as those found naturally in people. Marketers may describe bio-identical hormones as more “natural,” and buyers often think that they are safer than the more traditional drugs used to control menopause symptoms. But anything that contains estrogens or progestins must be prescribed, just as other hormone drugs are, and should be assumed to have the same health risks as any other type of hormone therapy. For information on herbal remedies (that you can buy without a prescription), see “Herbs and supplements” in the section called “What does it all mean?”

Estrogen-progestin therapy or EPT

Estrogen-progestin therapy (EPT) uses both estrogen and progestin, a progesterone-like hormone. It is prescribed for women who have not had hysterectomies (they still have a uterus). Adding the progestin to the estrogen protects the lining of the uterus (the endometrium) from the harmful effects of estrogen. EPT can be given 2 ways:

• Continuous EPT means giving the same dose of estrogen and progestin each day.
• Sequential (cyclical) EPT uses different amounts of each hormone on specific days during the month so that the hormone levels are more like the natural menstrual cycle.

Estrogen therapy or ET

Estrogen therapy (ET) means only estrogen is given. It’s used to raise estrogen levels in the body. Conjugated equine estrogens (CEE Premarin®) are the most common ET in the US and have been used for the longest time. Estrogen alone is prescribed mainly for women who have had hysterectomies (surgery to remove the uterus or womb).

How hormone therapy is given during menopause

Systemic hormones

Hormones that are given as pills or as a patch are absorbed through the digestive system or the skin and reach all parts of the body through the bloodstream. This type of therapy is referred to as a systemic treatment. There is also a type of vaginal ring that delivers a large dose of hormone to the whole body, so that it would also be considered systemic treatment. It gives a much higher dose than the topical vaginal ring discussed below.

Topical hormones

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 absorbed depends on the type of hormone and the dose.

Dry or thinned vaginal tissues respond to very small doses of estrogen. These small 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. (As noted earlier, there is a type of vaginal ring that delivers high doses of hormones to the whole body, which would be considered systemic treatment. If you are unsure about the type of ring you have, check with your doctor.)

Hormone therapy and cancer risk

Several large studies have looked at the possible links between systemic hormone therapy in menopausal women and different types of cancer.

A general note about cancer risk

As you read this information, keep in mind that the percentage of increased or decreased risk listed in the text is called “relative risk.” Relative risk is the percentage of people with cancer who have been exposed compared to those who were not exposed. It is easy to calculate in research studies, but it does not say anything about the actual risk of cancer for a particular woman.

To give you an idea of what this means, 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. This is because her risk for ovarian cancer is much lower to begin with.

For example, in a group of 100 women with a 12% lifetime 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 the women’s absolute risk of ovarian cancer would still be much lower than their risk of breast cancer.

Hormone therapy and endometrial cancer risk

Estrogen-progestin therapy (EPT) and endometrial cancer risk

Studies show that EPT may help menopause symptoms in women who still have a uterus without increasing their risk of endometrial cancer (cancer in the lining of the uterus).

One study showed that about 1 in 9 women treated with ET (only estrogen) for 3 years developed a type of pre-cancerous change in their endometrium (lining of the uterus) called atypical hyperplasia. Women treated with EPT did not develop this change any more often than women not taking any hormones.

The Women’s Health Initiative (WHI), a large, randomized trial of women getting either continuous EPT or a placebo (an inactive substance used for comparison, also known as a “sugar pill”) also found that EPT did not increase endometrial cancer risk. But more of the women getting EPT had abnormal vaginal bleeding (a possible sign of endometrial cancer) that needed further testing.

A woman who has had her uterus removed (hysterectomy) is not in danger of developing endometrial cancer, regardless of whether she takes ET or EPT. But because the only reason for giving progestin is to protect the lining of the uterus, a woman without a uterus will most likely be given ET.

Estrogen therapy (ET) and endometrial cancer risk

Using systemic ET as a pill, patch, or the high-dose vaginal ring increases a woman’s risk of endometrial cancer (cancer of the lining of the uterus). The risk remains higher than average even after ET is no longer used.

Because of this increased cancer risk, estrogen alone is almost never given to women who have gone through menopause and who still have a uterus. Progestins are used along with estrogen to counter the risk of estrogen on the endometrium.

Long-term use of vaginal creams, rings, or tablets containing topical estrogen doses may also increase the levels of estrogen in the body. Very little information about health risk is available on this, but the amounts of hormone are much smaller than systemic therapies.

Hormone therapy and breast cancer risk

Estrogen-progestin therapy (EPT) and breast cancer risk

Results from the Women’s Health Initiative (WHI) have shown that daily use of EPT raises women’s risk of developing breast cancer when compared to those who don’t take hormones. To put this into numbers, if 10,000 women took EPT for a year, this would add up to about 8 more cases of breast cancer per year than if they had not taken any hormone therapy (HT). The longer HT was used, the more the risk increased.

In this study, women who took EPT also had a higher risk of having breast cancer found at a more advanced stage and were more likely to have breast density changes seen on mammograms. Lean women or women with dense breasts who take EPT may be at particularly high risk of breast cancer.

Risk of breast cancer from EPT applies only to current and recent users. Breast cancer risk is thought to decrease after stopping HT. The risk returns to that of women who never used HT (the usual risk) within 3 years of stopping.

Women who have had hysterectomies can take estrogen therapy (ET) instead of EPT. These women do not need progestin to protect against uterine cancer, and they are increasing their risk of breast cancer by taking EPT.

Estrogen therapy (ET) and breast cancer risk

Part of the Women’s Health Initiative (WHI) looked at women who no longer had a uterus, and whose ovaries were either removed or had stopped working. Those who were taking ET had a slightly lower 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 ET, compared to women who took the placebo.

Hormone therapy and ovarian cancer risk

Ovarian cancer is rare, which makes it harder to study its risk factors. Even when something increases the relative risk of developing ovarian cancer, the risk of actually getting this cancer is still likely to be low.

But there are no good screening tools for ovarian cancer and it’s often fatal, so even the small risk linked to hormone therapy (HT) may be worth considering.

Estrogen-progestin therapy (EPT) and ovarian cancer risk

It’s still not known for certain if hormone therapy (HT) increases the risk of ovarian cancer. If it does increase risk, it increases it only slightly.

The Women’s Health Initiative (WHI) found that continuous EPT may increase the risk of ovarian cancer a bit. But this finding may have been due to chance because of the small number of women who developed ovarian cancer during the study. Other studies also suggest that EPT may increase risk slightly, but less than estrogen therapy (ET) does.

Estrogen therapy (ET) and ovarian cancer risk

Studies have shown that women who take ET have a higher risk for ovarian cancer compared with women who take no hormones after menopause. The risk of ovarian cancer increases the longer a woman uses ET.

The largest study so far found that women who had used ET for 5 or more years had about a 50% increased risk of developing ovarian cancer. This link was confirmed in another large study. The risk of ovarian cancer appeared to increase further the longer was used.

Hormone therapy and colorectal cancer risk

Estrogen-progestin therapy (EPT) and colorectal cancer risk

The Women’s Health Initiative (WHI) found that EPT 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 EPT was stopped. This risk reduction has also been found in some other studies.

Estrogen therapy (ET) and colorectal cancer risk

In the Women’s Health Initiative (WHI) group that took estrogen only, ET did not seem to have any effect on the risk of colorectal cancer. Other studies have found a slightly lower risk of colorectal cancer in women who have used ET for many years.

Hormone therapy and risk of other cancers

Hormone therapy may play a role in other cancers, such as lung cancer and melanoma. There is not enough evidence to determine any effect at this time.

What does it all mean?

The decision to use hormone therapy (HT), either estrogen therapy (ET) or estrogen-progestin therapy (EPT), during menopause should be made by each woman and her doctor after weighing the possible risks and benefits. Things to think about include:

• The risk of breast, endometrial, ovarian, and other types of cancer
• The risks of other serious conditions affected by HT that are not covered here, like heart disease, stroke, serious blood clots (deep vein thrombosis, clots in the lungs), and effects on the brain
• Other medicines that may be used to treat menopausal symptoms or osteoporosis

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

Reducing the cancer risks of hormone therapy

If a woman and her doctor decide that estrogen therapy (ET) or estrogen-progestin therapy (EPT) is the best treatment for certain symptoms of menopause or health problems, it’s 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’s important that any woman taking ET or EPT 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.

Adding progestin to estrogen (EPT) reduces the risk of endometrial cancer, but may not entirely get rid of it. Women using vaginal cream, rings, or tablets containing only estrogen should talk to their doctors about follow-up and the possible need for progestin treatment.

For women who have had a hysterectomy (surgery to remove the uterus), progestin does not need to be added because there is no risk of endometrial cancer. Adding progestin does raise the risk of breast cancer, so ET is a better option for women without a uterus.

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

There are still questions about EPT and breast cancer risk. Most of the increased risk of breast cancer from EPT 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, but still protect the endometrium.

Herbs and supplements during menopause

Many over-the-counter “natural” (herbal) products are promoted in stores and on the Internet as helpful with menopausal symptoms. These include vitamins, soy-based, and herbal products (like black cohosh and red clover). There are also endless arrays of special blends of herbs and vitamins that claim to reduce the discomforts of menopause.

These products are considered dietary supplements (as opposed to drugs). They have not been evaluated by the Food and Drug Administration (FDA) to be sure that they work or even that they are safe. Some of the herbs 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.

Most of the plain herbs that are touted for menopausal symptoms carry a low risk of harm for most women, but some can interact with other drugs or cause unexpected problems. You should discuss herbs or supplements with your doctor before taking them.

Well-controlled scientific studies are needed to help find out if these products work and if they are any safer than the hormone therapy drugs now in use.

Beware of products with “secret formulas” or hormone-like ingredients that may cause harm. Recently, some “natural herbal supplements” made in other countries have been found to contain actual drugs, some of which have been banned from the United States because they are dangerous. It’s your right to know exactly what you’re taking and what side effects and drug interactions it may have.

You can learn more by reading Dietary Supplements: How to Know What Is Safe either on our Web site at www.cancer.org, or call us at 1-800-227-2345 to have a copy sent to you.

To learn more

National organizations and Web sites*

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.womenshealth.gov/Menopause/

Food and Drug Administration (FDA)
Toll-free number: 1-888-463-6332
Web site: www.fda.gov

Information on menopause in English and Spanish can be found at: www.fda.gov/ForConsumers/ByAudience/ForWomen/WomensHealthTopics/ucm117978.htm

National Institutes of Health
Telephone number: 301-496-4000
Web site: www.nih.gov

Menopausal Hormone Therapy Information page: http://www.nih.gov/PHTindex.htm

No matter who you are, we can help. Contact us anytime, day or night, for information and support. Call us at 1-800-227-2345 or visit www.cancer.org.

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