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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 that MHT didn’t just help with hot flashes and other symptoms – it had important health benefits. But well-conducted studies have led doctors to conclude that the risks of MHT often outweigh the benefits. Still, each woman should discuss her concerns with her doctor.

This document will cover how MHT can affect a woman’s risk of getting certain cancers. It will not go into the possible effects of MHT on other diseases like osteoporosis (bone thinning), stroke, heart disease, blood clots, and dementia.

This is not 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 MHT should talk with their doctors about the information here. Women should also understand the risks and benefits of MHT and the follow-up they will need if MHT 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 often a good idea to stop MHT.

What is menopause?

Menopause is the time in a woman’s life when the ovaries stop working and she stops having menstrual periods for good. Menopause is sometimes called the change of life, or just the change. The ovaries stop releasing eggs and making the female hormones, estrogen and progesterone. In the months or years leading up to natural menopause, menstrual periods may become less frequent and irregular, and hormone levels may go up and down. This time is called perimenopause or the menopausal transition. Since periods can become less frequent during this time, it can be hard to know when they have actually stopped (and you have gone through menopause) until you look back at a later time.

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 (without the menopausal transition).

Women who have had their uterus removed (a hysterectomy) but still have their ovaries stop having periods, but they don’t really go through menopause until their ovaries stop working. This is often determined based on symptoms, but your doctor can tell for certain by testing your blood for levels of certain hormones made by the pituitary gland, called luteinizing hormone (LH) and follicle stimulating hormone (FSH). These hormones help regulate the ovaries before menopause. When levels of female hormones get lower during menopause, the levels of FSH and LH go up. High levels of FSH and LH, along with low levels of estrogen, can be used to diagnose menopause in a woman who has had her uterus removed.

Some drugs can turn off the ovaries and cause menstrual periods to stop for a time. Although this is not the same as menopause, it can lead to many of the same symptoms.

Most of the symptoms of menopause are linked to lower estrogen levels. Some symptoms – hot flashes and night sweats, for instance – tend to fade away at some point, whether or not they are treated. Other problems, like dryness and thinning of vaginal tissues and bone thinning can start after menopause, and may get worse over time.

Because many of the symptoms and problems of menopause are linked to low levels of estrogen, this hormone has often been used in the past to treat menopause.

What hormones are used to treat the symptoms of menopause?

The most commonly prescribed hormones are estrogens and progesterones or progestins (drugs that act like progesterone). Often, these 2 hormones are used together, but some women are given estrogen alone. It is important to know which hormones you are talking about when looking at the risks. Here estrogen therapy (ET) means estrogen alone, and estrogen-progestin therapy (EPT), often called combined HT, means estrogen and progestin together. There are a number of versions of estrogen and progestin available, both in terms of the hormone itself and how it is given.

ET and EPT are sometimes used to relieve symptoms of menopause. These treatments can also help with some other health problems linked to low estrogen levels, like osteoporosis.

Androgens (male hormones like testosterone) are also sometimes used to treat some menopausal symptoms. This is not common, though, and because only a few studies have looked at this practice, it isn’t clear how safe this is in the long run.

Tibolone is a synthetic hormone drug that can act like estrogen, progesterone, and testosterone in different tissues of the body. Because this drug is not available in the US, it is not discussed further in this document.

Estrogen-progestin therapy or EPT

EPT is the use of both estrogen and progestin to treat menopausal symptoms. Although estrogen alone improves the symptoms of menopause, it increases the risk of cancer of the uterus. Adding a progestin to the estrogen protects the lining of the uterus (the endometrium), so this combination is given to women who still have a uterus (those who have not had a hysterectomy). EPT can be given 2 ways:

  • Continuous EPT means the same dose of estrogen and progestin is taken each day. Women often prefer continuous EPT because it rarely leads to menstrual-like bleeding.
  • Sequential (cyclical) EPT means different amounts of each hormone are taken on specific days during the month so that the hormone levels are more like the natural menstrual cycle. This produces bleeding like a menstrual period, although it can be less often than monthly.

Common estrogen preparations used to treat menopausal symptoms include conjugated equine estrogens (CEE; Premarin®) and estradiol, but several forms or types of estrogen are available. There are many progestins available, but medroxyprogesterone acetate (MPA; Provera®), is often used with an estrogen to treat menopausal symptoms. Some preparations contain both an estrogen and a progestin.

Bio-identical hormones

The word “bio-identical” is sometimes used by sellers to describe hormones that contain estrogens and progesterone with the same chemical structure as those found naturally in people. Marketers often describe bio-identical hormones as “natural,” and buyers often think that they are safer than other forms of estrogen and progestin used to control menopause symptoms. But so far, no study has shown that bio-identical hormones are any safer than other forms of these hormones. For this reason, bio-identical hormones should be assumed to have the same health risks as any other type of hormone therapy.

Some herbal remedies and supplements are also described as natural ways to treat the symptoms of menopause. For more information, see “Herbs and supplements” in the section called “What does it all mean?”

Estrogen therapy or ET

ET means only estrogen is given. Estrogen alone is only safe for women who do not have a uterus (such as those who have had a hysterectomy).

How are hormones given during menopause?

Systemic hormones

Hormones that are given so that they enter the bloodstream and circulate to reach all parts of the body are called systemic hormones. These hormones can be taken as pills or used in a patch where they are absorbed through the skin. Some forms of estrogen and progestin can be given as injections (like into a muscle or under the skin), but these are not often used to treat the symptoms of menopause. There is also a type of vaginal ring that delivers a large dose of estrogen 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.

Systemic hormones can help with certain symptoms of menopause, such as hot flashes and night sweats, as well as problems from thinning of the lining of the vagina (such as dryness that can make sex painful). They can also help prevent and treat osteoporosis (severe bone thinning).

Topical hormones

As another option, hormone treatments may be used topically, meaning that the hormone is placed in or near the place that needs treatment. If small doses are used, little of the hormone is absorbed into the bloodstream, so it has little if any effect on the rest of the body.

For women in menopause, topical estrogen may be used in the vagina to help treat dry or thinned vaginal tissues. These problems often improve with very small doses of estrogen that are placed inside the vagina in the form of creams, rings, or tablets. Even though tiny amounts of hormone may enter the blood, most of it stays in the vaginal tissues.

(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

Types of studies used to look at the effects of hormone therapy

Different types of studies have been used to look at cancer risk from MHT (or other drugs).

Randomized controlled trials: In this kind of study, a group of patients get the drug being studied, and another (control) group gets a placebo (sugar pill). Results from this kind of study are powerful because which group a patient is in is based on chance. This helps assure that the groups are similar in terms of other risk factors for cancer, so that any difference in outcome is likely to be from the drug. These types of studies are often double-blinded as well, meaning that the women and their doctors don’t know which group they are in. This lowers the chance that their thoughts or opinions about treatment could affect the study results. Unfortunately, these kinds of studies are costly to run, which limits the number of people in the study and the number of studies that can be done.

Observational studies: These kinds of studies collect information about a large group of women, some of whom have decided to take MHT. The women and their doctors decide what hormone drugs, if any, the women take and for how long. These kinds of studies can also gather information about other factors that can influence cancer risk. They then follow (observe) the women for years to look at how these factors (including MHT) affect cancer risk.

The major drawback of these studies is that the group of women taking the hormones may have different cancer risk factors than the women who aren’t. It isn’t always clear if differences seen in these kinds of studies are only due to the thing being studied (like MHT) and not other factors. Still, these studies can be less costly than randomized clinical trials, so they are more common and often enroll many more patients.

When observational studies and randomized controlled trials have different results, most experts give more weight to the results of the randomized controlled trial.

Major studies

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

The main randomized studies of MHT were part of the Women’s Health Initiative (WHI). The WHI included 2 randomized placebo-controlled clinical trials of MHT in healthy women:

  • One study looked at ET in post-menopausal women who didn’t have a uterus. Over 5,000 women in the ET group took a daily dose of estrogen in the form of conjugated equine estrogen (CEE) for an average of about 6 years. The researchers then continued to follow them for several years to look for any further effects of the hormone. The women were compared to more than 5,000 in the placebo group.
  • The other study looked at EPT in post-menopausal women who still had their uterus. Over 8,500 women in the EPT group took a daily dose of CEE plus a progestin called medroxyprogesterone acetate. This group was compared to a group of more than 8,000 women in the placebo group.

The WHI also conducted some observational studies. However, when this document mentions a WHI study, it is referring to one of the randomized studies.

Many observational studies have looked at MHT and cancer risk. One example is the Million Women Study. It enrolled over a million women aged 50 to 64 in the UK, collected information about hormone use and other health and personal details, and followed the women for many years. Not all of the women in the Million Women Study took MHT. Some of the women taking MHT were on ET, some were on EPT, and some took another drug. Some of the women on ET still had their uterus.

Estrogen-progestin therapy (EPT) and cancer risk

Endometrial cancer

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.

In the WHI EPT study, the women taking EPT did not have an increased risk of getting endometrial cancer compared with the women taking placebos. But more of the women getting EPT had abnormal vaginal bleeding. Because vaginal bleeding after menopause can be a symptom of endometrial cancer, these women 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.

Breast cancer

In the WHI study, the women taking EPT had a higher risk of developing breast cancer compared with those who didn’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 hormone therapy (HT). The longer HT was used, the more the risk increased.

In this study, women who took EPT also had increases in breast density (as seen on their mammograms). Increased breast density can make it harder to find breast cancer on a mammogram. The women on EPT also were more likely to have breast cancer found at a more advanced stage. Lean women or women with dense breasts who take EPT may be at particularly high risk of breast cancer.

The risk of breast cancer from EPT is increased only in current and recent users. The risk returns to that of a woman who never used HT (the usual risk) within 3 years of stopping.

Ovarian cancer

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

It’s still not known for certain if hormone therapy increases the risk of ovarian cancer. If it does increase risk, it increases it only slightly. But there are no good screening tools for ovarian cancer and it’s often fatal, so even a small increase in risk may be worth considering.

The WHI did not find a real difference in ovarian cancer risk with EPT. Although there were more cases of ovarian cancer in the women on EPT, this may have been due to chance because of the small number of women who were affected with this cancer.

Observational studies suggest that EPT may increase the risk of ovarian cancer. Although the amount of the increased risk varied depending on the study, the overall risk was still low.

Colorectal cancer

In the WHI study of EPT, the results were mixed. Women who took EPT had a lower risk of getting colorectal cancer at all, but the cancers they got were more likely to have spread to lymph nodes or distant sites.

Some observational studies have found a lower risk of colorectal cancer in women taking EPT, but some did not. So far, though, observational studies have not linked EPT with a higher risk of colorectal cancer.

Lung cancer

In the WHI study, EPT was not linked to a higher risk of getting lung cancer, but it was linked to a higher risk of dying from lung cancer.

Skin cancer

In the WHI study, there was no higher risk of any type of skin cancer (including both melanoma and other types of skin cancer) in the women taking EPT.

Estrogen therapy (ET) and cancer risk

Endometrial cancer

In women who still have a uterus, using systemic ET (estrogen as a pill, patch, or the high-dose vaginal ring) has been shown to increase the 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, women who have gone through menopause and who still have a uterus are given a progestin along with estrogen. Studies have shown that EPT does not increase the risk for endometrial cancer.

Long-term use of vaginal creams, rings, or tablets containing topical estrogen doses may also increase the levels of estrogen in the body. It is not clear if this leads to health risks, but the amounts of hormone are much smaller than systemic therapies.

Breast cancer

In the WHI study of ET in women who didn’t have a uterus, ET was not linked to a higher risk of breast cancer. In fact, certain groups of women taking ET, such as women who had no family history of breast cancer and those who had no history of benign breast disease, had a slightly lower risk of breast cancer.

Ovarian cancer

The WHI study of ET did not report any results about ovarian cancer.

Observational 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 overall risk remains low, but it does increase the longer a woman uses ET. The risk of ovarian cancer goes down after a woman stops taking the hormone.

Colorectal cancer

In the WHI study, ET did not seem to have any effect on the risk of colorectal cancer.

Observational studies have found a lower risk of colorectal cancer in women who have used ET for many years.

Lung cancer

In the WHI study, ET did not seem to have any effect on the risk of lung cancer.

Skin cancer

In the WHI study, there was no higher risk of any type of skin cancer (including both melanoma and other types of skin cancer) in the women taking ET.

What does it all mean?

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

  • The woman’s baseline risk of breast, endometrial, ovarian, and other types of cancer, and how much this might be affected by hormone therapy
  • The risks of other serious conditions affected by hormone therapy that are not covered here, like heart disease, stroke, serious blood clots (deep vein thrombosis, clots in the lungs), and effects on the brain
  • What other medicines might be used to treat menopausal symptoms or osteoporosis instead

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 MHT 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 MHT 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 symptom of endometrial cancer. A woman who takes EPT does not have a higher risk of endometrial cancer, but she can still get it. She should not ignore vaginal bleeding – it can still be caused by endometrial cancer.

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), a progestin does not need to be a part of hormone therapy because there is no risk of endometrial cancer. Adding a 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 website 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 and 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 supplements have been tested in small clinical trials, but often the studies only looked at taking the substance for a short time (months), so it isn’t clear how safe it would be if taken for a long time. Another concern has been applying the results of a study of a particular version and dose of a supplement to others that weren’t tested.

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. In the past, 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: What Is Safe? on our website or by calling us at 1-800-227-2345 to have a copy sent to you.

To learn more

National organizations and websites*

Office on Women’s Health
Toll-free number: 1-800-994-9662 (1-800-994-WOMAN)
Website: www.womenshealth.gov

    Menopause page: http://womenshealth.gov/menopause/
    Menopausal hormone therapy page: http://womenshealth.gov/menopause/symptom-relief-treatment/menopausal-hormone-therapy.html

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

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

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

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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Last Medical Review: 08/01/2013
Last Revised: 08/01/2013