Menopausal Hormone Replacement Therapy Use and Cancer: 

Questions and Answers 

Key Points

• Menopausal hormone use (sometimes referred to as hormone replacement therapy or 

postmenopausal hormone use) involves taking either estrogen alone or estrogen in 

combination with progesterone or progestin, a synthetic hormone with effects similar 

to those of progesterone (see Question 2). 

• The most comprehensive evidence about the risks and benefits of taking menopausal 

hormones after menopause comes from the Women’s Health Initiative Hormone 

Program, which was sponsored by the National Heart, Lung, and Blood Institute and 

the National Cancer Institute (see Questions 4–8).

1. What is menopause?

Menopause is the time in a woman’s life when menstruation (having a period) ends. It is 

part of a biological process that begins, for most women, in their mid-thirties. During 

this time, the ovaries gradually produce lower levels of natural sex hormones—estrogen 

and progesterone. Estrogen promotes the normal development of a woman’s breasts and 

uterus, controls the cycle of ovulation (when an ovary releases an egg into a fallopian 

tube), and affects many aspects of a woman’s physical and emotional health. 

Progesterone controls menstruation and prepares the lining of the uterus to receive the

fertilized egg. 

“Natural menopause” occurs when a woman has her last menstrual period, or stops 

menstruating, and is considered complete when menstruation has stopped for 1 year. 

This usually occurs between ages 45 and 55, with variations in timing from woman to 

woman. Women who undergo surgery to remove both ovaries (an operation called 

bilateral oophorectomy) experience “surgical menopause”—an immediate end to 

menstruation caused by lack of hormones produced by the ovaries. 

By the time a woman has reached natural menopause, estrogen output has decreased 

significantly. Even though low levels of this hormone are produced by other organs after 

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menopause, these levels are only about one-tenth of the level found in premenopausal 

women. Progesterone is nearly absent in menopausal women. 

2. What are menopausal hormones and why are they used? 

Doctors may recommend menopausal hormones to counter some of the problems often 

associated with the onset of menopause (hot flashes, night sweats, sleeplessness, and 

vaginal dryness) or to prevent some long-term conditions that are more common in 

postmenopausal women, such as osteoporosis (a condition characterized by a decrease in 

bone mass and density, causing bones to become fragile). Menopausal hormone use 

(sometimes referred to as hormone replacement therapy or postmenopausal hormone use) 

usually involves treatment with either estrogen alone or estrogen in combination with 

progesterone or progestin, a synthetic hormone with effects similar to those of 

progesterone. Among women who are prescribed menopausal hormones, women who 

have undergone a hysterectomy (surgery to remove the uterus and, sometimes, the cervix) 

are generally given estrogen alone. Women who have not undergone this surgery are 

given estrogen plus progestin, which is known to have a lower risk of causing 

endometrial cancer (cancer of the lining of the uterus). 

3. How does medical research determine the benefits and risks of taking menopausal 

hormones? 

Researchers commonly conduct two very different, yet important types of studies with 

people to examine the benefits and risks of hormone use: clinical trials and observational 

studies. In clinical trials, the participants are given either hormones or placebos 

(look-alike pills that do not contain any drug) to determine the effect of the hormones on 

various conditions and diseases. In observational studies, the investigators do not try to 

affect the outcome; they compare the health status of women taking hormones to that of 

women not taking hormones. 

4. What has medical research found out about the risks and benefits of hormone use 

after menopause? 

The most comprehensive evidence about the risks and benefits of taking hormones after 

menopause to prevent disease comes from the Women’s Health Initiative (WHI) 

Hormone Program, which was sponsored by the National Heart, Lung, and Blood 

Institute (NHLBI) and the National Cancer Institute (NCI), parts of the National Institutes 

of Health (NIH). This research program examined the effects of menopausal hormones 

on women’s health. The WHI Hormone Program involved two studies—the use of 

estrogen plus progestin for women with a uterus (the Estrogen-plus-Progestin Study), and 

the use of estrogen alone for women without a uterus (the Estrogen-Alone Study). In 

both hormone therapy studies, women were randomly assigned to receive either the 

hormone medication being studied or the placebo. 
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The WHI Estrogen-plus-Progestin Study was stopped in July 2002, when investigators 

reported that the overall risks of estrogen plus progestin, specifically PremproTM, 

outweighed the benefits (1). The researchers found that use of this 

estrogen-plus-progestin pill increased the risk of breast cancer, heart disease, stroke, 

blood clots, and urinary incontinence. However, the risk of colorectal cancer and hip 

fractures was lower among women using estrogen plus progestin than among those taking 

the placebo (1). In addition, the WHI Memory Study showed that estrogen plus progestin 

doubled the risk for developing dementia (a decline in mental ability in which the patient 

can no longer function independently on a day-to-day basis) in postmenopausal women 

age 65 and older. The risk increased for all types of dementia, including Alzheimer’s 

disease (2). 

The WHI Estrogen-Alone Study, which involved PremarinTM, was stopped in February 

2004, when the researchers concluded that estrogen alone increased the risk of stroke and 

blood clots. In contrast with the WHI Estrogen-plus-Progestin Study, the risk of breast 

cancer was decreased in women using estrogen alone compared with those taking the 

placebo (see Question 5). Use of estrogen alone did not increase or decrease the risk of 

colorectal cancer (3). Similar to the results seen in the Estrogen-plus-Progestin Study, 

women using estrogen alone had an increased risk of urinary incontinence and a 

decreased risk of hip fractures. 

Another large epidemiologic study, the Million Women Study, enrolled 1.3 million 

women in the United Kingdom. This study evaluated health outcomes in women using 

and not using menopausal hormones. Several analyses have been published to date, and 

many more are expected in the future (4, 5, 6). 

5. How does menopausal hormone use affect breast cancer risk and survival? 

The WHI Estrogen-plus-Progestin Study concluded that estrogen plus progestin increases 

the risk of invasive breast cancer. After 5 years of follow-up, women taking these 

hormones had a 24 percent increase in breast cancer risk compared with women taking 

the placebo. The increase amounted to an additional 8 cases of breast cancer for every 

10,000 women taking estrogen plus progestin for 1 year compared with 10,000 women 

taking the placebo (7). 

A detailed analysis of data from the WHI Estrogen-plus-Progestin Study showed that, 

among women taking estrogen plus progestin, the breast cancers were slightly larger and 

diagnosed at more advanced stages compared with breast cancers in women taking the 

placebo. Among women taking estrogen plus progestin, 25.4 percent of the cancers had 

spread outside the breast to nearby organs or lymph nodes compared with 16.0 percent 

among nonusers. Women taking estrogen plus progestin also had more abnormal 

mammograms (breast x-rays that require additional evaluation) than the women taking 

the placebo (7). 

The WHI Estrogen-Alone Study concluded that taking estrogen did not increase the risk 

of breast cancer in women with a prior hysterectomy, at least for the 7 years of follow-up 
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in the study. Further analysis of data from the study indicated a 20 percent decrease in 

risk of breast cancer in women taking estrogen alone, although this decrease was seen 

mainly in the occurrence of early-stage breast cancer and ductal breast cancer (a specific 

type that begins in the lining of the milk ducts in the breast) (8). The observed reduction 

amounted to 6 fewer cases of breast cancer for every 10,000 women taking estrogen for 1 

year compared with 10,000 nonusers, but this lower incidence was not statistically 

significant; i.e., the lower incidence could have arisen by chance rather than being related 

to estrogen-alone use (8). The Estrogen-Alone Study also showed a substantial increase 

in the frequency of abnormal mammograms (8). 

A comprehensive review of data from 51 epidemiological (population) studies published 

in the 1980s and 1990s found a statistically significant increase in breast cancer risk 

among current or recent users of any hormone replacement therapy compared with the 

risk among nonusers. Most women in the analysis (88 percent) had used estrogen alone, 

and data for estrogen-plus-progestin users was not analyzed separately. Analysis of the 

pooled data also showed that the risk of breast cancer increased with increasing duration 

of hormone use, and this effect was more prominent in women with low body weight or a 

low body mass index. However, breast cancers in hormone users were less likely to have 

spread to other parts of the body compared with the breast cancers in nonusers. The 

increase in breast cancer risk largely, if not completely, disappeared about 5 years after 

cessation of hormone use (9). 

As part of the Million Women Study, researchers examined six types of breast cancer 

among users and nonusers of menopausal hormones. The results showed that the effects 

of hormone use varied among breast cancer types. Overall, breast cancer risk was 

significantly increased among current users, although the risk was lower among women 

with higher body mass index (5). 

6. What are the effects of hormone use on the risk of endometrial cancer? 

Studies have shown that long-term exposure of the uterus to estrogen alone increases a 

woman’s risk of endometrial cancer. The risk associated with estrogen plus progestin 

appears to be much less, but some data suggest that the risk is still increased compared 

with the risk for nonusers. The long-term effects of estrogen plus progestin on 

endometrial cancer risk remain uncertain (10). 

The WHI Estrogen-plus-Progestin Study showed that endometrial cancer rates for women 

taking estrogen plus progestin daily were the same as or possibly less than those for 

women taking the placebo pill. Uterine bleeding, however, was a common side effect, 

leading to more frequent biopsies and ultrasounds for women taking estrogen plus 

progestin compared with those taking a placebo (11). 

The Million Women Study confirmed a lower risk of endometrial cancer in women 

taking estrogen plus progestin in comparison with those taking estrogen only or tibolone, 

a synthetic steroid that is not available in the United States (6). 
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7. How does menopausal hormone use affect the risk of ovarian cancer? 

Several observational studies have found that the use of estrogen alone is associated with 

a slightly increased risk of ovarian cancer for women who used this hormone for 

10 or more years. One observational study that followed 44,241 menopausal women for 

approximately 20 years concluded that women who used estrogen alone for 

10 or more years were twice as likely to develop ovarian cancer compared with women 

who did not use menopausal hormones (12). Another large observational study also 

found an association between estrogen use and death due to ovarian cancer. In this study, 

the increased risk appeared to be limited to women who used estrogen for 10 or more 

years (13). 

The results from the Million Women Study showed that women currently using 

menopausal hormones had an increased risk of developing ovarian cancer and a 20 

percent likelihood of dying from the disease compared with nonusers. However, the 

increased risk disappeared after hormone use stopped (4). 

Data from the WHI Estrogen-plus-Progestin Study indicate that there may be an 

increased risk of ovarian cancer with use of estrogen plus progestin (11). After 5.6 years 

of follow-up, a 58 percent increased risk of ovarian cancer was reported in women using 

estrogen plus progestin compared with nonusers, but the increased risk was not 

statistically significant. One observational study suggested that regimens of estrogen plus 

progestin do not increase the risk of ovarian cancer if progestin is used for more than 15 

days per month (14), but this study was too small to draw firm conclusions. More 

research is needed to clarify the relationship between menopausal hormone use, 

particularly for estrogen plus progestin, and the risk of ovarian cancer. 

8. How does menopausal hormone use affect the risk of colorectal cancer? 

After 5 years of follow-up of women taking estrogen plus progestin, the WHI 

Estrogen-plus-Progestin Study reported a 37 percent reduction in colorectal cancer cases 

compared with women taking the placebo (1). On average, the researchers found that if a 

group of 10,000 women takes estrogen plus progestin for a year, 6 fewer cases of colon 

cancer will occur than in a group of nonusers. These findings are consistent with 

observational studies, which have suggested that the use of postmenopausal hormones 

may reduce the risk of colorectal cancer (1, 15). The WHI Estrogen-Alone Study 

concluded that estrogen alone had no significant effect on colorectal cancer risk (3). 

9. Should women with a history of cancer take menopausal hormones? 

One of the roles of naturally occurring estrogen is to promote the normal growth of cells 

in the breast and uterus. For this reason, it is generally believed that menopausal estrogen 

use by women who have already been diagnosed with breast cancer may promote further 

tumor growth. Studies of hormone use to treat menopausal symptoms in breast cancer 

survivors have produced conflicting results. 
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In one trial, 434 breast cancer survivors receiving either estrogen alone or estrogen plus 

progestin were followed for 2 years before the study was stopped because researchers 

concluded that even short-term use of hormone replacement therapy posed an 

unacceptable risk of breast cancer recurrence. Among these study participants, 

26 women in the group receiving hormone replacement therapy had another occurrence 

of breast cancer compared with 7 women in the group receiving no hormone replacement 

therapy (16). In another study, which included 378 women who were followed for 

4 years, 11 women receiving hormone replacement therapy had another occurrence of 

breast cancer compared with 13 women receiving no hormone replacement therapy, so 

the risk of breast cancer recurrence was not increased (17). A review of 15 studies 

comprising a total of 1,416 breast cancer survivors and 1,998 women without a history of 

breast cancer found no increase in risk of cancer recurrence with hormone replacement 

therapy use (18). 

There is limited research on the risks associated with menopausal hormone use by 

women who have had other cancers, particularly gynecological cancers. One review of 

the published research found that no firm conclusion could be drawn about the safety of 

hormone use in women with a history of cancer. However, survivors of gastric and 

bladder cancer and meningioma may be at higher risk of a recurrence. Survivors of 

gynecological cancers may be at higher risk because these cancers tend to be more 

hormone-dependent, but more studies are needed (19). 

10. Does the way in which hormones are administered make a difference? 

Most of the data on the long-term health effects of hormones come from studies in which 

hormones (estrogen alone or estrogen plus progestin) are administered orally in the form 

of pills. Hormones in the form of transdermal patches or gels are also used to treat 

menopause-related symptoms. Estrogen-containing vaginal creams and rings can be used 

specifically for vaginal dryness. Progesterone is also available as a pill or gel. The 

amount of estrogen that enters the bloodstream from estrogen-containing vaginal creams 

and rings depends on the types of hormones and the dose. Generally, vaginal 

administration of hormones results in lower levels of circulating hormones compared 

with an equivalent oral dose. Because the vaginal epithelium (thin layer of tissue that 

covers the vagina) responds to very small doses of estrogen, low-dose 

estrogen-containing creams or gels can be used. 

11. What should women do if they are concerned about taking menopausal hormones? 

Although menopausal hormones have short-term benefits such as relief from hot flashes 

and vaginal dryness, several health concerns are associated with their use. Women 

should discuss with their health care provider whether to take menopausal hormones and 

what alternatives may be appropriate for them. The U.S. Food and Drug Administration 

(FDA) currently advises women to use menopausal hormones for the shortest time and at 

the lowest dose possible to control symptoms. The FDA publication Menopause & 

hormones provides additional information about the risks and benefits of hormone use for 
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menopausal symptoms. This resource is available at 

http://www.fda.gov/womens/menopause/mht-FS.html on the Internet. 

12. What are the alternatives for women who choose not to take menopausal hormones? 

To decrease the risk of chronic disease, women can adopt a healthy lifestyle by 

exercising regularly, eating a healthy diet, limiting the consumption of alcohol, and not 

starting to smoke or, for smokers, trying to quit. Eating foods rich in calcium and 

vitamin D or taking dietary supplements containing these nutrients can help prevent 

osteoporosis. Results from the WHI showed that taking calcium and vitamin D 

supplements provided some benefit in preserving bone mass and preventing hip fractures, 

particularly in women age 60 and older. Although generally well tolerated, these 

supplements were associated with an increased risk of kidney stones. Other drugs, such 

as alendronate (Fosamax®), raloxifene (Evista®), and risedronate (Actonel®), have been 

shown to prevent bone loss. In addition, parathyroid hormone (Forteo®) is approved by 

the FDA for osteoporosis treatment. 

Short-term menopause-related problems may go away on their own and frequently 

require no therapy at all. Local therapy for specific symptoms, such as vaginal dryness 

and urinary bladder conditions, is available. Some women seek relief from menopausal 

symptoms with nonprescription complementary and alternative therapies containing 

estrogen-like compounds. Some sources of these estrogen-like compounds include 

soy-based products, whole grain cereal, oilseeds (primarily flaxseed), legumes, and the 

botanical black cohosh. The benefits and risks of most of these agents have not been 

proven, however. 

One NIH-funded study, the Herbal Alternatives (HALT) for Menopause Study, involved 

351 women, some of whom were postmenopausal while others were approaching 

menopause. All of these women experienced hot flashes and night sweats and were 

given herbal supplements, menopausal hormones, or no therapy. Women in the herbal 

supplement groups received black cohosh alone, a multibotanical supplement (including 

black cohosh), or the multibotanical supplement plus counseling to increase their intake 

of dietary soy. Women in the herbal supplement groups had no significant reduction in 

the number of hot flashes and night sweats compared with women who received no 

therapy. The women who received menopausal hormones had significantly fewer 

menopausal symptoms compared with the women who received no therapy (20). 

Women should talk with their doctor about the option best for them. 

13. What research still needs to be done? 

Unresolved questions include whether different forms of the hormones, lower doses, 

different hormones, or different methods of administration are safer or more effective; 

whether risks and/or benefits persist after women stop taking hormones; whether women 

might be able to take hormones safely for a short period of time; and whether certain 
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subgroups of women, including women with a history of cancer, might be at higher or 

lower risk than the general population. 

The WHI continues to evaluate the longer-term effects of calcium and vitamin D 

supplements on preserving bone mass, preventing hip fractures, and reducing colon 

cancer risk, and continues long-term follow-up of women in the hormone trials. 

The NIH continues to sponsor research to evaluate the effects of estrogen-like 

compounds on menopausal symptoms and long-term health after menopause. Several 

NCI-sponsored studies are evaluating the effectiveness of nonhormonal treatments, such 

as the botanical St. John’s wort and the antidepressant drug citalopram hydrobromide, in 

reducing hot flashes in women with a history of breast cancer. 

14. Where can people get more information about menopausal hormone use? 

The following resources provide additional information about menopausal hormones and 

the WHI: 

• NIH Menopausal Hormone Therapy Information home page

(http://www.nih.gov/PHTindex.htm). 

• WHI Participant Web site (http://www.whi.org). 

• NCI Menopausal Hormone Replacement Therapy (HRT) digest page 

(http://www.cancer.gov/clinicaltrials/digest-postmenopausal-hormone-use). 

• NHLBI Postmenopausal Hormone Therapy Web site

(http://www.nhlbi.nih.gov/health/women/). 

• National Center for Complementary and Alternative Medicine (NCCAM) 

Menopause Treatments Web page (http://nccam.nih.gov/health/menopause.htm). 

Selected References 

1. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus 

progestin in healthy postmenopausal women: Principal results from the Women's Health 

Initiative randomized controlled trial. Journal of the American Medical Association

2002; 288(3):321–333. 

2. Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of 

dementia and mild cognitive impairment in postmenopausal women: The Women's 

Health Initiative Memory Study: A randomized controlled trial. Journal of the American 

Medical Association 2003; 289(20):2651–2662. 
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3. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in 

postmenopausal women with hysterectomy: The Women's Health Initiative randomized 

controlled trial. Journal of the American Medical Association 2004; 291(14):1701–1712. 

4. Beral V, Million Women Study Collaborators. Ovarian cancer and hormone replacement 

therapy in the Million Women Study. Lancet 2007; 369:1703–1710. 

5. Reeves GK, Beral V, Green J, Gathani T, Bull D. Hormonal therapy for menopause and 

breast cancer risk by histological type: A cohort study and meta-analysis. Lancet 

Oncology 2006; 7:910–918. 

6. Beral V, Bull D, Reeves G, Million Women Study Collaborators. Endometrial cancer 

and hormone-replacement therapy in the Million Women Study. Lancet 2005; 

365(9470):1543–1551. 

7. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on 

breast cancer and mammography in healthy postmenopausal women: The Women's 

Health Initiative randomized trial. Journal of the American Medical Association 2003; 

289(24):3243–3253. 

8. Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens 

on breast cancer and mammography screening in postmenopausal women with 

hysterectomy. Journal of the American Medical Association 2006; 295(14):1647–1657. 

9. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone 

replacement therapy: Collaborative reanalysis of data from 51 epidemiological studies of 

52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 

1997; 350(9084):1047–1059. 

10. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement 

therapy and endometrial cancer risk: A meta-analysis. Obstetrics and Gynecology 1995; 

85(2):304–313. 

11. Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on 

gynecologic cancers and associated diagnostic procedures: The Women's Health 

Initiative randomized trial. Journal of the American Medical Association 2003; 

290(13):1739–1748. 

12. Lacey JV Jr., Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and 

risk of ovarian cancer. Journal of the American Medical Association 2002; 

 288(3):334–341. 

13. Rodriguez C, Patel AV, Calle EE, Jacob EJ, Thun MJ. Estrogen replacement therapy and 

ovarian cancer mortality in a large prospective study of US women. Journal of the 

American Medical Association 2001; 285(11):1460–1465. 
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14. Riman T, Dickman PW, Nilsson S, et al. Hormone replacement therapy and the risk of 

invasive epithelial ovarian cancer in Swedish women. Journal of the National Cancer 

Institute 2002; 94(7):497–504. 

15. Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal hormone therapy and the risk 

of colorectal cancer: A review and meta-analysis. American Journal of Medicine 1999; 

106:574–582. 

16. Holmberg L, Anderson H. HABITS (hormonal replacement therapy after breast canceris it safe?), a randomised comparison: Trial stopped. Lancet 2004; 363(9407):453–455. 

17. von Schoultz E, Rutqvist LE. Menopausal hormone therapy after breast cancer: The 

Stockholm randomized trial. Journal of the National Cancer Institute 2005; 97(7):533–

535. 

18. Batur P, Blixen CE, Moore HC, Thacker HL, Xu M. Menopausal hormone therapy (HT) 

in patients with breast cancer. Maturitas 2006; 53(2):123–132. 

19. Biglia N, Gadducci A, Ponzone R, Roagna R, Sismondi P. Hormone replacement 

therapy in cancer survivors. Maturitas 2004; 48(4):333–346. 

 

20. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor symptoms of 

menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: A 

randomized trial. Annals of Internal Medicine 2006; 145(12):869–879. 

# # # 

Related NCI materials and Web pages: 

• National Cancer Institute Fact Sheet 2.11, Clinical Trials: Questions and Answers

(http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials) 

• What You Need To Know AboutTM Breast Cancer

(http://www.cancer.gov/cancertopics/wyntk/breast) 

• What You Need To Know AboutTM Cancer of the Colon and Rectum

(http://www.cancer.gov/cancertopics/wyntk/colon-and-rectal) 

• What You Need To Know AboutTM Cancer of the Uterus

(http://www.cancer.gov/cancertopics/wyntk/uterus) 

• What You Need To Know AboutTM Ovarian Cancer

(http://www.cancer.gov/cancertopics/wyntk/ovary) 

• Menopausal Hormone Replacement Therapy (HRT) Digest Page 

 (http://www.cancer.gov/clinicaltrials/digest-postmenopausal-hormone-use) 
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For more help, contact: 

NCI’s Cancer Information Service 

Telephone (toll-free): 1–800–4–CANCER (1–800–422–6237) 

TTY (toll-free): 1–800–332–8615

LiveHelp® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp

 This fact sheet was reviewed on 10/5/07