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 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.

The WHI Estrogen-plus-Progestin Study was stopped in July 2002, when investigators reported that the overall risks of estrogen plus progestin, specifically Prempro™, 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 Premarin™, 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 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).

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.

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 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 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.
   
   
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.
    
    
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 cancer-is 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 ¹
  (http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials)
• What You Need To Know About™ Breast Cancer ²
  (http://www.cancer.gov/cancertopics/wyntk/breast)
• What You Need To Know About™ Cancer of the Colon and Rectum ³
  (http://www.cancer.gov/cancertopics/wyntk/colon-and-rectal)
• What You Need To Know About™ Cancer of the Uterus ⁴
  (http://www.cancer.gov/cancertopics/wyntk/uterus)
• What You Need To Know About™ Ovarian Cancer ⁵
  (http://www.cancer.gov/cancertopics/wyntk/ovary)
• Menopausal Hormone Replacement Therapy (HRT) Digest Page ⁶
  (http://www.cancer.gov/clinicaltrials/digest-postmenopausal-hormone-use)

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Glossary Terms

A process in which anything complex is separated into simple or less complex parts.

A drug used to treat depression.

Affecting both the right and left sides of the body.

Pertaining to biology or to life and living things. In medicine, refers to a substance made from a living organism or its products. Biologicals may be used to prevent, diagnose, treat or relieve of symptoms of a disease. For example, antibodies, interleukins, and vaccines are biologicals. Biological also refers to parents and children who are related by blood.

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

An eastern North American perennial herb. A substance obtained from the root of the plant has been used in some cultures to treat a number of medical problems. It is being studied in the treatment of hot flashes and other symptoms of menopause. The scientific name is Cimicifuga racemosa. Also called black snakeroot, rattlesnake root, bugwort, and bugbane.

Cancer that forms in tissues of the bladder (the organ that stores urine). Most bladder cancers are transitional cell carcinomas (cancer that begins in cells that normally make up the inner lining of the bladder). Other types include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). The cells that form squamous cell carcinoma and adenocarcinoma develop in the inner lining of the bladder as a result of chronic irritation and inflammation.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

A measure of the amount of minerals (mostly calcium and phosphorous) contained in a certain volume of bone. Bone mass measurements are used to diagnose osteoporosis (a condition marked by decreased bone mass), to see how well osteoporosis treatments are working, and to predict how likely the bones are to break. Low bone mass can occur in patients treated for cancer. Also called bone mineral density, BMD, and bone density.

Having to do with, or derived from, plants.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

A mineral found in teeth, bones, and other body tissues.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

The lower, narrow end of the uterus that forms a canal between the uterus and vagina.

A disease or condition that persists or progresses over a long period of time.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called CAM.

The process of identifying a disease, such as cancer, from its signs and symptoms.

A method used to identify a disease.

The things a person eats and drinks.

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

The amount of medicine taken, or radiation given, at one time.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

In medicine, a tube or vessel of the body through which fluids pass.

Cancer that forms in the tissue lining the uterus (the small, hollow, pear-shaped organ in a woman's pelvis in which a baby grows). Most endometrial cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

Cancer that occurs in the cells on the surface of the ovary. Also called ovarian epithelial cancer.

A thin layer of tissue that covers organs, glands, and other structures within the body.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

A slender tube through which eggs pass from an ovary to the uterus. In the female reproductive tract, there is one ovary and one fallopian tube on each side of the uterus.

The seed of the flax plant. It is a rich source of omega-3 fatty acid, fiber, and a compound called lignin. It is being studied in the prevention of prostate cancer. Also called linseed.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

Having to do with the stomach.

Having to do with the female reproductive tract (including the cervix, endometrium, fallopian tubes, ovaries, uterus, and vagina).

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

HRT. Hormones (estrogen, progesterone, or both) given to women after menopause to replace the hormones no longer produced by the ovaries. Also called HRT and menopausal hormone therapy.

Treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes or menopause), hormones are given to adjust low hormone levels. To slow or stop the growth of certain cancers (such as prostate and breast cancer), synthetic hormones or other drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. Also called hormonal therapy, hormone treatment, or endocrine therapy.

A sudden, temporary onset of body warmth, flushing, and sweating (often associated with menopause).

Surgery to remove the uterus and, sometimes, the cervix. When the uterus and part or all of the cervix are removed, it is called a total hysterectomy. When only the uterus is removed, it is called a partial hysterectomy.

The number of new cases of a disease diagnosed each year.

Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer.

One of a pair of organs in the abdomen. Kidneys remove waste from the blood (as urine), produce erythropoietin (a substance that stimulates red blood cell production), and play a role in blood pressure regulation.

Treatment that affects cells in the tumor and the area close to it.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.

An x-ray of the breast.

The use of x-rays to create a picture of the breast.

A type of slow-growing tumor that forms in the meninges (thin layers of tissue that cover and protect the brain and spinal cord). Meningiomas usually occur in adults.

The time of life when a woman's menstrual periods stop. A woman is in menopause when she hasn't had a period for 12 months in a row. Also called change of life.

Periodic discharge of blood and tissue from the uterus. From puberty until menopause, menstruation occurs about every 28 days when a woman is not pregnant.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

NIH. A federal agency in the U.S. that conducts biomedical research in its own laboratories; supports the research of non-Federal scientists in universities, medical schools, hospitals, and research institutions throughout the country and abroad; helps in the training of research investigators; and fosters communication of medical information. Access the National Institutes of Health Web site at http://www.nih.gov. Also called NIH.

NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.

A medicine that can be bought without a prescription (doctor's order). Examples include analgesics (pain relievers) such as aspirin and acetaminophen. Also called over-the-counter and OTC.

A chemical compound (such as protein, fat, carbohydrate, vitamin, or mineral) contained in foods. These compounds are used by the body to function and grow.

A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).

Surgery to remove one or both ovaries.

By or having to do with the mouth.

A part of the body that performs a specific function. For example, the heart is an organ.

A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.

Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

The release of an egg from an ovary during the menstrual cycle.

A substance made by the parathyroid gland that helps the body store and use calcium. A higher-than-normal amount of parathyroid hormone causes high levels of calcium in the blood and may be a sign of disease. Also called parathormone, parathyrin, and PTH.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Having to do with the time after menopause. Menopause (“change of life”) is the time in a woman's life when menstrual periods stop permanently.

Having to do with the time before menopause. Menopause ("change of life") is the time of life when a woman's menstrual periods stop permanently.

A doctor's order for medicine or another intervention.

A type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone can also be made in the laboratory. It may be used as a type of birth control and to treat menstrual disorders, infertility, symptoms of menopause, and other conditions.

A drug used to reduce the risk of invasive breast cancer in postmenopausal women who are at a high risk of developing the disease or who have osteoporosis. It is also used to prevent and treat osteoporosis in postmenopausal women and is being studied in the prevention and treatment of other conditions. Raloxifene blocks the effects of the hormone estrogen in the breast and increases the amount of calcium in bone. It is a type of selective estrogen receptor modulator (SERM). Also called raloxifene hydrochloride and Evista.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

A substance that is being studied in the prevention and treatment of osteoporosis. It belongs to the family of drugs called bone resorption inhibitors.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

Glycine max. A plant of Asian origin that produces beans used in many food products. Soy products contain isoflavones (estrogen-like substances) that are being studied for the prevention of cancer, hot flashes that occur with menopause, and osteoporosis (loss of bone density). Soy products in the diet may lower cholesterol levels and reduce the risk of heart disease. Also called soya, soybean, and Glycine max.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

Treatment.

A group or layer of cells that work together to perform a specific function.

Absorbed through the unbroken skin.

Having to do with urine or the organs of the body that produce and get rid of urine.

Inability to hold urine in the bladder.

The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a baby grows. Also called the womb.

The muscular canal extending from the uterus to the exterior of the body. Also called birth canal.

Having to do with the vagina (the birth canal).

Affecting the narrowing and widening of the blood vessels.

A nutrient that helps the body use calcium and phosphorus and make strong bones and teeth. It is found in fatty fish, eggs, and dairy products. The skin can also make vitamin D when exposed to sunshine. Not getting enough vitamin D can cause a bone disease called rickets. Vitamin D is being studied in the prevention and treatment of some types of cancer. Also called cholecalciferol.

A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.