Introduction

Oral contraceptives (OCs) first became available to American women in the early 1960s. The convenience, effectiveness, and reversibility of action of birth control pills (popularly known as “the pill”) have made them the most popular form of birth control in the United States. However, concerns have been raised about the role that the hormones in OCs might play in a number of cancers, and how hormone-based OCs contribute to their development. Sufficient time has elapsed since the introduction of OCs to allow investigators to study large numbers of women who took birth control pills for many years.

This fact sheet addresses only what is known about OC use and the risk of developing cancer. It does not deal with other serious side effects of OC use, such as the increased risk of cardiovascular disease for certain groups of women. Recently, alternative methods of delivering hormones for contraception have been developed, including a topical patch, vaginal ring, and intrauterine delivery system, but these products are too new to have been tested in clinical trials (research studies) for long-term safety and other effects (1). They also are not covered in this fact sheet.

1. What types of oral contraceptives are available in the United States ? Why do researchers believe that oral contraceptives may influence cancer risk?

Currently, two types of OCs are available in the United States . The most commonly prescribed OC contains two man-made versions of natural female hormones (estrogen and progesterone) that are similar to the hormones the ovaries normally produce. This type of pill is often called a “combined oral contraceptive.” The second type of OC available in the United States is called the minipill. It contains only a type of progesterone.

Estrogen stimulates the growth and development of the uterus at puberty, causes the endometrium (the inner lining of the uterus) to thicken during the first half of the menstrual cycle, and influences breast tissue throughout life, but particularly from puberty to menopause.

Progesterone, which is produced during the last half of the menstrual cycle, prepares the endometrium to receive the egg. If the egg is fertilized, progesterone secretion continues, preventing release of additional eggs from the ovaries. For this reason, progesterone is called the “pregnancy-supporting” hormone, and scientists believe that it has valuable contraceptive effects. The man-made progesterone used in OCs is called progestogen or progestin.

Because medical research suggests that some cancers depend on naturally occurring sex hormones for their development and growth, scientists have been investigating a possible link between OC use and cancer risk. Researchers have focused a great deal of attention on OC users over the past 40 years. This scrutiny has produced a wealth of data on OC use and the development of certain cancers, although results of these studies have not always been consistent. The risk of endometrial and ovarian cancers is reduced with the use of OCs, while the risk of breast and cervical cancers is increased (1). A summary of research results for each type of cancer is given in Questions 2–5.

2. How do oral contraceptives affect breast cancer risk?

A woman’s risk of developing breast cancer depends on several factors, some of which are related to her natural hormones. Hormonal factors that increase the risk of breast cancer include conditions that may allow high levels of hormones to persist for long periods of time, such as beginning menstruation at an early age (before age 12), experiencing menopause at a late age (after age 55), having a first child after age 30, and not having children at all.

A 1996 analysis of worldwide epidemiologic data conducted by the Collaborative Group on Hormonal Factors in Breast Cancer found that women who were current or recent users of birth control pills had a slightly elevated risk of developing breast cancer. The risk was highest for women who started using OCs as teenagers. However, 10 or more years after women stopped using OCs, their risk of developing breast cancer returned to the same level as if they had never used birth control pills, regardless of family history of breast cancer, reproductive history, geographic area of residence, ethnic background, differences in study design, dose and type of hormone, or duration of use. In addition, breast cancers diagnosed in women after 10 or more years of not using OCs were less advanced than breast cancers diagnosed in women who had never used OCs. To conduct this analysis, the researchers examined the results of 54 studies. The analysis involved 53,297 women with breast cancer and 100,239 women without breast cancer. More than 200 researchers participated in this combined analysis of their original studies, which represented about 90 percent of the epidemiological studies throughout the world that had investigated the possible relationship between OCs and breast cancer (2).

The findings of the Women’s Contraceptive and Reproductive Experiences (Women’s CARE) study were in contrast to those described above. The Women’s CARE study examined the use of OCs as a risk factor for breast cancer in women ages 35 to 64. Researchers interviewed 4,575 women who were diagnosed with breast cancer between 1994 and 1998, and 4,682 women who did not have breast cancer. Investigators collected detailed information about the participants’ use of OCs, reproductive history, health, and family history. The results, which were published in 2002, indicated that current or former use of OCs did not significantly increase the risk of breast cancer. The findings were similar for white and black women. Factors such as longer periods of use, higher doses of estrogen, initiation of OC use before age 20, and OC use by women with a family history of breast cancer were not associated with an increased risk of the disease (3).

In a National Cancer Institute (NCI)-sponsored study published in 2003, researchers examined risk factors for breast cancer among women ages 20 to 34 compared with women ages 35 to 54. Women diagnosed with breast cancer were asked whether they had used OCs for more than 6 months before diagnosis and, if so, whether the most recent use had been within 5 years, 5 to 10 years, or more than 10 years. The results indicated that the risk was highest for women who used OCs within 5 years prior to diagnosis, particularly in the younger group (4).

3. How do oral contraceptives affect ovarian and endometrial cancer risk?

Studies have consistently shown that using OCs reduces the risk of ovarian cancer. In a 1992 analysis of 20 studies of OC use and ovarian cancer, researchers from Harvard Medical School found that the risk of ovarian cancer decreased with increasing duration of OC use. Results showed a 10 to 12 percent decrease in risk after 1 year of use, and approximately a 50 percent decrease after 5 years of use (5).

Researchers have studied how the amount or type of hormones in OCs affects ovarian cancer risk reduction. One of the studies used in the Harvard analysis, the Cancer and Steroid Hormone Study (CASH), found that the reduction in ovarian cancer risk was the same regardless of the type or amount of estrogen or progestin in the pill (6). A more recent analysis of data from the CASH study, however, indicated that OC formulations with high levels of progestin reduced ovarian cancer risk more than preparations with low progestin levels (7). In another recent study, the Steroid Hormones and Reproductions (SHARE) study, researchers investigated new, lower-dose progestins that have varying androgenic properties (testosterone-like effects). They found no difference in ovarian cancer risk between androgenic and nonandrogenic pills (8).

OC use in women at increased risk of ovarian cancer due to BRCA1 and BRCA2 genetic mutations has been studied. One study showed a reduction in risk, but a more recent study showed no effect (9, 10).

The use of OCs has been shown to significantly reduce the risk of endometrial cancer. This protective effect increases with the length of time OCs are used, and continues for many years after a woman stops using OCs (11).

4. How do oral contraceptives affect cervical cancer risk?

Evidence shows that long-term use of OCs (5 or more years) may be associated with an increased risk of cancer of the cervix (the narrow, lower portion of the uterus) (12). Although OC use may increase the risk of cervical cancer, human papillomavirus (HPV) is recognized as the major cause of this disease. Approximately 14 types of HPV have been identified as having the potential to cause cancer, and HPVs have been found in 99 percent of cervical cancer biopsy specimens worldwide (12). More information about HPV and cancer is available in Human Papillomaviruses and Cancer: Questions and Answers at http://www.cancer.gov/cancertopics/factsheet/risk/HPV on the Internet.

A 2003 analysis by the International Agency for Research on Cancer (IARC) found an increased risk of cervical cancer with longer use of OCs. Researchers analyzed data from 28 studies that included 12,531 women with cervical cancer. The data suggested that the risk of cervical cancer may decrease after OC use stops (13). In another IARC report, data from eight studies were combined to assess the effect of OC use on cervical cancer risk in HPV-positive women. Researchers found a fourfold increase in risk among women who had used OCs for longer than 5 years. Risk was also increased among women who began using OCs before age 20 and women who had used OCs within the past 5 years (14). The IARC is planning a study to reanalyze all data related to OC use and cervical cancer risk (12).

5. How do oral contraceptives affect liver cancer risk?

Several studies have found that OCs increase the risk of liver cancer in populations usually considered low risk, such as white women in the United States and Europe who do not have liver disease. In these studies, women who used OCs for longer periods of time were found to be at increased risk for liver cancer. However, OCs did not increase the risk of liver cancer in Asian and African women, who are considered high risk for this disease. Researchers believe this is because other risk factors, such as hepatitis infection, outweigh the effect of OCs (15).

6. What screening tests are available for the cancers described?

Studies have found that regular breast cancer screening with mammograms reduces the number of deaths from breast cancer for women ages 40 to 69.  Women who are at increased risk for breast cancer should seek medical advice about when to begin having mammograms and how often to be screened. A high-quality mammogram, with a clinical breast exam (an exam done by a professional health care provider), is the most effective way to detect breast cancer early.

Abnormal changes in the cervix can often be detected by a Pap test and treated before cancer develops. Women who have begun to have sexual intercourse or are age 21 should check with their doctor about having a Pap test. Researchers are working on developing screening tests for ovarian and endometrial cancer.

Women who are concerned about their risk for cancer are encouraged to talk with their health care provider. More information is also available from the Cancer Information Service (see below).

Selected References

1. Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. American Journal of Obstetrics and Gynecology 2004; 190(4 Suppl):S5–22.

2. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347:1713–1727.

3. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. New England Journal of Medicine 2002; 346(26):2025–2032.

4. Althuis MD, Brogan DD, Coates RJ, et al. Breast cancers among very young premenopausal women (United States). Cancer Causes and Control 2003; 14(2): 151–160.

5. Hankinson SE, Colditz GA, Hunter DJ, et al. A quantitative assessment of oral contraceptive use and risk of ovarian cancer. Obstetrics and Gynecology 1992; 80(4):708–714.

6. Centers for Disease Control and Prevention and the National Institute of Child Health and Human Development. The reduction in risk of ovarian cancer associated with oral-contraceptive use. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. New England Journal of Medicine 1987; 316(11):650–655.

7. Schildkraut JM, Calingaert B, Marchbanks PA, Moorman PG, Rodriguez GC. Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. Journal of the National Cancer Institute 2002; 94(1):32–38.

8. Greer JB, Modugno F, Allen GO, Ness RB. Androgenic progestins in oral contraceptives and the risk of epithelial ovarian cancer. Obstetrics and Gynecology 2005; 105(4): 731–740.

9. Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. New England Journal of Medicine 1998; 339(7):424–428.

10. Modan B, Hartge P, Hirsh-Yechezkel G, et al. Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. New England Journal of Medicine 2001; 345(4):235–240.

11. Emons G, Fleckenstein G, Hinney B, Huschmand A, Heyl W. Hormonal interactions in endometrial cancer. Endocrine-Related Cancer 2000; 7(4):227–242.

12. Franceschi S. The IARC commitment to cancer prevention: The example of papillomavirus and cervical cancer. Recent Results in Cancer Research 2005; 166: 277–297.

13. Smith JS, Green J, Berrington de GA, et al. Cervical cancer and use of hormonal contraceptives: A systematic review. Lancet 2003; 361(9364):1159–1167.

14. Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: The IARC multicentric case-control study. Lancet 2002; 359(9312):1085–1092.

15. Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology 2004; 127(5 Suppl 1):S72–S78.
    
    

# # #

Related Resources

Publications (available at http://www.cancer.gov/publications)

• National Cancer Institute Fact Sheet 3.20, Human Papillomaviruses and Cancer: Questions and Answers ¹
• What You Need To Know About™ Breast Cancer ²
• What You Need To Know About™ Cancer of the Cervix ³

National Cancer Institute (NCI) Resources

Cancer Information Service (toll-free)

Telephone: 1–800–4–CANCER (1–800–422–6237)

TTY: 1–800–332–8615

Online

NCI’s Web site: http://cancer.gov
LiveHelp, NCI’s live online assistance:
https://cissecure.nci.nih.gov/livehelp/welcome.asp

Glossary Terms

Not normal. An abnormal lesion or growth may be cancerous, premalignant (likely to become cancer), or benign.

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

Tissue removed from the body and examined under a microscope to determine whether disease is present.

A gene on chromosome 17 that normally helps to suppress cell growth. A person who inherits a mutated (changed) BRCA1 gene has a higher risk of getting breast, ovarian, or prostate cancer.

A gene on chromosome 13 that normally helps to suppress cell growth. A person who inherits a mutated (changed) BRCA2 gene has a higher risk of getting breast, ovarian, or prostate cancer.

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 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.

CIS. The Cancer Information Service is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER (1-800-422-6237), or by using the LiveHelp instant-messaging service at https://cissecure.nci.nih.gov/livehelp/welcome.asp. Also called CIS.

Having to do with the heart and blood vessels.

Cancer that forms in tissues of the cervix (the organ connecting the uterus and vagina). It is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests (a procedure in which cells are scraped from the cervix and looked at under a microscope).

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

An exam of the breast performed by a health care provider to check for lumps or other changes.

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.

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

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

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).

The layer of tissue that lines the uterus.

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 record of a person's current and past illnesses, and those of his or her parents, brothers, sisters, children, and other family members. A family history shows the pattern of certain diseases in a family, and helps to determine risk factors for those and other diseases.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Disease of the liver causing inflammation. Symptoms include an enlarged liver, fever, nausea, vomiting, abdominal pain, and dark urine.

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.

A member of a family of viruses that can cause abnormal tissue growth (for example, genital warts) and other changes to cells. Infection with certain types of human papillomavirus increases the risk of developing cervical cancer. Also called HPV.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

Primary liver cancer is cancer that forms in the tissues of the liver. Secondary liver cancer is cancer that spreads to the liver from another part of the body.

An x-ray of the breast.

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.

The monthly cycle of hormonal changes from the beginning of one menstrual period to the beginning of the next.

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.

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

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.

By or having to do with the mouth.

Having to do with the ovaries, the female reproductive glands in which the ova (eggs) are formed. The ovaries are located in the pelvis, one on each side of the uterus.

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).

A procedure in which cells are scraped from the cervix for examination under a microscope. It is used to detect cancer and changes that may lead to cancer. A Pap test can also show noncancerous conditions, such as infection or inflammation. Also called a Pap smear.

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.

Any natural or laboratory-made substance that has some or all of the biologic effects of progesterone, a female hormone.

The time of life when a child experiences physical and hormonal changes that mark a transition into adulthood. The child develops secondary sexual characteristics and becomes able to have children. Secondary sexual characteristics include growth of pubic, armpit, and leg hair; breast enlargement; and increased hip width in girls. In boys, they include growth of pubic, face, chest and armpit hair; voice changes; penis and testicle growth, and increased shoulder width.

Something that may increase the chance of developing a disease. Some examples of risk factors for cancer include age, a family history of certain cancers, use of tobacco products, certain eating habits, obesity, lack of exercise, exposure to radiation or other cancer-causing agents, and certain genetic changes.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

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.

A hormone that promotes the development and maintenance of male sex characteristics.

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

On the surface of the body.

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

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