Oral Contraceptives

At a Glance

Oral contraceptives, otherwise known as birth control pills, are among the most common medications used by women. They have been classified as human carcinogens by the International Agency for Research on Cancer.

What are oral contraceptives?

Oral contraceptives contain synthetic versions of the female sex hormones estradiol (an estrogen) and progesterone.[1] The body naturally alters the levels of these hormones in preparation for pregnancy, and oral contraceptives prevent these alterations from occurring.[2] There are two types of oral contraceptives prescribed in the United States. The more commonly prescribed oral contraceptive includes a combination of synthetic estrogen and progesterone, while the other contains only progesterone.[3]

What evidence links oral contraceptives to breast cancer?

They have been classified as human carcinogens by the International Agency for Research on Cancer.[4] Several studies have found an association between the use of oral contraceptives and elevated risks of breast cancer.[5],[6],[7] These risks are further impacted by variables that include age at initiating use, length of use, genetic makeup and race/ethnicity.[8],[9],[10] Risk levels return to normal years after suspending use of the pill. A study of post-menopausal women who used oral contraceptives for eight or more years, but who had discontinued use for at least a decade, showed no significant increase in breast cancer rates.[11],[12]

Women who used oral contraceptives within five years of their first menstruation had an elevated risk of breast cancer. Those who used oral contraceptives for longer than five years also had a higher risk for developing breast cancer.[13]

One study found that women under 35 years of age who used oral contraceptives were more likely to develop breast cancer. In addition, their cancer was more likely to be diagnosed at a later stage.[14]

Several studies have explored the risk of breast cancer in women who are carriers for the breast cancer genes BRCA1 and BRCA2. Mutations in these genes increase a women’s susceptibility to breast cancer. In carriers of BRCA1 and BRCA2, the use of oral contraceptives further increases the risk of breast cancer.[15],[16],[17]

When breast cancer cells are removed and tested in a biopsy, they can be analyzed and classified into subgroups. This classification is based, in part, on whether estrogen or progesterone receptors are present.[18]

  • A study conducted on a group of African American women beginning 1995 found a greater incidence of estrogen-receptor-negative cancer among women who used oral contraceptives. Estrogen-receptor-negative breast cancer is an aggressive cancer that is difficult to treat.[19]
  • A study conducted on Hispanic and non-Hispanic white women found that use of oral contraceptives for more than 20 years significantly increased the risk of estrogen-receptor-negative breast cancer.[20]

Formulations of oral contraceptives have changed over the years. A 2014 study looked at formulation differences and reconfirmed that recent oral contraceptive use (within the prior year) was associated with an increased breast cancer risk. Three specific formulations of oral contraceptives were associated with particularly elevated risks. These included: 1) high-dose estrogen, 2) ethynodiol diacetate (a type of progestin); and 3) triphasic dosing (in which the pills have three different doses of hormones in the three weeks of active pills) including norethindrone (a progestin) at an average of 0.75 mg. Other types, including low-dose estrogen oral contraceptives, were not associated with elevated risks.[21]

Who is most vulnerable to the health effects of oral contraceptives?

Young women who have used oral contraceptives for longer than five years are most vulnerable to the health effects of oral contraceptives.[22] Women who are carriers of BRCA1 and BRCA2 genes are also vulnerable.[23]

What are the top tips to avoid exposure?

To minimize health effects, women who elect to use oral contraceptives should wait five years after beginning menstruation and should use them for the shortest time possible.[24]

[1] National Cancer Institute. (2012). Oral Contraceptives and Cancer Risk. http://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet. Retrieved July 21, 2016.

[2] Urban, M., Banks, E., Egger, S., Canfell, K., O’Connell, D., Beral, V., & Sitas, F. (2012). Injectable and oral contraceptive use and cancers of the breast, cervix, ovary, and endometrium in black South African women: case–control study. Plos med, 9(3), e1001182.

[3] Marchbanks, P. A., McDonald, J. A., Wilson, H. G., Folger, S. G., Mandel, M. G., Daling, J. R., … & Norman, S. A. (2002). Oral contraceptives and the risk of breast cancer. New England Journal of Medicine, 346(26), 2025–2032.

[4] Schneider, H. P. G., Mueck, A. O., & Kuhl, H. (2005). IARC monographs program on carcinogenicity of combined hormonal contraceptives and menopausal therapy. Climacteric, 8(4), 311–316.

[5] White, E., Malone, K., Weiss, N & Daling, J. (1994). Breast Cancer Among Young U.S. Women in Relation to Oral Contraceptive Use. Journal of the National Cancer Institute, 86(7): 505–514.

[6] Sweeney, C., Giuliano, A. R., Baumgartner, K. B., Byers, T., Herrick, J. S., Edwards, S. L., & Slattery, M. L. (2007). Oral, injected and implanted contraceptives and breast cancer risk among US Hispanic and non‐Hispanic white women. International Journal of Cancer, 121(11), 2517–2523.

[7] Kumle, M., Weiderpass, E., Braaten, T., Persson, I., Adami, H. O., & Lund, E. (2002). Use of oral contraceptives and breast cancer risk the Norwegian-Swedish women’s lifestyle and Health Cohort Study. Cancer Epidemiology Biomarkers & Prevention, 11(11), 1375–1381.

[8] White, E., Malone, K., Weiss, N & Daling, J. Breast Cancer Among Young U.S. Women in Relation to Oral Contraceptive Use. (1994) Journal of the National Cancer Institute, 86(7): 505–514.

[9] Narod, S., Dubém, M.P., Klijn, J. et al. (2002). Oral Contraceptives and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. Journal of the National Cancer Institute, 94(23): 1773–1779.

[10] Rosenberg, L., Boggs, D. A., Wise, L. A., Adams-Campbell, L. L., & Palmer, J. R. (2010). Oral contraceptive use and estrogen/progesterone receptor–negative breast cancer among African American women. Cancer Epidemiology Biomarkers & Prevention, 19(8), 2073–2079.

[11] CGHFBC, C. G. on H. F. in B. C. (1996). 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, 347, 1713–1727.

[12] Vessey, M., & Painter, R. (2006). Oral contraceptive use and cancer: Findings in a large cohort study. Br J Cancer, 95, 385–389.

[13] White, E., Malone, K., Weiss, N & Daling, J. (1994). Breast Cancer Among Young U.S. Women in Relation to Oral Contraceptive Use. Journal of the National Cancer Institute, 86(7): 505–514.

[14] Jia, X., Liu, G., Mo, M., Cheng, J., Shen, Z., & Shao, Z. (2015). Reproductive factors and hormone receptor status among very young (< 35 years) breast cancer patients. Oncotarget6(27), 24571.

[15] Narod, S., Dubém, M.P., Klijn, J. et al. (2002). Oral Contraceptives and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. Journal of the National Cancer Institute, 94(23): 1773–1779.

[16] Ghimire, S., Shrestha, N., & Baral, B. K. (2015). Oral contraceptives as a risk factor for developing breast cancer in breast cancer (BRCA) gene carrier female in-the 30–60 years age group: a meta analysis. International Journal of Medical Research & Health Sciences, 4(1), 135-143.

[17] Gaffield, M. E., Culwell, K. R., & Ravi, A. (2009). Oral contraceptives and family history of breast cancer. Contraception, 80(4), 372-380.

[18] Rosenberg, L., Zhang, Y., Coogan, P. F., Strom, B. L., & Palmer, J. R. (2009). A case-control study of oral contraceptive use and incident breast cancer. American journal of epidemiology, 169(4), 473-479.

[19] Rosenberg, L., Boggs, D. A., Wise, L. A., Adams-Campbell, L. L., & Palmer, J. R. (2010). Oral contraceptive use and estrogen/progesterone receptor–negative breast cancer among African American women. Cancer Epidemiology Biomarkers & Prevention, 19(8), 2073-2079.

[20] Sweeney, C., Giuliano, A. R., Baumgartner, K. B., Byers, T., Herrick, J. S., Edwards, S. L., & Slattery, M. L. (2007). Oral, injected and implanted contraceptives and breast cancer risk among US Hispanic and non‐Hispanic white women. International journal of cancer121(11), 2517-2523.

[21] Beaber, E.F., Buist, D.S., Barlow, W.E., Malone, K.E., Reed, S.D. & Li, C.I. (2014). Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age. Cancer Res, 74(15):4078-89.

[22] White, E., Malone, K., Weiss, N & Daling, J. (1994). Breast Cancer Among Young U.S. Women in Relation to Oral Contraceptive Use. Journal of the National Cancer Institute, 86(7): 505-514.

[23] Narod, S., Dubém, M.P., Klijn, J. et al. (2002). Oral Contraceptives and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. Journal of the National Cancer Institute, 94(23): 1773-1779.

[24] White, E., Malone, K., Weiss, N & Daling, J. (1994). Breast Cancer Among Young U.S. Women in Relation to Oral Contraceptive Use. Journal of the National Cancer Institute, 86(7): 505-514.