Do contraceptives cause cancer?

Contraceptives play an important role in family planning. They also help to regulate women’s menstrual cycles and can be used in the management of certain health conditions, such as endometriosis.

Considerable research has evaluated the long-term effects of birth control use.

Population studies suggest contraceptive use may reduce the risk for certain cancers, including ovarian and endometrial cancers. However, research suggests they may increase risk for other malignancies, including breast, cervical and liver cancers.

Estrogen and progesterone that naturally occur in the body have been associated with the development and growth of certain cancer types. Because oral contraceptives — or birth control pills — are formulated with estrogen and progesterone, researchers have long examined the effect of oral contraceptive use on cancer risk.

Ovarian cancer

Last year, the Society of Gynecologic Oncology released several recommendations intended to help women reduce their risk for ovarian cancer.

“Oral contraceptives can reduce the risk for ovarian cancer among average-risk women, as well as BRCA mutation carriers,” the recommendations state. “Women should receive counseling about contraindications and side effects to help them weigh potential risks vs. benefits.”

A meta-analysis by Iodice and colleagues showed BRCA1 and BRCA2 mutation carriers who used oral contraceptives reduced their risk for ovarian cancer by half (summary relative risk = 0.5; 95% CI, 0.33-0.75).

Longer duration of use conferred additional benefit (summary relative risk for each additional 10 years of use = 0.64; 95% CI, 0.53-0.78).

Data from a prospective cohort study by Kolomeyevskaya and colleagues showed the use of oral contraceptives appeared to increase OS among women with epithelial ovarian cancer.

Researchers assessed the association between oral contraceptive use and survival among 387 women aged 18 to 99 years with epithelial ovarian cancer. Prior oral contraceptive use was associated with longer median OS (81 months vs. 46 months).

“Oral contraceptive use may have lasting effects on epithelial ovarian tumor characteristics, conferring favorable prognosis,” Kolomeyevskaya and colleagues wrote. “Putative mechanisms that affect tumor biology include complex interactions between ovarian cells, host immune cells and hormonal microenvironment during carcinogenesis. Future efforts should be directed to determine the role of reproductive factors in antitumor immunity.”

Endometrial cancer

Oral contraceptives appear to have a similar long-term protective effect on endometrial cancer risk.

Beral and colleagues from the Collaborative Group on Epidemiological Studies on Endometrial Cancer conducted a meta-analysis of 36 epidemiological studies that evaluated the use of hormonal contraceptives and reproductive history for 27,276 women with endometrial cancer and 115,743 women without endometrial cancer.

Researchers reported a significant association between longer duration of oral contraceptive use and greater reduction in risk for endometrial cancer (RR for every 5 years = 0.76; 95% CI, 0.73-0.78). The risk reduction persisted for more than 30 years after oral contraceptive use ended.

The risk reduction associated with ever use of oral contraceptives differed by tumor type, with a stronger risk reduction for carcinomas (RR = 0.69; 95% CI, 0.66-0.71) than sarcomas (RR = 0.83; 95% CI, 0.67-1.04; case–case comparison: P = .02).

“Medium- to long-term use of oral contraceptives (eg, for 5 years or longer) results in a substantial proportional reduction in the incidence of endometrial cancer, the magnitude of which is similar to that seen for ovarian cancer,” Beral and colleagues wrote.

These findings are “impressive and instructive,” Nicolas Wentzensen, MD, PhD, and Amy Berrington de Gonzalez, DPhil, both senior investigators in the division of cancer epidemiology and genetics at NCI, wrote in an accompanying editorial.

“[However], the important clinical and public health question now is whether or not the available data allow women to optimally balance the benefits and harms of oral contraceptives, and to assess whether an overall health benefit of oral contraceptive use exists that warrants specific recommendations for chemoprevention,” they wrote. “Research is ongoing to improve formulations that can shift the effects of oral contraceptives even further toward the benefits, and attempts have been made to develop strategies for combined hormonal prevention of breast, endometrial and ovarian cancer.”

Breast cancer

Oral contraceptives — particularly high-dose estrogen formulations — have been shown to increase breast cancer risk.

Beaber and colleagues assessed data on 1,102 women aged 20 to 49 years with invasive breast cancer who were enrolled in a group health system between 1990 and 2009. The researchers randomly sampled 21,755 controls from enrollment records and matched them with breast cancer cases based upon age, year, length of enrollment and availability of medical charts.

Results showed women who used oral contraceptives within the previous year demonstrated an increased risk for breast cancer (OR = 1.5; 95% CI, 1.3-1.9) compared with women who never used contraceptives or those who had stopped use more than 1 year earlier.

Researchers reported a significantly elevated risk among women who reported recent use of oral contraceptive formulations that included high-dose estrogen (OR = 2.7; 95% CI, 1.1-6.2), ethynodiol diacetate (OR = 2.6; 95% CI, 1.4-4.7), or triphasic dosing with an average of 0.75 mg norethindrone (OR = 3.1; 95% CI, 1.9-5.1). Results showed no association between breast cancer risk and use of low-dose estrogen formulations (OR = 1; 95% CI, 0.6-1.7).

“Our results require confirmation and should be interpreted cautiously,” Elisabeth F. Beaber, PhD, MPH, of the public health sciences division of Fred Hutchinson Cancer Research Center in Seattle, said in a press release. “Breast cancer is rare among young women, and there are numerous established health benefits associated with oral contraceptive use that must be considered. In addition, prior studies suggest that the increased risk associated with recent oral contraceptive use declines after stopping oral contraceptives.” – by Jennifer Southall

References:

Beaber EF, et al. Cancer Res. 2014;doi:10.1158/0008-5472.CAN-13.3400.

Collaborative Group on Epidemiological Studies on Endometrial Cancer. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00212-0.

Iodice S, et al. Eur J Cancer. 2010;doi:10.1016/j.ejca.2010.04.018.

Kolomeyevskaya NV, et al. Int J Gynecol Cancer. 2015;doi:10.1097/IGC.0000000000000540.

Walker JL, et al. Cancer. 2015;doi:10.1002/cncr.29321.

Additional information is available at the following websites:

www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet

www.cancer.org/cancer/news/features/birth-control-cancer-which-methods-raise-lower-risk