Does the Type and Duration of Hormonal Contraceptives Used Increase Cancer Risk?

Courtney Christopher, Pharm.D., Goodrich Pharmacy

Background: Evidence suggests an association between the use of hormonal contraception, particularly estrogen, and an increased risk of breast cancer may exist. Historical studies used only oral products that contain far more estrogen than current products on the market. Further exploration to review these new dosing regimens and hormonal products is necessary. New research takes a look at various routes of delivery including patches, rings, and implants that have differing doses of estrogen or progestin only to see if these products carry similar risks. Long term use data was also analyzed to see if duration of therapy or various lifestyle choices influenced the risks of specific cancers including breast, colon, ovarian, and endometrial.

Evidence: The Danish Sex Hormone study followed 1.8 million women between the ages of 15-49 years for an average of 10.9 years via Danish nationwide registries. These women had no history of cancer or venous thromboembolism (VTE) and had not received infertility treatments. Participants were taking either both combination estrogen and progestin products or progestin only products, both with various routes of administration. The researchers also looked at whether the risk of breast cancer was influenced by duration of use.

Of the 1.8 million women followed, a total of 11,517 cases of breast cancer occurred. When looking at women who were current or recent (discontinuation within the previous 6 months) users of hormonal contraception, the relative risk of breast cancer was 1.20 [95% CI 1.14 - 1.26] compared to women who had never used hormonal contraception. Less than one year of use correlated to a risk of 1.09 [95% CI 0.96 - 1.23] increasing to 1.38 [95% CI 1.26 - 1.51] with more than 10 years of use (P=0.002). Women who currently or recently used the progestin-only IUD also had a higher risk of breast cancer than women who had never used hormonal products RR 1.21 [95% CI 1.11 - 1.33]. The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 [95% CI 10 - 16] per 100,000 person-years, which equals approximately one case of breast cancer per 7,690 women using hormonal contraception for one year.

A prospective study by the National Institutes of Health and the American Association of Retired Persons (NIH-AARP) Diet and Health reviewed over 100,000 women who were using oral hormonal contraception and aged 50-71 at time of enrollment (1995-1996). A baseline questionnaire was sent to women to obtain duration of oral contraceptive use, demographics, and health and lifestyle characteristics. Women were followed from enrollment until cancer diagnosis, death, or the end-of-study follow up in 2011. Participants were predominantly white and excluded patients with a history of cancer, had menses stop due to chemotherapy or radiation, or who did not provide information on contraceptive use.

Data analysis conducted from September 2016 through April 2017 identified no significant correlation between oral contraception use and colorectal cancer risk or breast cancer risk, regardless of family history. However, long-term users (use of oral contraception for longer than 10 years) who were current smokers were found to have an increased risk of breast cancer HR 1.21 [95% CI 1.01 - 1.44]. Longer duration of use was associated with an increased risk reduction of ovarian cancer HR 0.60 [95% CI 0.47-0.76]; P<0.001 for trend. This trend was similar across all lifestyle modifiers including smoking, obesity, alcohol use, and physical activity. Analysis of endometrial cancer showed similar risk reductions with increased duration of use HR 0.66 [95% CI 0.56 - 0.78]; P<0.001 for trend. Risk reduction was stronger in patients who were smokers, were obese, and exercised rarely.

Discussion: Regardless of what type of hormonal contraception is being used, there is still data showing a potential risk of breast cancer that seems to increase with duration of use. It appears that even progestin only methods present an increased risk. Lifestyle choices do not appear to modify the risk of breast or colorectal cancer when using oral contraception, but may have a protective effect on ovarian and endometrial cancers. Further research is needed specifically addressing various hormone dosing in each formulation available and their associated risks/benefits of long term use to decipher how big of an impact hormonal contraceptives play in cancer risk and protection.

Clinical Impact: Prescribers should obtain a full health history and assess risk factors for each patient individually prior to prescribing hormonal contraceptives. Patients should be educated regarding duration of use of these products and the possible progression of risks or benefits of cancer. The decision to use hormonal contraceptives should be carefully considered based upon the patients’ full health profile and personal preference.

References:

  1. Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary hormonal contraception and the risk of breast cancer. NEJM. 2017;377(23):2228-2239. doi:10.1056/nejmoa1700732.

  2. Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncology. 2018 Jan 18. doi:10.1001/jamaoncol.2017.4942.