Contraceptive Pearls: Combined Oral Contraceptive and Cancer Risk
Written by Joane Huynh, Pharm.D. candidate and Regina Ginzburg, Pharm.D., CDCES, BC-ADM
Long-term evidence has shown that combined oral contraceptives (COC) decrease the risk for ovarian and endometrial cancers.1 Numerous meta-analyses have consistently shown a reduction in ovarian and endometrial cancer risk, with potential benefits for colorectal cancer.2-7 However, there is also a small increased risk of breast and cervical cancer in current or recent COC users.1
The protective mechanism of COC in ovarian cancer may stem from ovulation suppression. Normal ovulation involves cycles of epithelial disruption and healing, which increases the potential for DNA mutation.8 In a collaborative reanalysis of 45 epidemiological studies involving 23,257 women* with ovarian cancer and 87,303 controls, COC users had a reduced risk of ovarian cancer as compared to nonusers.2 This risk reduction was more pronounced the longer a person took COC, and persisted for up to 30 years after discontinuation. A 2024 systematic review and meta-analysis of 51 studies reinforced these findings; women using COC had a 38% (relative risk [RR] = 0.62, 95% confidence interval [CI] 0.57–0.68) lower risk for ovarian cancer.3
Endometrial cancer has been associated with unopposed estrogen, leading to proliferation of the endometrium.9 Progestins in COCs counteract this by suppressing endogenous estrogen and inducing the differentiation of the endometrium cells. A meta-analysis of 36 studies involving > 27,000 women with endometrial cancer found that women on COCs for several years vs those who never used COCs had a significantly lower risk of endometrial cancer.4 Their risk was reduced by 24% (RR = 0.76, 95% CI: 0.73–0.78) for every 5 years the COC was taken, and benefits were observed years after discontinuing the COC regardless of duration of use. Another systematic review and meta-analysis of 56 studies also demonstrated longer duration of use was associated with greater risk reduction for endometrial cancer.5
Modest evidence suggests COCs are associated with a moderate protective benefit against colorectal cancer.6,10 Though unconfirmed, the proposed effect is attributed to estrogen acting on the estrogen receptor-β in colonic epithelium, supplemented by systemic hormonal effects on bile acids and insulin-like growth factor-1.10 In one large longitudinal observational study of 91,912 postmenopausal women ages 50-75, participants who had ever used COC had a 26% reduced risk of developing colon cancer (hazard ratio [HR] = 0.74, 95% CI: 0.63–0.86) compared to those who never used COC.6 They did not find protective benefits from the duration of use. A recent pooled meta-analysis of 8 studies showed a 47% risk reduction in colorectal cancer among those who had ever used COCs compared to those who never used COC.7
The risk of breast cancer with COCs is from estrogen acting as a tumor promoter in preexisting cells, rather than a tumor initiator.10 Meta-analyses have shown a 1.5-fold increased risk with breast cancer, more specifically in those who carry the BRCA1 and BRCA2 gene rather than the general population. Cervical cancer in COC users have a 1.5-2.5 fold increased risk, mainly in those who use COC > 5 years or have had human papillomavirus (HPV).11 The absolute risk reported was 1 additional case of cervical cancer per 1,000 by age 50 with 10 years of use starting at age 20. The risk with both cancers was associated with longer duration of use, which returns to baseline roughly 10 years after discontinuation.1,10,11
Overall, COCs demonstrate protective effects against ovarian and endometrial cancers, with the risk reduction increasing with longer duration of use and persisting for years after discontinuation. There is also a potential protective association with colorectal cancer, although the mechanisms and duration-related effects are less certain. In contrast, COC use is associated with a small increase in the risk of breast and cervical cancers, particularly with current or prolonged use, with risk generally declining after discontinuation. Counseling regarding COC use should include its complex long-term cancer risk profile, incorporating duration of use, individual risk factors, and patient preferences into shared decision-making.
| Cancer type | Effect of combined oral contraceptives (COCs) | Estimated risk | Key details |
| Ovarian cancer | Lower risk | About 38% lower risk among COC users compared with non-users | Protection increases with longer use and can persist for many years after stopping. |
| Endometrial (uterine lining) cancer | Lower risk | About 24% lower risk for every 5 years of COC use | Protection increases with longer use and can continue years after stopping. |
| Colorectal cancer | Possibly lower risk | Studies suggest roughly a 25–45% lower risk among people who have ever used COCs | Evidence is less consistent than for ovarian and endometrial cancer. The benefit may not persist after stopping. |
| Breast cancer | Small increase in risk | Current or recent COC use is associated with about a 20% higher relative risk | The absolute increase is small, particularly in younger people. Risk decreases after stopping. |
| Cervical cancer | Increased risk with longer use | Risk may be roughly 1.5–2.5 times higher, particularly with use >5 years | HPV infection is the main cause of cervical cancer. The increased association with COC use decreases after stopping and approaches baseline over about 10 years. |
RHAP Resources:
Your Birth Control Choices Fact Sheet
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Partner Resources:
Reproductive Health Hotline (ReproHH): A free, confidential phone service (1-844-737-7644) offering evidence-based clinical information for healthcare providers across the US who have questions related to sexual and reproductive health.
Sources:
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