Hormonal contraceptives linked with lower ovarian and endometrial cancer risk: findings from a large US cohort

Overview of the study and why it matters

A large population-based cohort study conducted in the United States and published in JAMA Oncology examined whether duration of oral hormonal contraceptive use is associated with risks of several cancers and whether lifestyle factors modify these associations. The analysis included more than 100,000 women and focused on ovarian, endometrial, breast, and colorectal cancers. Because hormonal contraceptives remain widely used, high-quality evidence about their long-term safety and potential benefits is clinically important for counselling patients and informing public-health guidance.

Primary findings: ovarian and endometrial cancer

The investigators observed a consistent association between longer duration of oral hormonal contraceptive use and a reduced risk of ovarian cancer. In addition, oral contraceptive use was associated with lower risk of endometrial cancer. These protective associations were detected across the study population and were fairly consistent when the researchers examined common lifestyle behaviors.

Notably, for endometrial cancer the magnitude of risk reduction appeared strongest among several subgroups: current smokers, women with obesity, and women who exercised infrequently. This subgroup pattern suggests that the relative benefit of past or current oral contraceptive use for endometrial cancer may be more pronounced in certain populations defined by lifestyle characteristics recorded in the study.

No clear association with breast or colorectal cancer

The study did not find evidence that oral contraceptive use increased the risk of breast or colorectal cancer. This lack of association was consistent across the lifestyle factors the investigators examined, indicating that within this cohort duration of use was not linked to higher breast or colorectal cancer incidence regardless of smoking, body mass index or exercise frequency.

Study strengths that support confidence in the results

Several methodological features strengthen the study’s contribution to the evidence base. The large sample size—over 100,000 women—gives the analysis statistical power to detect associations and to examine effect modification by common lifestyle behaviors. The population-based cohort design reduces certain selection biases that can affect case-control studies. Publication in a peer-reviewed specialty journal also indicates that the methods and reporting were evaluated by expert reviewers.

Key limitations and what they mean for interpretation

The investigators acknowledged important limitations that affect causal interpretation. The analysis did not adjust for certain mediators that could lie on causal pathways between oral contraceptive use and gynecological cancer risk. In particular, the absence of adjustment for parity (number of births), which can influence both contraceptive use patterns and cancer risk, limits the ability to fully control for confounding. Because mediation-sensitive methods were not applied, residual confounding cannot be excluded.

Another important limitation is the lack of information about the specific formulations of oral contraceptives used by participants. The women included in this cohort were likely exposed predominantly to first- and second-generation contraceptive products marketed before 1989. These older formulations generally contained higher hormone doses than many newer products introduced later. Consequently, the observed associations primarily reflect the effects of older contraceptive preparations and may not directly generalize to contemporary lower-dose formulations.

Clinical and public-health implications

Taken together, these findings add to the body of evidence indicating that oral hormonal contraceptives are associated with reduced risks of ovarian and endometrial cancer. For clinicians, the results provide further data to incorporate into shared decision-making discussions about contraceptive choice, balancing contraceptive effectiveness, non-contraceptive benefits, and known risks. The absence of a detected association with breast and colorectal cancers in this study may be reassuring, but must be considered alongside other studies and individual patient risk factors.

Patients asking about long-term cancer risks associated with oral contraceptives should receive individualized counselling. Clinicians should discuss the known protective effects on ovarian and endometrial cancers demonstrated in multiple studies, while also acknowledging limitations in the evidence, particularly with respect to contraceptive formulation and potential confounders such as parity.

Need for future research

The researchers emphasized the need for further investigations that explicitly evaluate contemporary contraceptive formulations and account for mediating variables and confounders more comprehensively. Future studies that capture detailed information on product generation, hormone dose, and timing of use—and that apply mediation analysis where appropriate—will help clarify whether the protective associations observed historically persist with newer, lower-dose oral contraceptives and how lifestyle and reproductive factors influence these relationships.

Bottom line

In a large US cohort study reported in JAMA Oncology, longer duration of oral hormonal contraceptive use was associated with reduced risks of ovarian and endometrial cancers, with the endometrial benefit appearing most pronounced in certain lifestyle-defined subgroups. No association was observed with breast or colorectal cancer in this analysis. Limitations—especially lack of data on parity and on contraceptive formulation—mean that these findings should be interpreted alongside other studies and discussed individually with patients. This work contributes to the evidence clinicians can use when advising patients about the risks and benefits of oral contraceptive use.

Reference:
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 Oncol. 2018;4(4):516-521. doi:10.1001/jamaoncol.2017.4942

medichelpline — Medical writer, MPharm