Oral Contraceptive Use and Risks of Cancer in the NIH-AARP Diet and Health Study

Kara A. Michels; Louise A. Brinton; Ruth M. Pfeiffer; Britton Trabert


Am J Epidemiol. 2018;187(8):1630-1641. 

In This Article

Abstract and Introduction


Although use of oral contraceptives (OCs) is common, their influence on carcinogenesis is not fully understood. We used Cox proportional hazards models to examine OC use (never/<1 year (referent), 1–4, 5–9, ≥10 years) and development of incident cancers across body sites within the same base population: women in the prospective National Institutes of Health-AARP Diet and Health Study (enrolled 1995–1996 and followed until 2011). Adjustment for confounding varied by outcome; all models accounted for age, race, body mass index, and smoking status, and included at least 100,000 women. Any OC use conferred a 3% reduction in the risk for any cancer (hazard ratio = 0.97, 95% confidence interval: 0.95, 0.99). Expected risk reductions that strengthened with duration of use were identified for ovarian and endometrial cancers and were suggested for kidney cancer (all P for trend < 0.05). Non-Hodgkin lymphoma risk (hazard ratio = 0.79, 95% confidence interval: 0.64, 0.97) was reduced with 10 or more years of OC use. There was a 37% reduced risk for bladder cancer and 46% increased risk for pancreatic cancer among long-term OC users who were 60 years of age or younger at baseline. OC use did not influence risks for most other cancers evaluated. Given the high prevalence of use and changing formulations, additional studies are warranted to fully understand the chemopreventive effects of these medications.


Oral contraceptive (OC) use is ubiquitous in the United States and the benefits and risks associated with this use are fairly well documented.[1,2] However, the influence of OCs on processes such as carcinogenesis is not fully understood—a problem complicated by the long pathogenesis of cancer and the lack of detailed information on OC use in cancer cohorts. OCs could potentially influence cancer development by altering estradiol-to-progesterone ratios, immune responses, and even 1-carbon metabolism.[3,4]

Current OC use is associated with increased risk of breast cancer and longer duration of OC use reduces risks for ovarian and endometrial cancers.[5,6] Less is understood about risks for other cancers, and even among cancers for which enough literature exists to merit reviews and meta-analyses, there is considerable heterogeneity across studies. There is increasing evidence that suggests a hormonal etiology for many cancers in women, yet much remains to be learned about the influence of exogenous hormones. Furthermore, the formulation of OCs has changed considerably since their debut, which may mean that associations between OC use and cancer development will change over time.[2,7] As such, it behooves us to continue investigating OC use and cancer.

Relative to meta-analyses on OC use and individual cancers, using data from the same base population to explore cancer risks minimizes residual confounding and systematic bias through standardized recruitment and data collection. Therefore, we examined the associations between OC use and risks for cancer across organ sites in the large prospective National Institutes of Health (NIH)-AARP Diet and Health Study. To our knowledge, this is the largest US cohort used to explore OC use and cancer, and women also provided information on the duration of OC use.