Meta-analysis confirms protective effect of oral contraceptives against endometrial cancer

1. In this meta-analysis of epidemiological studies, oral contraceptives (OCPs) were shown to have long-lasting protective effects against endometrial cancer.

2. The protective effect varied by tumor type, and was stronger for carcinomas than sarcomas.

Evidence Rating Level: 1 (Excellent)

Study Rundown: As OCPs find clinical use outside of pregnancy prevention, such as dysmenorrhea and endometriosis, the benefits and risks of OCPs have been the subject of continuous research. While a well-known risk of OCP is increased venous thromboembolism, multiple prior studies have reported protective effects of OCPs against endometrial cancer. In this meta-analysis, investigators of the Collaborative Group on Epidemiological Studies on Endometrial Cancer pooled data of more than 140,000 individuals from 36 epidemiological studies and confirmed previous observations, noting a relative risk of 0.76 for endometrial cancer with every 5 years of OCP use. The authors estimated that OCP use has prevented about 400,000 cases of endometrial cancer before the age of 75 in the past 50 years, including 200,000 cases in the past decade (2005-2014), in 21 developed nations. The protective effect appeared to persist for 30 years after cessation of use. The study was strengthened by the large number of patients in the trials, as well as long-term follow up. The results could be slightly weakened by the heterogeneity of eligible studies, which had various designs, settings, and durations of OCP use. The results could also be slightly weakened as not all 44 identified eligible trials were included in the analysis – 4 groups of researchers had declined participation, and 4 additional groups had agreed in principle to provide data at a future date.

The study was funded by Cancer Research UK, Medical Research Council.

Click to read the study in The Lancet Oncology

Relevant Reading: Endometrial cancer and estrogen use. Report of a large case-control study.

In-Depth [meta-analysis]: This meta-analysis included data from 27,276 women with endometrial cancer (cases) and 115,743 women without endometrial cancer (controls) in 36 trials. Eligible trials were identified from PubMed and Medline up to 1/31/2012 using various search terms related to OCP use and endometrial cancer. 44 eligible studies were identified, of which 36 were included in the analysis.

The risk of endometrial cancer was significantly lower in women who had ever used OCPs than in women who had not (RR = 0.69, 95% CI, 0.67 – 0.72). The risk of endometrial cancer was also lower as the duration of OCP use increased, with each 5 year of use associated with an RR of 0.76 (95% CI, 0.73 – 0.78, p<0.0001). Duration of use between 10-15 years was associated with a relative risk of 0.52 (95% CI, 0.48 – 0.57). The relative risk reduction was not uniform among the various types of malignancy. RR for ever-users was 0.69 (95% CI 0.66 – 0.71) for carcinomas and 0.83 (95% CI 0.67 – 1.04) for uterine sarcomas. RR per 5 years use was 0.75 (95% CI 0.73 – 0.77) for carcinomas and 0.88 (95% CI 0.74 – 1.03) for sarcomas. In addition, it was estimated that among women of 21 developed nations in western Europe, North America and Australasia, approximately 400,000 endometrial cancers were averted with OCP use in the past 50 years (1965 – 2014), including 200,000 in the past 10 years alone (2005 – 2014).

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