Meta-analysis confirms oral contraceptives reduce endometrial cancer risk

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By Shreeya Nanda, Senior medwireNews Reporter

Oral contraceptive use protects against endometrial cancer, with effects persisting for decades after cessation of use, shows a meta-analysis of individual patient data published in The Lancet Oncology.

This prolonged protective effect “means that women who use it when they are in their 20s or even younger continue to benefit into their 50s and older, when cancer becomes more common”, study author Valerie Beral, from the University of Oxford in the UK, said in a press release.

The study included data for 27,276 women with and 115,743 without endometrial cancer enrolled in 36 epidemiological studies, of which 15 were prospective in design. In all, 35% of cases and 39% of matched controls were ever users of oral contraceptives, for a median of 3.0 and 4.4 years, respectively.

Ever users had a significant 31% lower relative risk (RR) of developing endometrial cancer than never users, with longer use associated with greater reduction in risk. Indeed, each 5 years of oral contraceptive use resulted in a significant 24% decrease in the RR of endometrial cancer.

Women who had discontinued oral contraceptives more recently had a “slightly greater” decrease in risk, but significant benefits were observed even after 30 years or more of discontinuation, reports the Collaborative Group on Epidemiological Studies on Endometrial Cancer, based in Oxford, UK.

The protective effect of oral contraceptives did not vary substantially with factors such as age, parity, body mass index, smoking status and timing of use, with comparable RRs per 5 years of use in women who used the pill in the 1960s, 1970s and 1980s.

Noting that the oestrogen doses were “much higher” in the oral contraceptives of the 1960s than the 1980s, the investigators say that the findings “show that the amount of oestrogen in the lower-dose pills is still sufficient to reduce the incidence of endometrial cancer”, which is in line with previous reports.

However, the RR was dependent on histological subtype – ever use compared with never use was significantly associated with a lower risk of developing uterine carcinomas (RR=0.69), but not sarcomas.

The researchers estimate that oral contraceptive use has led to a decrease in the cumulative incidence of endometrial cancer developing before 75 years of age from 2.3 cases per 100 never users to 1.7, 1.3 and 1.0 cases per 100 users for 5, 10 and 15 years of use, respectively.

Altogether, over the past 50 years, in 21 high-income countries, “oral contraceptive use has prevented a total of about 400,000 endometrial cancers, including 200,000 in the past 10 years (2005–14), at ages 30–74 years”, they conclude.

Commentators Nicolas Wentzensen and Amy Berrington de Gonzalez, both from the National Cancer Institute in Bethesda, Maryland, USA, find this estimate “impressive and instructive”.

But they add that “the important clinical and public health question now is whether or not the available data allow women to optimally balance the benefits and harms of oral contraceptives, and to assess whether an overall health benefit of oral contraceptive use exists that warrants specific recommendations for chemoprevention.”

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