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Oral contraceptive use provides long-term protection against endometrial cancer
The use of oral contraceptives conferred long-term protection against endometrial cancer, according to results of a meta-analysis.
Since 1965, contraceptives have prevented approximately 400,000 cases of endometrial cancer in high-income countries among women aged younger than 75 years, according to researchers with the Collaborative Group on Epidemiological Studies on Endometrial Cancer. About 200,000 cases have been prevented in the past decade, researchers determined.
“Use of oral contraceptives is known to reduce the incidence of endometrial cancer,” Prof. Valerie Beral, AC, DBE, FRS, professor of epidemiology and head of the cancer epidemiology unit at University of Oxford and Cancer Research UK, and colleagues wrote. “Because endometrial cancer is uncommon in young women but its incidence increases sharply with age, the public health effects of this inverse association depend mainly on the extent to which the reduced risk [for] endometrial cancer persists long after use ceases.”
Beral and colleagues conducted a meta-analysis of 36 epidemiological studies that evaluated the use of hormonal contraceptives and reproductive history. Eligible studies included retrospective analyses that enrolled at least 400 women with endometrial cancer, as well as prospective analyses that enrolled at least 200 women with endometrial cancer.
The study included data from 27,276 women with endometrial cancer (mean age, 63 years; interquartile range [IQR], 57-68) and 115,743 women without endometrial cancer.
Approximately 35% of women with endometrial cancer (n = 9,459) and 39% of women without endometrial cancer (n = 45,625) reported any oral contraceptive use. Women with endometrial cancer reported a median duration of contraceptive use of 3 years (IQR, 1-7), and women without endometrial cancer reported a median duration of contraceptive use of 4.4 years (IQR, 2-9).
Beral and colleagues observed a significant association between longer duration of oral contraceptive use and greater reduction in risk for endometrial cancer (RR for every 5 years = 0.76; 95% CI, 0.73-0.78).
The risk reduction persisted for more than 30 years after oral contraceptive use ended. Researchers observed no apparent decrease in RRs during the 1960s, 1970s and 1980s, despite higher estrogen doses in oral contraceptives during those decades.
However, reduction in risk associated with ever use of oral contraceptives differed by tumor type, with a stronger risk reduction for carcinomas (RR = 0.69; 95% CI, 0.66-0.71) than sarcomas (RR = 0.83; 95% CI, 0.67-1.04; case–case comparison: P = .02).
In high-income countries, 10 years of oral contraceptive use conferred an estimated reduction in the absolute risk for endometrial cancer before the age of 75 years from 2.3 per 100 women to 1.3 per 100 women.
“Since the introduction of oral contraception in the early 1960s, about 400 million women have used it in high-income countries alone, often for prolonged periods during early adulthood,” Beral and colleagues wrote. “Medium- to long-term use of oral contraceptives (eg, for 5 years or longer) results in a substantial proportional reduction in the incidence of endometrial cancer, the magnitude of which is similar to that seen for ovarian cancer.”
Because some oral contraceptives are associated with increased risks for venous thromboembolism and other adverse events, the protective benefits they may offer should be balanced with potential harms, Nicolas Wentzensen, MD, PhD, and Amy Berrington de Gonzalez, DPhil, both senior investigators in the division of cancer epidemiology and genetics at the NCI, wrote in an accompanying editorial.
“The authors estimate that up to 400,000 out of an estimated total of 3.4 million endometrial cancers might have been prevented by oral contraceptive use in high-income countries in the past 50 years,” Wentzensen and de Gonzalez wrote. “Although this finding is impressive and instructive, 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. … Research is ongoing to improve formulations that can shift the effects of oral contraceptives even further towards the benefits, and attempts have been made to develop strategies for combined hormonal prevention of breast, endometrial and ovarian cancer.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures. Wentzensen and de Gonzalez report no relevant financial disclosures.