Uppsala, Sweden—A large Swedish-led study provides compelling evidence that oral contraceptives protect against both ovarian and endometrial cancer and that the benefits can continue decades after use is discontinued.

The comprehensive study from Uppsala University involved more than 250,000 women. Results were published in the journal Cancer Research.

The authors recount how oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer and said the purpose of their study was to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. To do that, researchers performed an observational study in 256,661 women born between 1939 and 1970, from UK Biobank. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019.

Results indicate that the odds were lower among ever-users, compared with never-users, for ovarian cancer: OR = 0.72 (95% CI, 0.65-0.81) and endometrial cancer: OR = 0.68 (95% CI, 0.62-0.75). That association became stronger with longer use (P <.001), according to the researchers.

The study identified increased odds for breast cancer in women when limiting the follow-up to age 55 years: OR = 1.10 (95% CI, 1.03-1.17), but not for the full timespan.

“We only found a higher HR for breast cancer in former users immediately (≤2 years) after discontinued oral contraceptive use (HR = 1.55, 95% CI, 1.06-2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives,” the researchers write. “Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited.”

Ovarian and endometrial cancer are among the most common gynecological cancers, with a lifetime risk of just over 2%. Endometrial cancer is slightly more common but because it has clearer symptoms and is therefore often detected at an early stage, the mortality rate is low. However, ovarian cancer is among the deadliest cancers since it is often not detected until it has already spread to other parts of the body.

The first oral contraceptive pill was approved already in the 1960s, and 80% of all women in Western Europe have used oral contraceptives at some point in their life. Oral contraceptives include estrogen and progestin, which are synthetic forms of the female sex hormones. The estrogen and progestin in oral contraceptives prevent ovulation and thereby protect against pregnancy.

In the current study, the scientists compared the incidence of breast, ovarian, and endometrial cancers between women who had used oral contraceptive pills and never users.

“It was clear that women who had used oral contraceptive pills had a much lower risk of developing both ovarian and endometrial cancer. Fifteen years after discontinuing with oral contraceptives, the risk was about 50 percent lower. However, a decreased risk was still detected up to 30-35 years after discontinuation,” said coauthor Åsa Johansson from the Department of Immunology, Genetics and Pathology, Uppsala University.

Findings were also notable in terms of breast cancer, Johansson added, pointing out, “Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation. Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”

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