Women who use oral contraceptives during their reproductive years may gain long-term protection against endometrial cancer, a review of previous research suggests.

Researchers analysed 36 studies including more than 140,000 women from around the world. They found that every five years of taking birth control pills was linked to a 24 percent reduction in the risk for endometrial cancer, even more than three decades after women stopped using the contraceptives.

‘Our results show clearly, for the first time, that the protective effect of the pill on endometrial cancer lasts for over 30 years,’ senior study author Valerie Beral of Oxford University in the U.K. said by email.

The most commonly prescribed oral contraceptives contain man-made versions of the natural female hormones estrogen and progesterone. Past research has already linked these pills to a reduced risk of endometrial and ovarian tumors, but also an elevated risk for breast, cervical and liver malignancies, according to the U.S. National Cancer Institute (NCI).

Cancer of the endometrium, which is the lining of the uterus, typically strikes women around age 60, after the end of their reproductive years, according to NCI. Risk factors include obesity, never giving birth, starting menstruation at a younger age, entering menopause at an older age and taking estrogen therapy to ease menopause symptoms.

Since the first oral contraceptives were introduced in the 1960s, about 400 million women in high-income countries alone have used the pills, the researchers note in The Lancet Oncology.

To understand the connection between endometrial cancer and oral contraceptives, Beral and colleagues examined data on 27,276 women who got these tumors and another 115,743 who didn’t.

They drew on previous research done in what they described as high-income countries, including the U.S., Europe, Japan, China, Australia and South Africa.

Half the women in the analysis were at least 63 years old, and among those with cancer, half were diagnosed by 2001.

Among the women who did get endometrial tumors, roughly one third had used birth control pills, typically for around three years. Almost 40 percent of the women who didn’t get these malignancies took the pills, and they generally stayed on them for more than four years.

The risk reduction tied to contraceptives varied by tumor type. Oral contraceptive use was associated with 31 percent lower lifetime risk of developing endometrial carcinomas, which are more common. The pills were also associated with a 17 percent lower risk of less common sarcomas, which start in the uterine muscle and supportive tissue.

In the studied high-income countries, use of birth control pills was linked to a reduction in the risk of getting endometrial cancer by age 75. Among pill users, that meant 1.3 women in every 100 would get uterine cancer, compared with 2.3 women in every 100 who didn’t use the pill, the researchers estimated.

Over the past 50 years, up to 400,000 out of an estimated total 3.4 million endometrial cancers might have been prevented by oral contraceptive use in the study countries, the authors conclude.

More research is needed to understand why the pills appear to protect against cancer long after women stop taking them, the researchers note.

‘Oral contraceptives typically work by preventing ovulation,’ said Dr. Nicolas Wentzensen of the NCI. ‘We know that factors that reduce the number of ovulations during a woman’s lifetime are associated with a reduced risk for both uterine and ovarian cancers.’

Even though the amount of estrogen in birth control pills declined over the course of the 1960s, 1970s and 1980s, the study didn’t find differences in risk reduction for endometrial cancer over time, Wentzensen wrote in an editorial accompanying the study.

‘These findings suggest that there is a threshold effect, i.e. a low level of estrogen is sufficient for the cancer-protective effects and higher levels do not further increase these effects,’ he said by email.