Women who take oral contraceptives (OCs) for eight years and under may significantly reduce their risk of developing cancer, a cohort study conducted in the UK suggests.

In a smaller dataset, however, the relative risk of cancer was not significantly lower, the researchers reported in the British Medical Journal. Moreover, the study found that women who used OCs for more than eight years had a significantly higher cancer risk.

On balance, the authors concluded, oral contraception was “not associated with a significantly increased risk of any cancer; indeed it may even produce a net public health gain”. The estimated absolute risk reduction for any cancer was 12% (45 fewer cases per 100,000 women years) or 3% (10 fewer cases per 100,000 women years), depending on which of two datasets was analysed. “These results suggest that, at least in this relatively healthy UK cohort, the cancer benefits associated with oral contraception outweigh the risks,” they commented.

The researchers from the University of Aberdeen and the Centre for Rural Health in Inverness, Scotland analysed data covering a 36-year period from the Royal College of General Practitioners’ oral contraception study, which began in 1968 and recruited some 46,000 women with an average age of 29 years at the study outset. Around half of these women were using OCs and the other half had never used them. In the mid-1970s, about three-quarters of the original cohort were “flagged” at National Health Service central registries, so that subsequent cancers and deaths could be reported even if the women were no longer being followed up by their GP.

Because not all of the GPs involved were able to provide six-monthly health updates throughout the duration of the study, two datasets were compiled, both including women who were not flagged until they were lost to follow-up.

The general practitioner observation dataset, which analysed cancers reported while women were still registered with their recruiting GP, contained some 331,000 woman years of observation for women who had taken an OC at some time during their lives and 224,000 woman years for ‘never users’, with detailed information on the type and duration of contraceptives used. The more precise risk estimates came from the larger main dataset, which included the GP observation data as well as information on cancers notified by the central NHS registries after women had left their recruiting GP. The main dataset contained some 744,000 woman years of observation for ‘ever users’ of OCs and 339,000 woman years for never users.

Reduced risk

In the main dataset, ever users of oral contraceptives showed a statistically significant 12% decrease in the risk of developing any cancer compared with never users, the researchers found. Statistically significant reductions were seen in the rates of cancer of the large bowel or rectum, uterine body and ovaries as well as those of site unknown or ‘other’ cancers. Small, statistically non-significant increases were observed in the risk of cancers of the lung, cervix and central nervous system or pituitary gland. No material differences were found between users and non-users for the most common type of cancer, breast cancer.

In the GP observation dataset, the risk estimates were less precise, with many of the relative risks – including the overall risk of developing cancer – losing statistical significance, the authors noted. However, the reduced risk among ever users of developing cancer of the uterine body and ovaries remained statistically significant, with the risk reduction for the main gynaecological cancers combined (-29% in the main dataset) reaching borderline significance.

When all of the cancers were considered together in the GP observation dataset, women who used OCs for more than eight years had a statistically significant increased risk of any cancer, as well as cancers of the cervix, central nervous system or pituitary gland. Conversely, taking OCs for more than eight years was associated with a significantly lower risk of ovarian cancer. Analysis of the data by time since last use of oral contraception also suggested that the protective effect of OCs for ovarian cancer lasted for at least 15 years after coming off the pill.

As the researchers pointed out, current users of combination OCs are generally thought to have an increased risk of breast, cervical and liver cancer but a reduced risk of developing cancer of the endometrium, ovaries and, “possibly”, the colorectum. While many women, especially those who used the first generation of OCs, “are likely to be reassured by our results”, the findings may not reflect the experience of women taking oral contraceptives today “if currently available preparations have a different risk to earlier products, or if differences in patterns of usage (such as age at starting oral contraceptives or duration of use) materially affect cancer use”, they cautioned.

Moreover, the outcomes of the UK study may not be applicable to other countries, where levels of reduced cancer risk depend on variables such as OC usage, duration of use, age at which women come off the pill and incidence of different cancers, the authors noted. “Further work is needed therefore to quantify the likely balance of cancer risks and benefits in different parts of the world, including effects on mortality,” they said.