Oral Contraceptives Exonerated in Overall Cancer Risk

ABERDEEN, Scotland, Sept. 12 -- Contraceptive pills do not increase the overall risk of cancer and may even reduce some risks, according to a huge British cohort study.

However, women who used oral contraceptives for more than eight years had an increased risk for cervical, pituitary, and central nervous system malignancies, Philip C. Hannaford, M.D., of the University of Aberdeen, and colleagues, reported online in BMJ.

Some previous research has suggested increased risks for breast, cervical, and liver cancer. However, two large cohort studies examined the overall risk of death from cancer among ever- and never-users of oral contraception, and neither found significant differences between the groups.

The current findings emerged from standardized data from the Royal College of General Practitioners' oral contraception study, which began in 1968 and included more than a million patient-years. The mean age at recruitment was 29. All women were married or living in a stable relationship and most were white.

A subgroup analysis was done for women under general- practitioner follow-up. The information included cancers, periods of observation, information about type and duration of oral contraceptives used, and hormone replacement.

The researchers calculated adjusted relative risks between never- and ever-users of oral contraceptives for different types of cancer, gynecological cancers combined, and any cancer.

Standardization variables were age, smoking, parity, social class, and (for the general-practitioner-observation dataset) hormone replacement therapy.

The main dataset contained about 339,000 woman-years of observation for never-users and 744,000 woman-years for ever-users.

Compared with never-users, ever-users had statistically significant lower rates of colorectal, uterine body and ovarian cancers, tumors of unknown site, and other malignancies, as well as main gynecological cancers combined and any cancer.

The relative risk for any cancer in the smaller general practitioner observation dataset was not significantly reduced, the researchers said.

Increasing duration of oral contraceptive use produced statistically significant trends for a decreasing risk of uterine and ovarian malignancies but an increasing risk of cervical, central nervous system, or pituitary cancer.

The researchers said they were unable to explain the increased risks for the latter cancers, although the frequent lack of a post mortem may have resulted in some misclassification of CNS events.

The estimated absolute rate reduction of any cancer among ever- users was 12% or 3% (45 or 10 per 100,000 woman years) depending on whether the main or the smaller general-practitioner dataset was used.

The analyses of duration of use showed that long-term (? eight years) users had an increased risk of any cancer (adjusted relative risk 1.22, 95% CI, 1.07-1.39), although comparatively few women used oral contraceptives that long, Dr. Hannaford said.

Most of the agents used in the study were combined oral contraceptives containing 50 ?g of estrogen. Because most women did not stay with one estrogen dose, it was impossible to examine cancer risk by hormonal content of the pills used, the researchers said.

The study was prone to large losses to follow-up, the researchers wrote. Biased results could have occurred if there wee a relation between leaving the study, contraceptive use, and cancer risk.

However, the investigators had previously shown that women lost to general practitioner follow-up had the same mortality risks as those still under observations, suggesting no major bias from this loss.

Many women, especially those who used the first generation of oral contraceptives are likely to be reassured by these results, Dr. Hannaford said.

These results suggest that, at least in this relatively healthy cohort, the cancer benefits associated with oral contraception outweigh the risks, the researchers said.

The findings, however, might not reflect the experience of women using oral contraceptives today, if currently available preparations have a different risk or if usage patterns change (such as age at the start or duration of use), he said.

The balance of cancer risks and benefits, however, may vary in different parts of the world, depending on patterns of oral contraception use, duration of use, age at stopping, and the incidence of different cancers.

Further work, they concluded, is needed to quantify the likely balance of these cancer risks and benefits.

This study received funding from the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle.