Birth Control Pills and Ovarian Cancer Prevention
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: A prior use of oral contraceptives has been known to have an inhibitory effect on ovarian cancer development. The Collaborative Group on Epidemiological Studies of Ovarian Cancer pooled data from 45 epidemiological studies providing a definitive characterization of the magnitude of this effect. The substantial protective effects begins quickly, increases with increasing duration of use, and tapers off slowly after discontinuation of use. The authors calculate that given current patterns of use, at least 30,000 cases of ovarian cancer are prevented each year.
Source: Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303.
It has long been known that oral contraceptives reduce the incidence of ovarian cancer,1,2 but the overall magnitude of this effect in public health terms has yet to be determined. This is quite important because the potential for oral contraceptives to be associated with other adverse consequences including deep vein thrombosis, breast and cervical cancer has also been raised. To address the overall public health effect, the Collaborative Group on Epidemiologic Studies of Ovarian Cancer examined individual data for 23,257 women with ovarian cancer (cases) and 87,303 women without ovarian cancer (controls) that had been enrolled in 45 epidemiological studies in 21 countries. Consolidating the numerous studies, the Corroborative Group directly addressed the quantitative effects of oral contraceptive use, age at start, duration of use, time since association, and era of use by finely stratified analyses accounting for key a priori confounders and design variables.
From the total group of subjects, 31% of cases and 37% of controls had reported oral contraceptive use for average durations among users of 4.4 and 5.0 years respectively. The longer the woman had used oral contraceptives, the greater the reduction in ovarian cancer risk (P < 0.0001). This reduction in risk persisted for more than 30 years after oral contraceptive use, but became somewhat attenuated over time. Oral contraceptive use during the 1960s, 1970s, and 1980s was associated with similar proportion of risk reductions, although typical estrogen doses in the 1960s were more than double those in 1980s.
The authors extrapolate from these data and suggest that oral contraceptive use has already prevented some 200,000 ovarian cancers and 100,000 deaths from the disease. Furthermore, they speculate that over the next few decades the number of cancers prevented by the prudent use of oral contraceptives would be at least 30,000 per year.
Commentary
This is a very important and thought-provoking report. That there was an association of oral contraceptive use and reduced ovarian cancer was not unexpected, based upon a large number of prior reports. However, the power created by a sophisticated analysis of a large number of independent studies provides compelling evidence of the overall magnitude of prevention even decades after relatively short use of oral contraceptives. This is particularly important for this tumor type for which there is no proven effective screening strategy, and for which symptoms are sufficiently non-specific that the diagnosis is often made late and at a time when therapy is not curative. Thus, the concept of an effective primary prevention intervention becomes an attractive strategy, worth additional attention.
Currently, the most common oral contraceptives are combinations that include low-dose estrogen formulations and associated adverse cardiovascular effects although clearly present, are less common and of shorter duration than previously.3 The effect of oral contraceptives on cancer risk in general, however, is more complicated. Where it is now clear that the risk of ovarian and most likely endometrial cancers are reduced by oral contraceptives, breast and cervical cancer may possibly be increased.4 The current report, empowered by the large sample size and sophisticated analysis tools, demonstrates that the inhibitory effect on ovarian cancer exceeds the any possible enhancement of other tumors, such that the overall risk for cancer is less among oral contraceptive users, past or present. In fact, there are few interventions, if any, that confer such powerful and long-lasting protection against a highly lethal malignancy. The benefits of oral contraceptives in primary ovarian cancer prevention are independent of the preparation and vary little by ethnic origin, parity, family history of breast cancer, body mass index, and use of hormone replacement therapy. However, the matter requires further study. For some, such as those with a history of thromboembolism, heart disease, migraine headache, or liver disease the risks may be greater. For others, particularly those healthy young women considering various forms of birth control, the long-term anti-cancer effect of oral contraceptives should figure in the decision.
References
1. La Vecchia C. Oral contraceptives and ovarian cancer: an update, 1998-2004. Eur J Cancer Prev. 2006; 15(2):117-124.
2. Weiss NS, et al. Incidence of ovarian cancer in relation to the use of oral contraceptives. Int J Can. 1981:28;669-671.
3. Ness RB, et al. Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid Hormones and Reproductions. Am J Epid. 2000;152(3):233-241.
4. Beral V, et al. Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study. BMJ. 1999 Jan 9;318(7176):96-100.
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