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Excerpt
It is established that parity lowers the risk of developing epithelial ovarian cancer, and that the risk reduction associated with each pregnancy is greater than what would be expected based solely on the suppression of ovulation. 1 Oral-contraceptive (OC) use is also known to reduce the risk; it is uncertain, however, whether such protection is consistent with the amount of anovulation caused by these products. 1 Siskind et al2 recently examined this question. In their large and well-conducted case-control study, Siskind et al found that the magnitude of risk decrease for each year of OC use is 7% (95% CI = 4–9%), matched on age and adjusted for parity, smoking, hysterectomy, tubal ligation, and calculated lifetime number of ovulatory cycles. Because of the multivariate control of number of ovulatory cycles, the authors concluded that OCs have a protective influence on ovarian cancer beyond the anovulatory action. 2 While this conclusion could be true, it does not follow from their analysis at all, and in fact the statistical support for this conclusion from their data is low.
To compare the observed effect of OC use with what would be expected according to the duration of anovulation, it is required to compare the risk amount per year of OC use (7%) with the risk amount per year of ovulation. The latter value, while not published by Siskind et al,2 may be inferred from their data to be about 2%, based on the observed change in the effect of OC use with and without adjustment for number of ovulations and parity. Since their regression model containing lifetime number of ovulations also included additional terms for parity and OC use, the statistical information determining the 2% value comes essentially from age at menopause/diagnosis/interview less age at menarche. This variable is much less precisely related to risk than either parity or OC use. That is, its 95% confidence interval is wide and includes the 7%. Therefore, the risk reduction of 7% per year of OC use is consistent with the 2% per year of ovulation.
How large should the increase in risk be per year of ovulation? For most women, ovulations occur over at least 20 years. Thus, as we have observed, 1 the risk reduction for a year of anovulation should be no greater than 5% or so. This amount also is consistent with the 95% confidence interval (4–9%) of the 7% for each year of OC use. Thus, there are no grounds to conclude from the study of Siskind et al2 that OC use conveys a magnitude of protection beyond that from an equivalent duration of anovulation. On the other hand, contrary to the authors’ assertion, a full treatment of this question has been given by Risch et al,3 where the magnitude of protection per year of OC use (11.8%) differed from the effect per year of ovulation (2.9%).
