False alarm: postmenopausal hormone therapy and ovarian cancer

In a follow-up study of 948,576 women, based on respective relative risk (RR) estimates of 1.23 and 1.20 for incident and fatal ovarian cancer among current users of postmenopausal hormone therapy (HT), the Million Women Study investigators have estimated that, since 1991, HT has resulted in 1300 additional cases and 1000 deaths.

The association was almost entirely confined to hysterectomized women, some of whom would not have been at risk because their ovaries had been removed; the findings in that group were uninterpretable. Among non-hysterectomized women, the RR was 1.12 and compatible with chance. The response rate to a follow-up questionnaire was only 64%, and HT-exposed women who developed ovarian cancer may selectively have responded. The risk of ovarian cancer was no longer increased once women stopped using HT - an effect that was pathologically and clinically incompatible with causation. Symptoms of as yet undiagnosed ovarian cancer may have 'caused' HT use, rather than the reverse. The histological classification of the tumors was not centrally adjudicated. A meta-analysis of nine studies of current HT use, for which the aggregated RR was 1.28, was acknowledged by the investigators to be defective.

Only the findings among non-hysterectomized women were to some limited extent interpretable and, among them, there was virtually no evidence to suggest that current HT use increases the risk of ovarian cancer. It follows that the estimated numbers of additional cases of incident and fatal ovarian cancer that were attributed to HT use were spurious, and arbitrary extrapolation back to 1991, which was many years before the Million Women Study, had no scientific rationale.