Hormone replacement therapy: to use or not to use?

In reply: We acknowledge that not all statisticians agree on the place of adjusted confidence intervals. However, we and others1,2 believe they represent a conservative choice for secondary endpoints in a study with multiple endpoints, such as the WHI trial.

Results of recent randomised controlled trials of hormone replacement therapy (HRT) and cardiovascular disease certainly support the notion that HRT confers no protection. However, any real harm of HRT must be questionable in light of the rapid review by Beral and colleagues, which, also using nominal confidence intervals, showed no change in relative risk for HRT users.3

We are surprised that, having emphasised the importance of nominal confidence intervals for primary endpoints, Coory did not mention that the breast cancer risk in the WHI report was not statistically significant using either nominal or adjusted CIs, or that the global index used was a non-validated instrument designed for and used only in the WHI study.4 Intention-to-treat analysis is used to avoid overestimates of both harm and benefit. While drop-in and drop-out rates (equal in both arms) may have led to underestimates of harm from HRT, they may also have led to underestimates of benefit, with no net change to risk–benefit assessment.

The aim of the WHI trial was to assess the benefit or otherwise of long-term HRT on disease processes in otherwise healthy women. There seems little doubt that in the group of older, overweight, somewhat hypertensive, women enrolled in this trial the use of HRT was not beneficial.

The aim of our article was to assess the case for and against HRT use.5 In reaching our conclusions, we drew on a broad range of published data, including, but not confined to, the WHI data. Our conclusions make it clear that we believe the use of HRT is primarily for short-term relief of symptoms during the menopause transition. However, we sought to defend the right of a small number of women to choose to continue HRT for long-term improvement of quality of life and symptom relief after appropriate, balanced, individualised counselling about the risks and benefits of such a decision.

We do not agree with Coory’s final comment. The thousands of Australian women who stopped taking HRT on learning the results of the WHI trial did so in fear and ignorance in an environment where their physicians were unable to offer balanced counsel — hardly a formula for good medicine.