Invited papers: putting risk into perspective

Abstract

The main focus in relation to the menopause over the last two or three years has been the issue of benefit and harm. Uncritical reading, and often inappropriate extrapolation, from the Women’s Health Initiative (WHI) and the Million Women Study (MWS), fuelled by the media and some of the licensing authorities, has led to many women losing the benefits of hormone replacement therapy (HRT). Prescribing figures in many countries, including the UK, have dropped sharply and are currently showing little sign of recovery. The dangers of responding to published research while it is still hot off the press are clear. This paper briefly reviews some of the more recent publications that may help us develop a perspective on how best to prescribe for the patients we see. Numerous experiments carried out by Clarkson’s team in North Carolina, using the macaque monkey as an animal model, have predicted much of what we have subsequently found in relation to the benefit and harm of HRT in women, and particularly the findings of the WHI.1 There clearly are distinctions, as the WHI has shown, between the initiation of HRT for the perimenopausal or early postmenopausal woman and its use for long-term health protection starting many years after the menopause.2,3 Further evidence has been provided from more detailed analysis of observational studies and trials. The MWS was widely criticized when it first published data on the association between HRT and breast cancer, in 2003. At the end of April 2005 the authors and others published findings on the association with different types of HRT, including tibolone.4,5 Progestogens have been added to HRT regimens for good reason but there is accumulating evidence that the combination of estrogen and progestogen is associated with a higher level of breast cancer risk than is associated with the use of estrogen alone. Some recent data also support the WHI finding that the risk of thrombosis may be higher with combined preparations.6 In order to gain the benefits of HRT with the minimum of risk, two main strategies are being developed by many clinicians: the use of systemic estrogen with intrauterine progestogen; and the use of lower doses of estrogen, in some cases in unopposed form.7 Good-quality trials of these strategies are urgently needed to guide our clinical practice.