The end of WISDOM
In this edition, Vickers and colleagues give details of this 15-year trial which was to involve 22 000 postmenopausal women being treated with placebo, estrogen alone or combined HRT for 10 years with 5 years of further follow-up, and say it is unlikely that there will ever be a long-term Level 1 trial of combined H RT.
Abstract
The Women’s International Study of long Duration Oestrogen after Menopause (WISDOM) was the world’s only remaining trial, and perhaps the last chance, to examine the long-term effects of combined hormone replacement therapy (HRT). It was arguably the world’s largest and longest randomized, placebo-controlled trial of any therapy. In this edition, Vickers and colleagues1 give details of this 15-year trial which was to involve 22 000 postmenopausal women being treated with placebo, estrogen alone or combined HRT for 10 years with 5 years of further follow-up. Further commentaries on the demise of WISDOM have been offered in this edition by Dr Beverley Lawton2 (WISDOM, New Zealand), Dr Paul Komesaroff3 (WISDOM, Melbourne) and in a letter from Dr James Fiorica4 who had no association with WISDOM and offers an independent view. WISDOM was designed to look at the ‘whole woman’ and all major morbidities and mortalities occurring during the trial. It included, in particular, measurements of quality of life, cognitive function and menopausal symptoms. It had the potential to recruit younger and healthier women than those recruited in the Women’s Health Initiative (WHI) and might have better investigated the still untested hypothesis that HRT may have a primary cardioprotective role in the early postmenopausal woman, by helping to prevent atherosclerosis. Secondary prevention studies do not support a role for the treatment of established atherosclerosis and HRT may even have an early adverse effect in these circumstances. The debate about whether many of the so-called ‘healthy’ women in the WHI study could have had established atherosclerosis will go on and on, but probably WHI is a mixed primary and secondary study in terms of the prevention of cardiovascular disease. Therefore, one cannot state that the data from WHI have shown that HRT is or is not cardioprotective in women treated from menopause. It is very important that all the data from WHI becomes freely available to allow analysis of where and when events occurred. Ideally, the data should be accessible on a website. The early cessation of the combined HRT arm of WHI after 5 years means that this arm of WHI was only a medium-term trial, and that, with the withdrawal of the major funding for WISDOM, it is unlikely that there will ever be a long-term Level 1 trial of combined HRT. It is important to note that the estrogen-only arm of WHI continues and will run to 8.5 years. This should give further valuable information. As the dust settles after the unfortunate media response to the WHI data, which caused fear and ill-advised responses in many HRT users, questions are being asked about the clinical and statistical relevance of the data from this trial. Such questions include: