HRT in the early menopause:

scientific evidence and common perceptions

International Menopause Society

Summary of the First IMS Global Summit on menopause-related issues

March 29-30, 2008

A. Pines, D. W. Sturdee, M. H. Birkhäuser, T. de Villiers, F. Naftolin, A. Gompel, R. Farmer, D. Barlow, D. Tan, P. Maki, R. Lobo and H. Hodis, et al. on behalf of the International Menopause Society 

(Reproduced with permission from IMS


Hormone replacement therapy (HRT) remains the first-line and most effective treatment for menopausal symptoms. But, despite massive, good-quality clinical outcome data on efficacy and safety when HRT is begun for symptoms in the early postmenopause, many physicians and lay people believe that hormones are risky and undesired even in the most appropriate case scenarios. Many misconceptions and misperceptions play roles in this complicated situation: some are purely scientific, others are cultural or social. The importance of the media and internet as effective, but unmonitored, means for dissemination of information, interpretation and recommendations cannot be ignored. Actual scientific facts and data have become trivialized in the mass media, often receiving less editorial scrutiny than normal journalism. Furthermore, many HRT prescribers and users do not attempt to broaden their knowledge on menopause and its treatment beyond capturing headlines or short commentaries, often produced by unqualified or prejudiced sources or unprofessional people.

As a result, a gap has formed between the actual clinical evidence and the way it is perceived by all concerned.

The results of the Women's Health Initiative (WHI), a very large, government-sponsored study of hormone treatment regardless of indications (in contradistinction to normal practice that is based on clinical symptoms and signs), were prematurely released before the study was completed and before the results could be properly evaluated. As a result, the results were over-interpreted and negatively slanted. It was viewed as a negative study by its investigators and failed to emphasize the data, which pointed at the vast importance of age and time since menopause as major determinants of the benefit-risk equilibrium of HRT and the many benefits from timely employment of HRT. This was a catalyst for negative sentiments toward HRT. By the time that more detailed analyses from the WHI study could be published in the past 2 years, much ground was lost for all concerned and much remains to be set right for patients and caregivers, alike. At present, it is clear that the WHI showed that properly timed HRT is safe for healthy women in their early postmenopause and has major preventative effects against fractures. It reduces mortality and this may be, in large part, due to prevention of heart disease.

The premature evaluation of the WHI includes statements and warnings from many health authorities, such as the US Preventive Services Task Force (USPSTF) and the European Agency for the Evaluation of Medicinal Products (EMEA) that sent a message that still prevails: the use of HRT is dangerous and therefore should be avoided, unless there is a substantial reduction in quality of life because of menopausal symptoms, in which case treatment should be given for the shortest possible duration. This seems untenable in light of the presently available data, the opinion of skilled and experienced health professionals, and even some of the WHI investigators themselves.

The aim of the International Menopause Society (IMS) in developing the Zürich Summit was to openly discuss and better understand the current situation in various areas of the globe. The knowledge and perspectives of scientists, consumers and the media were sought to recommend ways to narrow the gap between the evidence and its perception by health professionals and the lay public. The forum, which included experts from the various fields of menopause medicine and representatives of 40 national and regional menopause societies, agreed that the following summary of the scientific data will be addressed as the ‘Evidence'. Each statement will quote its scientific level of evidence, and a list of the corresponding references is attached at the end of the document. Level A evidence refers to data from

randomized controlled trials, whereas Level B evidence comes from case-control/observational studies. As pointed out in the Summit's title, the focus of discussions was the effects of HRT first administered during the early postmenopausal period.

Quality Of Life And Menopause

The perception of menopause and its impact on quality of life vary in different areas of the world1-5. In some places, menopause leads to a higher social status, in others - not. The forum agreed that the issue of quality of life is pivotal for any discussion on menopause management and the evaluation of the benefits versus the risks of HRT. Quality of life may be defined in many ways, based on medical, cultural and social parameters, but is largely subjective and therefore not easy to evaluate under a global, unified scale. Some may say that menopause is just a physiological stage during a woman's life cycle and therefore its associated adverse consequences of quality of life should not be medicalized. Others may argue that the risks of HRT do not justify its use unless quality of life is substantially compromised. The negative sentiments coming from the WHI publications and the related media coverage intimidate women and health-care providers and in a way lead to confusion and to a degraded credibility of the medical profession over these issues, but the WHI Quality of Life analysis started with only 11% of subjects who had moderate or severe hot flushes and did not have the power to determine a comparative improvement in the treatment vs. placebo group6. Such a low incidence of climacteric symptoms is not representative of the healthy peri- and early postmenopausal women treated in everyday practice.

Perceptions Vs. Scientific Data (The ‘Evidence')

HRT, coronary heart disease, stroke and thromboembolism


The evidence



The evidence



The evidence



The evidence

Actions to be Taken

The forum agreed that education and dissemination of the clinical data are crucial in the process of closing the gap between the scientific evidence on HRT and its

perception. Three main targets were identified: the health-care providers, the consumers and the journalists. The forum did not believe that actions should be taken vis-à-vis the regulatory/health authorities, since the chance of changing their opinion at this moment is slim. In order to avoid any debate over the ‘Evidence', it was based entirely on high-quality information, derived from randomized clinical trials whenever possible. Through presentations from each continent, it became quite clear that menopause symptoms and the incidence of illnesses associated with menopause or HRT may vary to a large extent in different parts of the world, as well as priorities in medical care. In addition, cultural and social attitudes may have a substantial impact, all affecting perceptions and decision-making in regard to menopause management and the use of hormones. Therefore, each regional/national menopause society should adapt the general framework according to its local situation and needs. The message to be delivered should be simple and clear, stressing the benefits of HRT and relieving fears according to the best quality clinical evidence. The most frequent misperceptions should therefore be identified and balanced by the corresponding data that were published in the medical literature. The above bullet points may serve as a template to be used locally by the societies.

Disclosure of Interest

The International Menopause Society was able to hold the Global Summit Meeting with the assistance of unrestricted educational grants received from three pharmaceutical companies: Wyeth Pharmaceuticals, Bayer Schering Pharma and Novo Nordisk Femcare. The industry had no influence on the choice of speakers, the content of the meeting, the discussions or the final statement. The signatories to the summary statement have no associations or financial links with any pharmaceutical company, but have received honoraria for lecturing at scientific meetings and research grants.


Quality of life

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HRT, coronary heart disease, stroke and thromboembolism

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Content Updated 30 March, 2008