Report on the 8th European Congress on Menopause

Abstract

The 8th European Congress on Menopause (EMAS), held 16–19 May 2009 in London, UK, was organized by the European Menopause and Andropause Society and hosted by the British Menopause Society (BMS). The Congress invited speakers from a range of European countries as well as some from the USA, Ecuador, Chile, Australia and South Africa, and attracted 1470 participants from over 70 countries as far a field as the Americas and East Asia.

The overall theme of the congress ‘Securing a Healthy Future Today!’ expressed the concept that health is vital in an aging society and needs to be addressed at the time of the menopause, where there is converging evidence of a window of opportunity for safe and effective intervention in symptomatic women and those at risk of morbidity or unhealthy aging. The demographic fact that, in the very near future, the population of people over the age of 65 years and elderly will be supported by an unsustainable low number of working-age adults highlights the imperative of healthy aging. With an increasing life expectancy, most women in the developed world can expect to live more than a third of their life past the menopause, with the far-reaching consequences of hormone depletion on their aging bodies and quality of life.

The Congress featured strong presentations from eminent experts, including a range of stimulating keynote themes, debates and presentations. These also reflected the perception of the participants that whilst the evidence behind the recent scare stories in the press is unfounded, their impact on women and their physicians' response to the menopause remain a concern.

Keynote themes

Whole-life perspective on aging: insights from the British Birth Cohort

Geeta Mishra (University College London, Medical Research Council Unit for Lifelong Health and Ageing, London, UK) reported on the MRC National Survey of Health and Development study, an epidemiological study using a nationally representative sample of 2547 women. Her study investigated the age of menopause and the associations of various factors across the lifecourse. Analysis of annual questionnaires, completed by women between the ages of 47 and 54 years and at 57 years in 2003, described a negatively skewed frequency distribution curve for the age of menopause. Mishra suggested that the data was a better fit for a model with two overlapping normal distribution curves, reporting mean ages at menopause at 45.5 years (SD = 4.7) and 51.4 years (SD = 2.5), proposing the hypothesis of a biological or behavioral heterogeneity in menopausal age. Further analysis of this model found that women who weighed the least amount at 2 years of age, had childhood experience of parental divorce or whose mother had an earlier menopause were more strongly associated with having an earlier menopause. However, being breastfed, increasing cognitive ability and increasing parity were each significantly associated with delayed menopause uniformly across the whole sample. The speaker concluded that the determination of menopausal age was the result of an interaction of genetic and early-life environmental factors.

Making sense of risk

In his keynote lecture, Peter Van de Weijer (Geire Teaching Hospital, Apeldoorn, The Netherlands) noted that most clinical decisions are associated with some degree of scientific uncertainty regarding the benefit:risk ratio, and the clinical decision is further complicated by how the doctor and patient each value the magnitude of the benefit:risk ratio. “Much more weight is commonly attributed by patients to risk than to benefit, and high risk estimates will be made as a result of disproportionate visibility, such as substantial media coverage or personal experience.”

Risk is socially constructed and meaning varies amongst individuals; the dispersal of research data by the media tends to report relative risk as opposed to the equivalent but more relevant absolute risk. “Epidemiological research links a putative risk with a putative cause”, and the media reports such studies as suggesting a causal relationship that cannot in fact be demonstrated by such methodology.

Clinicians should estimate risk by assessing the quality of study design, the study population (e.g., the Women's Health Initiative [WHI] study included asymptomatic women who were generally older than those usually prescribed hormone-replacement therapy (HRT) for symptom relief), the time and duration of the study, the absolute risk rather than relative risk, and the cause–effect relationship. The Million Women Study, for example, was an epidemiological study and the perceived causality is unfounded.

Anne Gompel (University of Paris, France) and Richard Farmer (University College London, UK) argued the methodological short-comings of studies that purported increased breast cancer risk and the use of HRT, including those studies that referred to the decline in breast cancer incidence following the publication of the WHI study. The decline in breast cancer diagnosis started in 1998; 4 years prior to the publication of the WHI study, Gompel noted. She also commented that the time-lag between the observation of a “decrease in breast cancer incidence due to the promoter effect of HRT is very likely to be more than just a few months.” In another challenge to the data, Richard Farmer suggested that a causal relationship would also predict a previous rise in the incidence of breast cancer associated with the rise of HRT usage, but this has not been observed.

Making sense of sex hormones & dementia

Much of the evidence of a protective effect of HRT on dementia are contradictory, where observational studies have suggested that HRT is protective against Alzheimer's disease, later randomized, controlled trials have suggested that HRT is not protective. The criticisms that apply to the WHI Memory Study (WHIMS) are the use of a cross-sectional design with a wide age range, including a significantly large proportion of women who would not normally start HRT at that advanced age. In his keynote lecture, Declan Murphy (Kings College Hospital, London, UK) explored the influence of gonadal steroids on neuronal growth, neural plasticity and patterns of neuransmitters synthesis and release. Data was presented on the positive association of HRT with improved visual and verbal memory and findings that women who have bilateral oopherectomy when young are at significant risk of Alzheimer's disease. Ovarian suppression with gonadotropin-releasing hormone analogs resulted in a significant reduction in cognitive function, which was restored after the restitution of estrogen. He concluded that differences in brain function during the menstrual cycle were related to estrogen levels.

Murphy postulated a critical period (or ‘window of opportunity’) when “HRT may help to protect against Alzheimer's disease – if initiated early in the menopause.”

Aging with health & dignity

The demographic reality of this century is that 21% of those living in Europe are over 60 years of age, and by 2050 each person over 65 years of age will be supported by only two working-age adults (aged 15–64 years). With this in mind, Bruno Lunenfeld (Bar-Ilan University, Ramat Gan, Israel) introduced in his keynote lecture the important concepts of life expectancy and health expectancy. The increase in life expectancy was not matched with a rise in health expectancy and women suffer more morbidity whilst men die earlier. This increases the burden on national healthcare systems; at present, five out of six people aged in their 60s have one or more diseases.

Strategies aimed at decreasing, delaying or preventing some illnesses are being developed, and preventative strategies by optimizing lifestyles have been promoted widely in many regions. Lunenfeld concluded that while these efforts should increase health expectancy, a better understanding of healthy aging, aimed at improving quality of life, will necessitate “a quantum leap in multidisciplinary and internationally coordinated research efforts, supported by new and fair partnerships between industry and governments, philanthropic and international organisations.”

FRAX®: the WHO risk calculator for fracture risk

As risk of fracture varies worldwide, models are available for several countries in Europe, as well as China and the USA. John Kanis (University of Sheffield Medical School, WHO collaborating centre for Metabolic Bone Diseases, Sheffield, UK) acknowledged that the setting of intervention thresholds are a matter for national consideration and guidance; these are currently being developed to determine thresholds for both treatment and assessment for BMD in the UK, Europe, Japan and the USA.

Kanis presented the FRAX® Risk Calculator for Fracture Risk that provides a 10-year probability of fracture in light of the present method of assessment for fracture risk, based on the definition of osteoporosis by bone density measures (BMD). The FRAX calculator incorporates readily used risk factors that are independent of BMD. These risk factors have been identified and validated by the WHO Collaborating Centre and include age, previous fragility fractures, a family history of hip fracture, rheumatoid arthritis, smoking, exercise, alcohol and the use of glucocorticoids. The combined use of these factors “with (or without) BMD enhances the sensitivity to detect fracture risk without sacrificing specificity.”

Debates

The European Congress on Menopause (EMAS) adopted debate themes that contrasted available evidence on three main topics: the role of HRT in reducing cardiovascular risks in postmenopausal women, whether progesterone and progestins are much the same agents and whether long-term prevention of osteoporosis starting at the menopause is preferable to later targeting of women at high fracture risk. These sessions proved very popular and thoroughly informative.

HRT has a place in reducing cardiovascular risk

Malcolm Whitehead (King's College, London, UK) argued that there was overwhelming evidence for the use of HRT in reducing cardiovascular risk. He highlighted that the published evidence of an increased risk was marginal and was associated with the preliminary findings of the WHI study where they initiated HRT in women up to 20 years past their menopause using a conjugated equine estrogen at higher doses than are usually prescribed.

Later analyses of the WHI study data in women aged 50–59 years demonstrated that there was a 40% reduction in risk when HRT (estrogen and progestrogen) was initiated within 10 years of the menopause, with an increasing risk with age. The use of estrogen-only HRT demonstrated a 60% reduction in risk of cardiovascular events. Whitehead also highlighted that there were high cardiovascular risks with smoking, hypertension, diabetes, raised cholesterol and obesity.

Sven Skouby (University of Copenhagen, Denmark) argued that there was no evidence that HRT had a significant effect on coronary heart disease prevention. However, he suggested that HRT could be given to women around the time of menopause without risk, based on meta-analysis evidence of a significant effect when younger women were compared with older women.

Skouby also highlighted that the WHI study was limited in its methodology, but had informed practicing physicians not to treat with HRT to prevent heart disease. He described it as a narrow study in terms of type and dosage of HRT and timing of its effects, whilst using a wide age range, with results that were not statistically significant. In addition, the apparent adverse effect was due to an unexpected drop in risk in the placebo group rather than a significant rise in the treatment groups.

He also highlighted that there is evidence of an overall benefit of HRT use initiated within 10 years of the onset of menopause, and in direct contrast with the effect that the WHI study had on practices, the self-use of HRT in obstetrics and gynecology professionals is at pre-WHI study levels. However, with regard to the motion, he found the data poor and insufficient to support the use of HRT to reduce cardiovascular risk.

The vote was near unanimous in supporting the motion that HRT has a place in reducing cardiovascular risk.

Progestin or progesterone: there is no real difference

Martina Doren (Charite-Universitatsmedizin Berlin, Germany) defined the role of progestogen (including natural progesterone and any synthetic progestin) in women using HRT as protecting the endometrium from estrogen stimulation and the risk of hyperplasia and adenocarcinoma. However, she cited evidence from large, randomized, controlled trials suggesting that the effects of the addition of progestin to HRT increases the relative risk of breast cancer, and said it was unknown whether all progestogens have the same potency of risk increase since there is varying quality of evidence regarding the present day available range of progestogens.

Joelle Desreux's (Centre Hospitalier Universitaire de Liege, Senology, Liege, Belgium) argued that there is a real difference between progesterone and progestins. Although there is a lack of comparative studies between progestins and progesterone, three observational studies have demonstrated no excess of breast cancer risk in users of estrogen with progesterone. She argued that progesterone, unlike most progestins, does not oppose the benefits of estrogens on the cardiovascular system, especially in the long term, and when administered near the onset of the menopause.

The vote was against the motion and near unanimous that it had been demonstrated that there was a difference between progesterone and progestins.

Long-term prevention of osteoporosis starting at the menopause is preferable to later targeting of women at high fracture risk

Claus Christianson (Nordic Bioscience, A/S Herlev, Denmark) spoke for the motion, indicating that in postmenopause, “osteoporosis is a net result of increased bone resorption that is not adequately balanced by bone formation, leading to increased bone fragility and eventually fractures”, and that estrogen replacement restores premenopausal state of bone turnover. He cited data on women treated with a 2-year course of HRT at the age of 50 years that resulted in an 8% rise in BMD and a 15% drop in fractures. In these women, he also observed a decline in arthritis and improved cognitive function. Although after stopping treatment BMD is lost at the same rate as before treatment, the drop in fractures remains for life. He added that despite an increasing range of intervention options of antiresorptive treatments, including bisphosphonates, strontium ranelate, selective estrogen-receptor modulators and calcitonin, HRT achieved the best results. He also cautioned that these alternatives were also not without risks (e.g., bisphosphonates have a half-life of 12 years, suppress the resorption process with as yet unknown long-term consequences, and are associated with necrosis of the jaw, atrial fibulation, nephrotic syndrome and musculoskeletal pain). Christianson concluded that when started at the time of the menopause, HRT slows down the resorption process and that “the extraskeletal effects of each intervention need to be carefully considered when evaluating the treatment options.”

Julie Compston (University of Cambridge School of Clinical Medicine, Cambridge, UK) spoke against the long-term prevention of osteoporosis. First, she argued that HRT usage for up to 5–7 years is effective in reducing fractures, but there is no persisting benefit and it needs to be continued life-long. She listed a number of points: that unless prevention is targeted at those at high risk of fracture then it is not cost effective; risks of side effects associated with long-term use may not outweigh the benefits in women without high risk; and that long-term suppression of bone turnover may lead to fragility fractures. No vote was taken.

A later presentation by John Stevenson (Imperial College, London, UK) highlighted the accumulating evidence of low trauma transverse femoral fractures related to the long-term use of bisphosphonates, as well as the other documented adverse effects previously mentioned.

Other themes covered

Complementary & alternative medicines

Edzard Ernst (Peninsula Medical School, Universities of Exeter and Plymouth, UK) acknowledged, “Alternative and complementary therapies are an attractive option for many women,” and commented that 45% use complementary and alternative medicines, and only 45% of users mentioned it to their physicians.

He found that complementary and alternative medicines was largely under-researched, but reviewed the evidence from good quality research studies and found that “there is (in some cases) encouraging but not convincing” evidence that they are effective, and that “all are associated with direct and indirect risks”, including interactions with conventional medicine and other complementary and alternative medicines.

He concluded, “Currently, we know too little about their efficacy and safety to make positive recommendations for their routine usage. It follows that more research is required in this area and adequate funds are needed to conduct it.”

Sexuality & the menopause transition

The topic of Female Sexual Dysfunction (FSD) was introduced in the official precongress course on: ‘FSD in the Office: Tool to Meet the Challenge’ [1]. This half-day course was run by pre-eminent European experts on FSD, on all aspects of FSD. An important message was that, contrary to perceived wisdom, “testosterone is a female hormone” that is depleted in women who undergo surgical menopause, leaving them with depression, low energy levels, low libido and loss of pubic hair, as well as symptoms associated with estrogen depletion.

Summary

The 8th EMAS Congress in London, UK, represented a turning point in elucidating the real benefits of postmenopausal HRT that have been documented in literature over the last 3 decades. It was successful in conveying to the delegates the uncritical analyses within the WHI studies and the Million Women Study, which had instilled exaggerated concerns and dissuaded women as well as their doctors from using well-suited hormonal medications that would have effectively cured symptoms of estrogen deficiency and improved their quality of life. These messages have to be disseminated to all doctors interested in women's health to enable them once again to provide individualized advice and treatment.