Yorkshire Menopause Group

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Position Statement by the International Menopause Society (IMS)
30 November 1999

Position Statement by the International Menopause Society (IMS)

Following the publication of the Million Women Study (MWS) and the combined arm of the WHI, in 2003, the IMS published a position statement on the use of HRT in the management of the menopause, in February of this year. The position statement has been reviewed, and amended, since the publication of the oestrogen only arm of the WHI which was terminated in March 2004. The full statement can be found in Climacteric and also on the IMS website at www.imsociety.org

The bullet points in the statement are summarised as follows;


- Recent reanalysis of the combined arm of WHI found a transient and unexplained fall in adverse events, in year five, in the placebo group, rather than a rise in the HRT group. The absolute differences were, however, so small that any conclusions drawn, from which clinical implications have been made, may be invalid.
- The unopposed arm of WHI was stopped early owing to a lack of proven cardioprotection and higher incidence of stroke, although those women taking oestrogen had a 23% lower incidence of new invasive breast cancers than those on placebo.
- Results from recent RCTs including WHI, HERS and ERAS may not be applicable, and should not be generalised to women who are unlike those tested. Symptomatic women in WHI were limited to only around 10% of the study population and the average ages of women in the above studies were 63, 67 and 65 years respectively. Few women were in the critical first years after menopause leaving many with higher indices of heart disease and risk factors at the outset, perhaps reflecting the longer period of oestrogen deficiency.
- The MWS reported that all types of HRT induce an increase in breast cancer risk from the first year of use. This strongly suggests that the surplus of breast cancers arose from observational bias and was not induced by the hormones.
- Crucial differences have been identified between the observational studies, which suggested a cardioprotective effect of HRT, and the RCTs which have so far not demonstrated a similar effect e.g.;
o HRT in observational studies was generally prescribed to symptomatic women under the age of 55 years. In the three RCTs 89% of women were over 55 when starting HRT.
o Older women in the RCTs were mainly past the point of being symptomatic, and therefore in an altered physiological state that could be related to differences in outcomes. This is consistent with the findings of the WHI and an age-dependent occurrence of VTE.
- Rather than being a primary prevention trial testing the cardioprotective effect of HRT, the WHI is a study of the effects of one particular regimen of HRT, on aging women, many of whom will have had sub-clinical vascular and cardiovascular disease at the time they entered the trial. This was not the case in the observational studies which showed a cardioprotective effect.
- The combined arm of WHI was tenfold underpowered to detect an early oestrogen cardioprotective effect of the magnitude reported by the Nurses Health Study. Nevertheless, analysis of women between 50 and 59 years in the oestrogen only arm found 3 fewer cases of CHD and only one extra case of VTE and 0.1 of stroke/10 000 women.
- At present the only valid studies of HRT for cardioprotection of women in the menopausal transition are the epidemiological and observational studies, that agree with lab and animal studies, in suggesting cardioprotection by oestrogen initiated during menopausal transition.


In summary;
- The possibility that HRT causes an increase in breast cancer is not clarified by either the WHI or MWS and remains to be resolved
- RCTs to date cannot indicate whether HRT started in menopausal transition is effective for primary prevention of CVD or other long-term consequences of sex steroid withdrawal..

GUIDELINES FOR HORMONE TREATMENT OF WOMEN IN THE MENOPAUSAL TRANSITION AND BEYOND.

In the light of the above points, these are the summarised guidelines proposed by the IMS Executive Committee;

- HRT is recommended, during the menopausal transition, for the relief of menopausal and urogenital symptoms, avoidance of bone-wasting and fractures, and atrophy of connective tissue and epithelia. Benefits to the CVS and nervous system seem likely but have yet to be confirmed.
- There are no new reasons to place mandatory limits on the length of HRT treatment, including arbitrary cessation of HRT in women who started HRT during menopausal transition and remain symptom-free whilst on treatment. Cessation of HRT may even be harmful in view of the accelerated rate of cardiovascular events after premature menopause and loss of cardioprotection after HRT is stopped.
- Annual patient counselling about current data on risks and benefits should be undertaken.
- Risks associated with HRT include a small absolute risk DVT with subsequent stroke and PE. The WHI adds further conflicting results in relation to breast cancer and reduction in the risk of colorectal cancer and bone fractures, including hip fracture.
- Hormone replacement will become increasingly important in the care of the aging population. In general;
o Prevention is better than cure, to include general lifestyle modification.
o There is no evidence that HRT is beneficial for existing heart disease or dementia, although treatment started during menopausal transition appears to protect against fractures and potentially heart disease and brain disease.
o The dose and regimen of HRT need to be individualised. Older and postmenopausal women tend to need lower doses.
o Apart from the benefit of avoiding the first pass effects in women with risk factors for VTE, the effects of the different routes of HRT remain an issue.
o Different types of HRT may have different metabolic effects.

o Progestogens are required only for endometrial protection. Direct genital delivery systems may have some advantages but this is not yet proven.
o Population studies may not be applicable to each individual but may be used as general guidance.

Climacteric 2004;7:333-7

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