Learn from the past: Protect the future

It is wonderful to see awareness and interest in menopause and treatment options at a high level, and to once again see more investment and research taking place. At the fantastic BMS annual scientific conference 2024, we were delighted by the buzz, the energy and enthusiasm of a whole new generation or two, or three! However, we were also reminded of the huge amount of research and progress in menopause care more than 20 years ago, which should not be forgotten.

Let’s start with the route of HRT. Recent trends have been to preferentially recommend transdermal HRT, often with complex regimens. We often hear comments such as: “it has all changed”, “newer types of HRT are safer”, “there wouldn’t have been many HRT options in the past”, “we shouldn’t use old-fashioned HRT”…. The superb lecture at our recent congress by Professor John Stevenson and Professor Peter Collins, “Arterial disease matters: HRT before, during and beyond an arterial event”, explained findings of research carried out in the 1990s, demonstrating the overall benefits of HRT in reducing cardiovascular disease, when started during the “window of opportunity” in the early years of menopause. While we did previously have access to transdermal preparations (patches gel, a nasal spray and systemic estrogen from a vaginal ring), in fact more options than we have now, much research using oral HRT demonstrated clear benefits. NICE guidance from 2015 weighed the evidence and advised us that overall transdermal HRT is preferred, especially when taking HRT with established cardiovascular and thromboembolic disease. There is definitely a place for all preparations, but let’s not forget the simple tablet which many women take and are happy to continue!

More than 20 years ago we were also very aware of the association of HRT and a small increased risk of breast cancer, which was considered duration dependant and not route dependant, but agreed that for most women, HRT, when used appropriately, provided more benefits than risks. This knowledge was behind many of the risk-benefit discussions we would have had. So, the current confidence in the use of HRT is not a new position, we just have better data and of course improved tools to aid decision making. But a massive impact on our discussions in the early 2000s was the downturn in confidence that accompanied the publication of several high-profile studies. It has widely been stated that what followed was a decade of harm to confidence in HRT as a treatment option. However, for those of us involved in frontline menopause care we saw many women denied access to basic care in menopause, whether this involved HRT or not. So many suffered the symptoms of menopause, untreated and unsupported and of course missed out on many of the preventative benefits of a fully holistic approach to menopause and the opportunity to consider the full range of options available to them at that time.

If we wind the clock back further to the 1970s and 1980s, there are numerous publications from authors, some of whom are past chairs of the BMS, that show clearly the effects of exogenous estrogen on the endometrium if given unopposed, and the endometrial response to various doses of progestogens of varying types. The evidence, duplicated numerous times over the years and covered in several key systematic reviews, demonstrates that progestogens, when given in the correct dose alongside estrogen, prevent hyperplasia and ultimately cancer of the endometrium. During the 1990s, many drug companies developed different mixed preparations of estrogen and progestogen, and to get a licence from the MHRA or FDA, endometrial safety had to be clearly demonstrated as part of the research in the development of these preparations. Without this research, we just wouldn’t have available to us the many preparations that exist today.

So, are we learning? Well, of course, we are. As editors of this journal, we have worked through most of these times (perhaps not the 1970s!) and speak from experience. The 2015 NICE guidance was as groundbreaking as some of those original studies as it brought together the evidence around management of the menopause and also presented the risk/benefit evidence around HRT in a way that has been so useful to all of us in clinics for the past nearly 10 years.

The resurgence of interest and awareness in menopause is undoubtedly a good thing and the attendance figures at the BMS conference, and the expansion of our membership is a wonderful demonstration of how the BMS has been at the centre of all of this. Further, the thirst for education is fantastic, and the BMS has expanded its educational offering to improve access to knowledge and evidence to support your practice.

Whilst we hesitate to end on words of caution, we think that from a patient safety perspective it is our duty to do so. Firstly, we now live in an age with the most amazing communication tools. These tools will have helped to raise awareness amongst both women and clinicians, and many of you reading this will have contributed to this. The world of social media contains lots of great facts, tools and information. It is, as we have written before, also full of myths and misinformation, and sometimes this is presented as fact. The world of menopause is no exception, and it is important that as we come across such opinions and statements that are not supported by the evidence, we call that out. In fact, it is our duty as clinicians to make sure that this is done. This is an area that tests even the most eloquent of communicators at times!

Secondly, we live in a world where we can adjust HRT in a way that is totally unique to that woman. We use blood tests, we add in testosterone, we sometimes use novel routes such as vaginal administration of progesterone. Every time we do such a thing, we have to be aware that the reassurance that comes from all the research that pharmaceutical companies had to do to ensure safety of HRT combinations, may not exist. We have all seen a massive increase in referrals to secondary care because of abnormal bleeding on HRT, not only adding strain to services but causing concern and discomfort for numerous women, yet we know that abnormal bleeding is less likely with oral combined HRT than transdermal, and less likely with standardised, tested regimens rather than separating estrogen and progestogen which may not be in proportion. So again, it is our duty to carefully explain to patients why an unlicensed combination may or may not help them, the potential risks, and also put in appropriate safety netting and mitigations.

Scientific evidence is a wonderful thing. We hope you can see the evidence for HRT in the management of the menopause has been building for about 7 decades. Every study, good or bad, has contributed in some way to where we are now. It is our responsibility to ensure that lessons from the past are learned. Our final observation is that if we, as a collective group, are not careful with how we prescribe HRT today this could result in our collective actions severely harming the reputation of HRT as part of menopause management once more. Not only would we not have learned from the past but we would have contributed to all the potential harms to women from the denial of access to menopause care that could so easily follow. No-one wants history to repeat itself in this way again.