When talking about sex- and gender specific aspects of health, disease prevention and health care, a lot of work is still to be done. What is needed to get available knowledge into health care practice, for instance into treatment protocols? Who needs to do what to make that happen? And what are important knowledge gaps that need to be addressed in health research?
‘The whole system needs to move. From the person developing guidelines to the patient. And this is not just a women’s issue. Men benefit from sex and gender sensitive health care too.’ - Cara Tannenbaum
On October 6th, 2017 the Gender and Health Knowledge program organised a symposium at ZonMw in The Hague. Approximately 50 experts and stakeholders discussed a possible roadmap for implementation of sex- and gender specific knowledge into practice.
The day started with an introduction by Radjesh Manna. Based on the research cycle and the quality cycle in the health field he explained the purpose of the day: how does new knowledge from research get into medical practice?
To effectively disseminate relevant knowledge on sex and gender to the knowledge users, level one evidence is indispensable. But at the same time it is very useful to inform patients – in particular female patients – on this topic, so they can ask their doctor about it themselves. At the end of the day the conversation has to happen in the interaction between doctor and patient. What we need are sex- and gender sensitive education, and the inclusion of sex and gender specific knowledge in medical guidelines. It is very relevant to embed sex and gender in the GRADE-guidelines for medical guideline developers. Panel member Debby Keuken wholeheartedly agrees with this last point: ‘Hard scientific proof to underpin medical guidelines are extremely important in convincing medical specialists and general practitioners. Only when the evidence is convincing enough will it really work.’
‘As a doctor in internal medicine, I also treat a lot of women. Questions for research that can improve daily practice at the point of care continuously pop up. Daily practice is where you can literally make a difference.’
With this statement Cara Tannenbaum opens the second symposium Gender and Health, which focuses on effective knowledge dissemination into health care practice.
One slide introduces Jane and Phillip. Tannenbaum challenges the crowd: if they walked into your doctor’s office, would you treat these 2 patients differently? Let’s be honest: both patients would probably end up receiving the same treatment.
‘The more you know about sex differences, the more questions arise.’ - Jeanine Roeters van Lennep
Of course we all know men and women differ in profound ways. And that they can, for instance, react to medication differently. We know hormonal differences and differences in fat distribution have a big influence on how medication is metabolized in the body. But at the point of care we don’t use this knowledge nearly enough, Tannenbaum establishes. Only on rare occasions do overwhelmingly clear differences lead to sex specific advice. For example the warning on the Canadian packaging of sleeping drug Zolpidem. Eight hours after intake, this drug is still so active in many women that it is dangerous to drive a car in the morning.
Tannenbaum illustrates her discourse with more impressive examples. One thing is clear: a lot still needs to be done. According to her, part of the solution is a change in the research publication guidelines through initiatives like SAGER guidelines of the European Association of Science Editors (EASE). Mandatory reporting on sex and gender differences in research publications will lead to new knowledge that could subsequently resonate in daily medical practice.
But even if sex and gender sensitive publishing is reality, this will not automatically lead to change. Tannenbaum refers to a Dutch research article with suggestions for guideline developers to take sex and gender into account. ‘I was curious to see if Canada had taken the advice of the Dutch. A systematic review revealed 2 out of 3 guideline developers had taken the Dutch advice on board. A third of those had even translated the suggestions to sex specific treatment advice.’ We are not there yet, concludes Tannenbaum, but we can see movement on this issue. ‘Let’s keep working together to further accelerate the movement.’
‘Doctors prefer not making a difference between people. They see all their patients as equal. So it’s a tricky message to say that it can be better to treat people differently.’ - Yvonne Dabekausen
This observation of Jeanine Roeters van Lennep illustrates the big challenges faced by clinical practice in responding to differences between men and women.
So research into sex and gender differences is not finished by far. A thought-provoking statement in 1 of 3 short presentations on real-world examples from daily medical practice.
The classic notion of a heart attack is a man desperately clutching his chest. And that’s where it immediately fails, says Jeanine Roeters van Lennep, vascular internist at Erasmus MC. A woman suffering a heart attack often doesn’t feel it in her chest. Large differences exist between men and women in cardiovascular disease, and risk factors can work out differently too. As a vascular specialist Roeters van Lennep sees there’s a lot of knowledge about the heart, but a lot less is known about the vasculature. While women in particular are at greater risk for brain hemorrhages, for example. ‘We shouldn’t just talk about the heart, but about the vasculature as well. Adequately addressing sex and gender requires a broader view.’
Women with rheumatic disease are not that lucky. Not so much because the disease has less impact in men, but because a gap in knowledge means treatment of the disease in women is suboptimal. Irene van der Horst, rheumatologist at VUmc, sees it in her medical practice every day. Especially in rheumatic diseases that are more prevalent in men, such as Bechterew’s disease, women are even less well off. Which means there are insufficient leads to make treatment options sex specific. What helps? Asking pharmaceutical companies to reanalyze their existing data, focusing on sex differences. This way ‘old’ data can lead to new insights, according to Van der Horst.
An important responsibility for regulators when assessing drugs for licencing is to consider what needs to be included in the label (SmPC), according to Christine Gispen of the Medicines Evaluation Board (CBG). The question that continuously needs to be asked therefore, is if the right information is available on relevant differences that need to be included. Should the label contain warnings for specific groups within the population, for instance? ‘The next question is of course evident: what are relevant differences? There are no clear rules on this. Small genetic differences between men and women are currently often not included in the product information. If that is the right choice, should be openly discussed with all stakeholders involved.’
Obstetricians and gynaecologists are ideal ambassadors for sex and gender specific health care. They work with sex and gender issues on a daily basis. When it comes to knowledge dissemination, professional societies such as the Society of Obstetricians and Gynaecologists of Canada play a pivotal role.
Jocelynn Cook, chief scientific officer of the Society of Obstetricians and Gynaecologists of Canada, makes a case for specific focus on sex and gender in health. ‘We speak the language, we know the issues, we know what works. And we have the passion to talk about it.’
For effective implementation, according to Cook, it is not enough to say: here’s the evidence, good luck with using it for your patients. You need to take that extra step with scientific evidence. Cook: ‘So: here’s the evidence, and this is why it matters to you. To the doctor, the patient and the decision maker. We need to make people understand why certain evidence is important.’ And it is exactly that which professional societies can do like no other, notes Cook. The connect science with practice. And they can influence other organizations, policy makers and the media.
This influencing can take many shapes, varying from offering refresher training for professionals to advocating the issue through social media. Health care professionals, researchers and pharmaceutical companies can discuss relevant issues together at networking events. But also think for example about creating a loop with thought-provoking statements to show between two presentations at a congress. Practical tips for inclusive language in the doctor’s office also work well. Cook gives an example from gynaecology practice. Don’t ask: ‘Will your husband join you at the ultrasound?’ But instead: ‘Will your birthing partner join you?’
Students are invaluable allies in effective communication, according to Cook. They know best how to work with modern communication methods and social media. And they know how to tell a story that truly resonates with other future professionals and researchers. ‘The traditional platforms – the scientific journals – remain important for the dissemination of knowledge. But include the general public at the same time, so people will start asking their doctors for more information.’ Be creative in conveying your message, concludes Cook. As an example she refers to a public campaign created by her organization, that reached many women: an HPV ad at the movie theatre, right before the movie Fifty Shades of Grey.
‘The professional societies are there to get new scientific knowledge into practice. That’s how they accelerate the turnover of knowledge, but it can’t be done without data.’ - Evert-Jan de Kruijf
In subgroups, participants talked about knowledge dissemination and utilization on the basis of funded projects of the Gender and Health Knowledge Program. What is needed to better implement sex and gender specific knowledge in medical practice? Who can do what? And what knowledge is lacking that could speed up the implementation process? A panel of 3 subsequently reflects on the discussion points coming out of the subgroup discussions.
‘Show that it is clinically relevant. The importance of paying attention to sex and gender needs to move away from being an opinion.’
There are many knowledge gaps when it comes to drugs and pregnancy, one of the reasons being it is hard to include pregnant women in drug trials. It is of course also an ethical question if you can expose pregnant women to drugs that have not yet been approved for market. Nevertheless, it is important to create awareness for good quality data. For example with the help of the network of gynaecologists and through patient groups. Furthermore we can do more with existing data through public-private partnerships with pharmaceutical companies. Dick de Vries of Janssen Biologics: ‘Data from our research is available through the Yoda project at Yale. Researchers can ask for datasets there for further analysis. But we should realise that there are big statistical challenges to distill relevant knowledge on drug use during pregnancy from this.’
In rheumatic diseases the picture is varied. There are many different rheumatic diseases and it matters at what stage of the disease the patient is. For meaningful implementation of sex specific knowledge, we need more data. This implies we also need to invest in clinical trials more to obtain more specific data, as well as reanalyze existing data for sex specific outcomes. The question is: who pays for this? We need to lobby more for including attention to sex and gender in trials, as well as in basic science. However, it is not only on researchers, but also on health care professionals and patients. Panel member Evert-Jan de Kruijff also sees a role for the knowledge institute of the Federation Medical Specialists. We need more data, he says. ‘In rheumatic diseases this is even more urgent that with some other diseases.’
Sex and gender is not a very sexy topic. This is reflected in the academic world, where only a fraction of published articles report on sex and gender. But it is also reflected in medical practice. A spectacular new technique for angioplasty will get much more attention than a new treatment option that differentiates between men and women. It is therefore also a question of culture, and to influence that you need behavioural specialists. Plus Gender Champions, as advocated by Cara Tannenbaum. In this group a prime candidate for this role has been identified: Hans Bosker, vice-chair of the Dutch Society for Cardiology. Panel member Evert-Jan de Kruijff underlines the importance of gender champions, but stresses that evidence is even more important. ‘Show that it is clinically relevant. The importance of paying attention to sex and gender needs to move away from being an opinion.’
‘Hard scientific proof to underpin medical guidelines are extremely important in convincing medical specialists and general practitioners. Only when the evidence is convincing enough will it really work.’
‘In rheumatic diseases this is even more urgent that with some other diseases.’
‘We should realise that there are big statistical challenges to distill relevant knowledge on drug use during pregnancy from this.’
The recently founded Dutch Society for Gender and Health (NVG&G) offers researchers a platform for the exchange and deepen their scientific endeavours in sex and gender specific health issues. The NVG&G aims to promote a sex and gender specific approach to health research, education and health practice. See genderengezondheid.nl for more information.
ZonMw stimuleert gezondheidsonderzoek en zorginnovatie. ZonMw financiert gezondheidsonderzoek en stimuleert het gebruik van de ontwikkelde kennis - om daarmee de zorg en gezondheid te verbeteren. ZonMw heeft als hoofdopdrachtgevers het ministerie van VWS en NWO.
Colofon Tekst Marc van Bijsterveldt, Fotografie Sannaz Moghaddam