There’s a lot to learn about how sex and gender play into disease manifestation and clinical care, says the editor-in-chief of The Lancet Rheumatology.
After September’s inaugural Sex and gender in rheumatology summit, we invited Dr Heather Van Epps to share some of her highlights and insights from the summit.
The first thing I’d say is it’s really difficult to pin-point highlights from the meeting – all of the speakers were really terrific and engaging!
One of the broad take-home messages of the Summit was around awareness, and promoting the importance of considering sex and gender – as well as other aspects of diversity – at all stages of clinical research.
I think there is already general consensus that sex and gender are important and impact clinical care and research in various ways, but meaningful action has been slow – whether from funding bodies, ethics boards, and regulators in terms of incorporating sex and gender into the design of research and clinical trials, to journals asking authors to be more transparent in their reporting of sex and gender in published papers.
This is starting to change, and I hope that the Summit helped to raise awareness that we need to do better in rheumatology. Real progress on this is going to require buy-in across all stakeholders involved in research design and conduct, as well as better engagement with patient populations that span the spectrum of diversity.
Another clear theme from the Summit was the need for more and better data to start to address these questions in a robust way – including in gender diverse populations that continue to be underrepresented in clinical studies. We can’t improve if we don’t know where we are now, so gathering high-quality data is a key starting point, not only for rheumatology but for all specialities.
One of the themes that really struck me during the Summit was around healthcare provision and differences that emerge when we start to think more carefully about sex and gender.
There was a fascinating presentation from Julia Simard (Stanford University, USA), who presented data from a diagnostic simulation study where they created a hypothetical clinical case of lupus that they presented to rheumatologists and asked them to make a diagnosis.
The key to this study was that all of the clinical details of the cases were identical apart from sex and race – there were four distinct ‘cases’ that varied based on the hypothetical patient being Black or White and male or female.
The results showed really clearly that when patients don’t fit into our view of the ‘classical’ presentation of disease (in this case, lupus disproportionately affects Black women), it has a real impact on both the speed and accuracy of diagnosis.
Why do patients with “non-textbook” disease presentation have worse outcomes? Julia Simard @RheumEpi @StanfordMed kicks off the #LancetSummitRheum session on #SLE with a fascinating talk on implicit bias. pic.twitter.com/ZyKPBGX6hP
— The Lancet Rheumatology (@TheLancetRheum) September 22, 2022
It shows us how our perceptions can have a meaningful impact on clinical care, and this is perhaps something we don’t think about enough.
We also saw examples of this in some of the other presentations; it’s clear, for example, that in populations in which a disease is much rarer (for example, axial spondyloarthritis in women or lupus in men), patients are often diagnosed later and with more severe disease. And among patients with inflammatory arthritis, women are prescribed anti-inflammatory drugs like NSAIDs and opioids more commonly than men.
There are undoubtedly many factors that play into such observations, and we need to do more to understand what drives these clinical differences.
From the standpoint of biology, there was a terrific talk from Owen Woodward (University of Maryland, USA) on the genetics of gout.
His research has shown really remarkable biological differences between males and females in the regulation of genes encoding urate transporter molecules in the kidney. The regulation of these genes is essentially opposite in males and females – when they challenged mice or human cells with a bolus of urate, genes that were turned on in females were turned off in males – really black and white differences.
The data provide a really clear biological basis for the differences in manifestations of gout in men and women and the predominance of the disease in males.
Which urate transporter is your favourite? Owen Woodward (@goutyprof) @woodward_lab @UMmedschool on sex differences in the biology of urate transport. #LancetSummitRheum pic.twitter.com/4ePmTsDZlO
— The Lancet Rheumatology (@TheLancetRheum) September 23, 2022
And although we don’t publish studies done in animal models in The Lancet Rheumatology, his talk was a great reminder of the importance of these models and of basic research for understanding clinical disease.
There is just so much that we don’t yet understand about how aspects of sex and gender play into disease manifestations, responses to treatment, and really all aspects of clinical care. And it means that there is a lot of exciting research to be done that will, hopefully, eventually translate into better and more inclusive patient care.
At this stage, we haven’t determined whether we will organise another Lancet Summit on the same theme, but I have no doubt that there will be plenty of advances in the coming years, so this is something we will discuss going forward.
We will also discuss the possibility of repeating our sex and gender ‘theme’ issue (see the October 2022 issue of The Lancet Rheumatology) on a yearly basis.
Dr Heather Van Epps is the founding Editor-in-Chief of The Lancet Rheumatology, co-chair of The Lancet Gender & Diversity Taskforce and a member of Elsevier’s Gender Equity Taskforce. You can still register to access content presented at the Summit.
