Tag Archive for: SGBA

Ensuring Medical Research Accounts for Sex and Gender: The MESSAGE Project

Authors: Marina Politis, The George Institute for Global Health UK and Newcastle University; Alice Witt, The George Institute for Global Health UK; Kate Womersley, The George Institute for Global Health UK, Imperial College London and NHS Lothian | Editors: Romina Garcia de leon, Janielle Richards (Blog Co-Coordinators) | Expert Reviewer: Dr. Liisa Galea

Published: December 13th, 2024

From the girl who doesn’t receive an ADHD diagnosis, but instead is labelled an anxious daydreamer, to the trans woman who faces dire outcomes following a heart attack and is not counted by clinical trials, to the man with depression who is less likely to reach out for help, neglecting sex and gender negatively harms us all. 

Why Sex and Gender Matter in Research

What springs to mind when asked about the factors influencing our health? Socioeconomic status, lifestyle factors such as smoking or alcohol use, and genetic risk are all variables that are ingrained in the public’s, clinicians’ and researchers’ consciousness as crucial considerations. Sex and gender, despite being fundamental to us all, remain neglected across medical research, with over five times more male than female cells and animals used in preclinical research and only 20% of participants being women in phase I clinical trials.

The MESSAGE Project 

Enter the MESSAGE (Medical Science Sex & Gender Equity) project, a UK initiative aiming to ensure that biomedical and healthcare researchers incorporate sex and gender considerations at every stage of their research project. Unlike sex and gender policies that have been designed and implemented by individual funders in the US and Canada, MESSAGE brings together the wider UK research sector – from government organizations to charitable funders to ensure change doesn’t happen in silos. 

As a sector, MESSAGE stakeholders have created a policy framework, designed as a template, that can be adopted as is or adapted based on the individual needs of research funders to enable tangible action across the research pipeline. Adoption of policies based on this framework will mean that any researcher applying for funding will need to state in their application how they plan to account for sex and gender dimensions.  This would bring sex and gender dimensions to the forefront of researchers’ thinking right from the outset of the study design. 

The Policy Lab Process

The MESSAGE project has been structured around four Policy Labs and consists of collaborative workshops which bring together diverse stakeholders to tackle the specific challenges related to integrating sex and gender considerations into research. The first Policy Lab focused on: articulating a vision for sex and gender policy change, emphasizing a lack of awareness about the relevance of sex and gender in medical research, recruitment challenges and the challenges surrounding inflammatory public and political discourse, for example inappropriately essentializing sex. Subsequent labs focused on refining the policy framework, implementation strategies and developing a five-year roadmap for sector-wide change.

The MESSAGE Policy Framework

The MESSAGE policy framework requires researchers to justify four key aspects to account for sex and gender: sex and/or gender characteristics, target distribution of participants in terms of sex/gender, strategies for recruitment and retention and the sex and/or gender distribution in secondary data from original datasets. Researchers must also detail any planned sex/gender disaggregated analyses or justify their absence. Researchers are not expected to have sample sizes powered for statistically significant results for each sex or gender group, but they should consider how sex and gender may impact study outcomes and report on these dimensions transparently. 

The policy also aims to address gaps in medical evidence regarding trans, non-binary, and intersex individuals, encouraging their inclusion and outlining recruitment strategies. Reporting data, even in small numbers, can facilitate meta-analyses and novel conclusions. 

International Collaboration & Global Standards

MESSAGE is not working in isolation, and is informed by a precedent of robust sex and gender policies set by other nations, notably the Canadian Institutes for Health Research (CIHR) (2010), the National Institute for Health (NIH) in the United States (2016) and countries in the European Union under Horizon (2016). 

These policies are not merely documents resigned to paper as recent evaluations demonstrate that sex and gender policies are a critical first step to enacting change. A 10-year evaluation of the effect of the CIHR policy on proposed studies for research funding found a four-fold increase in the number of studies accounting for sex, and a three-fold increase in studies accounting for gender. Even here, it is important to highlight that when analysis moved beyond mandatory boxes, which is where we may see tokenism, to published abstracts, only a small 2% mention sex or gender, with no huge increase in reporting of sex or gender in Canadian funded research and the same is true of NIH funding. Evidently, more work is needed in this space.

A Call to Action

All of us, whatever role we have in the research pipeline – bench scientist, trialist, statistician, person with lived experience, participant, clinician – can change the norms surrounding sex and gender considerations in our work. From funders, who can update funding application systems to reflect sex and gender principles to leaders in higher education who can reflect on the research culture they create and  embed sex and gender principles into curricula. Researchers can also critically review literature, interpret the research they read and incorporate sex and gender considerations into their own projects from initial methodology to final reporting.

As MESSAGE concludes its first project, the resulting policy framework sets a new standard for medical research, ensuring that sex and gender considerations are no longer an afterthought but a core component of scientific inquiry.

An Honest Look into Sex & Gender Health Research in Canada

Authors: Tori N.Stranges, MPK, B.Kin, PhD Student | Editors: Romina Garcia de leon, Shayda Swann  (Blog Coordinators) 

Published: May 19th, 2023

It is well understood that sex and gender impacts individual and population health across the lifespan. It is also well understood that marginalized and systemically oppressed groups including women—particularly women of color, Indigenous women, disabled women, and immigrant women, as well as members of the Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, Intersex, and Asexual (2S/LGBTQIA+) community—face health disparities when accessing health care in Canada. Differences exist in disease manifestation, diagnosis time, misdiagnosis, treatment efficacy, and progression of disease resulting in devastating health effects in these populations.

These disparities can be partially attributed to the lack of funding for women’s and 2S/LGBTQIA+ specific health. Studying sex and gender influences is only one step in understanding why health disparities exist across sex or gender. Gender identity and sexual orientation are also key considerations for health research from a health equity lens. The large knowledge gaps in the health of these populations has prompted the Canadian Institutes of Health Research (CIHR) to mandate the incorporation of sex and gender into research. First by recommending the inclusion of Sex and Gender-based Analysis (SGBA) in project proposals in 2010 and then by mandating the incorporation of SGBA into grant proposals in 2019.

A group of recent grads and current grad students (including Tori Stranges, Amanda Namchuk & Tallinn Splinter) were curious how these changes in SGBA resulted in increased mention of sex or gender in funded research proposals. With the leadership of Dr. Liisa Galea and the Women’s Health Research Cluster (WHRC), we searched the publicly available database of grant abstracts funded by CIHR. We analyzed the amount of funded research that mentioned sex or gender in the abstract as well as funded grant abstracts that mentioned either female-specific health research or research within the 2S/LGBTQIA+ community. 

In total, we reviewed 8,964 Project and Operating grant abstracts awarded from 2009-2020. We found that under 3% of research funded by CIHR explicitly mentioned SGBA, with 1.94% of grants mentioning sex, and 0.66% mentioning gender within their abstracts. As one of the goals of SGBA is to inform on health equity and understudied populations with respect to SGBA, we also found that 5.92% investigated female-specific outcomes, and 0.35% focused on the 2S/LGBTQIA+ community. 

So, what does this all really mean? Our findings suggest more work needs to be done to increase researcher utilization of SGBA as well as to advance health equity in research. It is important to highlight that much of the existing work in this field has unfortunately been focused on binary understandings of sex and gender. Looking beyond this narrow focus allows for a more nuanced understanding of complex issues that include multiple perspectives. Although our understanding of the need for, and recognition of, SGBA in research may be improving, it has yet to be translated into increased research focus and funding. The research community needs to acknowledge that for publications, clinical trials, and grant funding applications, SGBA has not been fully realized despite numerous attempts to support its integration.

So, where does this leave us? The hope of SGBA is that widespread adoption of its principles will result in an equitable future for health where female-specific health, 2S/LGBTQIA+ health, racialized, disabled and gendered experiences, and more are considered. Together we have the power to improve health and reduce disparities, one SGBA at a time.

 

Figure 1: An infographic depicting the change in percentage of grants and funding between 2009 and 2020 for awarded Canadian institutes of Health Research (CIHR) grants for the different categories. The change in percentage (%) of grants (A) and funding amount (B) in the years 2009 and 2020 that “omitted” mention of sex and gender in their grant abstracts or mentioned female-specific health, female-specific health not including cancer based grants, sex, gender, or 2S/LGBTQIA+ health. Reprinted with permission from Stranges et al. 2023

Key Takeaways:

  • The percentage of funded grants in which the abstracts mentioned sex or gender in health research remained largely unchanged from 2009 to 2020 with the largest increase of 1.57% for those mentioning sex.
  • Total funding amounts for grants that mentioned sex or gender in the abstract stagnated or declined from 2009 to 2020.
  • The percentage of funded grants in which the abstracts focusing on female-specific health did not change across 2009-2020, but the percentage of funding dollars increased by 3.47%.
  • The percentage of grants in which the abstracts mentioned 2S/LGBTQIA+-specific health more than tripled across 2009-2020 but remained less than 1% of all funded grants. 

 

Using the Power of Sex Differences in Research: What a difference 10 years Did Not Make

Authors: Rebecca Rechlin, BSc Behavioural Neuroscience; Tallinn Splinter, BSc Biology, University of British Columbia | Editors: Negin Nia, Romina Garcia de leon  (Blog Coordinators).

Published: August 26th, 2022.

Females have been overlooked in health research for decades, and despite 10 years of advancements and improvements in knowledge, this has still not changed significantly.  Historically, there has been a long-standing bias of using males predominantly in scientific research instead of females, and as male and female health differ, this has led to health disparities for both males and females. Biological differences between females and males exist in diseases, such as in disease progression, symptomatology, and drug efficacy in many neurological and physiological diseases.

The study of these sex differences is essential for the understanding and advancement of disease treatment and precision medicine. For example women have double the risk for adverse drug reactions compared to men, which may in part be due to incorrect dosing (for instance despite both men and women being recommended the same dose for acetaminophen, an active ingredient in Tylenol, women break down the drug 60% slower than men). The biomedical and clinical research community is beginning to make corrections for these inequalities by issuing mandates for including females in clinical trials (such as by the NIH in 1993), and frameworks from funding agencies to address sex and gender in upcoming research (CIHR: Sex and Gender based Analysis (SGBA)) in 2010, and NIH: Sex As a Biological Variable (SABV) in 2016), however, there is still a long way to go to reach equality. Despite these mandates and increased approving attitudes towards these policies, the literature shows very little improvement in the analysis or examination of any potential sex differences.

Our study aimed to investigate whether and how possible sex differences were being investigated in neuroscience and psychiatry research. We looked at over 3,000 neuroscience and psychiatry studies in 2009 and in 2019 to see whether researchers were including both sexes in their studies. We found that only 53% of these studies actually included both males and females, and only 16.5% of these used an equal number of males and females throughout their study. Of the papers that used both sexes only 6% actually analyzed sex as a discovery variable. We found that the majority (60%) of the papers that used both sexes did not do any analysis by sex. This is concerning, as this means that we will lose out on important scientific discoveries if researchers are failing to embrace the power of studying potential sex differences. 

 

Figure 1: An infographic depicting the change in percentages of total papers sampled reporting studies in 2009 and 2019 that used both sexes, a single sex, omitted sex, papers reporting studies that used an optimal design or analyses for the discovery of possible sex differences irrespective of discipline. Reprinted with permission from Rechlin et al. 2022

It is important to note that biology sex and gender are two different things, and neither one is binary. Sex refers to the biological and physiological attributes of females and males, whereas gender is a psychosocial construct that includes one’s gender identity, and the norms and expectations set out by society. In our analysis we focused on studies using males and females (or sex) in rodents, humans and in research using cell lines, but the study of gender differences is also important to study and examine in regards to disease and treatments.

However studying sex differences, while important is not the only path towards equitable findings and discoveries in both men and women’s health research. With that in mind we found that although 27% of all studies in 2019 were conducted in males, only 3% were in females only! That means there were 9x more studies in males than in females! This greater focus on male health likely contributes to the health disparity and contributes to the historical male bias in assuming females and males are the same. Single sex studies are still essential for the discovery of sex-specific diseases/conditions such as prostate cancer in males and cervical conditions in females. Females specific factors, such as pregnancy and menopause, contribute to health outcomes and disease risk. For example, depression has a higher prevalence in women than men, and the risk of depression is largely increased during perimenopause and during the postpartum period.

So what can we do to improve these disparities? For starters, researchers need to actually analyze their data by using sex as a factor (or discovery variable). This essentially means including sex as one of the independent variables of the study (and not just controlling for it), allowing for the discovery of potential sex differences. It is also important for researchers to use a balanced and consistent study design, meaning they need to use both males and females consistently and in relatively equal numbers throughout their study. And even if they don’t find any sex differences, then the paper should make that statement with supporting statistics and a table to show the means and variation of the dependent variables by sex. This information of no sex differences is just as important as the discovery of them.

For funding agencies, one solution is to have funding dedicated specifically for SABV and SGBA proposals and not as a supplement to regular funding. More training modules from funders or scholarly organizations with an SABV focus may help, however, enticing researchers to explore the influence of sex and gender in their data may be a more fruitful approach. If journals, especially those with higher visibility, adopt calls for papers using sex and gender-based analyses this may serve as a catalyst to ensure more researchers consider possible sex differences and further promote the notion that this research is important to publish. Since we published our paper – Nature journals have committed to ensuring sex and gender are considered in their study design, by requiring authors to state how and why sex/gender was considered, or to state why it was not. If implemented as intended, this is a good first step to increase the amount of studies considering sex and gender in their analysis, and may be a great leap towards fixing these health disparities. 

 

The Gut-Brain Connection: Why Biological Sex May Matter

Author: Avril Metcalfe-Roach, PhD student, University of British Columbia | Editors: Negin Nia and Arrthy Thayaparan (Blog Coordinators) 

Published: November 12th, 2021

If you had to build your own house from scratch, what supplies would you bring to the job? High-quality building materials would certainly make the house much more durable, and having a diverse array of tools on hand will make construction much easier. 

Joe, on the other hand, brought just four zip ties and a wrench and is probably in for a tough time. If you live in a hot climate, you might consider installing air conditioning; in cold climates, good insulation and a heater will help you avoid freezing during the winter. In any case, putting love and effort into the home helps ensure that it keeps you comfortable for many years.

Similarly, the food we eat directly impacts every facet of our health. The links between diet, obesity, and cardiovascular disease are well known. However, more research indicates that dietary habits also directly impact issues like cancer, mental health, and even neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Healthy eating can also indirectly reduce disease burden by ensuring that your body has the tools it needs to heal and combat infection.

So, how do different foods actually exert these effects? 

Each food, of course, has a different nutritional profile and will provide your body with different tools. We can anticipate what tools we will need and provide them before problems arise. For example, people who menstruate require more iron in their diets, and oral contraceptive use can lower the absorption of multiple vitamins and minerals. 

Humans also have a little problem: we’re more complex than our genetics allow. While our bodies directly absorb and create many nutrients, a lot of essential nutrients are created solely by the 100 trillion bacteria living in our intestines. In exchange for some energy and a warm place to call home, these beneficial bacteria help to prevent other harmful bacteria from infecting the gut. This keeps our gut tissue working properly, and produces vitamins and other compounds that can leave the gut and promote health throughout the body. For example, certain types of fiber are broken down by bacteria into molecules that enter the bloodstream and help to reduce inflammation.

Even the ‘happy’ chemical, serotonin, is mostly produced in the gut. Like us, each type of bacteria has its own nutritional requirements that mostly revolve around fiber-rich foods such as fruits and whole grains. By eating a variety of nutrient-dense foods, we foster a gut environment full of healthy, anti-inflammatory bacteria that in turn keep us healthy. 

What type of diets are sustainable and have health benefits?

Dietary research is progressing at a staggering rate, and it can be overwhelming to stay up to date. When the research is clarified, however, certain dietary patterns emerge that are consistently linked with specific health outcomes. 

The Mediterranean diet, which promotes plant-based foods, fish, and healthy oils, while limiting red meat and other animal products, is perhaps the best-studied healthy diet in the world. It has been associated with lower rates of cardiovascular disease, obesity, glucose sensitivity and diabetes, and overall mortality.

More recently, a few studies have suggested that the Mediterranean diet may improve brain health. Neurodegenerative diseases are not yet well understood, and there are very few known factors that help to prevent them. Recognizing this, Dr. Martha Clare Morris unveiled the MIND diet in 2015, which optimizes the Mediterranean diet against cognitive decline.

What is the MIND diet and how does it benefit us?

Most food groups are conserved between the two diets; crucially, however, the MIND diet also promotes brain-healthy berries and leafy greens, while restricting pro-inflammatory sugary, fried, and processed food. These latter foods are becoming increasingly common, especially in North America; some research suggests that their overconsumption can even negate some of the health benefits normally associated with the Mediterranean diet. 

As a result, the MIND diet has since been associated with significantly reduced rates of many neurodegenerative diseases, including Alzheimer’s, cognitive decline, and general motor decline; what’s more, the strength of these associations seems to exceed those of the Mediterranean diet.

We recently investigated the MIND diet in a group of individuals with Parkinson’s disease, where we assessed their normal dietary intake and assigned a score based on how closely their intake resembled the MIND diet. Female participants had higher scores on average, indicating closer MIND diet resemblance. Participants with high scores developed Parkinson’s disease significantly later than those with low scores; unexpectedly, this association was especially strong in the female participants, where dietary habits accounted for up to 17 years’ difference in disease onset. Interestingly, the MIND diet accounted for only 10 years in men, and the Mediterranean diet accounted for 10 years with no apparent sex differences.

How do these diets work exactly?

While the complexity of these diets means that it is difficult to know exactly how they work, a sizable amount of research has zeroed in on our microscopic friends as a key factor. Brain-healthy diets help anti-inflammatory bacteria to thrive, which may help to limit inflammation in the brain. Regulation of the immune system is known to be partially sex-specific – for example, women are more prone to autoimmune disease, where the immune system attacks healthy body tissue – and these differences might impact how effective the diets are against neurodegeneration. Indeed, women make up only 1/3 of all Parkinson’s disease cases. 

While our findings here are only correlational, they highlight the importance of including sex as a factor in further research. With a strong enough framework, everyone can design a house that will keep them happy and healthy for a lifetime.

 

COVID-19 Differences Between Men and Women

Authors: Maria Tokuyama, PhD, Assistant Professor at UBC Microbiology & Immunology; Joshua Mao, University of California Berkeley, Summer Intern at the Tokuyama Lab, UBC Microbiology & Immunology | Editors: Negin Nia and Arrthy Thayaparan (Blog Coordinators) 

Published: September 10th, 2021

Since March 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drastically changed our lives and has killed over four million people worldwide. Although people of all ages and sex get COVID-19, a striking observation is that the number of female COVID-19 deaths were half of what was seen in males. Data analysis from New York City Health found that of all death cases 38.2% were female and 61.8% were male. So what are the factors that contribute to this sex difference in COVID-19 outcomes? Several research studies have shown that differences in immune response and metabolism during disease may partly explain the worse outcomes in males than females. Here, we will summarize the key takeaways from those studies. 

The immune system is largely divided into two parts: the innate and adaptive immune system. The innate immune system is the body’s first line of defence against infection. It is able to recognize danger within minutes and rapidly fire inflammatory factors called cytokines and chemokines to recruit immune cells to sites of infection and set off alarms to engage the adaptive immune system. The adaptive immune response takes about five to seven days to fully kick-in, but once activated, it is very specific to the invading pathogen and provides long-term memory responses that can be quickly recalled to fight future infections by the same pathogen. The adaptive arm of the immune system is what is provided by vaccinations. During viral infection, both the innate and adaptive immune responses work together to fight the infection. Ultimately, the magnitude and quality of the immune response dictate disease outcomes. 

Male patients show increased activation of the innate immune response.

In a study published by Yale in August 2020, researchers compared immune responses between female and male hospitalized COVID-19 patients, who were not taking anti-inflammatory drugs. They found that male patients had higher amounts of key inflammatory molecules, interleukin 8 (IL-8) and 18 (IL-18), in their blood compared to female patients, despite having similar amounts of SARS-CoV-2 RNA. In addition, male patients had a higher amount of a type of innate immune cells called non-classical monocytes. These findings are supported by another study that reported worsening health conditions in males due to SARS-CoV-2 infection was related to increased innate immune activation. Although the immune response is intended to fight the infection, over activation of the innate immune response can lead to tissue damage and may be one explanation for why males have worse outcomes than females in COVID-19.  

Female patients have a stronger adaptive immune response.  

The two major players of the adaptive immune responses are B cells and T cells. B cells make virus-specific antibodies that bind to the virus and prevent the virus from infecting cells. T cells recognize cells that are infected and destroy them to prevent further spread of the virus. T cells also help B cells make more antibodies and strengthen the immune response. 

From the same Yale study, researchers found no difference in the amount of antibodies against SARS-CoV-2 between male and female COVID-19 hospitalized patients. However, female patients had a higher amount of fully activated T cells than males. This means that female patients are better able to control the infection through their T cells, and the weaker T cell response in males may be another reason for worse outcomes with COVID-19. 

Kynurenic acid levels correlate with deteriorating disease in males. 

The metabolism regulates the immune system through metabolites, which are small molecules that are produced through chemical reactions in the body. A study published in July 2021 found that a higher amount of a key metabolite called kynurenic acid (KA) produced from kynurenine was related to higher innate immune responses in both female and male COVID-19 patients, but this association was more pronounced in males. Male patients with worse COVID-19 had a higher ratio of kynurenic acid to kynurenine (KA:K), which also seemed to predict higher innate immune responses and lower amounts of activated T cells. A higher Body Mass Index and increased age were associated with worsening disease in male COVID-19 patients. Overall, the metabolic status of individuals seems to contribute to disease outcomes, where certain amounts of KA predicted over activation of the innate immune response and worse disease in males. 

Different levels of sex hormones in COVID-19 patients.

Estradiol and estrone are major and minor female sex hormones, and testosterone is a major male sex hormone. Sex hormones can affect many aspects of the immune system and are important to consider. A preprint article, that has not yet been peer-reviewed, reported that both male and female COVID-19 patients have higher levels of estradiol and estrone compared to healthy individuals. However, only male COVID-19 patients had decreased testosterone levels. Whether lower testosterone levels in male patients results in worse disease is not known, but it will be an important factor to monitor moving forward.     

Concluding remarks:

A wide range of disease outcomes have been observed in COVID-19 including a major difference between males and females. These studies highlight key sex differences in SARS-CoV-2 infection that affect severity of COVID-19 including differences in the coordination between the innate and adaptive immune response, metabolism and potentially, sex hormones. These differences between sexes may be important factors that explain why fewer females have died from COVID-19 than males.  

Bibliography

“Worldometer Coronavirus Death Toll.” Worldometer, 2020, https://www.worldometers.info/coronavirus/coronavirus-death-toll/. (Accessed 1 August 2021).

Takahashi, Takehiro et al. “Sex differences in immune responses that underlie COVID-19 disease outcomes.” Nature. 2020 Dec;588(7837):315-320.

Petrey, Aaron C, et al. “Summary of Cytokine release syndrome in COVID-19: Innate immune, vascular, and platelet pathogenic factors differ in severity of disease and sex.” J Leukoc Biol. 2021 Jan;109(1):55-56. 

Cai, Yuping, et al. “Kynurenic acid may underlie sex-specific immune responses to COVID-19.” Sci Signal. 2021 Jul 6;14(690):eabf8483.

Schroeder, Maria, et al. “Sex hormone and metabolic dysregulation are associated with critical illness in male Covid-19 patients.” MedRxiv, 2020, https://www.medrxiv.org/content/10.1101/2020.05.07.20073817. (Accessed September 2021).

 

 

High Blood Pressure: Misunderstood in Women and Not Just for Men

Authors: Arrthy Thayaparan and Alex Lukey (Blog Coordinators)

Published: May 21st, 2021

What do eight percent of pregnant women from around the world, including the likes of Beyoncé and Kim Kardashian, have in common? Complications due to high blood pressure. 

Known as the ‘silent killer’ due to its ability to go undetected, high blood pressure is often misdiagnosed and treated less in women than in men, said Professor Angela Maas director of the Netherlands Women’s Cardiac Health Program. 

For middle-aged women, symptoms such as hot flashes and heart palpitations, are often attributed to menopause. This mislabelling puts women at risk for serious heart conditions that could be avoided. 

“A woman’s life provides clues that you need to start early with prevention. We have to assess female patients differently to men, and not just ask about high cholesterol,” said Professor Maas in a recent article with Science Daily.

But before understanding how high blood pressure can be better diagnosed and supported in women, we need to know exactly what high blood pressure is. 

What is high blood pressure?

Also known as hypertension, high blood pressure happens when the blood vessels that carry blood around the body constrict, narrowing the blood’s space to pass. This constriction causes damage as blood pushes against the walls of the vessels. High blood pressure also makes the heart work harder to pump blood around the body.

The risk of untreated high blood pressure impacts almost every system in the body. As blood vessels around the body accumulate damage, they become weaker and less elastic. The organs that vessels bring blood to can become damaged over time, leading to the risk of multiple diseases. High blood pressure contributes to many life-threatening conditions such as heart disease, stroke and kidney damage. 

Why might high blood pressure be dismissed in women?

Until the onset of menopause, women are at lower risk for hypertension than men due to the protective effects of estrogen on blood vessels. 

After menopause, there is evidence that high blood pressure is not as well recognized and treated in women.  As many as 41% of post-menopausal women have high blood pressure.  For many women, symptoms related to high blood pressure are attributed to stress or menopause symptoms.

Here is the list of potential symptoms of menopause that may mask signs of high blood pressure 
  • Palpitations
  • Hot flushes 
  • Headaches 
  • Chest pain
  • Tiredness 
  • Sleeping disturbances

According to Professor Maas, there are several subgroups of women that can be identified as high-risk before it is too late.

“High blood pressure during pregnancy is a warning sign that hypertension may develop when a woman enters menopause … If blood pressure is not addressed when women are in their 40s or 50s, they will have problems in their 70s when hypertension is more difficult to treat,” she said. 

How do I know if I have high blood pressure?

It is essential to know what your baseline blood pressure numbers are to track changes over time. 

You can take your blood pressure at most pharmacies. Taking your blood pressure outside of the doctor’s office may give a more accurate measure of blood pressure since many people feel nervous in appointments, potentially leading to an artificial increase in blood pressure. 

Hypertension Canada Guidelines state that if your systolic blood pressure (top number) is more than 135 or diastolic blood pressure (bottom number) is more than 85, you may have high blood pressure.  

If you are concerned that you have high blood pressure, you should talk to your primary care doctor or nurse practitioner. 

How can women be safeguarded from hypertension?

Dr. Maas and her team authored a publication for the European Society of Cardiology with recommendations on how to help middle-aged women prevent heart problems due to high blood pressure. 

They stress the importance of a healthy lifestyle and diet, especially in women who are at higher risks of high blood pressure during pregnancy and women who have type 2 diabetes.

But most importantly, the need for collaboration between cardiologists, gynecologists, and endocrinologists is needed to provide women with the best care. 

Dr. Maas notes that women need to work as a team with their doctors to watch for signs and symptoms of high blood pressure.

“Women can help their doctors prevent heart problems and make earlier diagnoses by mentioning issues like complicated pregnancies and early menopause and monitoring their own blood pressure.”

 

Photo by Hush Naidoo on Unsplash

Learning to Forget: Making the Case for Sex-Specific Approaches to the Treatment of PTSD


Author: Dr. Luzia Troebinger, Post-Doctoral Fellow, University College London – Clinical Psychopharmacology Unit | Editors: Alex Lukey and Arrthy Thayaparan (Blog Coordinators) 

Published: April 8th, 2021

What’s your worst memory? If I offered you a pill that could erase it, would you take it? Or let’s rephrase the question: How bad would your worst memory have to be to take that pill? What if you couldn’t leave your house without reliving this memory? You might think this scenario is exaggerated, but for people suffering from post-traumatic stress disorder (PTSD), this might be a daily reality. For many people with PTSD, the impact on quality of life is so severe that they would not hesitate to take that pill. 

Research suggests that women are twice as likely to develop PTSD, even though rates of trauma exposure are higher in men.[1-3]  The reason for this disparity is complicated and dependent on environmental and biological factors.[4]  With regard to biological factors, the role of sex hormones in the context of stress and fear memory has become a primary target for research in this area.[5-7]

Studying fear memories in the laboratory can help improve our understanding of the mechanisms involved in PTSD. In the lab, a ‘fear memory’ is first established through a learnt association between a neutral and an adverse stimulus (e.g. a tone paired with an electric shock). This is similar to what happens in PTSD: a previously neutral stimulus becomes associated with the traumatic event. Extinction learning refers to the process of suppressing or reversing that learnt association. This is typically accomplished through repeated exposure to the neutral but not the adverse stimulus. Finally, extinction recall refers to how well this ‘extinction memory’ is remembered when confronted with the neutral stimulus later in time. 

Fear extinction plays an important role in exposure therapy, a type of behavioural treatment commonly prescribed in PTSD.[8-10] Briefly, this type of therapy involves repeated exposure to trauma-related memories in a safe context. Just as in the laboratory models, the idea is that repeated exposure will result in the ‘extinction’ of learnt associations between environmental stimuli and the traumatic event. Although this type of treatment is effective for many people, it has limitations. 

Try to think about your worst memory again.  Now imagine doing this over and over again. Not exactly pleasant, is it?

There is a host of factors that influence if exposure therapy will benefit an individual. One aspect that might be highly relevant for women is the level of sex hormones at the time of treatment.

Evidence from rodent studies suggests that low estrogen levels in females are associated with poor extinction recall. These findings also seem to translate to studies in human subjects, with extinction recall being worse during low-estrogen stages of the menstrual cycle.[5,11] Moreover, the suppression of the body’s natural estrogen through the administration of hormone-based contraceptives has also been found to impair extinction recall.[12] This is an issue because impaired extinction recall could render exposure therapy ineffective or even counter-productive. If patients go through the difficult process of recalling traumatic memories without an understanding that doing so is safe and effective, they may lose motivation to continue treatment.

What are the possible implications of this in a clinical context? Timing could be a crucial factor in prescribing exposure therapy in naturally cycling women. Also, women with chronically low estrogen levels may benefit from pairing exposure therapy with pharmacological interventions. For instance, a recent study in rodents has shown that a certain type of blood pressure drug could reverse the adverse effects of low estrogen on extinction recall, possibly by making up for low-estrogen-related deficits in the regulation of the physiological stress response.[13]

Another approach to dealing with intrusive, distressing trauma memories is to reduce their impact near the time they are formed. This could be achieved by using pharmacological treatments to prevent traumatic memories from being further strengthened. As with exposure therapy, the case can be made that such treatments should take sex into account.

Previous research suggests that high progesterone levels at the time of trauma exposure could contribute to a strengthening of the traumatic memory, resulting in the type of intrusive, ‘flashback’ memories associated with PTSD.[14] Another study found that women who had been exposed to sexual assault had differing levels of PTSD depending on if they received hormone-based emergency contraceptives and what hormone the contraceptive contained. [15] One of two types of emergency contraceptives was administered, with one containing both synthetic estrogen and progestin (Ogestrel), while the other drug contained a synthetic progestin-only (Plan B). Interestingly, the women who took Ogestrel reported fewer intrusive memories than those who took Plan B. This might point to a combined effect of estrogen and progesterone on the formation of trauma memories. In any case, these studies highlight the importance of considering sex in the development of pharmacological treatments intended for use in the immediate aftermath of a trauma.

Given this research, why are we not prescribing treatments – behavioural or pharmacological – in a sex-specific way?  

Treatments need to be well-studied before they can be used in clinical practice. Particularly in the case of pharmacological interventions, this process can be lengthy, costly and complex. The reality of research is that resources are limited, and drug studies are expensive. Testing for the influence of the menstrual cycle phase would increase the sample size required and would also put further demand on resources by necessitating the acquisition, storage, and analysis of biological samples for rigorous testing of hormone levels.  At this time, there is a need for more evidence regarding hormonal influences on PTSD treatments. With the emergence of funding opportunities dedicated to the field of women’s health, there is hope that this will change. What is clear from the evidence is that there are hormonal influences on the development of PTSD. By including sex differences, we are presented with an opportunity to drastically improve the treatment of mental health disorders.

About the author

Dr. Luzia Troebinger currently works as a postdoctoral research fellow in Professor Sunjeev Kamboj’s group at University College London’s Clinical Psychopharmacology Unit. Her research focuses on both behavioural and pharmacological approaches to the treatment of PTSD and is funded by the Sir Bobby Charlton Foundation.

Twitter: @UCL_SBCF

Bibliography

1. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51(1):8-19. doi: 10.1001/archpsyc.1994.03950010008002 [published Online First: 1994/01/01]

2. Breslau N. Gender differences in trauma and posttraumatic stress disorder. J Gend Specif Med 2002;5(1):34-40. [published Online First: 2002/02/28]

3. Kessler RC, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52(12):1048-60. doi: 10.1001/archpsyc.1995.03950240066012 [published Online First: 1995/12/01]

4. Christiansen DM, Berke ET. Gender- and Sex-Based Contributors to Sex Differences in PTSD. Curr Psychiatry Rep 2020;22(4):19. doi: 10.1007/s11920-020-1140-y [published Online First: 2020/03/04]

5. Milad MR, Zeidan MA, Contero A, et al. The influence of gonadal hormones on conditioned fear extinction in healthy humans. Neuroscience 2010;168(3):652-8. doi: 10.1016/j.neuroscience.2010.04.030 [published Online First: 2010/04/24]

6. Maeng LY, Milad MR. Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones. Horm Behav 2015;76:106-17. doi: 10.1016/j.yhbeh.2015.04.002 [published Online First: 2015/04/19]

7. Goel N, Workman JL, Lee TT, et al. Sex differences in the HPA axis. Compr Physiol 2014;4(3):1121-55. doi: 10.1002/cphy.c130054 [published Online First: 2014/06/20]

8. Foa EB, McLean CP. The Efficacy of Exposure Therapy for Anxiety-Related Disorders and Its Underlying Mechanisms: The Case of OCD and PTSD. Annu Rev Clin Psychol 2016;12:1-28. doi: 10.1146/annurev-clinpsy-021815-093533 [published Online First: 2015/11/14]

9. Kothgassner OD, Goreis A, Kafka JX, et al. Virtual reality exposure therapy for posttraumatic stress disorder (PTSD): a meta-analysis. Eur J Psychotraumatol 2019;10(1):1654782. doi: 10.1080/20008198.2019.1654782 [published Online First: 2019/09/07]

10. Steenkamp MM, Litz BT, Hoge CW, et al. Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials. JAMA 2015;314(5):489-500. doi: 10.1001/jama.2015.8370 [published Online First: 2015/08/05]

11. Wegerer M, Kerschbaum H, Blechert J, et al. Low levels of estradiol are associated with elevated conditioned responding during fear extinction and with intrusive memories in daily life. Neurobiol Learn Mem 2014;116:145-54. doi: 10.1016/j.nlm.2014.10.001 [published Online First: 2014/12/03]

12. Graham BM, Milad MR. Blockade of estrogen by hormonal contraceptives impairs fear extinction in female rats and women. Biol Psychiatry 2013;73(4):371-8. doi: 10.1016/j.biopsych.2012.09.018 [published Online First: 2012/11/20]

13. Parrish JN, Bertholomey ML, Pang HW, et al. Estradiol modulation of the renin-angiotensin system and the regulation of fear extinction. Transl Psychiatry 2019;9(1):36. doi: 10.1038/s41398-019-0374-0 [published Online First: 2019/01/31]

14. Ney LJ, Gogos A, Ken Hsu CM, et al. An alternative theory for hormone effects on sex differences in PTSD: The role of heightened sex hormones during trauma. Psychoneuroendocrinology 2019;109:104416. doi: 10.1016/j.psyneuen.2019.104416 [published Online First: 2019/09/01]

15. Ferree NK, Wheeler M, Cahill L. The influence of emergency contraception on post-traumatic stress symptoms following sexual assault. J Forensic Nurs 2012;8(3):122-30. doi: 10.1111/j.1939-3938.2012.01134.x [published Online First: 2012/08/29]

Sex-and-Gender-Based Considerations in Exercise-Based Randomized Controlled Trials in Individuals with Stroke: A Road of Opportunities Ahead


Author: Elise Wiley, Ph.D. Student, McMaster University | Editors: Alex Lukey and Arrthy Thayaparan (Blog Coordinators) 

Published: March 19th, 2021

There is a growing body of research focused on the biological differences between males and females in pharmaceuticals, risk factors, pathology, severity, and prognosis of different diseases [1]. In contrast to this large body of evidence related to sex-based differences, we know far less about how gender impacts the risk of disease. For example, how does the risk for stroke or heart attack differ in a heterosexual man versus a transgender non-binary individual? While more research is accounting for sex differences, this is not the case for gender identity. The lack of sex and gender considerations are causing a significant gap in knowledge for many health conditions.

Stroke is a leading cause of disability and death worldwide [2]. Over the past 20 years, there has been a growing body of literature showing that exercise-based interventions are beneficial in improving physiological and psychosocial health markers in individuals with stroke [3]. However, the extent to which sex-and gender-based considerations were implemented into exercise trials in individuals with stroke has not been previously reviewed. 

In this blog post, I will share results from a study that I conducted, which aimed to examine the extent to which stroke researchers include sex-and gender-based considerations in their exercise trials. In this study, we surveyed publications of exercise trials in stroke and applied the Sex and Gender Equity in Research (SAGER) tool as a framework to determine whether sex and gender considerations were implemented in each section of a study (i.e., introduction, study design/methods, results and discussion) [4]. We were also interested in examining whether the incorporation of sex- and gender-based considerations had increased since the publication of the SAGER guidelines in 2016. 

I will preface the summary of the results by stating that we have a long way to go in addressing sex-and gender-based considerations in exercise-based trials in individuals with stroke. Over the past ten years, sex-and gender-based considerations have gained recognition for their importance in health research. This is thanks to the pioneer Canadian researchers in the field of sex and gender research who advocated for more inclusive research practices. Unsurprisingly, before 2016, the vast majority of stroke and exercise studies did not include any sex or gender considerations in any section of the research article. After 2016, we found a slight increase in the proportion of studies incorporating sex-based considerations since the publication of the SAGER guidelines. However, we also noted that researchers continued to use terminology related to “sex” and “gender” interchangeably. 

Of note, there were no exercise-based studies in stroke that included gender-based considerations. While this is unsurprising, I do wonder why we, as researchers in the field of exercise and stroke, have neglected gender in our studies? Is it that there isn’t enough awareness of the available gender-based resources to guide its inclusion or assessment? Or is the reason more deep-seated? It is important to acknowledge that it is indeed challenging to incorporate gender-based considerations into research studies when self-reported gender measures are unavailable, and there is no firm consensus on how various constructs of gender are to be measured [5]. 

We hope that our research findings will serve as a call to action for researchers in the field of exercise and stroke to acknowledge the opportunities that lie ahead in being able to address the knowledge gaps related to sex-and gender-based considerations in exercise trials in individuals with stroke. We must continue to reinforce the idea that although sex and gender are interrelated, they are not interchangeable. I urge researchers to consult the resources that I’ve provided to ensure that their participants are being addressed properly. It may also be that there is a greater onus on journal editors to ensure that, at minimum, authors submitting to their journal are incorporating proper sex and gender terminology. 

Stroke researchers are well-equipped to move forward in the area of sex and gender research. We have access to resources such as the SAGER  guidelines, the CIHR e-learning modules Integrating Sex and Gender in Health Research, and the Gender-based Analysis Plus course [4,6,7].

As an advocate for sex and gender implementation in health research, the findings from this work suggest that we have a long way to go, but the positive trend is encouraging. I am optimistic for the years to come and continue to be inspired by my fellow researchers who advocate for enhanced sex and gender implementation in health research.  

References 

1.     Melloni Chiara, Berger Jeffrey S., Wang Tracy Y., et al. Representation of Women in Randomized Clinical Trials of Cardiovascular Disease Prevention. Circulation: Cardiovascular Quality and Outcomes. 2010;3(2):135-142. doi:10.1161/CIRCOUTCOMES.110.868307
2.     Campbell BCV, De Silva DA, Macleod MR, et al. Ischaemic stroke. Nature Reviews Disease Primers. 2019;5(1):1-22. doi:10.1038/s41572-019-0118-8
3.     Saunders DH, Sanderson M, Hayes S, et al. Physical fitness training for stroke patients. Cochrane Database of Systematic Reviews. 2020;(3). doi:10.1002/14651858.CD003316.pub7
4.     Heidari S, Babor TF, De Castro P, Tort S, Curno M. Sex and Gender Equity in Research: rationale for the SAGER guidelines and recommended use. Research Integrity and Peer Review. 2016;1(1):2. doi:10.1186/s41073-016-0007-6
5.     Lacasse A, Pagé MG, Choinière M, et al. Conducting gender-based analysis of existing databases when self-reported gender data are unavailable: the GENDER Index in a working population. Can J Public Health. 2020;111(2):155-168. doi:10.17269/s41997-019-00277-2
6. Government of Canada CI of HR. IGH Learning – CIHR. Published September 2, 2015. Accessed February 25, 2021. https://cihr-irsc.gc.ca/e/49347.html
7. Government of Canada CI of HR. Gender-Based Analysis Plus (GBA+) at CIHR – CIHR. Published May 15, 2018. Accessed June 5, 2020. https://cihr-irsc.gc.ca/e/50968.html

Sex Differences Are No Afterthought

Authors:  Jolande Fooken, Xiuyun Wu, & Doris Chow | Editors: Alex Lukey and Arrthy Thayaparan (Blog Coordinators) 

Published: November 12th, 2020

In recent years more scientists have advocated an increased focus on the role of sex and gender differences in neuroscience research. Specifically, it is important to study sex-related mechanisms in the brain and how they affect sensory processing and motor behaviour. 

Considering that historically most research included only male participants, research standards are trending in the right direction. Today, researchers are strongly encouraged to take sex and gender into consideration for their research. However, is it enough to simply collect the same number of male and female participants or should we think about sex as a scientifically relevant and meaningful variable?

Missed Opportunities in Present Research

A recent study by Mathew and colleagues investigated the effect of sex as a biological variable on hand-eye coordination and processing by the brain, led us to reconsider how sensory and motor neuroscience currently take sex differences into account.[1] It’s true that researchers pay greater attention to sex and gender balance in their research than in the past. However, we still know very little about how visuomotor function might vary between people of different sex and gender. 

Driven by that very question, Mathew and colleagues decided to analyze how the ability to manually track a moving target varies between self-reported male and females.[1] Whereas the general research question could fill a large gap in our current literature, the authors missed their chance to make a significant contribution and advance our knowledge about the importance of sex as a biological variable.

The study, entitled “Sex Differences in Visuomotor Tracking”, was published in July 2020 in Scientific Reports and could potentially reach a high impact in the field. Yet, this study has several gaps, which we will later discuss,  that are not sufficiently addressed in the paper. Therefore, the conclusions drawn should raise red flags as they may mislead some readers and future research. In the following, we will comment on three major points that scientists—interested in sex differences in behavioural neuroscience—should take into account

1. Sex differences are no afterthought

We are living in a time where there are vast amounts of data being used for scientific research. Often scientists publish a subset of the full dataset that was collected, reporting only those measures that address the current research question. At the same time, there may be additional information about the participants, such as age, handedness, or biological sex not included in the analysis. Therefore, it is very tempting to later re-analyze the data to look for differences across various variables. Such differences are exactly what Mathew and colleagues reported.

The authors analyzed data from a manual-tracking baseline task that usually preceded the main experiment in their lab. Manual tracking is a common task in sensorimotor research, in which participants move a joystick to align a visual cursor with a moving target. Typically, experiments aim to investigate how participants adapt their visuomotor control to changes in the visual scene. In the study by Mathew et al., the baseline task required participants to track the moving target as closely and accurately as possible. The authors observed differences between female and male participants: females tracked the unpredictably moving target with a larger time lag than their male counterparts.

These findings should spark interest in any curious scientist. However, there is also a problem: the authors did not have an a priori hypothesis (reasoning based on inference before the study, rather than evidence) about the role of biological sex with respect to visuomotor tracking. Instead, they performed their analyses after the fact. Accordingly, several factors that may influence the role of sex and gender on the results were not controlled for. 

One factor that may have skewed the results of this study is video-gaming, an activity more common among males.[2, 3] Video game experience most likely influences participants’ ability to accurately use a joystick to track a moving target. Additionally, general personality traits could explain the observed individual differences in manual tracking behaviour. For example, risk-averse individuals may track the target with a higher time lag to be able to adjust their hand movements more precisely to sudden changes of target motion. All of this is of course speculative. The study was not designed to study sex differences and therefore cannot answer if visuomotor tracking truly differs between males and females.

 

2. The battle of the sexes: what is a male advantage?

Some readers may cringe when they read that Mathew and colleagues wrote that they found, “a clear male advantage in hand tracking accuracy”. The study shows differences, yes, but an advantage? Tracking a target as fast as possible does not necessarily translate to advantages in everyday life in which timing is often relevant. 

Imagine getting into a car with someone who is trying to follow the car in front as closely as possible—keeping a larger distance may in fact be the safer option. Driving and many other naturalistic scenarios may require us to choose a tracking behaviour that differs from a pure distance minimization. To study optimal visuomotor behaviour we need to first define normative models that allow us to evaluate a decision or judgement.[4] What is the goal of the actor? What does it mean to be successful in a task? What is the error we should aim to minimize?

In motor control, there may be some tasks in which action accuracy is easy to judge. For example, how well a person can throw a ball can be measured in the distance the ball has travelled. However, when we change the definition of success, we also change our measure of accuracy. For daily activities, it may be relatively easy to judge success, but in basic sensorimotor research, it is less clear. 

Thus, optimal performance during manual tracking can be defined in different ways: it may be optimal to track a moving target as closely as possible or to track it as smoothly as possible and thereby reduce overall movement cost. Defining optimal task performance is key to understanding individual strategies when solving any given task. Only then can we draw conclusions about so-called advantages.

3. Males are different from females, now what?

For a moment let’s assume that, despite all the weaknesses in the study by Mathew et al., that we have pointed out, that there is a difference between male and female participants during visuomotor tracking. What does that mean? 

First, we should aim to investigate where such a difference originates. Mathew and colleagues conclude that males may rely on “faster decisional processes dynamically linking visual information of the target with forthcoming hand actions”.[1] However, some of these proposed processes, such as visual processing and early visual brain regions have relatively fixed time scales.

So the question that arises is at what stage of the decision process do differences occur? Does the transformation from visual information into motor commands take longer in female participants? Why? Does this difference change with experience or training? Or are there other factors, such as knowledge about motor uncertainty, that influence visuomotor tracking? Again, we simply don’t know yet and we need more carefully designed research to find these answers.

Another important question that we should ask ourselves is what the implications of the observed differences are. For example, visuomotor control has become very important in the medical field, where robotic devices enable complicated brain surgeries. Are such devices tailored to an average operator? Should we design different devices for female neurosurgeons as compared to males? Is there an actual physiological difference between males and females or are we just measuring differences along a spectrum of individual performance variability? At this time we do not have concrete answers to these questions. So, until we have better answers to the questions of how these differences arise, it may be harmful to make sweeping statements of sex-based advantages. 

We have the opportunity to study sex differences in sensory and motor neuroscience in a meaningful and thorough way. Let’s not report sex differences as an afterthought, but instead study biological sex as an interesting and important factor at the centre of our research agenda.   

REFERENCES

1. Mathew, J., Masson, G. S., & Danion, F. R. (2020). Sex differences in visuomotor tracking. Scientific reports, 10(1), 1-12. https://doi.org/10.1038/s41598-020-68069-0

2. Terlecki, M.S., Newcombe, N.S. (2005). How Important Is the Digital Divide? The Relation of Computer and Videogame Usage to Gender Differences in Mental Rotation Ability. Sex Roles, 53, 433–441. https://doi.org/10.1007/s11199-005-6765-0

3. Quaiser-Pohl, C., Geiser, C., & Lehmann, W. (2006). The relationship between computer-game preference, gender, and mental-rotation ability. Personality and Individual Differences, 40(3), 609-619. https://doi.org/10.1016/j.paid.2005.07.015

4. Körding, K. (2007). Decision theory: what” should” the nervous system do?. Science, 318(5850), 606-610. https://doi.org/10.1126/science.1142998

Images courtesy Joel Staveley, Jehoots and Photologic on Unsplash

Sex/Gender Research: Resources for the Early Integrator to the Advanced Champion

Author: Jennifer Williams, PhD Candidate, McMaster University | Twitter: @jennyswilliams

The importance of integrating sex/gender in health research has been evident in the calls for action by researchers, funding organizations, and peer-reviewed journals alike. Especially in the midst of the global COVID-19 pandemic, this remains at the forefront of study design, illuminated recently by the first of the Women’s Health Research Cluster blogs. Over the past few years as a graduate trainee, I have been involved in research projects either integrating sex-based differences or examining female-specific conditions to fill gaps evident in cardiovascular research. Mentored by leaders in the field, much of my passion for sex/gender research has also been directed to supporting education of undergraduate and graduate trainees through mentorship, teaching, and volunteering with the CIHR Institute of Gender and Health Trainee Network. 

However, in reflecting on my research journey, it occurred to me that many trainees may be presently searching for resources and a network of colleagues considering these important questions. As the upcoming semester approaches, my hope is that this blog will serve as a useful guide to explore sex/gender in your future research studies, whether you’re an early integrator (like me) or an advanced champion (like many of my mentors). By no means is this an exhaustive list, so I encourage you to continue the conversation by sharing your favourite resource on Twitter with the #sexandgender.

Getting Started

What is Sex? What is Gender? When I started to ask myself these questions, I found the following definitions and infographic on the CIHR website helpful in finding the answers. Furthermore, this video (3min) provided me with an explanation about why learning about sex/gender is important. 

The CIHR Institute of Gender and Health curates an excellent list of resources for researchers to consider when integrating sex/gender into research. Check out their guide here, which is updated frequently with new resources and published studies. 

Training Modules

The following training courses/modules served as a foundation for developing my understanding of sex/gender in health research. 

Resources for Grant Applications

In addition to the training modules provided by CIHR, this video (5min) is a helpful resource for understanding what grant reviewers are looking for in assessing your integration of sex/gender into your research study design. This video, alongside a resource for reviewers, entitled “Key considerations for the appropriate integration of sex and gender in research”, can provide insight into what makes a strong research design, and hopefully a successful grant application.

The following article by Day et al. (2017) is a useful guide for understanding how to create your study proposal, based on some essential metrics outlined in their paper: “Essential metrics for assessing sex & gender integration in health research proposals involving human participants”. See Table 1 to do an early evaluation of your proposal (or your trainee’s proposal) and recognize gaps to fill prior to grant submission.

What are Researchers Saying? Research Articles & Guideline Documents 

The following article about the Sex and Gender Equity in Research (SAGER) guidelines are recommended for all researchers to review and include in their research study designs. Find out more here (Table 1 includes a comprehensive checklist of considerations).

Strategies have also been well detailed by the following articles:

Finally, this website from Gendered Innovations, curated by a worldwide group of researchers, has a Health & Medicine Checklist for considering sex/gender at each stage of the research process and case studies on sex/gender in health to use as examples for researchers and educators. 

Journal Clubs: One of the most impactful ways I’ve found for integrating sex/gender into discussions within my lab is in suggesting journal articles during journal club gatherings. Here’s an extensive list of articles curated by the NIH and a list of articles from the CIHR here.

Championing Sex/Gender Research: Organizations to Get Involved With 

Become a Sex and Gender Champion on collaborative research initiatives with CIHR. Similarly, consider joining the Institute of Gender and Health Trainee Network as a trainee mentee or Faculty mentor, and spearhead local initiatives at your institution with the support of this network. You can subscribe to the trainee network’s newsletter here.

CIHR Institute of Gender and Health also provides resources and events to engage with. Find out about Sex & Gender Events here, and consider becoming involved in the Organization of the Study of Sex Differences (OSSD) through their annual conference and journal. 

Finally, look for mentors and collaborators who are experienced in exploring sex and gender in research. If exploring women’s health, the Women’s Health Research Cluster directory is useful for connecting with individuals from across Canada, but primarily in BC, and similar for this directory in Ontario.

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Have a resource to share not on this list? Continue the conversation by sharing your favourite resource on Twitter with the #sexandgender.