seX & whY

Show Notes for Episode Twenty-Five of seX & whY, Part 2: Global Health and Pandemic Responsiveness Through a Sex and Gender Lens

Host: Jeannette Wolfe Guests: McKinzie Gales and Emelie Yonally Phillips

Phase 1 of the sex and gender equity in research (SAGER) for Integrated Outbreak Analytics (IOA) study involved A systematic literature review to better understand what is already known about the influence of sex and gender in outbreaks and to investigate if sex-disaggregated data and gendered data is being collected, analyzed, and used. Five different databases were searched and articles meeting the inclusion criteria were included. All included articles were published in English between 2012-2022, included the key terms “sex,” “gender,” or “pregnancy,” and discussed infectious disease outbreaks (e.g., cholera, dengue, Ebola, zika, hepatitis E, Malaria, influenza, yellow fever) in a low- and middle-income countries. Notably, they intentionally excluded articles focused on covid and tuberculous as sex and gender research is being extensively conducted on these diseases. 

Of the 15,000+ articles in their original search, only 71 articles examined potential sex and/or gender related factors associated with outbreaks in low- and middle-income countries. 

Although currently there is very limited data on the impact that sex and/or gender play in outbreaks and pandemics, what is known, underscores the complexity of these relationships. Studying specific outbreaks in specific contexts is important because who is most likely to get infected and how rapidly an infection is spread is influenced by several intersecting factors. These include the infectious agent, sex specific immunological factors and local socio-cultural practices and norms.

McKinzie highlighted that when there is a lack of gender and sex sensitive responses in outbreaks, evidence suggests that women, girls, and those with female anatomy are disproportionately negatively affected. For example, women are at greater risk for gender- based violence during a lock down and those with female anatomy are more directly impacted by the diversion of health care resources from clinics that offer reproductive health and pregnancy related services.

We went through an example as to how the SAGER IOA model might work in a theoretical outbreak. In establishing a functioning multi-disciplinary team, Emelie emphasized the importance of working within local systems to build long term relationships, community trust and capacity.  She underscored how critical it was to understand the values and priorities of the individuals most impacted by the outbreak and to ensure they had a voice in decision-making. She also discussed the importance of effective and transparent community health messaging- particularly if new data suggests a change from current practice. A recent example of this was the confusion experienced by many pregnant women surrounding the safety of Ebola vaccination. 

Emelie also spotlighted the opportunity to better understand how gender nonconforming and sexual minorities experience outbreaks as there is currently an absence of data on these groups. Finally, she emphasized that the failure of considering sex and gender specific needs in an outbreak can have tremendous downstream effects. Specifically, generational poverty, educational and professional inequities, gross domestic product, global trade, and security can all be impacted.

One of the other interesting areas we touched upon was how personal protective equipment (PPE) and other medical related equipment was initially designed for the anatomy and physiology of a male body and may not always work for a female one. Below are a few articles on this point.

Respiratory Personal Protective Equipment for Healthcare Workers. This study reported findings on adequate mask fitting in one hospital system’s fit test data for FF3 masks.  Their data set suggested that 18% of women had an inadequate FF3 mask fit compared to 10% of men. 

Unions say coronavirus crisis has brought ‘into sharp focus’ the problem of women being expected to wear PPE designed for men.

Here is a very interesting article that further explores whether medical equipment should be adjusted to better fit the anatomical variations of different users. The article - Does surgeon sex and anthropometry matter for tool usability in traditional laparoscopic surgery? makes a strong argument that most of the advances in laparoscopic surgical equipment have previously focused on accommodating different patient related factors and that their remains an opportunity to modify products to better align with anatomical characteristics of different users.  In turn, this may help enhance performance, outcome, and injury prevention of the users - AKA in this case the surgeons. 

Thanks for listening and be well.

Show Notes for Episode Twenty-Five of seX & whY: Global Health and Pandemic Responsiveness Through a Sex and Gender Lens

Host: Jeannette Wolfe Guests: 

Definitions

IOA - Integrated Outbreak Analytics SAGER - Sex and Gender Equity in Research 

The Integrated Outbreak Analytics (IOA) initiative is a collaborative partnership between UNICEF, WHO, US-CDC, ITM, Epicentre, IFRC, under the umbrella of GOARN.

The IOA concept started in earnest in 2018 during the Ebola outbreak in the Democratic Republic of Congo after it became clear that more real time, comprehensive on the ground data was needed to best manage outbreaks in an efficient and effective manner. The larger-picture concept is that the IOA model sets up a system for increased interagency data sharing and a process for data collection that produced more comprehensive information about:

The IOA - Creates a more holistic response to outbreaks along the entire pipeline from prevention to treatment. It creates a model that puts lots of partners at the table including major players like Unicef, WHO, CDC, Doctors Without Borders in addition to local governmental agencies and boots on the ground health care providers.

Examples of data that may be integrated to provide a clearer story of what is happening in an outbreak include: 

Goal is to apply a multi-disciplinary approach to outbreak analyses to provide a more holistic and timely understanding of outbreak dynamics and provide local Ministries of Health and response actors with rapid evidence to make decisions during an outbreak.

A key component of IOA is understanding the dynamics of both sex and gender within outbreaks and outbreak response for more adapted and appropriate responses. Therefore, IOA systematically works to collect, analyse and use data disaggregated by sex and inclusive of gender criteria across all phases of response:

Four phase project

Phase 1:

Phase 2:

Phase 3:

Phase 4:

Great resources

Show Notes for Episode Twenty-Four of seX & whY: Sex and Gender Differences in Conflict, Part 2

Host: Jeannette Wolfe Guest: Joyce Benenson, lecturer of evolutionary biology at Harvard and author of the book Warriors and Worriers

In this podcast we continue our discussion about women interacting with each other at the workplace and how women often manage hierarchy differently than men. We got into a spirited discussion about a question posted on a female physician’s list serve querying whether women physicians want to be addressed as  “Doctor” by other staff members. (My own preference was “yes” in front of patients, and “no” once we were outside of exam rooms.) Benenson believes that when women are interacting with women who are not family, they tend to act incredibly egalitarian. This can be challenging for women in hierarchical positions and lead to a downplay of their power. This intentional buffering may not only use up a lot of cognitive energy, but it can also be a potential disadvantage in professional situations that require a clear chain of command to optimize team performance. This can put women on a professional tightrope that can be hard to balance. Ways to address this include acknowledging that this challenge is real, committing to direct communication and focusing on shared outcome goals of the entire team. Personally, I have also found it extremely helpful to humanize the other person and remind myself that most people don’t go to work with malicious intent to try and screw up another person’s day.

Next, we talked about likeability, and Benenson shared a fascinating economics paper called: I (Don’t) Like You! But Who Cares? Gender Differences in Same Sex and Mixed Sex Teams. This paper included a series of studies in which pairs participated in games that involved economic transactions and “likeability”. In pairs where men worked with other men, “liking” their partner was not intricately related to maximizing their profits. This was not the case in teams that involved at least one woman. In these pairs, likeability increased the chance of profits and dis-likability decreased overall profits. This suggests that when interreacting with each other, men may have a greater ability to compartmentalize their professional interactions from their personal opinions.

Next, we talked about the “tend and befriend” theory developed by Dr Shelly Taylor. This theory suggests that when stressed, that females may benefit less from a fight or flight response and more from coming together to pool resources and share childcare. Benenson’s impression is that there is little scientific evidence that this theory holds true.  She believes, contrary to the popular stereotype, that males are actually far more likely to be the communal sex and are much more likely to form intense group bonds. 

At the end, I briefly reviewed some of the findings of a recent paper Dr Benenson published called: Self Protection as an Adaptive Female Strategy which supports the “Staying Alive Theory”. From an evolutionary perspective, behaviors that are more likely to be found in groups of males than females, such as direct competition, physical aggression, resource accumulation and risk taking, have evolved because they provide a benefit to males in optimizing their mating opportunities and reproductive fitness. The question becomes, is there a parallel evolutionary driver for females. The Staying Alive Theory is one proposal. This theory originally developed by Campbell in 1999, suggests that compared to males, females are more likely to be innately wired to avoid conflict and be more physiologically responsive to threats that can jeopardize their health. By doing so, this helps females optimize their chance of their own fitness and the survival of their own offspring.  In their paper, Benenson and her group surveyed several different areas of science to look for support of the Staying Alive Theory and here are some of their findings. 

This is a great paper and worth a full read if you are interested in this material.

Thanks for listening to Sex and Why! 

Show Notes for Episode Twenty-Four of seX & whY: Sex and Gender Differences in Conflict, Part 1

Host: Jeannette Wolfe Guest: Joyce Benenson, lecturer of evolutionary biology at Harvard and author of the book Warriors and Worriers

Here is a link to Dr Benenson’s book Warriors and Worriers. 

This book dives deep into the evolutionary roots of human behavior and Dr Benenson makes a very clear and well referenced case that human males and females have evolved from slightly different playbooks.  The root of this difference is sexual selection in that adaptions and behaviors that optimize the chance that a male’s DNA gets into the next generation are slightly different than a female’s, specifically Benenson asserts that a female’s strategy relies more heavily on keeping herself and her children physically safe and healthy. Innate differences may then by amplified or attenuated by sociocultural norms and experiences that shape an individual’s “expected behavior."

Some bullet points from her work

This is Dr Benenson’s study that looked at how much time two players spent interacting with each other after the conclusion of a  competitive sports match. It showed that men typically engaged longer with their opponent than did women. She theorizes this behavior suggests that men tend to be more agile in realigning these relationships because the relationship may be needed for a future allegiance (i.e.  in war or hunting.)

Show Notes for Episode Twenty-Three of seX & whY: Issues Surrounding Men’s Health, Part 2

Host: Jeannette Wolfe Guests: Peter Baker – Director of Global Action on Men’s Health  Twitter: @pbmenshealth @globalmenhealth

Dominick Shattuck has a PhD in psychology and does Global Health Work at Johns Hopkins Bloomberg School of Public Health    

https://www.linkedin.com/in/dshattuck/        

Main topics discussed:

Challenges and barriers associated with optimizing men’s mental health and the role of men in reproductive health-related issues.

Men’s mental health is important not just for men but for the health of communities. Maladaptive coping mechanisms such as substance use disorder and aggression can impact gender-based violence, sexual and reproductive health, and the well-being of children. Part of tackling gender-based violence needs to include helping men better manage anger and stress.

Barriers to mental health for men

From a young age, many boys are taught to suck things up and not show signs of physical or emotional weakness. They also may struggle to find words to adequately articulate their emotional state or to appropriately label the challenges which they are experiencing.  This may be further confounded by social media in which most posted photos portray men as carefree and perfect which can leave the viewer feeling inadequate and questioning their masculinity. Today many men may also have decreased contact with their extended families and thus may miss out on many of the informal connections and conversations that have historically helped men cope with common life challenges.

We then discussed some unanticipated and potentially detrimental consequences of “gender blind” policies.  For example, due to concern of exclusivity, there has been a decrease in what historically were Men’s Only spaces. These closures can be costly for men who already have a fragile support system and who relied on these organizations to help them connect and bond with other men. Dominick then talked about the importance of code switching for men (using different communication styles with different audiences) and that in the ideal world we would create opportunities for men to become more proficient in the different roles they play (i.e. father, husband, employee etc) by exposing them to spaces with different audiences like men’s only, couples, and mixed gender gatherings.

Peter also brought up that mental health related depressive symptoms may just look differently in men. Consequently, many men and their health care professionals, may not be aware that some of the symptoms that men are describing (such as increased alcohol consumption) are often flags for depression.

Next, we discussed what roles men can play when it comes to areas surrounding reproductive health and reproductive justice. Dominick talked about some of the work he has done for a task force funded by the US Aid for use in low and middle-income countries to help better define these roles. He described a three-pronged framework- men as potential clients (i.e. work around condom use and vasectomies), as supportive partners to women, and as advocates for change. Messaging this framework so that men understand that these issues are not just relevant for women is critical.  Peter also believes that this is an area in which Men’s Advocacy Groups can likely help so that women are not shouldering this load alone.

One of the take home moments for me was a story Dominick shared about the first time in his entire life that he had a talk with a medical doctor about family planning was when he was in the urologist’s office getting his vasectomy.  I embarrassingly admitted that as an ER doctor when I am speaking to a male patient about condom use it is usually in the context of me treating them for an STD and my focus is primarily on preventing future infections not future babies. Made me realize that even in my speciality there are some opportunities.

Here are links to some of the information we discussed.

Mental Health Survey  

Here is the article about Dominick’s work and his commentary related to the Covid Trends and Impact Survey. This is an online survey on Facebook that has surveyed millions of people across the world. Dominick’s study focused on over 12 million participants in 115 countries from May 2021 to Sept 2021 and found that 37% of men reported feelings or depression and 34% of anxiety with younger men reporting higher levels than older ones. These numbers were similar to the percentages of anxiety and depression reported by women. Men also reported that getting more resources on how to maintain their mental health was one of their top priorities surrounding the pandemic. Their findings were somewhat atypical because outside of Covid, women are typically much more likely to report symptoms of anxiety and depression and men are much more likely to under-report their symptoms, suggesting that COVID has caused significant suffering for men. Interestingly, it also hints that COVID may have helped some men to be more open to the concept of counseling and mental health related services. 

Post-partum Depression in Men

Interestingly, when we think about post-natal depression, we tend to think it is something that only happens to newborn mothers, but Peter suggests that it is also relatively common in men.  As this shocked me, I dug around a little.

Per this JAMA article about 10% of men suffer from postpartum depression but the rate can be as high as 1 in 4, 3-6 months after birth.

Factors that might contribute to postpartum depression in men

Again, interestingly, fathers are usually not asked questions about their own coping

Here is a summary of the paper we discussed that helped a hyper-masculine profession - offshore oil workers - change their culture surrounding safety.

Take home points

Thanks for listening to seX & whY, Jeannette

Show Notes for Episode Twenty-Three of seX & whY: Issues Surrounding Men’s Health, Part 1

Host: Jeannette Wolfe Guests: Peter Baker – Director of Global Action on Men’s Health  Twitter: @pbmenshealth @globalmenhealth

Dominick Shattuck has a PhD in psychology and does Global Health Work at Johns Hopkins Bloomberg School of Public Health    

https://www.linkedin.com/in/dshattuck/        

Here is a list of Peter Baker’s publications including Men’s Health Policy: it is Time for Action.

Here is a list of Dominick Shattuck’s publications

Take home points

Please join us next month for a continuation of our conversation in which we will focus on issues surround men’s mental health and the roles that men may play in the shifting landscape of reproductive justice. 

Show Notes for Episode Twenty-Two of seX & whY: Sex, Drugs, and Rats

Host: Jeannette Wolfe Guest: Dr Irv Zucker, Faculty at UC Berkley since 1966. Interests include behavioral endocrinology, chronobiology, and sex differences in pharmacology

General discussion

Many times, the worlds of basic science and human clinical trials do not overlap to the degree that they should. Greater coordination between the two silos, especially as it comes to the examination of sex differences, would likely produce more robust, higher quality science that would benefit a greater number of patients. 

      1993 NIH Revitalization Act. To get NIH funding for human clinical trials researchers needed to include or explain why they were not including, both men and women in clinical trials

       2016 Sex as a Biological Variable. Applied above rules to basic science lab work. Irv and his team’s work were instrumental in triggering this policy change. 

Sampling of Dr Zucker's Research

This paper surveyed prominent journals from 10 different areas of basic science research and highlighted that the consideration of the existence of sex differences was rarely considered by pre-clinical researchers. Most studies included only male animals with less than 25% including both sexes.  Some concerning numbers in specific fields were totally lop-sided. For example, in neuroscience there was a 5:1 male to female animal ratio

Follow up research  reexamined these numbers after the 2016 guideline change and showed:  

Here is the paper we discussed that busted the myths surrounding female animal variability and numbers needed to study: Female mice liberated for inclusion in neuroscience and biomedical research. 

Next, we talked about pharmacokinetics: Sex differences in pharmacokinetics predict adverse drug reactions in women. They evaluated 86 drugs in which they could find published information about pharmacokinetics broken down by biological sex (for example, if the drug was absorbed, distributed, metabolized and excreted similarly or differently in male and female bodies) and then compared these findings with a data base that evaluated for adverse side effects. 

Bottom line - when giving a drug to a female start at the lowest dose possible and review other scripts they are taking to avoid potential drug/drug cross-reaction.

Also here is the amazing story of Dr Frances Kelsey who stood tall against the tremendous pressure by the manufacturers of  thalidomide to approve the drug in the United States. Her request to not approve the drug without additional data ultimately saved the lives and physical disabilities of countless babies. 

Take home points from podcast

Historically the vast amount of basic science research was done only on male animals thereby potentially missing important findings that may be unique to a specific sex. The inclusion of female animals in and by themselves do not produce greatly variability in basic science research results. In fact,  in many cases, using male animals may produce significant variability suggesting that male hormones may not be as consistent as once believed. The bottom line is, it depends on what you are studying and there are easy to apply scientific methods that can allow you to determine if hormonal variation may be playing a part in outcome results without using excessive amounts of animals. Pharmacokinetics of how a drug is absorbed, distributed, metabolized and excreted are often influenced by biological sex, yet very few drugs that are currently on the market have adequate and accessible data on pharmacokinetics broken down by biological sex. Drugs that have greater concentrations in a female body correlate to the chance of an increased likelihood of an adverse reaction. If you prescribe medications, it is a good rule of thumb to start at the lowest possible dose in a female and to ensure you review their med list to avoid predictably adverse cross reactions. The ethics around studying drugs in pregnant and lactating females are challenging especially as many of these drugs may have side effects that will not be apparent for decades. One way to help fill this gap is to run parallel basic science studies that examine long term behavior changes in animals after drug exposure.  

Thanks for listening!

Show Notes for Episode Twenty-One of seX & whY: Opioid Use Disorder

Host: Jeannette Wolfe Guests: Dr Alyson McGregor, author of Sex Matters: How Male-Centric Medicine Endangers Women's Health and What We Can Do About It Dr Lauren Walter

Here is link to American Psychiatric Association DSM 5 diagnosis for opioid use disorder from the CDC. Essentially the disorder is defined by continued craving and use of opioids despite significant social and professional consequences caused by its use.

This podcast is on sex and gender differences in opioid use disorder. Although sex (s) and gender (g) are rooted in different etiologies - biological sex via innate chromosomal and hormonal characteristics while gender is heavily influenced by sociocultural factors, they are often heavily interconnected. Experiences influence gene expression through epigenetics and if a man is exposed to different experiences than a woman, they can have different epigentic responses. Further complicating things, however, is that if a male and a female have the same experience, they can have a different pattern of gene expression because the process of epigenetics itself is influenced by innate sex. Currently, if researchers are even looking for s/g differences in their data, they are usually doing so at a very basic level like patient reported demographics, this makes further exploration as to whether discovered differences are rooted in innate physiology or cultural influences difficult. Essentially, appreciating the current limitations of research, we will use the term  “men” and “women” in this blog.

To highlight how recent the trend in research has been to even consider the potential influence of sex and gender as relevant factors in pain. A 2007 study that looked at over 10 years of research published in the journal Pain, found that almost 80% of their studies included only male animals and less than 4% looked at sex differences.

Stats

CDC- Opioid deaths accounted for > 70% of all deaths from drug overdoses (totally overdose deaths 70,630)

2019 Kaiser Family Foundation data

Opioid Overdose Deaths

2019 total deaths

Men

Women

49,860

34,635

15,225

2020 data https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm - total overdoses > 93,000 estimates that 69,710 from opioids.

For comparison 2020 mortality numbers for car crashes were 38,680

Sex and Gender Differences

Women

Men

Overall, in women compared to men, the prescription opioid abuse is decreasing more slowly while heroin use in increasing more quickly.

“From 1999 to 2010, overdose deaths increased 265% among men and 400% among women (CDC, 2018)”

Once in treatment have similar outcomes

Multidimensional approach - medical and psychosocial needs - these may be different for men and women

Sex and Gender gaps in the literature

Socioeconomic differences between typical methadone vs buprenorphine users

Increasing comprehensive services such as: housing, childcare and social support can help both men and women but what type of services they need and utilization of services may be sex/gender specific

May increase women’s participation by adding women support group and childcare services

Take Home Points

There are sex and gender physiological and sociocultural factors that come into play in substance use disorder

Finally, we talked about Alyson’s important work with the Sex and Gender Summit which is geared towards integrating sex and gender-based principles across health care curricula to better educate future providers.

Here are two great resources to learn more on how to do searches to include sex and gender:

www.sexandgenderhealth.org www.amwa-doc.org/sghc/

Show Notes for Episode Twenty of seX & whY: Interview With Dr Shirin Heidari Part 2: Gendro - Advancing Sex and Gender Equity in Science Research

Host: Jeannette Wolfe Guest: Shirin Heidari PhD, virologist and experimental oncologist, founding President of Gendro.

Part 2 of Interview with Dr Shirin Heidari

This podcast focuses on Dr Heidari’s work on systematically integrating the variables of sex and gender into different access points along the research pipeline. She helped start an organization called Gendro which is dedicated to this mission. 

The three major gatekeeping posts that Gendro and other organizations are targeting are: 

1)    Funding

Require the inclusion of both male and female animals or justify an exclusion

2)    Ethical Review Boards

These boards review research protocols prior to study enrollment to ensure that the researchers have designed their study to meet national and organization protocols designed to protect participants from being involved with unethical or dangerous practices. Traditionally these boards have been an overlooked area to target.  

3)    Journals

As many medical publishing house multiple journals, if they modify their standardized template to include query about sex and/or gender analyses, they have the power to rapidly change the expectations of authors and peer reviewers surrounding the inclusion of these factors.

In addition, we talked about the SAGER guidelines

SAGER guidelines a.k.a. Sex and Gender Equity in Research. These guidelines were put together by an international team of researchers in 2015 and geared towards giving researchers, journal editors, peer- reviewers and publishers better tools to include and evaluate the variables of sex and gender in scholarly work. Although the guidelines have increased the awareness and inclusion of these variables, and many journals have now adopted them, there continues to be a significant opportunity for more widespread use. A recent editorial highlights some of the barriers to utilization and possible concerns.

Here is a synopsis of some of the remaining barriers.  

Perceived Barrier

Solution

Mandated inclusion will significantly increase overall research costs from enrollment to additional statistical analysis

Underscore that several countries have already been successful in tying initial funding with inclusion criteria which suggests that some of resistance is likely due to ingrained culture rather than significant financial barriers. Highlight that some countries have developed new supplemental funding to enhance adoption. *

Journal editors may have significant time and resource limitations that prohibit their ability to formally introduce or monitor SAGER guidelines. 

Emphasize that optimizing science requires constant evolution and that as editors they are already well skilled in helping their journal comply with other required updates.  Including SAGER guidelines can enhance the quality of research their journal publishes and in turn enhance its reputation. 

In additional, engaging publishers to invest in better science by making system wide changes in both editorial expectations and technical support (see below) could rapidly accelerate adoption.

Peer reviewers may feel ill-equipped to evaluate for the proper inclusion of sex and gender in a review due to knowledge gaps in core principles surrounding sex and gender

Provide access to available online trainingmodules such as those offered by the Canadian Institutes of Health Research.

Enhance diversity training as who is at the table influences policy and priorities.

Technical challenges. Many publishers use the same templates across multiple journals which may limit an individual journal’s ability to change their own format.

Engage editors to encourage publishers to update digital templated formatting to reflect SAGER principles. The inclusion of a requested digital check off page in submission requirements confirming guideline compliance, could serve both as a reminder cue to the author and a screening tool to journal staff to ensure that it is completed prior to forwarding material to reviewer. This would help minimize any additional time the reviewer would need to spend to ensure SAGER compliance. 

* As an aside, identifying important sex-based differences in pre-clinical studies may ultimately be quite cost effective as they may lead to the design of more successful and cost-effective clinical trials

We also discovered the opportunities to include the variables of sex and gender in COVID vaccine research and here are two important papers that Dr Heidari just published in this area. 

A Systemic Review of the Sex and Gender Reporting in Covid-19 Clinical Trials.

75 initial published trials- 24% presented data broken down by sex and only 13% included in their discussion any discussion about potential sex differences.

Time for Action: towards an intersectional gender approach to COVID-19 vaccine development and deployment that leaves no one behind. 

Take home points from article

This now becomes very relevant as we now know that there are significant sex differences in side effects in the vaccines including increased risk of myocarditis for males in Pfizer and Moderna  (According to a recent Australian study done by their equivalent of the FDA, the Therapeutic Goods Administration (TGA) numbers may occur up to 1 in 10,000 in younger men. Of note, they suggest that chance of getting myocarditis from Covid is likely 8-10x this risk.) 

Conversely women are more likely to get increased risk of clotting with the J and J vaccine.

Show Notes for Episode Twenty of seX & whY: Interview With Dr Shirin Heidari Part 1: Sex and Gender Variables in Science Research

Host: Jeannette Wolfe Guest: Shirin Heidari PhD, virologist and experimental oncologist, founding President of Gendro.

Part 1 of this podcast spotlights the opportunity to do better science by paying more attention to the variables of sex and gender. 

Many times, we simply assume that when we study a medical question in a clinical trial that who is in the trial, adequately represents the population of folks who are affected by the condition being studied. When it comes to the consideration of gender, often this is not true. Dr Heidari and her team did  a systemic review that evaluated study participant’s gender in HIV research trials, although more than 50% of people who have HIV are women, only 19% of participants in anti-retroviral trials were women.

In 1993 the NIH passed the Revitalization Act in which NIH funded studies would be required to study both men and women. A parallel mandate for basic science research passed over 20 years later in 2015. In some ways this is incredibly nonsensical because most of medical research starts out in the basic science lab. If you don’t include animals of both sexes, in adequate numbers, from the beginning, you could be later blindsided in an expensive clinical trial by a physiological sex-based differences that could have been picked up earlier. 

Even though there has been progress over the past 30 years, Dr Heidari repeatedly makes the case that just because there are guidelines to include males and females in trials, this does not mean that these guidelines are adhered to or adequately enforced. In addition, there is often a large divide between including men and women in a study and doing an appropriate analysis to see what happens to those men and women. Essentially including both men and women isn’t all that helpful unless you breakdown your results also by gender. Importantly, the very best studies go even a step further - they include a calculation in the original study design to determine how many men and how many women would need to be included in a study so that if a difference is found that the researchers can be more confident that the difference represents a real finding and not a statistical blip. 

Another important point discussed, is the chance for skewing of study results if researchers don’t consider the gender breakdown of who drops out of a trial. Although it is not uncommon for studies to have a small number of participants drop out (and this can happen for a bunch of different reasons ranging from side effects to an inconvenient study location) it is uncommon for them to report the gender breakdown of the dropouts. If significantly more women, or men, drop out of a trial this could be a red flag that something else might be going on and hint to potential problems with the study’s conclusions. 

Our conversation then veered to discussing pharmacokinetics and pharmacodynamics. Pharmacokinetics tells us about how the body influences a drug - specifically how a drug gets absorbed, distributed, and metabolized. Pharmacodynamics, on the other hand, tells us how the drug influences the body. An example I like to use is to compare giving someone a medication to hiring a secret agent. In both cases, there is a break in, a job and an exit. Traditionally it was believed that, outside of extreme differences in body weight, that drugs worked similarly- break in/job/exit - in male and female bodies if the drug did not target a reproductive organ. We now know this default “no sex difference” assumption is not scientifically valid as there are many drugs which work differently in male and female bodies and that these differences have clinical relevancy. 

An example of this is a study we discussed on marijuana pharmacokinetics with women requiring far less amount of marijuana to experience the same cognitive effects. In the discussion section of this paper it suggests that previous studies may have under-appreciated this sex-based difference because they often had higher dropout rates in women which likely skewed their final study results. And here is the link to some of the material we discussed surrounding the knowledge gap on pregnancy and pot-smoking and how this gap has caused some pregnant women to reach out to non-traditional resources to get information. 

Other studies we mentioned

Here is a study that suggests that the gender of the researcher or lab tech may subtly influence research results. 

Here is a study that suggests that male and female animals both have similar amounts of hormonal variation.

Show Notes for Episode Nineteen of seX & whY: About Vaccine Research

Host: Jeannette Wolfe Guests:

Link to their paper: Sex Differences in Immunity: Implications for the Development of Novel Vaccines Against Emerging Pathogens

Take-home points

Other references:

Paper referred in podcast about Dr Klein: Bishof E, Wolfe J, Klein S - Clinical trials for COVID-19 should include sex as a variable.

Podcast from last summer with my interview with Evelyn Bishof and Sabra Klein about Sex Differences in Immunology and Drug Therapy

Herpes vaccine trial showing efficacy in females and not in males.

Here are some videos on the immune system:

Show Notes for Episode Eighteen of seX & whY: Mike Gisondi Announces Stanford's New, Open Access Course, "Teaching LGBTQ+ Health"

Host: Jeannette Wolfe Guest: Dr Mike Gisondi, Vice Chair of Education at the Department of Emergency Medicine at Stanford University

How prepared are you to teach the next generation of medical learners about issues surrounding care issues of LGBTQ patients?

What if you could have a free (yes, free) and totally cool resource to increase your knowledge and confidence about this material.

Drumroll……

Introducing- with perfect timing to align with LGBTQ health awareness week- an online CME course called:

Teaching LGTBQ+  Health: a faculty development course for health professions educators.  

Access through Stanford Educational Technology

Not a health care provider? No problem! You can access this information too! Did we say that it is free, free, free!

Trailer: http://bit.ly/TeachLGBTQHealth

Course Site: https://mededucation.stanford.edu/courses/teaching-lgbtq-health

Stanford’s Teaching LGBTQ+ Health course: Learners across the health professions demand improved LGBTQ+ health content and additional training opportunities in their schools’ curricula. However, most clinician educators received little, if any, training in LGBTQ+ health when they were students. This free, online, CME course addresses the gap between expected faculty teaching competency and a lack of previous faculty training.

The course is open access to educators across the health professions, as well as other providers, staff, trainees, and patients. It includes both LGBTQ+ health content and recommendations for teaching this material to trainees in any discipline or clinical department. Educators may freely download portions of the course for use in their daily clinical teaching or their school’s curriculum.

Authors: Michael A. Gisondi, MD Shana Zucker, MD/MPH/MS (cand.) Timothy Keyes, MD/PhD (cand.) Deila Bumgardner, MA

Show Notes for Episode Seventeen of seX & whY: Impact of Gendered Masculinity in Health Engagement and Decision-making

Host: Jeannette Wolfe

Guests: Dr Fahad Saeed, Nephrologist and Palliative Care Specialist from the University of Rochester

Dr Lauren J. Parker, PhD, Dual PhD in Gerontology and Health Promotion, scientist at the Johns Hopkins Bloomberg School of Public Health

The topic today discussed how masculinity and race can impact access to health and health related decisions.  

Take home points

Increase public messaging to normalize the need for men’s preventative health

Increase diversity amongst medical providers

Reach men where they are like sporting events, barber shops and churches

Acknowledge and appreciate the unique roles and challenges that many men face

Target and adjust messaging to engage men at different life points

Palliative care is a specialty that helps patients, and their families cope with a life shortening illness and to optimize their quality of life.  Patients in palliative care can still receive aggressive disease modifying therapy like chemotherapy with the except of patients receiving “hospice care”.   Hospice care, although still under the palliative care umbrella, has slightly different rules.  Under hospice, it is recognized that a patient is likely in their last 6 months of life and that they would no longer benefit from aggressive treatments, all care is redirected to optimize comfort.

Dr Saeed’s tips surrounding palliative care engagement in men with advanced cancer

Links

- Dr Lauren Parker’s paper that examines ways to more effectively engage men in their health. - List of her other publications- TEDX Rochester talk by Dr Saeed - Links to Dr Saeed’s publications - His specific research that we discussed - 2012 paper that Dr Saeed referenced by Susan Wong

Show Notes for Episode Sixteen of seX & whY: Interview with Dr Saralyn Mark

Host: Jeannette Wolfe

Dr Mark has had an incredibly interesting and eclectic career. She is trained in Endocrine, Geriatrics and Women’s Health and has worked for and/or consulted with:

The Office of Women’s Health in Department of Health and Human Services, NASA and 4 different Whitehouse Administrations

She has also written the book Stellar Medicine: A Journey through the Universe of Women’s Health 

In addition, she has founded two different companies 

Our discussion features some of the highlights of Dr Mark’s career as well as surveys a bunch of uncommonly recognized, yet important sex and gender based differences in medicine, technology and industry. We talk about sex and gender based differences in military equipment, PPE, laparoscopic tools, automobile safety and Covid-19. 

Show Notes for Episode Fifteen of seX & whY: Sex Differences in Immunology and Drug Therapy

Host: Jeannette Wolfe

Guests:

Evelyne Bischof MD, Associate Professor of Medicine at Shanghai University of Medicine and Health Sciences and internist at University Hospital of Basel Switzerland

Sabra Klein, PhD, Professor of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health

This podcast focused on sex differences in immunology and pharmacology and its relevance to the Covid-19 pandemic.

Key points

Two unexpected findings associated with COVID-19

References:

Bischof E, Wolfe J, Klein S: Clinical trials for Covid-19 should include Sex as a Variable. JCI 2020

Engler R, Nelson M, Klote M, et al. Half- vs Full-Dose Trivalent Inactivated Influenza Vaccine (2004-2005) Age, Dose, and Sex Effects on Immune Responses, JAMA Internal Medicine 2008

Gender and COVID-19 Working Group website

Global Health 50/50  global deaths disaggregated by sex

Klein S, Pekosz A, Park H. et al.  Sex, age and hospitalization drive antibody responses in a Covid-19 convalescent plasma donor population. JCI 2020

Roberts M, Genway S How Artificial Intelligence is transforming drug design. DDW

Souyris M, Cenac C, Azar P, et al. TLR7 Escapes X Chromosome Inactivation in Immune Cells. Autoimmune Disease 2018

Takehiro T, Ellingson M, Wong P et al. Sex Differences in Immune Responses that underlie COVID-19 disease outcomes. Nature 2020

Zucker I, Prendergast B.  Sex differences in pharmacokinetics predict adverse drug reactions in women. Biology of Sex Differences 2020

Special thanks to Doug Deems for help with editing

Show Notes for Episode Fourteen of seX & whY: COVID-19 through a Gender Based Lens Part 2

Host: Jeannette WolfeGuests: Dr Gary Barker CEO of Promundo- an organization that promotes healthy masculinity and gender equality

Dr Stephen Burrell Assistant Professor in the Dept of Sociology at Durham University - whose area of focus in on engaging men and boys in the prevention of violence against women.

Here are some of the take-home points of our discussion.

Here is the link to the Pew Study that Dr Barker mentioned.

Here is the link for the Harvard GenderSci

Here are some links for the challenges India is having with obstetrical care including this NY Times article

Amanda Nguyen's Rise UP 19 program that allows domestic violence victims to be helped by restaurant owners.

Special thanks to Doug Deems who helped me edit this podcast.

Show Notes for Episode Fourteen of seX & whY: COVID-19 through a Gender Based Lens Part 1

This is a discussion on how gender-associated norms impact disease process.

Host: Jeannette Wolfe Guests: Dr Gary Barker CEO of Promundo- an organization that promotes healthy masculinity and gender equality 

Dr Stephen Burrell Assistant Professor in the Dept of Sociology at Durham University- who’s area of focus in on engaging men and boys in the prevention of violence against women.

Today’s podcast features the first part of our discussion which focuses on how “gender” roles and norms impact general health and the COVID-19 pandemic. Both of our guests are experts on how societal perceptions and stereotypes surrounding “masculinity” influence the health and well-being of both men and women. Through Promundo, Dr Barker has done significant amounts of work in Brazil where toxic masculinity has been associated with the early deaths of millions of young men and Dr Burrell recently wrote the article: Coronavirus reveals just how deep macho stereotypes run through society. 

Our discussion focuses on:

Show Notes for Episode Thirteen of seX & whY: LGTBQI Health-related Issues Part 3

How best to support students and colleagues in the LGBTQ community

This is a very special podcast and I want to deeply thank Shana Zucker, Ellie Ragone and Mike Gisondi for sharing their very personal experiences.

Host: Jeannette Wolfe Guests: 

Shana Zucker, MS

Ellie Ragone DO

Michael Gisondi

Tips offered by the group

Accountability buddy article

https://www.aliem.com/peer-accountability-strategy-maintaining-commitment/

Special thanks to Doug Deems who helped me edit this podcast

Show Notes for Episode Thirteen of seX & whY: LGTBQI Health-related Issues Part 2

How to take better care of transgender patients when they seek medical care

Host: Jeannette Wolfe Guests: 

Quotes used are from Dr Samuel and her team’s paper: “Sometimes You Feel Like the Freak Show": A Qualitative Assessment of Emergency Care Experiences Among Transgender and Gender-Nonconforming Patients Ann Emerg Med 2018

 Here are 10 take-home points

Delivering Intentional habits to care for our transgender patients actually helps us deliver better care to our cisgender patients too. Appreciate that many trans and gender non-conforming patients are incredibly reluctant to seek out medical care due to previous discriminatory treatment, Don’t assume a trans patient is out to the other people in the room and offer to speak with them privately Ask their name, if different than expected ask them if they have a different legal name, then confirm how they would like to be addressed and what pronouns they use. Respectfully update other team members about this information so that the patient doesn’t need to unnecessarily repeat themselves. Importantly how we model this message to our staff can set the tone for how these patients will be treated, so take this responsibility seriously. When asking about past medical history, surgical histories and current medication make sure that you are clear as to why you are asking and how it relates to their current medical problem. In trans patients that present with abdominal pain, don’t assume because they physically look like their asserted sex that they lack organs from their biological one such as ovaries or a prostate. Remember to ask. When admitting a trans patient, if a private room is unavailable they should be roomed with patients of their asserted gender. If not already doing so, encourage your hospital to use software that allows an individual’s sexual orientation and gender identity to be included in a separate field of their medical record If you are a medical educator, look for ways to include an issue

Show Notes for Episode Thirteen of seX & whY: LGTBQI Health-related Issues Part 1

Host: Jeannette Wolfe Guests: 

This is the first of a three-part series that will cover LGTBQI health related issues. This podcast focuses on some basic definitions and general principles surrounding the care of gender non-conforming children and adolescents. It also discusses some of the gender affirming hormonal and surgical options available to patients. 

Resources that we discussed

The link to USCF’s Center of Excellence for Transgender Health

The link to the American Academy of Pediatrics statement on transgender and gender diverse children.

The link to the Gender Unicorn  

Basic definitions

Biological Sex 

Gender 

Gender Identity

Gender Expression

Gender Asserting

Gender Affirming

Gender Dysphoria

Hormones commonly used

Gender affirming surgeries

Transwomen

Transmen

Gender non-conforming health related issues that can occur in transgender and gender non-conforming patients

Take home points

Next month we will focus on how we can deliver better care to transgender and gender non-conforming patients in our emergency departments.

Show Notes for Episode Twelve of seX & whY: Sex and Gender Differences in CPR Part 3

Host: Jeannette Wolfe Guest: Dr Justin Morgenstern

Here is a link to Justin Morgenstern’s awesome First10EM blog site where you can find an excellent review of the two papers that we discussed today: Perman’s DNR paper and Huded’s Cleveland Clinic Study on gender gaps in 30 day survival after ST elevation myocardial infarctions.

Here are some take home points for this podcast: 

Here is a table that shows outcome data from Bosson’s JAHA paper from LA County data base that we briefly mentioned on the podcast.  

Men

Women

CPR

41%

39%

shockable

35%

22%

STEMI

32%

23%

Cath

25%

11%

TTM

40%

33%

Survival/CPC 1-2

24%

16%

Other studies discussed.

European study that examined sex-differences in atrial fibrillation study

Danish study on cardiac arrests in people less than 35 with 2 to one ratio of men to women

Korean eunuch study suggesting that a historical lineage of castrated males outlived several socioeconomically matched peers, supporting the concept of a disposable soma theory.

Cleveland Clinic informational sheet on arrhythmias in women

Study that suggests more women than men die or go to hospice after an intracranial hemorrhage and brings up idea of gender-based differences in “social capital” contributing to this difference

EOL choices in advanced cancer patients showing gender differences in palliative care and DNR preferences

Show Notes for Episode Twelve of seX & whY: Sex and Gender Differences in CPR Part 1 & 2

Host: Jeannette Wolfe Guest: Dr Justin Morgenstern

Two big databases surrounding cardiac arrest

Here are two great articles that cover this material in depth

What we know

(46% vs 52%  in one study)

(one study 29% men vs women 16% with initial shockable rhythm)

First study

Gender disparities among adult recipients of bystander cardiopulmonary resuscitations in the Public from Audrey Blewer in Cir Cardiovasc Qual Outcomes 2018

Primary study question- is there an association between an individual’s biological sex and the likelihood they will receive bystander CPR

Resuscitation Outcomes Consortium (ROC) 2011-2015

This was a retrospective analysis of data collected in a prospectively for several clinical trials in out of hospital cardiac arrests from 7 of these sites.

Exclusion:

Traumatic arrest

Occurs in a residential institution or hospital

Less than 18

CPR initiated by someone who was not a layperson (police EMS doc)

The variable they used in logistic regression modeling included whether event was witnessed, location, layperson CPR, time of event, and basic demographics including age, race, gender

Nontraumatic out of hospital cardiac arrests

19331 events

Mean age 64

63% male

17% public location (3297)

82% private (15788)

Overall 37% received CPR (38% of men and 35% of women)

If collapse occurred in public place

If collapse occurred in private place

Overall: Males had 29% increased odds of survival

Bottom line: If you have a OHCA in public you are about 6% more likely to receive CPR if you are a man than a woman

This is not the only study showing gender differences in CPR here is a   Netherland study and an avatar study which also highlight these differences.

There are also studies suggesting subtle gender differences in EMS treatment of chest pain/cardiac arrest:

Ok so why is that happening?

So first let’s talk about some general barriers to stepping up and doing CPR in public-

A 2008 study by Swor in Annals of EM interviewed almost 700 bystanders to an OHCA. Although about ½ of the bystanders had previous CPR training only about 20% actually started doing CPR.

Cited barriers to doing CPR included:

- feeling of panic (reported by about 38% )

- concern of doing it incorrectly (9%)

- concern they could cause harm (1%)

- reluctance to do mouth to mouth (1%)

In another study which surveyed community members from areas in which there were low rates of bystander CPR to understand why the rates were so low, answers included:  

- fear of getting sued

- emotional overtones of the situation

- lack of knowledge

- situational concerns 

A different study suggested that disagreeable physical characteristics- read dentures and vomit-  might hamper CPR initiation.

Overall you are more likely to step up and do CPR if

So the next question is, are these the reasons why there is a gender difference in who gets bystander CPR or are there additional factors to consider.

Second study

Public Perceptions on Why Women Receive Less Bystander Cardiopulmonary Resuscitation than Men in Out of Hospital Cardiac Arrest

Perman Circulation 2019

 Primary Question- what are the public perceptions as to why women are less likely to get bystander CPR?                                            

Methods- Electric survey via Amazon’s crowdsourcing platform- Mechanical Turk. Participants were English, >18 and familiar with CPR principles

Mechanical Turk- have “master users” people achieve this rate by apparently having a history of completing other surveys out appropriately in the past (essentially successfully answering planted “attention” surveys which suggests that they are actually reading the surveys)

Participants were asked 11 multiple choice questions and one free text- “ Do you have any ideas on why women may be less likely to receive CPR than men when they collapse in public?” Free text responses were coded and major themes were identified by using an inductive qualitative method.  

548 subjects

542 completed surveys

average age 38

equal number of males and females about 1% of participants were transgender

81% White 7% Black 6% Asian 3% Hispanic

45% college diploma

½ were trained at some time in CPR (top reasons for training were cited a work or volunteer related requirement)

24 had actually done CPR on a collapsed person-

Three major themes evolving:

1) Sexualization of woman’s bodies (40% of men mentioned versus 29% of women)

     - fear of making incidental contact with a woman’s breast

“I think that people are afraid to touch the breast region, so hesitate to administer CPR”

     - fear of being wrongfully accused of sexual abuse

“Bystanders, especially male bystanders, may be afraid to touch women especially in the chest area... anxious that their help my be unnecessary and therefore touching may be misconstrued”

“Men are afraid of seeming like perverts”

2) Perception that women are weaker and frailer and thus at greater risk for injury if CPR was not really needed

“People might be afraid of hurting them since women tend to be smaller and more fragile looking than men”

3)  Misperception of what actual distress looks like in females

”They are not known to have as many heart attacks in public, they are known to be healthier”

 “ Maybe people assume they are being dramatic and overreacting so CPR isn’t needed” 

Interestingly in the open- ended responses it was frequently implied by use of pronouns that the bystander initiating CPR would be a man. Along these lines, this European paper hints that gender related issues may also influence who steps up to start CPR.

My (liberal) summary of paper:

“Look I’m not super thrilled about the idea of touching a woman’s breast and quite frankly I’m a little scared about being accused of sexual assault.  And also, if I’m honest, I’m a little suspicious that the woman might be collapsing from something less serious, because most cardiac arrests seem to happen in guys. Finally, if I do start CPR on a woman and they really didn’t need it, I’m afraid I might accidentally physically hurt her.

Five take home points

Other references

High Sensitivity Troponin and Gender Differences in treatment after ACS

North Carolina’s Heart Rescue Intervention

Article about CPR and Good Samaritan laws

Show Notes for Episode Twelve of seX & whY: Sex and Gender Differences in CPR Part 1 & 2

Host: Jeannette Wolfe Guest: Dr Justin Morgenstern

Two big databases surrounding cardiac arrest

Here are two great articles that cover this material in depth

What we know

(46% vs 52%  in one study)

(one study 29% men vs women 16% with initial shockable rhythm)

First study

Gender disparities among adult recipients of bystander cardiopulmonary resuscitations in the Public from Audrey Blewer in Cir Cardiovasc Qual Outcomes 2018

Primary study question- is there an association between an individual’s biological sex and the likelihood they will receive bystander CPR

Resuscitation Outcomes Consortium (ROC) 2011-2015

This was a retrospective analysis of data collected in a prospectively for several clinical trials in out of hospital cardiac arrests from 7 of these sites.

Exclusion:

Traumatic arrest

Occurs in a residential institution or hospital

Less than 18

CPR initiated by someone who was not a layperson (police EMS doc)

The variable they used in logistic regression modeling included whether event was witnessed, location, layperson CPR, time of event, and basic demographics including age, race, gender

Nontraumatic out of hospital cardiac arrests

19331 events

Mean age 64

63% male

17% public location (3297)

82% private (15788)

Overall 37% received CPR (38% of men and 35% of women)

If collapse occurred in public place

If collapse occurred in private place

Overall: Males had 29% increased odds of survival

Bottom line: If you have a OHCA in public you are about 6% more likely to receive CPR if you are a man than a woman

This is not the only study showing gender differences in CPR here is a   Netherland study and an avatar study which also highlight these differences.

There are also studies suggesting subtle gender differences in EMS treatment of chest pain/cardiac arrest:

Ok so why is that happening?

So first let’s talk about some general barriers to stepping up and doing CPR in public-

A 2008 study by Swor in Annals of EM interviewed almost 700 bystanders to an OHCA. Although about ½ of the bystanders had previous CPR training only about 20% actually started doing CPR.

Cited barriers to doing CPR included:

- feeling of panic (reported by about 38% )

- concern of doing it incorrectly (9%)

- concern they could cause harm (1%)

- reluctance to do mouth to mouth (1%)

In another study which surveyed community members from areas in which there were low rates of bystander CPR to understand why the rates were so low, answers included:  

- fear of getting sued

- emotional overtones of the situation

- lack of knowledge

- situational concerns 

A different study suggested that disagreeable physical characteristics- read dentures and vomit-  might hamper CPR initiation.

Overall you are more likely to step up and do CPR if

So the next question is, are these the reasons why there is a gender difference in who gets bystander CPR or are there additional factors to consider.

Second study

Public Perceptions on Why Women Receive Less Bystander Cardiopulmonary Resuscitation than Men in Out of Hospital Cardiac Arrest

Perman Circulation 2019

 Primary Question- what are the public perceptions as to why women are less likely to get bystander CPR?                                            

Methods- Electric survey via Amazon’s crowdsourcing platform- Mechanical Turk. Participants were English, >18 and familiar with CPR principles

Mechanical Turk- have “master users” people achieve this rate by apparently having a history of completing other surveys out appropriately in the past (essentially successfully answering planted “attention” surveys which suggests that they are actually reading the surveys)

Participants were asked 11 multiple choice questions and one free text- “ Do you have any ideas on why women may be less likely to receive CPR than men when they collapse in public?” Free text responses were coded and major themes were identified by using an inductive qualitative method.  

548 subjects

542 completed surveys

average age 38

equal number of males and females about 1% of participants were transgender

81% White 7% Black 6% Asian 3% Hispanic

45% college diploma

½ were trained at some time in CPR (top reasons for training were cited a work or volunteer related requirement)

24 had actually done CPR on a collapsed person-

Three major themes evolving:

1) Sexualization of woman’s bodies (40% of men mentioned versus 29% of women)

     - fear of making incidental contact with a woman’s breast

“I think that people are afraid to touch the breast region, so hesitate to administer CPR”

     - fear of being wrongfully accused of sexual abuse

“Bystanders, especially male bystanders, may be afraid to touch women especially in the chest area... anxious that their help my be unnecessary and therefore touching may be misconstrued”

“Men are afraid of seeming like perverts”

2) Perception that women are weaker and frailer and thus at greater risk for injury if CPR was not really needed

“People might be afraid of hurting them since women tend to be smaller and more fragile looking than men”

3)  Misperception of what actual distress looks like in females

”They are not known to have as many heart attacks in public, they are known to be healthier”

 “ Maybe people assume they are being dramatic and overreacting so CPR isn’t needed” 

Interestingly in the open- ended responses it was frequently implied by use of pronouns that the bystander initiating CPR would be a man. Along these lines, this European paper hints that gender related issues may also influence who steps up to start CPR.

My (liberal) summary of paper:

“Look I’m not super thrilled about the idea of touching a woman’s breast and quite frankly I’m a little scared about being accused of sexual assault.  And also, if I’m honest, I’m a little suspicious that the woman might be collapsing from something less serious, because most cardiac arrests seem to happen in guys. Finally, if I do start CPR on a woman and they really didn’t need it, I’m afraid I might accidentally physically hurt her.

Five take home points

Other references

High Sensitivity Troponin and Gender Differences in treatment after ACS

North Carolina’s Heart Rescue Intervention

Article about CPR and Good Samaritan laws

Show Notes for Podcast Eleven, Part 2 of seX & whY

Host: Jeannette Wolfe

This is a continuation of my interview with Dr. Cara Tannenbaum, Professor in the Faculties of Medicine and Pharmacy at the Université de Montréal in Canada, and Scientific Director of the Institute of Gender and Health of the Canadian Institutes of Health Research

Our discussion and the following table is centered around this recent review article by Dr. Tannenbaum found in Pharmacology Research 2017

Type of experiment

Traditional way

Better way

                 Stem cells

-Male cells

-Unknown sex of stem cells

-Problems: in immortal cell lines the integrity of in vivo sex chromosomes diminishes over time and can complicate the identification of sex- based differences.

Similarly, although normal female cells have two X chromosomes- one from the mother and one from the father- one of those chromosomes is usually turned “off”. With Stem cells however, after multiple reproductive cycles there can get something called “X skewing” in which instead of some cells turning off the maternal chromosome and others the paternal one, there is overrepresentation of one line.

Conversely in “X escape”, the second X chromosome is no longer getting inactivated and this can cause trouble because too much X gene is getting expressed (for example this could lead to significant autoimmune problems) 

Use and record results of both male and female cell lines

Know sex & of donor     

-       Include cell lines with finite life spans

-       Add sex hormones to XX and XY cell

-       X chromosomes house genes that influence: cellular growth, metabolism and immunity

-       Y chromosomes contain genes beyond SRY (which makes testosterone), and if loss Y chromosome increased risk of Alzheimers and certain cancers

Gendered Innovations group in Korea has actually labeled sex of commercial cell lines

Lab animal

Standard use of male animals

-80% of traditional research done on males

-Females felt to be too variable due to estrous cycle* (average of 4 days)

Inclusion of female animals**

-analyze data by sex

-include factorial designs that allow for the identification of age or hormonal influence in outcome

-Consideration of housing conditions that can lead to hormonal fluctuations

Phase trials

Change began with The NIH Revitalization

Phase 1 and 2

Currently it is believed that women still make up less than 25% of Phase 1

Include sex and age as independent variables

Further query if discovered sex differences are due to sex-based differences in pharmacokinetics (how our body’s characteristics like our weight or liver function influence the drug) or pharmacodynamics (how the drug influences our body) 

Phase 3 trials

As it was believed that outside the reproductive organs that males and females were physiologically the same,  most studies focused on males and thus side effects in females were often missed or underappreciated  

Report and analyze data by sex and age

Use updated statistical models to calculate appropriate sample sizes prior to starting study so that any identified differences are likely to represent valid findings  

Further explore hormonal states of study participants. For example, if they are pre or post menopausal, pregnant, or if they are taking hormones such as estrogen or testosterone.

56% of participants in drug trials submitted to FDA in 2018 were women

Phase 4

As this is further analysis of a drug after it hits the market, it can take a long time to pick up sex-based differences.

Poster child of this is Ambien in which dosing adjustment for women took 20 years

Analyze results from “real world” use of drug and its side effects by sex and age

Go back to lab to identify etiology of discovered sex or age differences

Adjust dosing when important differences are discovered

Click here for a paper that nicely summarizes the reasons behind why females were underrepresented in scientific research during the 20th century.

Other points   

What we do (and what society allows us to do) influences our epigenetics and future gene expression.

For example, our gendered professions- men work more in coal mines and women in nail salons- can influence stuff we are exposed to which in turn can influence are future gene expression.  This is further complicated by males and females having potentially different DNA modifications after exposure to the same insult. Ultimately this can make it tricky to sometimes distinguish what is a sex- based difference versus a gender one.

Miscellaneous

2017 Tetris study on decreasing PTSD intrusive thoughts after C-section.

Show Notes for Podcast Eleven of seX & whY

Host: Jeannette Wolfe

Interview with Dr. Cara Tannenbaum, Professor in the Faculties of Medicine and Pharmacy at the Université de Montréal in Canada, and Scientific Director of the Institute of Gender and Health of the Canadian Institutes of Health Research

Definitions

Biological Sex- chromosomes, hormones, reproductive anatomy, usually binary

Gender- social and cultural construct- falls on a spectrum

Historically factors that limited the inclusion of women in clinical trials.

Interesting sex and gender differences in car crashes

What we know from NHTSA data and Insurance Institute for Highway Safety

Other evidence that the clinical relevance of studying different sized and biomechanical models in crashes is important is shown by data obtained in 2011 after the NHTSA changed their safety star ratings to include testing of a female sized dummy in the front passenger seat. Many cars found their ratings go down, for example the 2011 Sienna minivan saw its ratings for passenger frontal crashes go from 5 star to 2 after it was shown that at 35mph that 20-40% of female dummies were killed or seriously injured compared to the industry average of 15%.

Underscoring the “literal” blind spots that can occur if you don’t consider factors associated with diversity in study design, a recent study from Georgia Tech suggested that some of the visual recognitions systems used that are critical for self-driving car safety may not adequately recognize dark skinned faces showing a 5% increased chance of error in recognition compared to that of fair skinned faces. Of note, there is a significant lack of gender and racial diversity in the self-driving car technology teams and in artificial intelligence/tech research overall.

Who makes up the team influences what gets studied, click here for a recent Lancet article and here for a Nature Human Behavior one both  showing that sex-related outcomes are far more likely to be reported in medical research consisting of diverse teams.

Take home points

Next month we will look at the science pipeline from bench to bedside to identify opportunities to do better science.

Show Notes for Podcast Ten of seX & whY

Host: Jeannette Wolfe

Guests: Adam Kellogg, Associate residency directory and medical education fellowship director UMMS - Baystate and Mike Gisondi, Vice-chair of education at Stanford

Topic: How to Give Better Feedback

What is bad feedback -

Know what role you are playing (from Thanks for the Feedback)

We are most effective giving and receiving feedback if expectation of roles match up - ie a novice putting in their first central line needs a coach not an evaluator. 

Radical Candor- Develop as a Leader and Empower your Team by Kim Scott

Feedback formula by Lisa Stefanar KSE leadership

General tips

Suggested books

Thanks for the Feedback- Douglas Stone Sheila Heen

Radical Candor by Kim Scott

Articles by Mike Gisondi and Lisa Stefanac and the Feedback Formula

https://icenetblog.royalcollege.ca/2018/10/02/the-feedback-formula-part-1-giving-feedback/

https://icenetblog.royalcollege.ca/2018/10/23/the-feedback-formula-part-2-receiving-feedback/ 

Wise feedback intervention: https://www.apa.org/pubs/journals/releases/xge-a0033906.pdf

Harvard Business School article on gender differences in receiving feedback https://hbr.org/2016/04/research-vague-feedback-is-holding-women-back

Harvard Business School article with deals with managing emotional response to feedback

https://hbr.org/2016/09/how-to-give-feedback-to-people-who-cry-yell-or-get-defensive

Show Notes for Podcast Nine of seX & whY

Host: Jeannette Wolfe

Guests: Dr. Dan O’Connor, Dr. Anna Mueller

Topic: Gender Differences in Resident Evaluation

Welcome back to Sex and Why. In this episode I am joined by Dr. Dan O’Connor, a dermatology resident at Harvard and co-founder of Monte Carlo software that makes apps for medical educators, and Dr. Anna Mueller, who is a medical sociologist and Professor in the Department of Comparative Human Development at the University of Chicago. They are here to discuss their research showing gender disparities in evaluations of emergency medicine residents. 

First study

Comparison of Male vs Female Resident Milestone Evaluations by Faculty During Emergency Medicine Residency Training. JAMA Internal Medicine 2017

This study examined data from a real time milestone evaluation app used on emergency medicine residents. It involved 356 residents (66% male 34% female) and 285 faculty (68% male and 32% female) at 8 different sites and included over 33,000 evaluations. They showed that although male and female residents had similar evaluations during their first year of training, by their 3rd year male residents were evaluated statistically higher across all 23 core competencies and this occurred regardless of the gender of the evaluator.

Second study

Gender Differences in Attending Physicians’ Feedback to Residents: A Qualitative Analysis. Journal of Graduate Medical Education 

This follow up study was done to better understand why there are gender differences in the evaluations and focused on a qualitative analysis of comments written about third year residents at one of the above program sites. It involved analyzing and creating summaries of individual residents (who had at least 15 written evaluations) and included an analysis of over 1000 comments on more than 45 residents.

General findings:

Steps moving forward

 Stay tuned for next month in which we will tackle feedback.

Dayal, A., O’Connor, D. M., Qadri, U., & Arora, V. M. (2017). Comparison of Male vs Female Resident Milestone Evaluations by Faculty During Emergency Medicine Residency Training. JAMA Internal Medicine, 177(5), 651. https://doi.org/10.1001/jamainternmed.2016.9616

Mueller, A. S., Jenkins, T. M., Osborne, M., Dayal, A., O’Connor, D. M., & Arora, V. M. (2017). Gender Differences in Attending Physicians’ Feedback to Residents: A Qualitative Analysis. Journal of Graduate Medical Education, 9(5), 577–585. http://www.jgme.org/doi/10.4300/JGME-D-17-00126.1

Additional studies we talked about

MRI study about political views- evaluated how individuals with definitive political views may process contradictory information differently than individuals with more flexible mindsets.  Kaplan, J. T., Gimbel, S. I., & Harris, S. (2016). Neural correlates of maintaining one’s political beliefs in the face of counterevidence. Scientific Reports, 6, 39589. Retrieved from http://dx.doi.org/10.1038/srep39589

Thoracic surgery study that suggests that male surgical fellows may actually receive more advanced operative experience than their female matched peers

Meyerson, S. L., Sternbach, J. M., Zwischenberger, J. B., & Bender, E. M. (2017). The Effect of Gender on Resident Autonomy in the Operating room. Journal of Surgical Education, 74(6), e111–e118. https://doi.org/10.1016/j.jsurg.2017.06.014

JAMA study perceiving gender differences in implicit bias in academic medicine

Jagsi  R, Griffith  KA, Jones  R, Perumalswami  CR, Ubel  P, Stewart  A.  Sexual harassment and discrimination experiences of academic medical faculty.  JAMA. 2016;315(19):2120-2121. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526590/

Show Notes for Podcast Eight of seX & whY

Host: Jeannette Wolfe

Guests: Dr. John Coates

Topic: The Influence of Testosterone and Cortisol on Decision Making, With Neuroscientist Dr. John Coates

Dr. John Coates is a neuroscientist and author of The hour between dog and wolf- how risk taking transforms the body and mind.  He is an ex-trader and now runs Dewline Research. He studies how subtle unconscious changes in an individual’s physiology can shift their decision making and is particularly interested in the roles of testosterone and cortisol.  He is specifically focused on how the fluctuation of these hormones might influence volatility in the stock market. As it appears that both successful traders and emergency medicine are required to make high impact decisions in novel and often unpredictable situations, I think there is much we can learn from his work and I am thrilled he could join us for this discussion.

Before we delve in, I’d like to remind folks that my interest in this material is to better understand how individuals and teams can optimize their performance under stress. The material we are covering in this podcast- the possible influence of sex hormones on decision making- is undoubtedly going to make some listeners uncomfortable. I truly believe, however, that this topic is important and deserves an honest and curious appraisal. To be absolutely clear, I do not believe that there is a better sex equipped with a better brain, rather that there are simply different neurobiological ways that different brains use to approach and complete similar tasks. My goal here, is for us to develop better insight into how we individually react under different high stress scenarios. Hopefully, we can then use this information to explore new ways to play up our individual strengths and mitigate potential vulnerabilities. Let’s get started.

Over the years, Dr. Coates and his team have  conducted some pretty interesting “field work” studies especially his 2008 study on London short traders. In that study his team took twice daily saliva samples in 17 male traders over an 8 day period and found:

Since then he has done several additional studies and concludes that the only way to really understand the bubbles and crashes of the stock market is by better understanding the human physiology of the traders.  Here are some of his take home points.

 “Winner’s Streaks”

- In the research community there is still some controversy as to whether this phenomenon even exists or if such streaks simply represent statistical outliers that are selectively remembered due to their unusualness.

- Coates strongly believes that winner’s streaks are real and are crucial to understanding behavior under certain circumstances.

- There is good data in the animal kingdom to suggest that if two male animals are in a competition and if their size, motivation (i.e. being hungry versus well fed) and baseline aggression are all controlled, that the animal who wins that encounter will be statistically more likely to go on and win their next competitive encounter.

Some theories as to why this might occur:

Over a period of time, consistently elevated testosterone levels might offer an advantage by increasing:

Like most hormones, however, testosterone’s effects likely plot out on an inverted U shape curve in that depending on the circumstances:

Specific research done by Coates and his team

Tennis experiment

Question addressed: Are “winning streaks” a real phenomenon or simply statistical outliers?

What they did- Looked at large data base of historical tennis matches in which players who were similarly ranked went into an extended tiebreaker involving more than 20 points in the first set and in which the winner was determined by only two points. (They did this to essentially try and show that on the day of their competition that not only were both players similarly ranked but that they were also playing at a similar level- i.e. both were having a “good day”)

Results- Men (N=235 matches) who won their first set were 60% more likely to win second set but no significant difference in second set victory was found amongst women (N= 140), suggesting that this might be driven by testosterone as women have about 5-10% level of men. 

Cortisol study

In this study Coates and his team were interested in how an acute and a chronic elevation in stress hormones might affect risk preference. Using data from one of their previous studies which showed that during a period of increased market volatility that traders had a 68% increase in their daily cortisol levels, they went back to the lab to try and replicate this finding and then test decision making in a more controlled environment.  

What they did: randomized double-blind placebo controlled cross over-study involving 20 men and 16 women. In treatment arm, volunteers were given weight- based hydrocortisone 3x a day for 8 days to mimic cortisol increases seen in traders. All participants played a lottery style game in which they could choose an option in which they had a lesser chance of winning but a higher pay out if they did, or a less risky option in which they had an overall increased chance of winning but at a lower expected payout. The game was played after acute and chronic dosing.  

Findings- they did not find a difference in risk preference amongst volunteers after they received their initial hydrocortisone (as an aside, the literature on risk preference after acute cortisol increase is somewhat inconsistent) but in this study they did find that after 8 days of taking exogenous steroids that individuals became much more risk adverse and that men were affected more so than women.

Thoughts as to why chronically elevated steroids change our decision making

Using this data, Coates theorizes that prolonged periods of financial uncertainty in the stock market likely cause traders’ cortisol levels to increase and stay increased leading to an aversion to risk or an “irrational pessimism” that left unchecked can lead to a bear market.

Finally, attached below is a reference to a recent review article that Dr. Coates wrote summarizing his theories as to the relationship between cortisol and testosterone on bull and bear markets and emphasizing the importance of field work in scientific discovery and refinement. 

To learn about some complementary research being done at Wharton check out this interview with Gideon Nave and Amos Nadler in which they discuss their recent work evaluating decision making in men using exogenous testosterone. They found that that although certain cognitive functions appeared unaffected (like doing math problems), men who were given testosterone gel were more likely to rely on their gut instinct when answering questions. Which, again, depending upon the circumstances could be potentially helpful or harmful.

Coates, J. M., & Herbert, J. (2008). Endogenous steroids and financial risk taking on a London trading floor. Proceedings of the National Academy of Sciences of the United States of America, 105(16), 6167–72. https://doi.org/10.1073/pnas.0704025105

Kandasamy, N., Hardy, B., Page, L., Schaffner, M., Graggaber, J., Powlson, A. S.,Coates, J. (2014). Cortisol shifts financial risk preferences. Proceedings of the National Academy of Sciences of the United States of America, 111(9), 3608–13.

Page, L., & Coates, J. (2017). Winner and loser effects in human competitions. Evidence from equally matched tennis players. Evolution and Human Behavior. https://doi.org/10.1016/j.evolhumbehav.2017.02.003

Coates, J., & Gurnell, M. (2017). Combining field work and laboratory work in the study of financial risk-taking. Hormones and Behavior, 92, 13–19. https://doi.org/10.1016/j.yhbeh.2017.01.008

Show Notes for Podcast Seven of seX & whY, Part 2

Host: Jeannette Wolfe

Guests:

Dr. Neha Raukar, Emergency and Sports Medicine Physician

Katherine Snedaker, Executive Director of Pink Concussions

Topic: Sex and Gender Differences in Concussions

This is part II of our discussion about concussion with Katherine Snedaker and Neha Rauker.

Today’s podcast focuses on recovery and prevention.

Here are the take home points:

Thank you again to my guests!

Show Notes for Podcast Seven of seX & whY, Part 1

Thank you for Alyson McGregor for correctly pointing out that although the NIH, as of January 2016, does require its basic scientists to include both males and female animals in their grant proposals it is not called the “Research for All Act”. The Research for All Act of 2014 is actually a bill sponsored by Congressman Jim Cooper of Tennessee that would require, among other things, that the FDA have access to subgroup analysis of data by sex prior to granting expedited approval of a new product. As of now, this bill has not passed.

Host: Jeannette Wolfe

Guests:

Dr. Neha Raukar, Emergency and Sports Medicine Physician

Katherine Snedaker, Executive Director of Pink Concussions

Topic: Sex and Gender Differences in Concussions

Take home points

References:

http://www.pinkconcussions.com/science/concussion-info/

Collins, C.L., Fletcher, E.N., Fields, S.K. et al. Neck Strength: A Protective Factor Reducing Risk for Concussion in High School Sports J Primary Prevent (2014) 35: 309. https://doi-org.ezproxy.library.tufts.edu/10.1007/s10935-014-0355-2

Covassin T, Moran R, Elbin RJ. Sex differences in reported concussion injury rates and time loss from participation: an update of the National Collegiate Athletic Association Injury Surveillance Program from 2004-2005 through 2008-2009. J Athl Train. 2016;51:189-194.

Wilcox, B. J., Beckwith, J. G., Greenwald, R. M., Raukar, N. P., Chu, J. J., McAllister, T. W., … Crisco, J. J. (2015). Biomechanics of head impacts associated with diagnosed concussion in female collegiate ice hockey players. Journal of Biomechanics, 48(10), 2201–2204.

Wunderle K, Hoeger KM, Wasserman E, Bazarian JJ. Menstrual phase as predictor of outcome after mild traumatic brain injury in women. J Head Trauma Rehabil. 2014;29:

Show Notes for Podcast Six of Sex & Why

Hosts: Jeannette Wolfe and Dr. Anne Litwin PhD

Topic: New Rules for Women

In this episode, Dr. Anne Litwin PhD joined me to discuss the findings of her book New Rules for Women. This book highlights the results of her extensive research on the challenges women can face when working with other women in a professional environment. Dr. Litwin, through her in-depth interviews of women across the globe and working in different industries, began to notice a pattern of expectations or so called “friendship rules” that women often carry into the workplace and innocently set them up for inevitable conflict.

The key components of the rules are as follows:

The real kicker, however, is that it is actually considered taboo to talk about them.  Litwin claims that as these rules are so deeply ingrained into females as young girls, that by the time they enter the workplace they are simply assumed truths.

These rules set up a catch 22 as the very nature of most work environments is competitive and hierarchical. As such, women may often find themselves in positions in which they are not “equal” and not able to unconditionally back each other up. The result is that the friendship rules will predictably get broken and if unchecked, potentially leave women feeling unsupported, backstabbed or disillusioned with other women.

Fortunately, there are a few suggestions to better manage these relationships.

Some suggested wordsmithing:

“you are a strong woman and I want to support you, there are going to be times when due to our different job descriptions that we will inevitably face conflict, I ask that when this happens that we agree to work through them in a professional respectful manner so that we can continue to support each other and do our jobs to the best of our abilities.”  

“as we have different roles, there are going to be times in which I am going to have to put on my “professional” hat to do my expected job. To avoid confusion or misunderstanding, I will try and be as transparent as possible when I need to adopt that role.”

Try to discuss expectations up front and identify new ways, understanding the above constraints, in which you can continue to support each other.

Resources

Anne Litwin's New Rules for Women

Joyce Benenson's Warriors and Worriers

Douglas Stone's Thanks for the Feedback

Check back in mid-March for the release of my “X- the Skidmark Talk”  from the archives of the 2017 Feminem FIX national meeting.

Show Notes for Podcast Five of Sex & Why

Host: Jeannette Wolfe Guest Host: Justin Morgenstern

Topic: Stress Response - Part 3

Tricks for optimizing performance under stress

Preloading

In the moment

Selected Resources

Meditation App- Insight Timer

Justin Morgenstern’s Performance Under Pressure blog: https://first10em.com/2017/03/13/performance-under-pressure/

Adrian Plunkett’s SMACC talk https://www.smacc.net.au/2017/02/learning-from-excellence/

Recent Tetra study: Horsch A, et al: Reducing intrusive traumatic memories after emergency caesarean section: A proof-of-principle randomized controlled study. Behaviour Research and Therapy, 2017 https://doi.org/10.1016/j.brat.2017.03.018

Lauria, M. J., Gallo, I. A., Rush, S., Brooks, J., Spiegel, R., & Weingart, S. D. (2017). Psychological Skills to Improve Emergency Care Providers’ Performance Under Stress. Annals of Emergency Medicine. https://doi.org/10.1016/j.annemergmed.2017.03.018

Parkin, B. L., Warriner, K., & Walsh, V. (2017). Gunslingers, poker players, and chickens1 :Decision making under physical performance pressure in elite athletes. Progress in Brain Research (1st ed., Vol. 234). Elsevier B.V. https://doi.org/10.1016/bs.pbr.2017.08.001

Markway B, Stop Fighting your Negative Thoughts, Psychology Today May 7 2013 https://www.psychologytoday.com/blog/shyness-is-nice/201305/stop-fighting-your-negative-thoughts  

Show Notes for Podcast Five of Sex & Why

Host: Jeannette Wolfe

Topic: Stress Response

For Acute Care Medicine and Introduction to Sex and Gender Based Medicine CME Cruise Opportunity click here

Part 2 on biological sex differences in the stress response with special guest Justin Morgenstern

We started out with a discussion on different ways to frame potential sex and gender based research using a method described by  Dr. M McCarthy

A full discussion of this framework can also be found on my website

McCarthy MM et al, The Journal of Neuroscience: the official journal of the Society for Neuroscience. 2012;32(7):2241-2247.

There appears to be a significant amount of individual variation in how some individuals respond to and recover from similar stresses. Some of these differences may be influenced by our biological sex. Understanding how we react and respond to stress and how this may perhaps differ from other individuals around us may help us better communicate and lead under stressful situations.

Study #1

This was a follow up study to an infamous study the same team did three years before in which they looked at sex differences in reward collection on a computer balloon game (Balloon Analogue Risk Task or BART). In this game, players got 30 balloons and the farther they pumped them up the more points they got however, each balloon was also set to randomly pop somewhere between 1- 128 pumps and if the player popped their balloon before they cashed it in they lost points for that balloon. Study participants were randomized to control vs stress condition (placing hand in neutral versus ice water for 3 min) and then played the game. They found that in neutral conditions there was no significant difference in risk taking (number of pumps 39 for women versus 42 for men, but under stress women decreased their pumping to 32 while men increased to 48).

In this 2012 study, Lighthall’s group adjusted its protocol so that BART could now be played in an MRI scanner. Unfortunately, the new BART design subtly changed the game because now instead of going through 30 balloons, participants played the game for a set amount of time with unlimited balloons. This inadvertently added a second strategy to get lots of points as the new design allowed participants to get points by either pumping additional air into an individual balloon or rapidly moving through a greater number of balloons while pumping only a few pumps per balloon. Stress intervention was again either a cold or neutral temperature water bath and after submersion the researchers collected cortisol samples and scanned participants while they played the game.

Results- no difference in control conditions (room temp water) between men and women in number of balloon pumps or points earned

But under stress men acted more quickly and got increased rewards while women appeared to slow down their reaction time and decrease their rewards.

Men had higher baseline and stimulated cortisol but there was no difference b/w men and women in the amount of cortisol change between baseline and stressed condition.

Under basic non stress conditions- during the control testing it appeared that overall men and women utilized the same brain regions to complete the balloon task (i.e. suggesting that males and females approach the task by using similar neural strategies), however once stressed men and women seemed to use different areas of their brain. Men used their dorsal striatum and anterior insula more. Anterior insula has been associated with switching tasks from a riskier to a safer option (and in both sexes higher activity in this region correlated with higher collection rate) and the dorsal striatum is believed to be associated with obtaining predictable rewards and with integrating sensory, motor, cognitive and emotional signals.

Did not find that men had increased risk taking in this study but it may have been masked in that there was now a lower risk strategy available to them that still was associated with an increased reward (pumping balloon a small amount and quickly cashing in to get to next balloon).

Concept discussed is that under stress men may possible go into type one systemic thinking (automatic) while women may favor type 2 (deliberate cognitive inquiry).

Lighthall, N. R., Mather, M., & Gorlick, M. A. (2009). Acute stress increases sex differences in risk seeking in the balloon analogue risk task. PloS One, 4(7), e6002. https://doi.org/10.1371/journal.pone.0006002

Lighthall, N. R., Sakaki, M., Vasunilashorn, S., Nga, L., Somayajula, S., Chen, E. Y. Mather, M. (2012). Gender differences in reward-related decision processing under stress. Social Cognitive and Affective Neuroscience, 7(4), 476–84. https://doi.org/10.1093/scan/nsr026

Study #2: 

Goal to determine if:

What they did:

Results

Men and women appeared to have different strategies for guided visual tasks in general regardless of whether listening to neutral or stressful recordings:

Men:

More likely to light up areas associated with motor processing and action.

Caudate, midbrain, thalamus, and cingulate gyrus and cerebellum

Women:

More likely to light up areas associated with visual processing, verbal expression and emotional experience

            Right temporal gyrus, insula and occipital lobe

Women were also more likely to increase their HR regardless of condition (likely from having increased autonomic arousal- though other studies suggest that women have increased HR at baseline compared to men in general)

Under stress men and women had firing in opposite directions:

Men dampened while women increased firing in:

Dorsal Medial pre-frontal cortex, parietal lobes (including inferior parietal lobe and precuneus region) left temporal lobe, occipital area and cerebellum.

Believed functions of these different regions

Dorsal medial frontal cortex – executive functioning of cognitive control, self-awareness of emotional discomfort, strategic reasoning, and regulation

Precuneus- part of the parietal lobe associated with self-referential and self-consciousness

Inferior parietal lobe- cognitive appraisal and consideration of response strategies (also area often associated with mirror imaging)

Left temporal gyrus- processes verbal information

Occipital area- processes visual information

Cerebellum- besides coordinating motor movement also is involved in emotional and cognitive processing 

“Taken together, the observed differences in these regions suggest that men and women may differ in the extent to which they engage in verbal processing, visualization, self-referential thinking, and cognitive processing during the experience of stress and anxiety.”

They also suggest that under stress men may feel anxious due to “hypoactivity” while women may feel stress due to “hyperactivity” in above noted regions.

Conclusion:

 This research is still clearly in its infancy but suggests that under stress some men, may turn down activity in areas of their brains involved in executive functioning and that this might increase their vulnerability to impulsivity. Conversely, under stress some women may actually turn up activity in these regions that could lead to excessive rumination and possibly depression. The authors then extrapolate their data to suggest that men and women might possibly benefit from different stress reduction techniques in that some men might benefit more from cognitive behavioral therapy which enhances frontal lobe firing and some women from mindful meditation which dampens it. 

Seo, D., Ahluwalia, A., Potenza, M. N., & Sinha, R. (2017). Gender Differences in Neural Correlates of Stress-Induced Anxiety. Journal of Neuroscience Research, 125, 115–125.

Study #3

This study literally looks at what conditions men and women might seek out increased physical interaction with their dog after an agility competition. The background here is that in 2000 Dr. SE Taylor questioned whether the flight of fight response which has classically been described as a “universal” stress response, was actually applicable to both males and females. She questioned how realistic it was for a female who might be physically smaller and less muscular than her male peer to successfully fight or run away from a potential attacker. She suggested an alternative response of “tend and befriend” which suggests that under stress that women may naturally migrate towards their children as well as others within their intimate circle with the belief that a larger group may offer protection and a pooling of resources. Additional support for this theory is the idea that oxytocin, which has receptors throughout the brain and is usually found in higher amounts in women, may be released during this affiliative behavior and help to dampen the physiological cortisol stress response.

This study was done to see if men and women seek out physical contact with another being (in this case their dog) in similar fashion when they are stressed. They chose to study human contact with a dog versus an interaction with another human to try and mitigate the influence of any “gender expectation” violations. Which in English means that if Rob would normally seek out Carol when he is stressed, he might decide not to do so in public (and in this case being videotaped) because he doesn’t want to appear “less masculine”. As public affection with one’s dog is considered less gender biased, the authors chose this interaction as a marker for affiliative behavior. 

What they did: Videotaped and took cortisol saliva levels from 93 men and  91 women after they had run their dog through a competitive agility course. Recording and samples were taken as participants waited for their official score (although subjectively most participants pretty much already knew whether or not their dog had scored high enough to move on.) The researchers measured cortisol levels and how much participants petted their dog while waiting for this score.

Results:

Conclusions: women sought out affiliative behavior when they lost, men sought it out when they won.

Justin and I use this paper as a discussion point as to understanding how two people may get exposed to the same stressor and respond quite differently and importantly how they sort of bounce back from a stressful situation may also differ. This paper suggests that emotional debriefing after stressful experiences may be more helpful to some individuals than others.

For more on the stress response please see Justin’s new post on First10EM

Sherman G, Rice L, Shuo Jin E, et al: (2017) Sex differences in cortisol’s regulation of affiliative behavior. Hormones and Behavior 92, 20- 28

Show Notes for Podcast Five of Sex & Why

Host: Jeannette Wolfe

Topic: Stress Response

This Podcast focuses on the basics of the acute human stress response. Please see Dr Morgenstern’s excellent write up:

Performance Under Pressure Review: https://first10em.com/2017/03/13/performance-under-pressure/

Components of stress response

Things that affect cortisol response

Sensation of psychological stress is not always associated with physiological stress (i.e. cortisol stress response)

Conversely in psychological studies in which subjects get exogenous steroids (i.e take a hydrocortisone pill) although there are often associated behavioral changes from the steroids participants rarely feel anxious.

Somewhat ironic that women report more psychological stress but that men die on average 7 years earlier

Things that reliably trigger physiological stress:

 Demands >>> Resources

Learning on stress is U shaped curve

Some suggested sex differences:

In general women have higher baseline HR than men (despite this, women are believed to have a higher parasympathetic baseline tone)

Triggers:

Free Cortisol is the active form and men appear to have higher free cortisol levels

Women may be more sensitive to acth- similar cortisol level with less trigger.

Men more likely to respond to threat of hierarchy, women social exclusion

Stress resiliency:

Time to respond, magnitude of response time until return to baseline

To what, how quickly, how much, how long. 

Studies discussed in podcast

Alexander, G. M., Wilcox, T., & Woods, R. (2009). Sex differences in infants’ visual interest in toys. Archives of Sexual Behavior, 38(3), 427–33. https://doi.org/10.1007/s10508-008-9430-1

Ali, Amir; Subhi, Yousif; Ringsted, Charlotte; Konge, Lars. Gender differences in the acquisition of surgical skills : a systematic review. /I: Surgical endoscopy, Vol. 29, Nr. 11, 11.2015, s. 3065-3073.

Deane, R., Chummun, H., & Prashad, D. (2002). Differences in urinary stress hormones in male and female nurses at different ages. Journal of Advanced Nursing, 37 , 304–310.

Shane MD, Pettitt BJ, Morgenthal CB, Smith CD (2008) Should surgical novices trade their retractors for joysticks? Videogame experience decreases the time needed to acquire surgical skills. Surg Endosc 22:1294–1297

Theorell Tores, On Basic Physiological Stress Mechanisms in Men and Women: Gender Observations on Catecholamines, Cortisol and Blood Pressure Monitored in Daily Life. Psychosocial Stress and Cardiovascular Disease in Women, DOI 10.1007/978-3-319-09241-6_7  Published 2015 pp 89-105

Turecki, G., & Meaney, M. J. (2016). Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review. Biological Psychiatry, 79(2), 87–96. https://doi.org/10.1016/j.biopsych.2014.11.022 

Yael, Sofer, et al. "GENDER D. S. F. C. H. L. I. M. . E. P. (2016). (2015). Original Article GENDER DETERMINES SERUM FREE CORTISOL: HIGHER LEVELS IN MEN EP161370.OR. Endocrine Practice. https://doi.org/10.4158/EP161370.OR 

White MT, Welch K (2012) Does gender predict performance of novices undergoing fundamentals of laparoscopic surgery (FLS) training? Am J Surg 203:397–400

Show Notes for Podcast Four of Sex & Why - Part 3

"Body" Pod

Hosts: Jeannette Wolfe and Basmah Safdar

Topic: Sex & Gender Differences in Heart Disease

For full show notes, please visit the seX & whY website.

Show Notes for Podcast Four of Sex & Why - Part 2

"Body" Pod

Hosts: Jeannette Wolfe and Basmah Safdar

Topic: Sex & Gender Differences in Heart Disease

For full show notes, please visit the seX & whY website.

Show Notes for Podcast Four of Sex & Why - Part 1

"Body" Pod

Hosts: Jeannette Wolfe and Basmah Safdar

Topic: Sex & Gender Differences in Heart Disease

For full show notes, please visit the seX & whY website.

Can unconscious cues cause changes in behavior and performance? Can subtle cues can affect behavior and team performance? 

Show Notes for Podcast Three of Sex & Why

 “Behavior” Pod

Hosts: Jeannette Wolfe and Simon Carley

Topic: Unconscious Bias

Major Question: Can unconscious cues cause changes in behavior and performance?

Riskin Study

Examined the effect of rude statements on team diagnostic and procedural performance.

What they did: Had NICU providers (nurses and doctors) first go through a simulation and then attend a workshop on team “reflexivity” (i.e. team training). The workshop was taught by a neonatologist who said that he was “collaborating” with an American expert who was ostensibly watching via webcam.

At the end of the workshop, the coordinating neonatologist told the teams that the expert wanted to greet them and he then “dialed” up the expert (in reality this triggered a prerecorded message). The groups were randomized to hear either a neutral message in which the expert commented that he had been working with a lot of Israeli hospitals, or a rude message in which the expert commented that he had “observed a number of groups from other hospitals in Israel and compared with the participants he had observed elsewhere, he was not impressed with the quality of medicine in Israel.” 

Both groups then underwent a standardized written and procedural simulation case involving a neonate with rapidly progressing necrotizing enterocolitis. Ten minutes into the simulation the American “expert” spoke again with the control group hearing another neutral comment and the rude group hearing that although the expert liked some of what he saw during his visit to Israel that he hoped that he would not get sick in Israel and implied that most “wouldn’t last a week” in his own department. The teams then continued to complete the case.

The simulations of both the control and rude teams were then evaluated by blinded observers who reviewed written documents and team videos. Participants were rated on diagnostic performance, procedural performance, information sharing and help-seeking.

Results: 33 NICU providers were randomized to control group and 39 to rude statement group forming a total of 24 teams.

Diagnostic and procedural performance along with information sharing and help seeking behavior declined statistically significantly in the rude group. 

Table 1

Statistically significant differences in procedure performance

Procedure

Control-neutral phone calls

Mean (1-5 scale)

Intervention- rude phone calls

P value

resuscitation performed well

3.05

2.49

.002

Verified tube placement well

3.56

2.85

.0005

Ventilated well

3.43

3.01

.002

Asked for right lab tests

3.78

3.24

.01

Good general technical skills

3.17

2.61

.002

Overall procedure

3.26

2.77

.0002

Table 2

Statistically significant differences in diagnostic performance

Variable

Control- neutral phone calls

Intervention-rude phone calls

P value

Diagnosed shock

2.88

2.08

.003

Diagnosed NEC

3.08

2.62

.041

Diagnosed deterioration

4.05

3.54

.006

Suspected bowel perf

2.6

1.94

.012

Diagnosed cardiac tamponade

3.18

2.15

.001

Overall Diagnostic

3.18

2.65

.0003

Theory behind findings- At individual level rudeness can impair access to working memory (which is important for analysis, planning, and execution) which can then contribute to suboptimal task execution. At the team level, performance is further decreased because less information is shared (potentially limiting diagnostic considerations) and procedures may become more difficult because individuals stop asking for help.

Ultimately this study suggests that when an attribute (in this case being an Israeli physician/nurse) is challenged, behavior can be impacted. This has huge implications for how physician professionalism can directly affect patient care.

Shih Study:

This study is wonderful in its simplicity, it takes individuals who possess two attributes that are associated with opposing stereotypes (in this case Asian and female) and asks if their behavior (performance on a math test) is able to be manipulated depending upon which attribute is subtly cued.

 Shih asked a group of Asian college females to take a math test. Prior to taking the test she randomized the women into three groups.  In the first group, participants were subtly primed to identify with their “female” identity by asking them gender demographics and targeted questions about single sex versus coed dorm living. In the next group, women had their ethnic identity triggered by asking about relatives and languages spoken at home. And in the final group women were asked generic questions that avoided implicit triggering of either gender or ethnic attributes. The measured outcome was accuracy= number of test questions right/number attempted

 Results: Women who had their Asian identity triggered scored highest on the tests, the neutral group scored in the middle and the female identity primed scored the worst with statistical difference (p

Show Notes for Podcast Two of seX & whY Code Leadership and Gender “Behavior” Pod Hosts: Jeannette Wolfe and Simon Carley Major Question: Are there potential unique gender challenges associated with stepping into traditional code leadership roles? What we know- importantly there is no evidence that men and women differ in competence of running actual resuscitations (Wayne 2012). This discussion is based on whether unique gender associated variables should be considered when learning and then running resuscitations. Streiff Study This study looked at a code simulation run by randomized groups of three Swiss fourth year medical students. Before participating in the simulation, students filled out basic demographic information and then took tests that evaluated for certain personality traits and for basic resuscitation knowledge and experience. The authors main objective was to see which variables were associated with code leadership by using “leadership statements” as a surrogate marker.  Leadership statements were statements made by participants that could be categorized into one of four areas: what should be done; how it should be done; who should do it; direction/command to another person that prompted action or change of action. Results: 237 students Variables that were associated with leadership statements were: Male sex, extraversion and low scores on agreeableness personality trait. Factors not associated with leadership statements were: height, experience or(most concerningly) fund of knowledge. Study implications: