seX & whY

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

Host: Jeannette Wolfe Guests:

• Dr Elizabeth Samuels Assistant Professor of Emergency Medicine Warren Alpert School of Medicine at Brown University
• Dr Michelle Forcier
• Professor of Pediatrics at Warren Alpert School of Medicine at Brown University and Director of Gender and Sexual Health Services

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

• This is related to our innate sex chromosomes and hormones

Gender

• Influenced by biological sex and sociocultural constructs

Gender Identity

• How an individual internally perceives themselves within the norms and expectations of society in which they live

Gender Expression

• How an individual presents their gender publicly via mannerisms, appearance and clothing, etc

Gender Asserting

• How an individual perceives themselves and desires to be viewed by the world

Gender Affirming

• Hormones, procedures or clothing that align with asserted gender

Gender Dysphoria

• The distress a person may experience when their gender identity is not aligned with their assigned sex

Hormones commonly used

• To stall puberty
  • Gonadotropin-releasing hormone (GnRH) analogues

• Transmen
  • Testosterone

• Transwomen
  • Estradiol (and possible spironolactone or finasteride)

Gender affirming surgeries

Transwomen

• breast augmentation
• orchiectomy
• feminizing vaginoplasty
• reduction thyrochondroplasty
• voice surgery

Transmen

• hysterectomy
• oophorectomy
• vaginectomy
• metoidioplasty (clitoral release and enlargement)
• phalloplasty/scrotoplasty
• masculinizing chest surgery ("top surgery")

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

• Tucking of scrotum and penis that can lead to trauma/inflammation, infection, reflux
• Estradiol related thrombosis
• Testosterone related uterine bleeding
• Infection or emboli from body sculpting injections

Take home points

• When someone identifies themselves as transgender that simple means that their gender identity does not align with their assigned sex. It doesn't mean that they have necessarily had specific surgeries or that they are taking certain hormones.
• Gender identity is distinct from an individual's sexual preference.
• Some younger kids can experience their gender identity in a more fluid manner. This can often make it more difficult to predict what their gender identities will be later on as adults. Supporting and respecting these kids for where they are, and understanding that their gender identity may or may not later change, is important for their social and psychological development.
• As kids reach puberty their gender identity is generally less fluid and more permanent, for kids and their families who our struggling with gender identity, puberty blockers are an option to give people more time to process information and make decisions
• Currently there are multiple gender affirming treatments available to trans-individuals, including hormonal treatments and different types of surgeries some of which may become important when a transgender individual becomes a patient in our emergency department

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:

• We don't know what we don't study and when we don't consider sex and gender as legitimate variables, we can inadvertently miss opportunities to improve the health of all of our patients.
• There appears to be lots of sex-based differences in cardiac electrophysiology
  • females are more prone to AV nodal re-entrant arrhythmias, sick sinus syndrome, prolonged QTc and postural orthostatic tachycardia syndrome
  • males are more prone to AV block, early repolarization, Brugada's syndrome, accessory pathway-mediated arrythmias, idiopathy ventricular arrhythmias and dangerous arrythmias associated with arrhythmogenic right ventricular cardiomyopathies

• In many ways, biological sex represents a much "cleaner" variable to study in that most of us have a sex specific chromosomal pairing and hormonal cocktail that allows us to be more easily placed into a binary male or female category.
• Biological sex differences are often detected and treated by tweaking technology- adjusting the results of a blood test or using a different type of imaging modality to account for sex based physiologically differences.
  • Biological sex is akin to the variable of age- its importance is related to context. Although a 15 year and 50-year-old may get the same evaluation for an ankle sprain they should not get the same evaluation for chest pain. Similarly, how females and males react to any particular treatment may or may not be associated with a clinically important difference.
  • As the science of earnestly studying males and females side by side is still so new, we are just beginning to understand where differences actually exist and in what contexts they are clinically relevant.

• As the influence of gender can be quite subtle and often involves many touchpoints, recognizing and fixing gender-based differences can be challenging. For example, here is how an individual's gender might influence what happens to them if they have a heart attack.
  • Whether they live alone
  • If and when they call an ambulance
  • If they come in by car, how quickly they are triaged
  • Where they are geographically placed in the department
  • How they describe their symptoms
  • How their symptoms are perceived by providers (which in turn may be confounded by provider gender)
  • How quickly an EKG is done
  • How comfortable they are with procedural consent
  • How quickly they go to the cath lab
  • When and what type of medications they are prescribed
  • Who they are referred to for follow up
  • Whether they are compliant with their new meds or appointments
  • Whether they are referred to and participate in cardiac rehab

• Currently, I suspect that most of us in medicine would likely acknowledge that there are some legitimate examples out there of gender and race- based health inequities. The next step, however, requires an acknowledgement that those inequities are not just happening somewhere else, but that they have also likely creeped into our own practices. This can be difficult because it directly threatens our explicit belief that we deliver "the same" excellent care to all of our patients.
• Recognizing and mitigating gender disparities, especially those related to implicit bias, requires deep self-reflection along with an individual and organizational commitment to actually want things to change.
• Solutions include wide-spread "no-blame" educational forums and the development of technical safeguards to help reduce unintentional bias. For example, the creation of default "opt in" disease specific order sets and operational checklists.

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

• Cares- Cardiac Arrest Registry to Enhance Survival which is based on information from national EMS data input via the NEMSIS national EMS information system
• ROC- Resuscitation Outcomes Consortium (ROC) 2011-2015. The ROC is a network of National Institutes of Health -funded clinical trial network evaluating out of hospital cardiac arrests that collects data from 11 different sites around the United States

Here are two great articles that cover this material in depth

• AHA 2019 stats
• When the Female Heart Stops: Sex and Gender Differences in Out-of-Hospital Cardiac Arrest Epidemiology and Resuscitation

What we know

• Over 350,000 people will have a cardiac arrest this year
• Men account for about 2/3 of OHCA
  • average age for men 66
  • average age for women 72
• About 20-25% will occur in public place
  • Men are proportionately more likely to collapse in public place than women (19% versus 8.4% in one study)
• About half of cardiac arrests are witnessed (about 37% by layperson and 12% by EMS)
  • compared to men, women have higher rate of unwitnessed arrest.

(46% vs 52% in one study)

• Bystander CPR doubles to triples rates of survival
• Rates of bystander CPR are highly variable and depend heavily upon where you live and its demographics with CPR being less likely to be started in predominately minority and lower socioeconomic communities. Overall, it appears that about 35-40% or cardiac arrests will get bystander CPR
• Where you live is also dramatically associated with your rates of leaving the hospital neurologically intact.
  • One study that examined 132 different counties showed, depending upon the county, functional recovery rates ranging from 0.8%-20% (which again, is likely heavily influenced by variations in CPR and AED use.)
• CARES data bank stats suggest that out of hospital cardiac arrest (OHCA)
  • 28% live to hospital
  • 8% leave neurologically intact
• Usually less than 20% of initial rhythms of OHCA are shockable
  • though sex difference here also

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

• Per one survey about 2/3 of people has some type of CPR training with 20% being currently trained
  • CPR training noted to be lower amongst Hispanics, elderly, lower income, less formally educated
• Of those trained in CPR only about 1/3 of people will actually step up and do it when indicated

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

• 45% of men and 39% of women

If collapse occurred in private place

• 36% of men and 35% of women received CPR

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:

• time to CPR, time to first rhythm strip, IV placement, medication administration
• likelihood of getting lights and sirens or aspirin

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

• CPR training within last 5 years (OR 6.6)
• in public (OR 3.1)
• see them collapse (OR 2.3);
• bystander has greater than a high school education (OR 2.0)

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

• As more than 60% of cardiac arrests do not get bystander CPR, please consider sending out these CPR videos from the American Heart Association and The British Heart Foundation to friends or family members to teach and/or reinforce basic CPR principles as good CPR doubles to triples survival rates.
• There are innate biological sex differences associated with out of hospital cardiac arrests including: 2/3 of cardiac arrest occur in men who collapse on average collapse about 7-10 years earlier than women. Men are also more likely to have an initial shockable rhythm.
• Gender related issues, which can notoriously sneak under the radar if we don't intentionally look for them, can also impact cardiac arrests. The study we talked about today suggested about a 5-6% absolute differences in public bystander CPR rates with men receiving more CPR. Concerningly there is similar research suggesting gender based inequities of both the EMS and hospital management level of cardiac arrest and we will continue this discussion in part 2 of our series. Although more deductive research is needed, there are hints that some of these gender related CPR differences are rooted in concerns surrounding sexuality, perceptions about fragility and misconceptions that collapsing women are unlikely to be having a cardiac arrest.
• The first step to gender- based gaps in cardiac arrest is to simply validate they exist. If you teach CPR, recognize and normalize that for some learners, invading someone's personal space can feel totally awkward and then encourage them to mentally rehearse different scenarios in which they visualize themselves successfully starting CPR. Using tools like the womanikin can help.
• As it appears that only about 30% of people who already know CPR, will actually step up to do it, we must work on ways to close this gap. Considering the introduction of stress inoculation and introducing things like Mike Lauria's breath, talk, see and focus technique holds promise.

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

• Cares- Cardiac Arrest Registry to Enhance Survival which is based on information from national EMS data input via the NEMSIS national EMS information system
• ROC- Resuscitation Outcomes Consortium (ROC) 2011-2015. The ROC is a network of National Institutes of Health -funded clinical trial network evaluating out of hospital cardiac arrests that collects data from 11 different sites around the United States

Here are two great articles that cover this material in depth

• AHA 2019 stats
• When the Female Heart Stops: Sex and Gender Differences in Out-of-Hospital Cardiac Arrest Epidemiology and Resuscitation

What we know

• Over 350,000 people will have a cardiac arrest this year
• Men account for about 2/3 of OHCA
  • average age for men 66
  • average age for women 72
• About 20-25% will occur in public place
  • Men are proportionately more likely to collapse in public place than women (19% versus 8.4% in one study)
• About half of cardiac arrests are witnessed (about 37% by layperson and 12% by EMS)
  • compared to men, women have higher rate of unwitnessed arrest.

(46% vs 52% in one study)

• Bystander CPR doubles to triples rates of survival
• Rates of bystander CPR are highly variable and depend heavily upon where you live and its demographics with CPR being less likely to be started in predominately minority and lower socioeconomic communities. Overall, it appears that about 35-40% or cardiac arrests will get bystander CPR
• Where you live is also dramatically associated with your rates of leaving the hospital neurologically intact.
  • One study that examined 132 different counties showed, depending upon the county, functional recovery rates ranging from 0.8%-20% (which again, is likely heavily influenced by variations in CPR and AED use.)
• CARES data bank stats suggest that out of hospital cardiac arrest (OHCA)
  • 28% live to hospital
  • 8% leave neurologically intact
• Usually less than 20% of initial rhythms of OHCA are shockable
  • though sex difference here also

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

• Per one survey about 2/3 of people has some type of CPR training with 20% being currently trained
  • CPR training noted to be lower amongst Hispanics, elderly, lower income, less formally educated
• Of those trained in CPR only about 1/3 of people will actually step up and do it when indicated

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

• 45% of men and 39% of women

If collapse occurred in private place

• 36% of men and 35% of women received CPR

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:

• time to CPR, time to first rhythm strip, IV placement, medication administration
• likelihood of getting lights and sirens or aspirin

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

• CPR training within last 5 years (OR 6.6)
• in public (OR 3.1)
• see them collapse (OR 2.3);
• bystander has greater than a high school education (OR 2.0)

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

• As more than 60% of cardiac arrests do not get bystander CPR, please consider sending out these CPR videos from the American Heart Association and The British Heart Foundation to friends or family members to teach and/or reinforce basic CPR principles as good CPR doubles to triples survival rates.
• There are innate biological sex differences associated with out of hospital cardiac arrests including: 2/3 of cardiac arrest occur in men who collapse on average collapse about 7-10 years earlier than women. Men are also more likely to have an initial shockable rhythm.
• Gender related issues, which can notoriously sneak under the radar if we don't intentionally look for them, can also impact cardiac arrests. The study we talked about today suggested about a 5-6% absolute differences in public bystander CPR rates with men receiving more CPR. Concerningly there is similar research suggesting gender based inequities of both the EMS and hospital management level of cardiac arrest and we will continue this discussion in part 2 of our series. Although more deductive research is needed, there are hints that some of these gender related CPR differences are rooted in concerns surrounding sexuality, perceptions about fragility and misconceptions that collapsing women are unlikely to be having a cardiac arrest.
• The first step to gender- based gaps in cardiac arrest is to simply validate they exist. If you teach CPR, recognize and normalize that for some learners, invading someone's personal space can feel totally awkward and then encourage them to mentally rehearse different scenarios in which they visualize themselves successfully starting CPR. Using tools like the womanikin can help.
• As it appears that only about 30% of people who already know CPR, will actually step up to do it, we must work on ways to close this gap. Considering the introduction of stress inoculation and introducing things like Mike Lauria's breath, talk, see and focus technique holds promise.

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

• Important variables to consider when talking about biological sex
  • Sex chromosomes
    • X chromosome contains 1669 genes
    • Y chromosome contains 426 genes
  • Sex hormones
    • We all have testosterone, progesterone and estrogen it is the ratios that differ between men and women
    • Hormones influence us in two ways
      • The cocktail of hormones our brain is exposed to during prenatal and pubertal development leads to permanent wiring changes in the brain.
      • The fluctuating blips of hormones caused by multiple different triggers (like the estrous cycle or dominance posing) can lead to transient wiring changes.
      • Depending upon specific context organizational and activational hormones can potentially influence outcome data
      • There are new study designs that can help identify potential hormonal based differences that do not require an excessive sample size or budget
    • Age
    • Gender

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.

• The X chromosome has 1669 known genes on it and the Y chromosome 426 genes

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

• For a really nice summary of current use of definitions please see this excellent review.
• Excellent websites with tons of resources
  • Institute of Gender and Health- Canadian Institutes of Health Research
  • Video on how to conduct better science that considers the potential influence of sex and gender

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

• Belief that outside of reproductive zones, males and females were the same
• Dogma that the female estrous cycle screwed up data and that male animals produced "cleaner" results
  • Two interesting facts: 1) Many female rodents' entire estrous cycle is only 4 days!; and 2) We now know that male animals also have significant hormonal fluxes and that overall they are actually just as variable as females- see review
• Concern after the worldwide thalidomide nightmare* and the public backlash from the discovery of several unethical government sponsored clinical trials, that fetuses (along with prisoners and children) needed extra protection from the potential of unnecessary harm by participation in a research trial. This led to regulatory protection via the Common Rule. As any women of child-bearing age could theoretically become pregnant, they (and ultimately by cultural proxy all women) were essentially excluded from most human trials and early clinical phase drug trials from 1970's to the mid 1990's.
  • To read and an inspiring story as to why most of American was saved from the limb-shortening horrors of thalidomide, read here. (Essentially, FDA scientist Dr. Oldham Kelsey refused to sign off on its application, even amidst considerable pressure from the drug company, due to concern of inadequate evidence.)

Interesting sex and gender differences in car crashes

• Crash dummy 101
  • Historically crash dummy is Hybrid III which is 5'9'' 170 pounds representing an average male
  • Hybrid III female model- 5' 110 pounds
  • Other models- used by NHTSA
  • Why injury patterns may be different between men and women
    • Differences in baseline anthropometric measures (like height)
    • Biomechanical differences (women more prone to whiplash due to differences in neck muscular)
    • Mechanical design (Smaller adults sit closer to steering wheel and increase risk of lower extremity injury, and are more vulnerable to side impact since more of their head is in front of window)
  • NASS CDS data
    • Weight annual sample of US 5000 police reported tow away crashes
    • Collects data on
      • Occupant demographics (Age, sex, weight, BMI; Restraint use; Injuries obtained (via medical records and interviews) standardized into an abbreviated injury scale (AIS). It examines fatality and whole body and regional injuries, on a 1-6 scale of severity
      • Vehicle properties (Type, model year)
      • Crash conditions (Estimated speed, mechanism of impact)

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

• Overall, males represent about 70% of overall fatalities for crashes
  • Greatest gender differences is in 20-29 age group
  • Men more likely to have alcohol involved in accident
• On average men drive about 5000-6000 miles/yr more than women
  • Women more likely to work closer to home
    • Crashes more likely to be low speed and to occur in more congested areas
  • If a man and a woman are both in car
    • Males more likely to be driver
  • Summary of Bose study Vulnerability of female drivers involved in motor vehicle crashes: An analysis of US population at risk.
    • Question they asked- for a comparable crash do male and female drivers sustain similar rates of injuries.
      • Examined injury outcomes in men and women using 1998-2008 NASS CDS data set
      • For a comparable crash, women had 47% percent greater chance of being severely injured than men (had a higher risk of chest and spine injuries)
      • Of note the researchers controlled for weight and BMI

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

• Including the variables of biological sex and gender in research results in better science and has led to the discovery of huge knowledge gaps that need to be closed if we want to optimize the care of all of our patients
• Our historical medical research model has been predominately based on the study of male animals. There are multiple reasons for this including a true belief that: outside our reproductive zones that men are women are exactly the same; using males animal produces cleaner data; and including women of child bearing age in clinical research trials exposes women to unnecessary risks without significant benefit. We now know that all these reasons are fundamentally flawed. Every cell has a sex and the differences between men and women outside their reproductive zones are often quite clinically important. Studying males and females side by side helps us to optimize the care of both sexes. In women it allows us to double check that therapies that were originally developed in men actually work in women and have the same benefit/side effects profiles. And for men, in instances when it is discovered that women have more favorably outcomes, it allows us to go back to the lab, figure out why there is a difference and then to use that knowledge to develop new therapies to help men.
• To move the scientific community and its deeply ingrained culture to a new model that incorporates the variables of sex and gender will require a comprehensive multi-targeted approach. Key considerations include- engagement, education, skill building around research methodology and analysis, mentoring and funding incentivization. Of note Institutional review boards, journal editors, grant reviewers and conferences directors have great power to jump start this transition by including an expectation of sex and/or gender inclusion in submission requirements.
• As we live in an ever increasingly complex world, now more than ever, it is essential that we pay attention to who is actually doing the research and developing new technologies. A diverse world requires diverse teams.

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 -

• Vague
• Nonactionable
• Feedback on non-malleable attributes - like gender, age
• Sandwich model
• Done in public place in front of peers

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

• Cheerleading: encouragement
• Coach: real time pointers
• Evaluator: comparison of performance to peers or expected benchmark

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

• Caring personally
• Challenging directly

Feedback formula by Lisa Stefanar KSE leadership

• Ask permission
• State intention (be a better doctor)
• State behavior
• Describe impact
• Inquire about learner experience
• Identify desired change

General tips

• Feedback is also received best if the learner has a sense of belonging and a believe that you recognize their potential
• Is it the right time (asking them helps)
• Praise in public, give tough feedback in private
• Label it - as in "I'd like to give you feedback, is now a good time?"
• If you anticipate that you might get emotional during feedback, prepare and practice a response. For example, "I obviously have a powerful response to this information could we please take a 5 min break and regroup"
  • Emphasize your desire to hear feedback
  • If needed ask for clarification
• If you are giving feedback and the other person becomes emotional
  • Consider using "Name and Tame strategy
    • "Last time I gave you feedback, I noticed that you did…….. and I have to tell you, honestly now I'm a little more hesitant. As I want you to be the best doc you can be, is there a particular way that would work best for you to receive feedback?"
  • Switch-tasking- many times conversations can change
    • Recognize which conversation you are going to tackle
      • The one about a specific behavior
      • The one about an emotional tag

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:

• Evaluations often contained personality related comments even when the task that was being evaluated was objective or technical
• Men, compared to women, appeared to have more comments associated with praise versus criticism around these personality related comments
• Men appeared to have more concordant feedback by evaluators concerning how to improve in areas in which they struggled
• Women received more discordant feedback about ways to do things better in areas in which they struggled especially surrounding issues about autonomy and leadership
• Evaluators perceived that women were less likely than men to receive feedback appropriately.
• Evaluators were more likely to include encouraging comments concerning "a sense of belonging" to male residents

Steps moving forward

• Take a deep breath- this is difficult stuff to discuss and it can easily feel like an attack upon our character.
• Come to terms that this data is real and legit. This topic is incredibly important and we need to consciously move past our own visceral discomfort of it to find better ways to teach and evaluate the next generation of doctors.
• Do a private audit of your own evaluations
• Be more objective in suggestions for improvement
• Reinforce a sense of belief in ability and of belonging

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:

• Both cortisol and testosterone levels varied greatly throughout the study
  • Mean daily cortisol levels increased as much as 400%
  • Afternoon cortisol levels increased as much as 500% (in an unstressed individual cortisol typically peaks in the early morning.)
• Elevated AM testosterone levels correlated with afternoon profitability
• Elevated cortisol levels correlated with market volatility (but interestingly not with simple losses)

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.

• An individual's risk preference is probably far more dynamic than previously believed and is impacted by subtle, unconscious, shifts in physiology
• Individuals can have different risk preferences in different domains (participate in dangerous hobbies but are conservative with their finances)
• Individuals with increased interoceptive awareness may be quicker to recognize anomalous blips of data buried within piles of "expected" information. This may contribute to the phenomenon of a "gut instinct"
• Hormonal fluctuations likely contribute to risk preferences
  • Increasing testosterone levels likely shifts risk preferences to make individuals more open to riskier endeavors
    • Young males in competitive situations may be particularly vulnerable as they have significantly higher levels of baseline testosterone than women and older men
    • This risk shift is likely even more dramatic in individuals taking unnecessary testosterone supplementation (which is now a 2 billion dollar industry with 2/3 of the individuals who use testosterone not having a medically indicated reason for taking it.)
  • Increasing cortisol levels (in particular chronically increased levels) likely shifts risk preferences in the opposite direction and makes individuals act more risk adverse.
  • As these hormonal shifts are occurring unconsciously, it is difficult for individuals themselves to recognize their behavioral shift and depending upon the situation external safeguards (perceptive team members, monitoring systems) could be helpful.

"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:

• Actual competition gives each opponents and idea of how they might stand in future altercations
• Winners self-perception of their strengths increases, and they become more comfortable with additional confrontation
• The initial victory may physically increase the winner's resources allowing it to go into its next encounter with an advantage (i.e. access to more food increases its size)
• A potential physiological contributor to a winner's streak may be real time fluctuations in an individuals' testosterone levels (and possibly a change in the sensitivity of their testosterone receptors). Although many things can cause fluctuations in testosterone levels, two things that appear to consistently elevate it are competition and winning.

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

• muscle mass
• hemoglobin/oxygen capacity
• confidence, persistence and increased risk taking
• desire to seek out novelty

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

• small increases of testosterone levels might be advantageous as a slight increase in risk tolerance may lead to increased reward
• at some point, however, risk becomes excessive and becomes a disadvantage
  • in animal research this may lead to:
    • patrolling of unrealistically large areas
    • increasing exposure to dangerous situations
    • increasing fighting
    • neglecting parental duties
    • loss of energy stores
  • Research in humans shows that increasing testosterone levels
    • Increases risk preference
    • Quickens reaction time
    • Defaults to automatic thinking
  • In high levels, especially if given exogenously can lead to
    • Euphoria
    • Mania
    • Impulsivity
    • Sensation seeking

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

• Physical changes occur in the hippocampus that impair normal functioning (neurogenesis is suppressed and dendritic spines are reduced )
• Similarly, changes also occur in the prefrontal cortex
  • Negatively affect working memory
  • Decrease attentional control
  • Impair behavioral flexibility
• The amygdala, on the other hand, revs up, causing increased dendritic connections and increase corticotropin releasing hormone gene expression

• Bundled all together this may lead to:
  • Increased focus on imagined threat
  • Increased risk of anxiety, depression, and learned helplessness
  • Shift to habitual behavior and decreased motivation to try novel action

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:

• Concussion research is rapidly changing, and it is important to stay up to date on the literature
  • There is a large NCAA study whose results should be released soon
• Concussion treatment has to be individualized as symptoms can vary tremendously both within and between the sexes. Overall, however, women appear to be at greater risk for having an increased clustering of symptoms and a prolonged recovery
• Cocoon therapy (being isolated in a dark room with no stimulation) is out and has been replaced by the concept of "relative rest" which is the idea that you can do activities that don't exacerbate symptoms
• Screen time has pros and cons
  • Cons
    • the contrast of light between the screen and the environment and scrolling can lead to vestibular irritation
    • Much of the activities associated with "screen time" also increase cognitive demands
  • Pros
    • It often helps people stay connected with their social circles which can decrease feelings of isolation and depression
  • The new FDA blood test does not test whether or not someone has a concussion, it tests for specific proteins (UCH-L1 and GFAP) that are released by the brain into the blood after a severe injury and correlates with the likelihood of finding an intracranial bleed on CT.
  • Prevention research and intervention targets multiple different levels including:
    • Overall awareness
    • Equipment- both in design and in proper fit
    • Training of coaches/trainers
    • Rule Enforcement
    • Locker room culture
  • Although sports related concussions get the most press, traumatic brain injuries lead to more than 2.8 million (2013 CDC data) emergency visits per year with car accidents, physical assaults and falls being big contributors.
  • There is currently a large gap in treatment access and ownership for non-sports related TBI

Thank you again to my guests!