seX & whY Episode 23, Part 1: Issues Surrounding Men’s Health

Jeannette WolfePodcast Episodes

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

  • Somewhat ironically even though most major health related organizations are dominated by men in senior positions, men’s health is often left out of the agenda. Some of this may be due to a zero-sum game mentality in that it is commonly viewed that the only way to fund men’s health is to take away funding from women’s health. This isn’t necessarily true, and it is important to remember that healthy families and communities are rooted in healthy parents regardless of their biological sex or gender. Men have about a 5-year shorter live span than women and are increased risk for diabetes, early hypertension, substance you disorder and suicide.
  • Peter noted that men’s health has not had the grassroots advocacy that many women’s health initiatives have had. He attributes this to a belief held by many men that they are strong and independent and as they value the perception of being able to tough things out, advocating for increased health access to medical and mental health resources may be at odds with their desired self-image.
  • We also discussed the different challenges that men compared to women may face when trying to increase their health literacy or navigate access to appropriate services. This is particularly evident in early adulthood.  During this young adult period, females often have an increased awareness of their body and health related issues due to fertility associated concerns, while for many men health related issues often fall off their radar and if they are discussed, the information may be poorly vetted and inaccurate.
  • We talked about this two and even three decades long health care desert where men can find themselves and in where they have little to no interaction with traditional health systems.
  • We then spoke a great deal about health messaging and the importance of getting the right message to the right men via the right platform. As Dominick noted, currently a great deal of health messaging is geared towards the category of men that Dominick refers to as “the low-lying fruit” in that they may already have access to a pcp and have good baseline health literacy. He feels strongly that there is a great opportunity to increase engagement with a broader variety of men by respecting their different values and tailoring messages to specific subsets using different types of platforms like integrating important public health messages into radio and TV series.

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.

seX & whY Episode 22: Sex, Drugs, and Rats

Jeannette WolfePodcast Episodes


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.

  • In a good deal of drug research, the amount of basic science research done on a particular drug prior to market release is often quite limited. As significant drug side effects may only be identified after the drug’s release, using established animal models that match up well to conditions similarly experienced in humans, may help identify potential problems earlier in the drug development pipeline. Dr Zucker believes that this is particularly important when trying to evaluate for specific behavioral side effects in the offspring of pregnant or lactating females using certain drugs (see his paper here). As these side effects in humans may take 10-15 years to be identified, leveraging the shorter natural life cycles of lab animals could help flag potentially deleterious effects years before they might otherwise be identified by traditional post-release surveillance data.
  • There are two big governmental National Institute of Health policies that shifted research to become more inclusive of sex/gender.

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:

  • Almost 50% included both sexes in research but…..
  • 1/3 of researchers didn’t give breakdown of how many males and females they included in study. (Meaning researchers could have included 10, 50 or 70 percent of animals from one sex.)
  • Some fields like pharmacology still were underrepresented (less than 30% of research included both sexes)
  • When both sexes were included only about 40% broke down their outcome data by sex

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.

  • This is a meta-analysis of almost 300 different articles examining behavioral, physiological, and molecular trials in female and male mice without regards to estrous cycle and found that female animals were no more variable and at times even less variable than males. This was doubly surprising because the dogma had been that male hormonal variability was insignificant. Interesting both males and female animals became much more variable when housed with other animals.

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.

  • Of 86 drugs with available information (of note in the vast majority of currently used medications this information is NOT readily available) they found 76 of drugs had greater levels in women with an 88% correlation of higher levels being associated with adverse drug reactions in women

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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!

seX & whY Episode 21: Sex and Gender Differences in Opioid Use Disorder

Jeannette WolfePodcast Episodes

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

  • more rapid acceleration from first use to addiction and treatment entry
  • Greater medical and psychiatric co-morbidities
  • Younger
  • Greater barriers to accessing treatment including managing childcare, transportation, and drug use stigma
  • Increased risk of engagement of high risk sexual activity (risk further increased for sexual minorities)
  • Maybe more responsive to buprenorphine

Men

  • Older
  • History of more substantial use
  • increased history of legal/criminal activity

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

  • Many studies done before the explosion of the opioid epidemic
  • Limited data on people who are not in residential treatments or clinical trials
  • Many studies focus on methadone which has different treatment setting and clinical management

Socioeconomic differences between typical methadone vs buprenorphine users

  • Buprenorphine users more likely to be white, healthier, younger and from higher socio-economic class

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

  • Women tend to engage more in comprehensive services (may reflect greater psychosocial burden) and offering sessions with childcare or mother’s support group may help with follow through and improve outcomes
  • Stigma against women who are pregnant and/or mothers may also impair ability to access treatments

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

  • Statistically men are more likely to have an issue with opioid use disorder however those numbers are narrowing
  • Physiologically- females appear to be at greater risk for telescoping- in that they appear to be at greater risk for rapid acceleration in substance use an physiological dependence, they also may be more prone to side effects surrounding withdrawal such as nausea
  • How people spiral into abuse may also be heavily influenced by sex/gender related factors as men often get hooked due to increased use in social situations, while women often are using alone and self-medicating for depression and anxiety. How they pay for their drug use is also gender influenced with men often resorting to stealing or criminal activity and women to sex trafficking
  • Over the last few years there has been a cultural shift as to how to best manage patients with substance use disorder with a greater focus on harm reduction versus complete abstinence with the understanding supported by data, that harm reduction can dramatically decrease the morbidity and mortality associated with substance use disorder and improve the health of local communities.
  • Due to the opioid epidemic, there has been multiple initiatives to better identify and treat patients with substance use disorder including state wide prescription monitoring program, systemwide policies and electronic medical record prompted physician guideline for prescribing, and ED administered counseling, medical assisted therapies and harm reduction kits

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/

seX & whY Episode 20, Part 2: Gendro – Advancing Sex and Gender Equity in Science Research

Jeannette WolfePodcast Episodes

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

  • sex and age-based differences in immunology may influence vaccine dosing/side effects
  • sex based differences may influence gendered associated acceptance and uptake of vaccines (for example if it is known that women get more side effects with a vaccine it may influence another women’s readiness to get vaccinated.)
  • sociocultural associated factors can influence vaccine acceptance and uptake
  • it is critical to have meaningful inclusion of gender diverse voices in high level research and policy decisions.

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.

Thanks for joining us!

seX & whY Episode 20, Part 1: Sex and Gender Variables in Science Research

Jeannette WolfePodcast Episodes

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.

In part two we will discuss possible solutions.

seX & whY Episode 19: About Vaccine Research

Jeannette WolfePodcast Episodes

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

Host: Jeannette Wolfe
Guests:

  • Christine Dahlke, Biologist and vaccine researcher at University Medical Center Hamburg-Eppendor and The German Center for Infection Research
  • Marylyn M Addo, Physician, Professor, Infectious disease specialist and vaccine researcher from University Medical Center Hamburg-Eppendor and The German Center for Infection Research

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

Take-home points

  • Vaccine development has evolved over the years from having each vaccine be independently developed “one drug for one bug” to “plug and play” platform technology in which a vector that predictably and effectively triggers the immune system is attached to a new pathogen’s antigen (or mRNA or DNA that codes for that antigen), allowing for a much more accelerated development of new vaccines because researchers are not starting from scratch every time.
  • Researchers often test antibody levels to determine vaccine efficacy but, immunization changes other aspects of the immune system such as t cell response and some innate immunity too. These changes may be more difficult to test but may also be important for long term protection even if antibody levels fall.
  • Traditionally, drug companies have not been all that excited about developing vaccines due to the lack of a profit margin compared to a drug someone needs to take every day. The Coalition for Epidemic Preparedness Innovation (CEPI) helped jump start vaccine development in 2017 (apparently this was sparked by the realization that Ebola could have become a global pandemic and that we needed more tools to develop rapid turn- around vaccines.)
  • Sex differences – due to sex hormones and chromosomes – influence how a body’s innate and adaptative immune system works. Women generally having an advantage in fighting off infection by having a more robust innate and adaptative immune system. This may come at a cost of increased risk for autoimmune disease and in Covid, women are also much more likely to have long haul Covid symptoms. Age can act as an additional confounder with males having more impaired antibody response and increased innate inflammatory responses with age
  • Most immune cells have sex steroid receptors on them
  • Many genes that influence the immune system are housed on the X chromosome and some of them like Toll-like receptor 7 – aka the Paul Revere of the early immune response, may not undergo X-inactivation leading to it’s over expression in females and possibly giving them an advantage in decreasing their viral load compared to males after similar exposures.

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:

seX & whY Episode 18: Mike Gisondi Announces Stanford’s New, Open Access Course, “Teaching LGBTQ+ Health”

Jeannette WolfePodcast Episodes


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

seX & whY Episode 17: Impact of Gendered Masculinity in Health Engagement and Decision-making

Jeannette WolfePodcast Episodes

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

  • Overall, men have a shorter life expectancy than women and this is likely influenced by both biologically and sociocultural based factors associated with an individual’s gender identity
  • Race based stressors amplify these sociocultural mortality differences
  • Men are less likely to access preventative health care services and some of this is likely related to biological sex differences and behavioral patterns that begin in early adulthood as females are more likely to interact with health systems due to pregnancy and child related issues.
  • Sociocultural “masculinity norms” may discourage health engagement due to an individual’s desire to be perceived as tough and independent.
  • Ways to better engage men with their health (with an emphasis on men of color)

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

  • Men can get caught in a warrior-like mentality which may impact their end-of-life choices. In cancer patients this may make them less receptive to palliative care due to a concern that it may suggest that they are “giving up”.

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

  • Normalize messaging such that palliative care is considered a natural part of cancer treatment
  • Appreciate impact of non-verbal language- be authentic in conversation
  • Recognize that most conversations have a logical and emotional component and appreciate that both need to be addressed
  • Take time to know the patient’s story, this humanizes the interaction and increases empathy
  • Remember goal is to figure out their preferences and then honor them
  • Sometimes shifting focus from fighting terminal cancer to fighting for comfort and to ease families suffering can make patients more amenable to palliative care services

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

seX & whY Episode 16: Interview with Dr Saralyn Mark

Jeannette WolfePodcast Episodes

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

  • Solamed Solutions a boutique consulting firm that advances scientific and strategic direction for public and non-public sectors
  • The non-profit iGIANT (Impact of Gender and Sex on Innovations and Novel Technologies)

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.

This is the link to Jane Henry’s See Her Work site that Dr Mark references.

seX & whY Episode 15: Sex Differences in Immunology and Drug Therapy

Jeannette WolfePodcast Episodes

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

  • Males are more likely to be admitted to the ICU and die from COVID-19 compared to females
  • Males and females have differences in both innate and adaptive immunity (which likely are a combo of chromosomal, hormonal and epigentic differences)
  • One difference in Innate immunity (the initial non-specific reaction to a foreign pathogen) is Toll-like receptor 7 (TLR7) This is a major player in the initial physiological response to a foreign pathogen and the gene for it is on the X chromosome. X-lined genes (like Ace-2 which is the receptor which SARS-Cov-2 initially binds to in the body) are interesting because they immediately bring up two considerations.  First, if someone has a specific variant of that gene, it could change their susceptibility to certain pathogens. Males, as they have an XY pair of sex chromosomes, only have one X chromosome and thus could be more adversely impacted than females (XX) who have a second copy of the gene (which may or may not express the same variant)  from their other X chromosome. The second consideration is that in the cells of most females, one of the X chromosomes is automatically turned off (X inactivation). It appears however, that some X-linked immune cells- like TLR7- don’t do this, leading to the possibility of increased expression of the gene like getting an “extra dose”.
  • In adaptive immunity (which involved B and T cells), females generally have a greater immunological response to most pathogens.
  • As such, females generally exhibit a more robust immune response to natural infections and vaccinations. The flip side, however, is compared to men, women are also at greater risk for autoimmune diseases and are more likely to get local and systemic reactions after a vaccination.
    • When testing the effectiveness and side effects of SARS-CoV-2 vaccines it would be ideal to consider the variables of biological sex and age.
    • In an influenza study, when women were given a ½ dose of the flu vaccine, they mounted a similar immune response to males who got full dose. If the same held true for developing SARS-Cov2 vaccinations, it could potentially increase the amount of vaccine available (though it is unclear if this is even being considered in early vaccine trials).
    • Aging can also impair the immune response and older adults may require higher doses of booster doses of some vaccines to optimize their immune response
  • The use of Artificial Intelligence in drug development may revolutionize the pharmaceutical research industry by allowing more predictive drug modeling leading to more successful drug development.
  • This could also be used to better identify potentially important biological sex- based pharmacodynamic and pharmacokinetic differences earlier in drug development.

Two unexpected findings associated with COVID-19

  • Males appear to be more vulnerable to cytokine storm (mechanism still not entirely clear may be differences in ACE-2 receptors, or chromosomal/hormonal differences in innate/adaptive immune system)
  • Elderly sick males who survived COVID-19 appear to have significant protective antibody production against SARS-Cov2

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.