seX & whY

seX & whY explores how biological sex and gender influence our brain, body, and behavior. Dr. Jeannette Wolfe showcases some of this fascinating science to help us better understand ourselves and each other.

Sex and Gender Differences in Aging 11/29/2023

Sex and Gender Differences in Aging Show Notes for Episode Twenty-Six of seX & whY: Sex and Gender Differences in Aging Host: Jeannette Wolfe Guest: Dr Haag is a researcher in molecular epidemiology who studies human biological aging at the Karolinska Institute in Stockholm. Background - Dr Haag has a PhD in functional genomics and Post Doc in genetic and molecular epidemiology. She studies telomeres and molecular association with telomere length, she also has experience in molecular biology and computer science. Definitions and discussion points from podcast - a new field of biomedical science that looks at how the molecular, genetic, and cellular mechanisms associated with the aging process itself may interact and even trigger many diseases associated with aging. This research provides a different angle for potential intervention to enhance health and longevity. Life Span - time between birth and death. Heath Span - time within life span of good health. and Clinical are tools that evaluate a patient’s overall physical conditioning and their vulnerability to certain adverse outcomes including falls, increased care requirements, hospital admission, and mortality. - the study of how DNA expression can be modified by behavior or environmental factors (versus alteration in the actual DNA itself). One way I think of this is to imagine a huge library full of books, and that each book represents a gene coded from our DNA- epigenetics help determine which books get pulled off the shelfs and get read or pushed back deeper into the shelfs. This process is different than buying new books for the library (which would be equivalent to changing the DNA itself.) Aging Scales - as different elements of the body age differently, there is not a gold standard to measure aging. Dr Haag recently published a that evaluated a bunch of these different scales and determined that the “ideal” scale will vary dependent upon what you are studying- such as overall function or the biological aging of a specific organ (i.e. heart or liver). Two major theories of aging: Senescence theory of aging - the belief that with age, cellular systems due to repeat exposure to intracellular and extracellular stressors, eventually start to malfunction and breakdown. Things start slowly falling apart due to wear and tear. Programmed theory of aging - Aging is an innate active process which is highly regulated by an internal time clock. As the field of Geroscience and epigenetics evolves, the “truth” around aging is likely to be a combo of both theories. Sex Differences Hormones Estrogen Dr Haag talked about research involving telomere length (telomeres are the cap of the chromosome and they help protect the chromosomes from damage.) Typically, telomeres shorten with repeated division in somatic cells and when they shrink to a certain length the cell is more vulnerable to error and damage. Females have longer telomere length at birth compared to males and there is evidence that women with longer exposure to estrogen have longer telomeres. Testosterone Here is the study mentioned in the podcast. The researchers examined a genealogical record of 385 eunuchs and compared their life span to several other groups of men who lived during the same time periods including a bunch of kings. They found that the average life span of a eunuch was 70 which was 15-19 years longer than the comparison groups. One theory behind this difference in longevity is “the disposable soma theory”. This postulates that in males there is competition between two different intrinsic systems - somatic aging and reproduction- and that as both systems require significant energy to maintain, when energy is diverted to one system the other suffers. Sex Chromosomes In females each cell has two X chromosomes. In female cells, one of the X chromosomes is typically inactivated so that some cells have genes expressed that are inherited by their father, while others express genes inherited from their mother. Complicating this further is that several genes do not fully inactivate that second X chromosomes so that females may have an “extra” expression of some genes. A concrete example of this is the gene Toll like receptor 7 which codes for proteins that helps the immune system recognize the early invasion of certain types of viruses. As this gene doesn’t undergo X inactivation, it may give females an extra boost in warding off certain types of viral infections. With aging there can be “skewing” of the X chromosome in that females may have a disproportionate percentage of cells that express the X chromosomes of a single parent. As male cells age, some may actually lose their Y chromosome. suggests that his may happen relatively frequently as their work implied that 40% of all 70-year-olds had cellular evidence of it. The loss of Y chromosome can be associated with Alzheimer’s and heart disease in males. Take home points: 1) The field of aging is absolutely exploding. Someday it may be possible to actively manipulate epigenetic signaling to slow or even reverse aging processes. 2) Different biological processes in our bodies age at different rates. Plus, if you follow a group of people over time, as they get older there will be greater and greater differences within that group in their markers of aging. 3) In aging research, there has historically been two different camps- the senescence camp, and the programmed theory one. In the senescence camp is the belief that as we age, things just start breaking down due to natural wear and tear. This contrasts with the programmed theory camp which believes that aging is a pre-designed active process that is triggered with age. The “truth” likely is a combination of both theories with epigenetics being the bridge. 4) Sex differences in aging include the mortality-morbidity paradox in that although females tend to have poorer health and greater fragility risk, males still tend to die sooner. 5) Sex differences with aging may include changes in the X chromosome with increased skewing and even the loss of the expression of the Y chromosome, both of which can be associated with an increase of health-related issues. Thanks for listening. May you be well (and curious). Jeannette. /episode/index/show/sexandwhy/id/28844078

Global Health and Pandemic Responsiveness Through a Sex and Gender Lens Part 2 08/04/2023

Global Health and Pandemic Responsiveness Through a Sex and Gender Lens Part 2 Show Notes for Episode Twenty-Five of seX & whY, Part 2: Global Health and Pandemic Responsiveness Through a Sex and Gender Lens Host: Jeannette Wolfe Guests: McKinzie Gales and Emelie Yonally Phillips – Global Health Fellow at the CDC and co-lead for Phase I of the multi-agency SAGER IOA project aimed at facilitating better collection, analysis, and use of sex-disaggregated data and gendered data for outbreak response. – Global Health consultant (Epicentre/MSF) and core member of the Integrated Outbreak Analytics initiative Phase 1 of the sex and gender equity in research (SAGER) for Integrated Outbreak Analytics (IOA) study involved A systematic literature review to better understand what is already known about the influence of sex and gender in outbreaks and to investigate if sex-disaggregated data and gendered data is being collected, analyzed, and used. Five different databases were searched and articles meeting the inclusion criteria were included. All included articles were published in English between 2012-2022, included the key terms “sex,” “gender,” or “pregnancy,” and discussed infectious disease outbreaks (e.g., cholera, dengue, Ebola, zika, hepatitis E, Malaria, influenza, yellow fever) in a low- and middle-income countries. Notably, they intentionally excluded articles focused on covid and tuberculous as sex and gender research is being extensively conducted on these diseases. Of the 15,000+ articles in their original search, only 71 articles examined potential sex and/or gender related factors associated with outbreaks in low- and middle-income countries. Although currently there is very limited data on the impact that sex and/or gender play in outbreaks and pandemics, what is known, underscores the complexity of these relationships. Studying specific outbreaks in specific contexts is important because who is most likely to get infected and how rapidly an infection is spread is influenced by several intersecting factors. These include the infectious agent, sex specific immunological factors and local socio-cultural practices and norms. McKinzie highlighted that when there is a lack of gender and sex sensitive responses in outbreaks, evidence suggests that women, girls, and those with female anatomy are disproportionately negatively affected. For example, women are at greater risk for gender- based violence during a lock down and those with female anatomy are more directly impacted by the diversion of health care resources from clinics that offer reproductive health and pregnancy related services. We went through an example as to how the SAGER IOA model might work in a theoretical outbreak. In establishing a functioning multi-disciplinary team, Emelie emphasized the importance of working within local systems to build long term relationships, community trust and capacity. She underscored how critical it was to understand the values and priorities of the individuals most impacted by the outbreak and to ensure they had a voice in decision-making. She also discussed the importance of effective and transparent community health messaging- particularly if new data suggests a change from current practice. A recent example of this was the confusion experienced by many pregnant women surrounding the safety of Ebola vaccination. Emelie also spotlighted the opportunity to better understand how gender nonconforming and sexual minorities experience outbreaks as there is currently an absence of data on these groups. Finally, she emphasized that the failure of considering sex and gender specific needs in an outbreak can have tremendous downstream effects. Specifically, generational poverty, educational and professional inequities, gross domestic product, global trade, and security can all be impacted. One of the other interesting areas we touched upon was how personal protective equipment (PPE) and other medical related equipment was initially designed for the anatomy and physiology of a male body and may not always work for a female one. Below are a few articles on this point. . This study reported findings on adequate mask fitting in one hospital system’s data for FF3 masks. Their data set suggested that 18% of women had an inadequate FF3 mask fit compared to 10% of men. . Here is a very interesting that further explores whether medical equipment should be adjusted to better fit the anatomical variations of different users. The article - Does surgeon sex and anthropometry matter for tool usability in traditional laparoscopic surgery? makes a strong argument that most of the advances in laparoscopic surgical equipment have previously focused on accommodating different patient related factors and that their remains an opportunity to modify products to better align with anatomical characteristics of different users. In turn, this may help enhance performance, outcome, and injury prevention of the users - AKA in this case the surgeons. Thanks for listening and be well. /episode/index/show/sexandwhy/id/27664836

Global Health and Pandemic Responsiveness Through a Sex and Gender Lens Part 1 06/08/2023

Global Health and Pandemic Responsiveness Through a Sex and Gender Lens Part 1 Show Notes for Episode Twenty-Five of seX & whY: Global Health and Pandemic Responsiveness Through a Sex and Gender Lens Host: Jeannette Wolfe Guests: – Fellow at the CDC and co-lead for Phase I of the multi-agency SAGER IOA project aimed at facilities' better collection, analysis, and use of sex-disaggregated data and gendered data for outbreak response. – Global Health consultant and core member of the Integrated Outbreak Analytics initiative Definitions IOA - Integrated Outbreak Analytics SAGER - Sex and Gender Equity in Research The Integrated Outbreak Analytics (IOA) initiative is a collaborative partnership between UNICEF, WHO, US-CDC, ITM, Epicentre, IFRC, under the umbrella of GOARN. The IOA concept started in earnest in 2018 during the Ebola outbreak in the Democratic Republic of Congo after it became clear that more real time, comprehensive on the ground data was needed to best manage outbreaks in an efficient and effective manner. The larger-picture concept is that the IOA model sets up a system for increased interagency data sharing and a process for data collection that produced more comprehensive information about: How infections spread How individuals access health systems and how patterns might evolve over time How local sociocultural norms, behaviors and expectations, impact an outbreak response and community recovery The IOA - Creates a more holistic response to outbreaks along the entire pipeline from prevention to treatment. It creates a model that puts lots of partners at the table including major players like Unicef, WHO, CDC, Doctors Without Borders in addition to local governmental agencies and boots on the ground health care providers. Examples of data that may be integrated to provide a clearer story of what is happening in an outbreak include: Surveillance data Health information systems data Programs data Community data Timeline event data Climate, weather and ecosystems data Local economy data Goal is to apply a multi-disciplinary approach to outbreak analyses to provide a more holistic and timely understanding of outbreak dynamics and provide local Ministries of Health and response actors with rapid evidence to make decisions during an outbreak. A key component of IOA is understanding the dynamics of both sex and gender within outbreaks and outbreak response for more adapted and appropriate responses. Therefore, IOA systematically works to collect, analyse and use data disaggregated by sex and inclusive of gender criteria across all phases of response: Prevention Detection Management/Treatment Response Four phase project Phase 1: Systematic literature review - how are sex and gender being considered in outbreak response Phase 2: Participatory engagement in real time projects that are using an IOA and identifying what is already known about site specific sex and gender differences in tools/programs. Developing survey of response actors looking at their current understanding about sex and gender and how they are or are not collecting needed information and/or analyzing and using it to guide interventions. Create workshops and small groups to address challenges identified in survey and key informant interviews, identify capacities and brainstorm on how to overcome recognized barriers. Co-create practical recommendations and strategies to more systematically integrate sex and gender into the outbreak analysis process. Phase 3: Collate Phase 2 responses from several different outbreaks to develop a larger SAGER IOA model that can then be flexibly applied to future outbreaks. Phase 4: Pilot testing in different outbreaks Evaluating responses and further modification Great resources : Turning Oppression into Opportunity for Women Worldwide by Sheryl WuDunn and Nicholas Kristof More information about the Guidelines Link to previous podcast with who was one of the fundamental drivers of developing the SAGER Guidelines. /episode/index/show/sexandwhy/id/27081771

Sex and Gender Differences in Conflict - Part 2 01/18/2023

Sex and Gender Differences in Conflict - Part 2 Show Notes for Episode Twenty-Four of seX & whY: Sex and Gender Differences in Conflict, Part 2 Host: Jeannette Wolfe Guest: Joyce Benenson, lecturer of evolutionary biology at Harvard and author of the book In this podcast we continue our discussion about women interacting with each other at the workplace and how women often manage hierarchy differently than men. We got into a spirited discussion about a question posted on a female physician’s list serve querying whether women physicians want to be addressed as “Doctor” by other staff members. (My own preference was “yes” in front of patients, and “no” once we were outside of exam rooms.) Benenson believes that when women are interacting with women who are not family, they tend to act incredibly egalitarian. This can be challenging for women in hierarchical positions and lead to a downplay of their power. This intentional buffering may not only use up a lot of cognitive energy, but it can also be a potential disadvantage in professional situations that require a clear chain of command to optimize team performance. This can put women on a professional tightrope that can be hard to balance. Ways to address this include acknowledging that this challenge is real, committing to direct communication and focusing on shared outcome goals of the entire team. Personally, I have also found it extremely helpful to humanize the other person and remind myself that most people don’t go to work with malicious intent to try and screw up another person’s day. Next, we talked about likeability, and Benenson shared a fascinating economics paper called: . This paper included a series of studies in which pairs participated in games that involved economic transactions and “likeability”. In pairs where men worked with other men, “liking” their partner was not intricately related to maximizing their profits. This was not the case in teams that involved at least one woman. In these pairs, likeability increased the chance of profits and dis-likability decreased overall profits. This suggests that when interreacting with each other, men may have a greater ability to compartmentalize their professional interactions from their personal opinions. Next, we talked about the “tend and befriend” theory developed by Dr Shelly Taylor. This theory suggests that when stressed, that females may benefit less from a fight or flight response and more from coming together to pool resources and share childcare. Benenson’s impression is that there is little scientific evidence that this theory holds true. She believes, contrary to the popular stereotype, that males are actually far more likely to be the communal sex and are much more likely to form intense group bonds. At the end, I briefly reviewed some of the findings of a recent paper Dr Benenson published called: which supports the “Staying Alive Theory”. From an evolutionary perspective, behaviors that are more likely to be found in groups of males than females, such as direct competition, physical aggression, resource accumulation and risk taking, have evolved because they provide a benefit to males in optimizing their mating opportunities and reproductive fitness. The question becomes, is there a parallel evolutionary driver for females. The Staying Alive Theory is one proposal. This theory originally developed by Campbell in 1999, suggests that compared to males, females are more likely to be innately wired to avoid conflict and be more physiologically responsive to threats that can jeopardize their health. By doing so, this helps females optimize their chance of their own fitness and the survival of their own offspring. In their paper, Benenson and her group surveyed several different areas of science to look for support of the Staying Alive Theory and here are some of their findings. In humans and other mammals, females seem to consistently outlive males, this is particularly true in species in which grandmothers are more heavily involved in caring for infants. There is a health-survival paradox, however, in that although females may have greater longevity, they are also more likely to report the presence of daily symptoms and chronic illness and have higher prescription drug use. In the world of sex and gender-based medicine this phenomenon is nicely summed up with the phrase men die, women suffer. There are sex differences in most types of cancers, in fact, except for thyroid and breast cancers, males have higher incidences of most other cancers and usually have a worse prognosis after diagnosis. Compared to female, males are also more susceptible to most infectious diseases. An as an aside, when we talk about Covid, it is estimated that . During times of global threats, females are also more likely to follow through with public health messaging such as mask wearing and hand washing Females, compared to males, have a heightened sense of pain, which may enhance self-protective behavior to avoid situations in which injury may occur such as physical arguments In general, females are more likely to have more frequent night-time awakenings, suggesting they may be more vigilant to potential night threats than male counterparts. This tendency to break up their sleep however may be compensated by higher quality length and depth of different parts of the sleep cycle. As a group, women appear to be more concerned about environmental issues and according to a recent study involving more than 32 nations and 45,000 participants, women felt a greater urgency to protect the environment and were more likely to support policies that financially invested in it. When looking at how people communicate, females were more likely to use techniques associated with politeness including smiling and tentative language that included buffering and apologizing. Although the area of nonverbal recognition shows some mixed results, overall, it appears that females are better at identifying nonverbal expressions especially those related to fear, sadness and anger. This is a great paper and worth a full read if you are interested in this material. Thanks for listening to Sex and Why! /episode/index/show/sexandwhy/id/25647669

Sex and Gender Differences in Conflict - Part 1 12/05/2022

Sex and Gender Differences in Conflict - Part 1 Show Notes for Episode Twenty-Four of seX & whY: Sex and Gender Differences in Conflict, Part 1 Host: Jeannette Wolfe Guest: Joyce Benenson, lecturer of evolutionary biology at Harvard and author of the book Warriors and Worriers Here is a link to Dr Benenson’s book . This book dives deep into the evolutionary roots of human behavior and Dr Benenson makes a very clear and well referenced case that human males and females have evolved from slightly different playbooks. The root of this difference is sexual selection in that adaptions and behaviors that optimize the chance that a male’s DNA gets into the next generation are slightly different than a female’s, specifically Benenson asserts that a female’s strategy relies more heavily on keeping herself and her children physically safe and healthy. Innate differences may then by amplified or attenuated by sociocultural norms and experiences that shape an individual’s “expected behavior." Some bullet points from her work Evolutionary biology focuses heavily on the behavior of non-human primates Much of the behavior observed in other primates can also be seen in humans When studying human behavior, it can be very hard to untangle behavior rooted in biological sex versus sociocultural influence. This is because the two are tightly interwoven and even if you intentionally raise your child to be “gender blind”, the child will still be exposed to significant gendered expectations by peers and broader societal exposures. Many of the behaviors seen in adult humans can be visibly observed by watching pre-school children. Boys and girls (for this podcast we are concentrating on the book ends of the gender spectrum: boys/men and girls/women) typically exhibit different behaviors as children. Boys are more likely to participate in rough and tumble play and are more comfortable with hierarchy and rotating allegiances in groups. Girls prefer playing in smaller groups of two and three. Many girls find in quite difficult to participate in larger groups consisting only of females, as they feel increased pressure to effectively navigate the different relationships within that group. Chimpanzees, like human males, are two of the few species that engage in “warfare” or systematic behavior to attack other groups of their own species. Groups of male chimpanzees that are good at this behavior enhance the survival of the rest of their group by expanding food and territory. Benenson believes some of this warfare behavior has genetically evolved into humans and that it is further enhanced by learned sociocultural practices. Benenson has extensively studied conflict and how males and females have different evolutionary consequences to direct aggression. She strongly believes that females are wired to avoid direct conflict to optimize their physical ability to bear and rear children to their own reproductive age. This is Dr Benenson’s that looked at how much time two players spent interacting with each other after the conclusion of a competitive sports match. It showed that men typically engaged longer with their opponent than did women. She theorizes this behavior suggests that men tend to be more agile in realigning these relationships because the relationship may be needed for a future allegiance (i.e. in war or hunting.) Please tune in next month for Part 2 of this series. /episode/index/show/sexandwhy/id/25226610

Issues Surrounding Men’s Health - Part 2 09/08/2022

Issues Surrounding Men’s Health - Part 2 Show Notes for Episode Twenty-Three of seX & whY: Issues Surrounding Men’s Health, Part 2 Host: Jeannette Wolfe Guests: Peter Baker – Twitter: Dominick Shattuck has a PhD in psychology and does Global Health Work at Johns Hopkins Bloomberg School of Public Health Main topics discussed: Challenges and barriers associated with optimizing men’s mental health and the role of men in reproductive health-related issues. Men’s mental health is important not just for men but for the health of communities. Maladaptive coping mechanisms such as substance use disorder and aggression can impact gender-based violence, sexual and reproductive health, and the well-being of children. Part of tackling gender-based violence needs to include helping men better manage anger and stress. Barriers to mental health for men From a young age, many boys are taught to suck things up and not show signs of physical or emotional weakness. They also may struggle to find words to adequately articulate their emotional state or to appropriately label the challenges which they are experiencing. This may be further confounded by social media in which most posted photos portray men as carefree and perfect which can leave the viewer feeling inadequate and questioning their masculinity. Today many men may also have decreased contact with their extended families and thus may miss out on many of the informal connections and conversations that have historically helped men cope with common life challenges. We then discussed some unanticipated and potentially detrimental consequences of “gender blind” policies. For example, due to concern of exclusivity, there has been a decrease in what historically were Men’s Only spaces. These closures can be costly for men who already have a fragile support system and who relied on these organizations to help them connect and bond with other men. Dominick then talked about the importance of code switching for men (using different communication styles with different audiences) and that in the ideal world we would create opportunities for men to become more proficient in the different roles they play (i.e. father, husband, employee etc) by exposing them to spaces with different audiences like men’s only, couples, and mixed gender gatherings. Peter also brought up that mental health related depressive symptoms may just look differently in men. Consequently, many men and their health care professionals, may not be aware that some of the symptoms that men are describing (such as increased alcohol consumption) are often flags for depression. Next, we discussed what roles men can play when it comes to areas surrounding reproductive health and reproductive justice. Dominick talked about some of the work he has done for a task force funded by the US Aid for use in low and middle-income countries to help better define these roles. He described a three-pronged framework- men as potential clients (i.e. work around condom use and vasectomies), as supportive partners to women, and as advocates for change. Messaging this framework so that men understand that these issues are not just relevant for women is critical. Peter also believes that this is an area in which Men’s Advocacy Groups can likely help so that women are not shouldering this load alone. One of the take home moments for me was a story Dominick shared about the first time in his entire life that he had a talk with a medical doctor about family planning was when he was in the urologist’s office getting his vasectomy. I embarrassingly admitted that as an ER doctor when I am speaking to a male patient about condom use it is usually in the context of me treating them for an STD and my focus is primarily on preventing future infections not future babies. Made me realize that even in my speciality there are some opportunities. Here are links to some of the information we discussed. Mental Health Survey Here is the article about Dominick’s and his related to the Covid Trends and Impact Survey. This is an online survey on Facebook that has surveyed millions of people across the world. Dominick’s study focused on over 12 million participants in 115 countries from May 2021 to Sept 2021 and found that 37% of men reported feelings or depression and 34% of anxiety with younger men reporting higher levels than older ones. These numbers were similar to the percentages of anxiety and depression reported by women. Men also reported that getting more resources on how to maintain their mental health was one of their top priorities surrounding the pandemic. Their findings were somewhat atypical because outside of Covid, women are typically much more likely to report symptoms of anxiety and depression and men are much more likely to under-report their symptoms, suggesting that COVID has caused significant suffering for men. Interestingly, it also hints that COVID may have helped some men to be more open to the concept of counseling and mental health related services. Post-partum Depression in Men Interestingly, when we think about post-natal depression, we tend to think it is something that only happens to newborn mothers, but Peter suggests that it is also relatively common in men. As this shocked me, I dug around a little. Per this JAMA about 10% of men suffer from postpartum depression but the rate can be as high as 1 in 4, 3-6 months after birth. that might contribute to postpartum depression in men Decreasing Lack of sleep (and sex) No longer being partner’s primary focus Stress of feeling they must provide for partner and child Feeling guilty that they should be happier with their new child Postpartum depression in their female partner Again, interestingly, fathers are usually not asked questions about their own coping is a summary of the paper we discussed that helped a hyper-masculine profession - offshore oil workers - change their culture surrounding safety. Take home points We need more data that analyzes sex and gender differences in medical conditions. One area that Peter feels is particularly understudied is the economic cost associated with ignoring key aspects of men’s health. Having better numbers around these costs could help elevate the issue amongst researchers and policy makers When we talk about mental health, as there are both sex-based biological factors and gender based sociocultural expectations that contribute to it, there are different, often significantly different, challenges associated with the optimization of mental health for men compared to women. As a result, depression in men often goes unrecognized and undertreated and this can contribute to the increased rates of isolation and suicide in men. Tackling men’s mental health related issues requires a multi-prong approach including education and the intentional creation of different types of sociocultural accepted spaces where men can seek support and learn coping skills. When considering men’s role in reproductive health, Dominick shared a three-prong framework. Men as clients, men as supportive partners to women and men as advocates for change. The use of effective messaging to engage men in these issues is critical especially as to this point reproductive health has been considered a “women’s issue” in which men have by and large been excluded. Finally, there is a need to bridge many Men’s and Women’s Health Advocacy Groups more effectively. As the health of a community is dependent upon the health of all its members, these groups share a lot of common goals and there is significantly opportunity for greater coordination. Thanks for listening to seX & whY, Jeannette /episode/index/show/sexandwhy/id/24312726

Issues Surrounding Men’s Health - Part 1 07/28/2022

Issues Surrounding Men’s Health - Part 1 Show Notes for Episode Twenty-Three of seX & whY: Issues Surrounding Men’s Health, Part 1 Host: Jeannette Wolfe Guests: Peter Baker – Twitter: Dominick Shattuck has a PhD in psychology and does Global Health Work at Johns Hopkins Bloomberg School of Public Health Here is a of Peter Baker’s publications including Here is a 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. /episode/index/show/sexandwhy/id/23890569

Sex, Drugs, and Rats 05/31/2022

Sex, Drugs, and Rats 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 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 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 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: 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: . 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 who stood tall against the tremendous pressure by the manufacturers of thalidomide to approve the drug in the United States. Her request to not approve the drug without additional data ultimately saved the lives and physical disabilities of countless babies. Take home points from podcast Historically the vast amount of basic science research was done only on male animals thereby potentially missing important findings that may be unique to a specific sex. The inclusion of female animals in and by themselves do not produce greatly variability in basic science research results. In fact, in many cases, using male animals may produce significant variability suggesting that male hormones may not be as consistent as once believed. The bottom line is, it depends on what you are studying and there are easy to apply scientific methods that can allow you to determine if hormonal variation may be playing a part in outcome results without using excessive amounts of animals. Pharmacokinetics of how a drug is absorbed, distributed, metabolized and excreted are often influenced by biological sex, yet very few drugs that are currently on the market have adequate and accessible data on pharmacokinetics broken down by biological sex. Drugs that have greater concentrations in a female body correlate to the chance of an increased likelihood of an adverse reaction. If you prescribe medications, it is a good rule of thumb to start at the lowest possible dose in a female and to ensure you review their med list to avoid predictably adverse cross reactions. The ethics around studying drugs in pregnant and lactating females are challenging especially as many of these drugs may have side effects that will not be apparent for decades. One way to help fill this gap is to run parallel basic science studies that examine long term behavior changes in animals after drug exposure. Thanks for listening! /episode/index/show/sexandwhy/id/23281247

Sex and Gender Differences in Opioid Use Disorder 04/08/2022

Sex and Gender Differences in Opioid Use Disorder 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 . 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 Stats - Opioid deaths accounted for > 70% of all deaths from drug overdoses (totally overdose deaths 70,630) 2019 data Opioid Overdose Deaths 2019 total deaths Men Women 49,860 34,635 15,225 2020 data - total overdoses > 93,000 estimates that 69,710 from opioids. For comparison 2020 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 is decreasing more slowly while heroin use in increasing more quickly. “From 1999 to 2010, overdose 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: /episode/index/show/sexandwhy/id/22730108

Interview With Dr Shirin Heidari Part 2: Gendro - Advancing Sex and Gender Equity in Science Research 02/09/2022

Interview With Dr Shirin Heidari Part 2: Gendro - Advancing Sex and Gender Equity in Science Research 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 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 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 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 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 modules 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 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 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 , 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! /episode/index/show/sexandwhy/id/22076792

Interview With Dr Shirin Heidari Part 1: Sex and Gender Variables in Science Research 01/12/2022

Interview With Dr Shirin Heidari Part 1: Sex and Gender Variables in Science Research 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 , 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 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 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 that suggests that the gender of the researcher or lab tech may subtly influence research results. Here is a that suggests that male and female animals both have similar amounts of hormonal variation. In part two we will discuss possible solutions. /episode/index/show/sexandwhy/id/21753464

About Vaccine Research 08/03/2021

About Vaccine Research 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: 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 - from last summer with my interview with Evelyn Bishof and Sabra Klein about Sex Differences in Immunology and Drug Therapy showing efficacy in females and not in males. Here are some videos on the immune system: article nicely explaining how different vaccines work /episode/index/show/sexandwhy/id/20023262

Mike Gisondi Announces Stanford's New, Open Access Course, "Teaching LGBTQ+ Health" 03/22/2021

Impact of Gendered Masculinity in Health Engagement and Decision-making 02/11/2021

Impact of Gendered Masculinity in Health Engagement and Decision-making 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 that examines ways to more effectively engage men in their health. - List of her other - TEDX Rochester talk by - Links to Dr Saeed’s - His specific that we discussed - 2012 paper that Dr Saeed referenced by Susan /episode/index/show/sexandwhy/id/17911808