How Studying Female Rabbits led to Teaching Sex and Gender Topics to Medical Students

 From the March 31, 2023 issue of the Transformational Times

How Studying Female Rabbits led to Teaching Sex and Gender Topics to Medical Students 

Sandra Pfister, PhD 

 

“If we don’t look for differences, then we don’t know that there are differences or that sex and gender are relevant.”  

-- Juliana M. Kling, Professor of Medicine, Chair of the Division of Women's Health Internal Medicine, Department of Medicine, Mayo Clinic 

 

In the early 1980s, I was figuring out what it meant to be a basic science researcher as a graduate student in the Department of Pharmacology (University of Texas Health Science Center at San Antonio). What I failed to notice was that all the animals I used in my studies were males. On reflection, the only scientists I knew using female animals were those studying pregnancy or reproduction. I was interested in vascular disease and hypertension, so why would the sex of my animals matter? The year I received my PhD (1984), two publications in PubMed contained the terms sex and hypertension in the title field. By 1993, NIH had mandated women be included in clinical trials. Yet it took until 2016 for a NIH directive to include sex as a biological variable (SABV) in all studies, including those done in cells/tissues/animals. Fortunately, it did not take me 32 years to see the value of using female animals. 

 

In 1992, my career path led me to MCW as an assistant professor in the Department of Pharmacology & Toxicology.  My research investigated lipid mediators from arachidonic acid that contributed to contractile responses in pulmonary arteries from rabbits. About the same time, the Office of Research Women’s Health was established at NIH, and the first long-term national health study that included only women was established. It was called the Women’s Health Initiative (WHI) and had a clinical center at MCW led by Dr. Jane Kotchen. One goal was to find strategies for preventing heart disease in postmenopausal women. It was then I knew I should be studying females. I stopped checking “either sex” on my rabbit orders and more importantly, was intentional about comparing the experimental data results between females and males. Not surprisingly, based on all we now know about sex-based medicine, the data showed enhanced pulmonary vascular contractions in females compared to males. This purposeful decision to study female rabbits was the beginning of an exciting new research direction for my laboratory to explore novel mechanisms in pulmonary arterial hypertension, a known sex-based disease.  

We need to do better

Despite mandates to study women in clinical trials and incorporate SABV in basic science research studies, it has not been enough. Repeating my PubMed search for publications in 2022 with the terms sex and hypertension in the title field yielded a mere 57 results. I thought by 2022, the number would have generated at least 100s of publications. My “cursory search’’ is unfortunately supported by numerous published reports. Using cardiovascular disease as an example, only 25% of preclinical experiments included females1. Cardiovascular clinical trials did not do better with participation by males continuing to predominate2. When females are enrolled, the results of the studies are often not stratified by sex or gender. 

 

Language is important and the terms sex and gender cannot be used interchangeably. Simply defined, sex refers to the biological and physiological characteristics that define humans and animals as male, female, or intersex. Not as easily defined, Gender is a societal construct by humans that refers to roles, activities, and behaviors, and encompasses a wide range of identities beyond male, female, and intersex3. Not including females in clinical trials  -- or including them, but not analyzing the data by sex and gender -- is problematic as it translates to not diagnosing and/or best treating females. 

Building sex and gender studies into the curriculum

As a non-clinician, I wondered how I might be more impactful in promoting the importance of studying sex-based differences in health and disease. Could the path be through medical education? A national survey of medical schools (2014) indicated that 86% of medical students were aware of sex and gender medicine differences in medicine, and 94% believed that medical education should include teaching about sex and gender medicine4.  

 

I knew MCW did not have a formal sex and gender medicine curriculum. That motivated me to lead a team to assess our own faculty and students’ knowledge and interest in sex and gender curriculum development. Results showed that approximately 84% of our M1-M4 students said their education should include sex and gender medicine, and that this knowledge would improve patient care. However, more that 50% of students felt the MCW curriculum had not prepared them to treat sex and gender differences in their patients. Faculty surveyed also felt strongly that MCW medical education should include the teaching of sex and gender differences (96%) while only 20% felt their own training had prepared them to teach it to medical learners.  

 

Next steps involved recruiting three M1 (Kendall Trieglaff, Madeline Zamzow, Bryn Sutherland) and four M2 (Peter Johnson, Andrea H. Rossman, Nnenna Nwaelugo, Ramneet Mann) students to audit and analyze the specific sex and gender content of every M1 and M2 didactic lecture (2020-2021 years). Kendall, Maddie, and Bryn (now M3s) continue to participate in the project and their work has recently been accepted for publication in the Wisconsin Medical Journal.  Students recognized a major limitation of education materials was sex and gender are mostly presented in binary terms. There was little to no discussion that addressed intersexuality, nonbinary, transgender or any others on the gender spectrum. Looking ahead, there is opportunity to use these identified gaps in sex and gender health topics to innovate and expand content in MCWfusion.   

 

My optimistic hope is that a future survey of students and faculty shows not only faculty are better prepared to teach the sex and gender health topics, but students are better equipped to treat sex and gender differences in their patients. Combined with a dedicated focus on being inclusive of sex and gender in clinical trials and SABV in basic research studies, the chances of misdiagnosing or inappropriately prescribing treatments will be rare in every patient.   

 

“No scientific discovery can save a life without first traversing a learning environment...” 

-- Marjorie Jenkins, Founding Director of Laura Bush Institute for Women’s Health, Dean, University of South Carolina School of Medicine Greenville 

 

For further reading: 

1. DH Chang, SM Dumanski, SB Ahmed Female sex-specific considerations to improve rigor and reproducibility in cardiovascular research Am J Phys 324:H279 (2023).

2. 
   

2. SH Bots, NC Onland-Moret, HM den Ruijter Addressing persistent evidence gaps in cardiovascular sex differences research – the potential of clinical care data. Front. Glob. Womens Health 3:1006425, 2023 

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3. L Merone, K Tsey, D Russell, C Nagle. Sex Inequalities in Medical Research: A Systematic Scoping Review of the Literature. Womens Health Rep. 3:49, 2022 

4. 
   

5. MR Jenkins, A Herrmann, A Tashjian, et al. Sex and gender in medical education: a national student survey. Biol Sex Differ 7:45 (2016).

 

 

 

Sandra Pfister, PhD, is a Professor in the Department of Pharmacology & Toxicology at MCW. She is a member of the Faculty Pillar of the Robert D. and Patricia E. Kern Institute for the Transformation of Medical Education.  

 

When Science Isn’t Enough

From the March 31, 2023 issue of the Transformational Times - Women's History Month

When Science Isn’t Enough 

 

Stephanie Kellogg, PhD 

 

What do you do when your spark for a passion fades? Are you sure you fully understand your passion? My journey in biomedical research taught me to be mindful of my authentic self and to meet needs that are important for how I am wired... 

 

There was a time in my life when I would excitedly get out of bed, get to the lab before daybreak, and stay past dinner time. No one told me that was the expected schedule. There was no unseen or unspoken pressure to do that. I just did it, and I was happy doing it. 

But over time, the spark faded. It did not happen overnight. And looking back, it happened before I even noticed it. My unhindered steps to the lab turned into heavy, sticky steps that I had to force. Things were not as fun as they used to be. I still enjoyed my research projects and going to seminars and conferences, but something was missing. After much time and frustration wondering why “the science” was not enough for me anymore, I finally figured it out. For me, “the science” on its own was not enough.  I needed a social structure around science to fuel the spark. 

Of course, the pandemic has made this crystal clear. But to be honest, I was wrestling with these thoughts and feelings years before the pandemic. The experiences of funding droughts, moves, leadership changes, and poor work-life balance wore down my professional and personal social structures.

At the time, I didn’t have the maturity to recognize the importance of relationships while I had them. But they drove my training; they accepted my curiosity and enhanced my relationship with science. Without them, my passion for science would never burn as bright.  

When I first realized this, I felt a bit of shame. Why do I need others to help feed my passion? Maybe science is not my passion if I need others to help keep the flame going. Am I in the wrong field?

But then, the pandemic made us confront our realities, and I was able to find peace with these thoughts. It started with me accepting that I am a human being and part of the species Homo sapiens. Humans are wired to be social and are more successful with relationships and cooperativity. So, it made sense at a primitive level when my social structures wore down or disappeared, my flame went down, too. But why did it seem to affect me more than others? Pandemic aside, the examples I listed above are “normal” in research, so why did my fuel tank feel so empty? Is there still something wrong with me and my choice to be in science?  

After exploring my relationship to Homo sapiens, I took time to understand myself as a human being. My most insightful work has been with a strengths-based coach who helped me realize that I am highly attuned to the social and emotional needs of myself and others. This is how I am wired, and I should feel no shame in that. Meeting my relational needs opens the door for higher fulfillment, joy, and productivity. 

Not filling these needs impedes progress and fulfillment. My highs and lows in science and research finally made more sense. I now keep a stable social structure inside and outside of my profession and use my natural strengths to help develop resiliency in others who work in STEM and medicine. Although it looks and feels different than before, I feel like I have my spark back.  

How about you? Are you at a high or low point of your journey? Every twist and turn will help you grow into your authentic self. Listen to these whispers, be brave along the path, and stay connected with others. 

 

Stephanie Kellogg, PhD, is a Research Scientist in the Department of Microbiology & Immunology. She supports research and administrative programs of the department with her scientific training and relational strengths. She enjoys connecting with others along their self-discovery journey and being a coach in our academic setting.