The Silent 50%

Women and Men Are NOT Equal
Feb 2021
Rumya
R.
Harvard-MIT Health Sciences and Technology

Every year, I look forward to the annual Harvard-MIT Health Sciences and Technology (HST) Fall Dinner. Not for the free food, open bar or rare opportunity to dress up (although they surely don’t hurt), but almost exclusively for the company. HST is a unique program that allows PhD, MD and MD-PhD students to take classes and conduct research together. While I love my classes, my favorite way to learn is truly through the high-octane conversations I’ve gotten to have with my classmates about their thoughts on lectures, their research or their favorite new Science article. But while the program is nothing but intellectually diverse, in terms of racial and gender diversity, it has a long way to go.

At dinner, two of my MD classmates and I were discussing the pros and cons of gene therapy research for sickle cell anemia. My MD classmates were discussing the devastating effects of sickle cell anemia that they’ve seen in the clinic and out of curiosity, I asked how much worse the disease presentation was in women than men. The two men stared back blankly and said that they hadn’t noticed sex-based differences (ref 1). One jokingly elbowed me, “Men and women are equal Rumya, didn’t you get the memo.” I laughed it off and we continued with our conversation. The sister of one of my classmates had just gotten married, and we were all soon excitedly swiping through wedding photos.

Soon, the speaker stepped up to the podium.

Our speaker for the evening was the second reason I had attended the HST Fall Dinner.

Paula Johnson (ref 2), a cardiologist and the current president of Wellesley College, began her talk as most others had, with a recognition of the HST program and the course staff, professors and administrators that make it possible. But then she began talking about gender inequalities in health care, specifically about how little we truly know about cardiovascular health in women.

I was floored.

Women constitute 50% of the world’s population and were excluded from analysis in one of the leading causes of death for decades. Many women who come into the hospital having a heart attack are often misdiagnosed because a heart attack in a premenopausal woman is “less likely” due the preconceived notions of the protective effects of estrogen (ref 3). In fact, many researchers now have evidence to suggest that the presentation of a heart attack in a man and a woman may be completely physiologically different. While men present the “classical” symptoms such as left sided chest pain and shortness of breath, women often only present fatigue and mild pain (ref 3). In fact, 33% of patients have an ‘atypical’ presentation of a heart attack without chest pain and the majority of this population was shown to be young women under 65 years of age (ref 4). Similarly, stroke may present in women more as a migraine-like headache or change in mental state rather than the loss of feeling in one side of the body as seen in the canonical male model. If women were simply included in pioneering cardiovascular health studies, we would not define the male model as ‘typical’ and the constellation of symptoms that appear primarily in women as ‘atypical.’

There was an entire 50% of the population that the modern medical system was failing to effectively triage and treat.

I looked over to my MD colleagues, prepared to see the same shock plastered across their faces as on mine. But their faces remained unchanged, lit by the glares of their phone screens as they continued to scroll through wedding photos.

These were future physicians. The same professionals who would treat the woman who came to the ER complaining of chest pain. The same doctors who would make the decision to order an EKG or send her away with anxiety medication.

This is not a criticism of my classmates, of whom I still think the world of their ambition and natural scientific curiosity, but rather an illustration of a failing of the medical education system. The medical school curriculum is peppered with passing discussions of how “landmark” trials that shape the way diseases are diagnosed and treated do not accurately reflect the entire population of patients. But, despite being told to be broadly aware of this problem, my future physician colleagues are never taught what to do about it. With no actionable strategies to practice in this uncertainty, physicians fail to break out of the systems that perpetuate these inequities. We should be teaching our future physicians and researchers that in the development of these therapeutics, men and women ARE NOT equal but deserve to have their biologies equally considered.

The differences between men and women are not limited to the realm of cardiology. One of the fundamental flaws of medicine that is often overlooked is the notion that if a drug and dosage works in a man, then it must also work in a woman. In every aspect, our current medical model is based on, tailored to, and evaluated according to male models and standards (ref 3). While many organ systems appear similar, the very cellular makeups of men and women are functionally different due to the influence of sex chromosomes and their corresponding responses to sex hormones. Research has found that certain genes responsible for lung cancer are actually differentially regulated by estrogen, making women three times more susceptible to developing lung cancer without a prior history of smoking (ref 2).

Even the drugs that women are prescribed fail to account for female metabolisms and hormonal fluctuations. Menstrual fluctuations are offered as a confounding variable and grounds for exclusion from clinical trials but for some reason not considered when actually prescribing these medications to women. This leads to women’s bodies responding very differently to what is considered medically “normal” for men. Women were not formally included in clinical trials until 1993 (within the lifetimes of many current graduate students!) but are still excluded in studies as recently as 2019 (ref 6). Unfortunately, even when included in clinical research, the divisions between men and women are not upheld in the downstream data analysis since both groups are merged when looking at overall drug effects. This means that, even if women are included in clinical trials, many of the drug effects that may be exclusive to women are lost, and we are no closer to understanding how drugs should be prescribed differentially based on sex. With no good data available, physicians are forced to rely on poorly constructed data, making researchers as culpable as physicians in propagating medical misconceptions about women.

It is now 2021, a full 28 years since women have been included in clinical trials, but without much greater understanding of drug effects or disease presentation in women. Are we, as a society, afraid to have this discussion because admitting that the sexes are truly different at a biological level will present a basis for discrimination and endanger the already fragile social equilibrium of the sexes? Or is it far more dangerous to continue to live in ignorance and let diseases go misdiagnosed and treatments remain ineffective?

My personal opinion is that staying silent is the far greater risk. Our research studies should discriminate on the basis of sex, and modern medicine should stop turning a blind eye to the biological differences in the treatment and triage of female patients. As graduate students in medical science, we have a responsibility to 50% of our population, to include them and their differences in our research, clinical trials, and data analysis. And if we don’t, we run the risk of remaining the silent 50%, overlooked by science and medicine alike*.

But we have a choice.

We could speak up and be heard. And in that moment, I had a choice to make as well.

I looked at my MD colleagues and saw them continue to chatter excitedly. I leaned over, and whispered, “Hey do you think we could do this later? I think we should really listen to what she has to say.” My friends turned a light pink from embarrassment and immediately put away their phones, whispering hushed apologies. This conversation has to begin somewhere, and it is the charge of our generation, our graduate programs and medical schools, and our dinner table conversations, to not let the 50% be silent any longer (ref 5).

 

Ref 1: Women are at a much higher risk of complications from sickle cell anemia and suffer multiple more complications than their male counterparts due to hormonal changes and menstrual cycles. Ref: https://pubmed.ncbi.nlm.nih.gov/16635275/

Ref 2: While I am a firm believer that those accomplishments should stand on their own without mention of her race or gender, for the purposes of this blog it is important to include that she is the first black woman to ever serve this role. Her TED talk can be found here: https://www.ted.com/talks/paula_johnson_his_and_hers_health_care#t-425249

Ref 3: Sex Matters: How Male-Centric Medicine Endangers Women’s Health and What We Can Do About It

Ref 4: Statistical Research on the differential presentation of heart attacks in women https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/770038?resultClick=1

Ref 5: Steps in the right direction. A bra to promote heart health in women because of the different ways heart attacks present in men and women. https://www.bloomertech.com/when-where#stay-warm

Ref 6: A 2019 study that excluded women on the basis of hormonal fluctuations: https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24379 

 

*The discussion of discrepancies in health care and medicine does not even scratch the surface of other non-gender based discrepancies. Namely, race-based discrepancies have plagued the field for centuries, and many common diagnoses continue to ignore the obvious fact that some symptom presentations (such as redness or skin discoloration) will appear very different in a darker skin tone than in the white skin tone that these studies are typically conducted on.