Women know this is true: They often come away from the doctor’s office feeling uneasy, unsure whether or not they’ve been heard. However well-meaning the physician, women sometimes sense that medical science doesn’t really see us, let alone understand us. A look at history suggests this feeling is well founded—and reveals what impact a legacy of women’s invisibility has had on women’s health.
From the biblical origin story of Eve being created from Adam’s rib to the U.S. Constitution’s assertion that all men are created equal, we’re used to thinking of female as a subset of male. “Mankind” is an umbrella category that encompasses the smaller, more specific category of women. We can extrapolate truths about the human species from men to women, but not necessarily vice versa. Men are general; women are particular.
This assumption has left women woefully underrepresented in biomedical research, pharmaceutical development, and clinical trials for most of modern medical history and directly impacted the quality—or lack thereof—of women’s healthcare.
“Apart from reproductive health concerns, medicine pays little attention to potential differences between men and women, instead taking a one-size-fits-all approach to clinical research and practice,” writes Twin Cities journalist Maya Dusenbery in her book Doing Harm: How Bad Medicine and Lazy Science Leave Women Dismissed, Misdiagnosed, and Sick. “For decades, that one size was specifically a 70-kilogram white man.”
The Rise of Sex-Specific Research
Until the early 1990s, women of childbearing age were largely excluded from clinical research, and they were expressly forbidden by the FDA from participating in early-phase drug trials out of fear of adverse effects on their potential future pregnancies or offspring. When medical research did focus on women’s needs, it tended to take a “bikini approach,” focusing exclusively on the breasts and reproductive system. Meanwhile, the top three causes of death for women are the same as those for men (heart disease, stroke, and cancer). These conditions may present differently in women or respond to different treatments than those indicated for men, but when it comes to the big killers and their treatments, researchers have historically assumed that what was good for the goose was good for the gander.
In the lab, researchers defended their preference for male animal subjects by arguing that female hormonal cycles present an added layer of complexity to study results. (A recent meta-study in Neuroscience and Biobehavioral Reviews laid this concern to rest.)
Dr. Marilyn Carroll, a psychiatry professor and researcher who studies sex differences in drug addiction at the University of Minnesota, rejected this argument for male-only study subjects well before the biomedical research community caught up. She had long wanted to experiment with female rats in her addiction research throughout the 1970s and ’80s, but she kept encountering the familiar objections among her (mostly male) peers.
In 1988, one of Carroll’s graduate students at the University of Minnesota pressed her on why they couldn’t use female rats in a lab study. “I had my own research grant then, so I said, ‘Let’s do it.’ We were the first to start using female rats in the lab,” Carroll says. “We’re recognized as the people who broke that glass ceiling.”
How Sex-Specific Studies Have Influenced Medicine
The following year, Carroll and her team published groundbreaking results highlighting differences in how male and female test subjects experience addiction and respond to treatment, an area she has continued to explore ever since. “Females are more avid drug-seekers than males,” she explains. “They acquire addictive behavior more rapidly. They take more drugs per body weight, and they escalate to higher levels of addiction than males. But they also respond better to treatment interventions than males.”
Carroll and her fellow researchers have identified hormones, particularly progesterone, as a key factor affecting addictive behavior in females. Her research has led to experimental forays into precision treatments for addiction, tailored to the specific needs of men and women. None of this would have been possible without including female rats in her research.
Carroll was on the early side of the curve, but by the early 1990s, awareness of gender inequity was spreading through biomedical research. In 1993, Congress passed the National Institute of Health (NIH) Revitalization Act, mandating the inclusion of women and minorities in federally funded clinical studies. (It wasn’t until 2016 that the NIH required females to be included in preclinical research on animals.)
Since sex-specific research took off in the early ’90s, researchers have identified how sex and gender contribute to differences in symptoms, risk factors, and prevalence of conditions including autoimmune diseases, heart attacks, and lung cancer, among many others. Such insights have saved millions of lives.
In 2002, the NIH established the Specialized Center of Research (SCORE) on Sex Differences program to support established scientists and institutions focusing on the interaction of sex, gender, and health. Minnesota’s Mayo Clinic became a designated SCORE on Sex Differences in 2010, one of 11 such centers nationally. Dr. Virginia Miller leads the center’s research on female-specific conditions as well as age-related cognitive challenges in women.
“If you go out into the street and ask if men and women are different, people are going to say yes. It’s obvious. Our biology is different. But to get that concept embedded into scientific and medical education is hard,” Miller says, noting that it was only two years ago that the NIH mandated that sex be considered as a biological variable in the design and reporting of preclinical research.
Miller points to the potential of sex-specific research to more effectively diagnose and treat both men and women, plus impact medical costs. “You don’t want people coming back to the doctor time and again because their treatment isn’t working or they’re having side effects,” she explains.
Women and Heart Health
Heart health is one of the biggest areas where knowledge of sex differences is critical for women and their care providers. Women tend to develop heart disease about a decade later than men, and more men than women die of heart disease in middle-age. These are among the reasons that the majority of heart disease research has historically focused on men. Thanks to this research, heart attacks in men between the ages of 35 and 54 are on the decline. But heart attacks among women in the same age group are on the rise.
In his recent book Heart Solution for Women, Dr. Mark Menolascino writes, “To this day, women with heart disease are less likely to be tested to determine its severity…and the prognosis for a woman who has a heart attack is much worse than is typical for a man.”
Women’s cardiovascular health is one of the primary areas of focus for the Mayo Clinic SCORE on Sex Differences. “The biggest elephant in the room [in the area of sex-specific healthcare] is cardiovascular disease,” Miller says, noting that it’s the number one killer of both men and women around the world, but the conditions that predispose women to cardiovascular disease are different in women than in men.
“Some of the risk factors for women are related to ovarian function and hormones. Certain pregnancy complications can predispose women to cardiovascular disease as well. This is a major area that needs attention,” Miller explains. Research underway at Mayo’s SCORE on Sex Differences aims to shed light on how hormonal shifts related to pregnancy and menopause affect women’s cardiovascular and cognitive functioning, hopefully narrowing the knowledge gap that currently puts women at greater risk of dying from heart attacks than men.
The Autoimmune Sex Gap
Sex also seems to play a significant role in the prevalence and treatment of autoimmune disease. Taj is an actor and improviser in Minneapolis. In 2015, at age 28, she began experiencing excruciating abdominal pain. “I went to my doctor, and she did some tests and blood work, but they came back showing nothing wrong,” Taj says. “My doctor said it was probably just psychosomatic.” It took Taj another five months of persistence to finally get a referral to a specialist and receive a diagnosis of ulcerative colitis, an autoimmune condition that affects between 250,000 and 500,000 people in the U.S.
An estimated 75 percent of people with an autoimmune disease are women, and rates of many autoimmune conditions, including lupus and celiac disease, are on the rise. But there’s still a pervasive lack of understanding of these conditions among doctors, with many sufferers struggling with debilitating symptoms for months or years before receiving a diagnosis.
This lack of knowledge affects all patients, but multiple studies have shown that, globally, men with autoimmune diseases tend to get diagnosed faster than women. A 2005 study found that men with rheumatoid arthritis were referred to a rheumatologist within three weeks of their initial doctor’s visit. For women, it took 10 weeks on average, even though the condition is three times more common in women than in men.
This gender disparity in the length of time before diagnosis indicates a problem beyond doctors’ general lack of knowledge about autoimmune diseases. In her book, Dusenbery refers to this problem as the “trust gap.” Women’s self-reported symptoms and sensations are considered untrustworthy—regardless of the gender of their care provider.
Dr. Ruby Nguyen, a women’s health epidemiologist at the University of Minnesota, says that women’s pain is often dismissed as “all in their heads.” Such disregard can compound the underlying problem causing pain in the first place, and it can lead to mental health issues. “When women aren’t supported in their reports, [their pain] can get worse. It can affect their relationships and put them at risk for depression,” Nguyen explains. “Women’s pain is often dismissed as a symptom of depression, when it’s really the cause.”
The medical field no longer brushes off women’s health concerns as “hysterical,” but a tendency to assume that their symptoms are psychosomatic or overblown persists. “When women come into the ER with pain, it’s handled very differently than it is with men,” says Dr. Elizabeth Grey, a cardiologist with Allina Health. “Even if pain is in someone’s head, it’s still a problem,” she stresses. “Fix it!”
Sex Versus Gender
The truth is that we’re learning more all the time about the complicated interplay between our psychology, environments, relationships, and physical health. Medical practitioners sometimes find themselves in a paradoxical position: trying not to discount women’s health complaints as being “all in their heads” while simultaneously working to understand how our heads may in fact participate in our overall biological functioning.
“This is a tricky thing with health in general,” Grey says. “There are all sorts of pathways where we take in what’s going on in the world and filter it through our billions of neurons, and it affects our bodies in ways we don’t fully understand.” In this way, it’s not just biological sex that accounts for differences in male and female health, through our different chromosomes and hormones. It’s also gender—the way a person moves through and interacts with the world. “There are hormonal differences between men and women, but it goes beyond that,” Grey explains. “The way we treat each other differs as well, and that can really impact care.”
The gender of the provider, too, can impact care. Recent studies have shown that patients of female doctors tend to have better outcomes than those cared for by male doctors. Speculation as to why has ranged from females being better listeners to their having a higher baseline level of compassion and empathy. Grey thinks it might come down not to a difference in how women doctors act but in how they are perceived.
“Sometimes I enter a room, and a patient might assume I’m a nurse,” she says. “They’ll say what they’re really thinking. They won’t try to be polite.” The hospital staff treats women doctors differently, too, Grey says. Nurses tend to page her more than her male colleagues with the same title and status, perhaps feeling that the male doctors are too important to bother. “It’s a tiny difference, but it might make a difference in my patients’ outcomes,” Grey says. “I don’t think it’s that women doctors are necessarily more compassionate or better listeners, but it’s more about how we’re treated and valued, which is a benefit for our patients.”
Here, at least, it might make sense to reverse the historical pattern and to apply lessons from the female experience to the male. Don’t treat female doctors the same as men, but treat male doctors more like we treat their women colleagues: as approachable, accessible, and human.