Instead, it would be two years until Ward, whose name has been changed to protect her identity, was able to eat normally again.

Ward, a retiree living in Olathe, Kansas, continued to feel severe stomach pains long after she finished her antibiotic. She returned to her doctor’s office for testing, in addition to multiple trips to the ER and urgent care facilities, but no one could tell her what was wrong.

  She lost 90 pounds in three months because she could not keep food down, yet she was sent home from the hospital each time when her labs came back normal. When she tried to get an appointment with a specialist at a larger health system, as her doctor recommended, she was told it would be a five-month wait. Her husband told her, “I’m worried you won’t make it that long.”

Eventually, seemingly out of options, Ward’s doctor told her, “This pain is just all in your head.”

Ward didn’t know what to think, she said. She’d seen her doctor for over 10 years and trusted him. The sudden dismissal of her pain took her by surprise.

“I thought, for a second, ‘Well, maybe it is,’” Ward said. “He’s the doctor, and they ran all kinds of tests. But something just really didn’t feel right. The pain I was feeling was not normal.”

Ward’s story is not uncommon. It’s an open secret among women that medical professionals are often dismissive of their pain. Women are often stereotyped as being dramatic or anxious, leading to longer wait times for treatment and worse health outcomes. A 2008 National Institutes of Health (NIH) analysis of 981 emergency room visits showed that women with acute abdominal pain were up to 25% less likely than their male counterparts to be treated with powerful opioid painkillers.

The reasons for these disparities are wide and varied. But Kimberly J. Templeton, M.D., professor of orthopedic surgery and sports medicine at the University of Kansas Medical Center and past president of the American Medical Women's Association, said the key to solving them may lie in research.

“Women’s health has been sort of sidelined to a degree into what was called ‘bikini medicine’ — breast disease and reproductive health,” Templeton said. “The powers that be said, ‘That’s the extent of women’s health, and everything else that women face is just like men.’ We know now that’s simply not true.”

A History of Exclusion

But it is not just clinical care where women are being affected by health disparities. Throughout history, women have also largely been excluded from participating as subjects in medical research, both due to guidelines that explicitly banned them and a misunderstanding of the differences between men and women on a biological level.

“For a long time, it was assumed that women were just like men, except they were smaller and had different reproductive organs,” Templeton said. “But we’ve known for a while that’s not the case. Every cell has a sex. It’s not just the influence of hormones, though that’s a significant thing. There are a lot of differences based both on sex and gender.”

From the early days of medical research until the 1960s, this exclusion was not seen as an important mainstream issue. Then the civil rights era gave rise to the women’s health movement, which drew more attention to inequities in health and research.

Out of this rise in awareness came the highly influential book, Our Bodies, Ourselves, published by the Boston Women’s Health Book Collective in 1972. The book, which has since been updated nine times, provides information related to many aspects of women's health and sexuality, including sexual health, sexual orientation, gender identity, birth control, abortion, pregnancy and childbirth, violence and abuse and menopause.

But regulations were slow to catch up to the increase in knowledge about women’s health. As an example, in 1977, the FDA released guidelines that banned women of childbearing potential from participating in Phase I and early Phase II clinical drug trials.

Pregnancy and reproductive health were major areas of concern for researchers, who thought that the hormonal changes that women of childbearing age go through during their menstrual cycle would negatively impact the results of their studies. They were also concerned that, if a woman was pregnant, there would be additional risks to the fetus along with even more hormonal changes that would impact results.

Templeton said that these differences are not a reason to exclude women from clinical trials, but to include them, because without data from women participating in these studies, clinicians are basically operating in the dark when it comes to treating women. 

“Of course, for women who are pregnant, you need to be cautious of her health and the health of the fetus,” Templeton said. “But there are health conditions beyond pregnancy that happen to women who are pregnant. You need to know what the interventions are going to do and how the responses of pregnant women may differ from women who aren’t pregnant, or may differ from postmenopausal women or men of the same age.”

While all women have been historically underrepresented in research, women of color are included even less often.

“In previous years, when there weren’t as many women scientists or researchers of color, oftentimes researchers didn’t even think about including women of color in their studies,” said Margaret Smith, M.D., MPH, associate professor of family and community health and associate dean for diversity and inclusion at KU Medical Center.

This exclusion is attributed not just to discriminatory practices, but to a culture of mistrust that stems from decades of mistreatment of women of color who were research subjects.

In the mid-1800s, many enslaved people were subjected to medical experiments such as electric shocks, brain surgery and amputation, all without their consent. James Marion Sims, often called the “father of modern gynecology,” developed pioneering tools and surgical techniques related to women’s reproductive health in the 1800s. But Sims’ research was conducted on enslaved Black women without anesthesia, because he falsely believed that Black people didn’t experience pain like white people did.

In another case, American researchers tested an early, high-dose version of birth control pills on poor Puerto Rican women in the 1950s. The women who participated were not told what the side effects might be because the effect of the drug was largely unknown at the time. At least three women died during the trial, but no autopsies were done to determine the cause.

Although today there are more clinical trials than ever looking to recruit women of color, it can be difficult to find participants because of this nightmarish history, Smith said.

“That legacy has led to mistrust of the medical system as a whole, but even more specifically a mistrust of medical researchers,” Smith said.

In recent decades, federal guidance began to change to allow more women to participate in clinical research. In 1993, the NIH passed its Revitalization Act, which mandated that women be included in studies for conditions that impact both sexes. In the same year, the FDA developed new gender guidelines that recognize the need for adequate representation of women in drug trials, reversing its 1977 recommendation to exclude them. Then in 2014, the NIH released its Sex as a Biologic Variable policy, which requires projects funded by the NIH to include male and female subjects in both human and non-human trials.

There have also been some advancements for racial health equity, starting in 1984 when the NIH started the National Black Women’s Health Project, now the Black Women’s Health Imperative, to begin addressing the reproductive and general health of African American women. Then in 1986, the NIH enacted the Inclusion of Women and Minorities in Clinical Research policy, which urged researchers applying for NIH funding to include women and minorities in studies involving human subjects.

While these policies have successfully gotten more women and women of color into clinical trials, they have no power over privately funded projects, which make up the vast majority of medical research, Templeton said. 

“Those policies have played an important role in raising awareness, but until other funders have the same requirements, the impact is going to be limited,” Templeton said.

This means that women are still often underrepresented in research, despite the many differences in how various conditions present themselves between the two sexes, sometimes leading to dangerous outcomes.

The Impact of Exclusion

Today, research into women’s health has revealed that women experience some conditions differently than men. One of the most cited examples is that women are more likely to experience vague, subtle symptoms during a heart attack. In 2023, the Journal of the American Heart Association reported that women who visited emergency departments with chest pain waited 29% longer than men to be evaluated for possible heart attacks.

After reading the results of a recent cardiology study, Templeton said she was frustrated that the research used to create clinical practice guidelines did not include an analysis on any sex and gender differences in the data, despite the widely accepted fact that women experience cardiac disease differently.

“We have an area like cardiac disease, where we know there are differences, but we don’t really know what they are because health care providers aren’t looking for them,” Templeton said. “If you don’t look, you don’t find.”

Women also experience conditions such as chronic migraines, mental health issues and chronic fatigue syndrome at a higher rate than men. But the reasons for this are largely unknown because they are understudied and underfunded.

Even within diseases that primarily impact women and are heavily researched, such as breast cancer, questions remain because of a lack of diversity within clinical trials. Black women are less likely to be diagnosed with breast cancer, but when they are, they are 40% more likely to die as a result. This is often attributed to socioeconomic disparities, but with women of color still underrepresented in research, many mysteries remain.

The lack of women in FDA trials for decades has also had a particularly negative impact on women’s health. Eight of the 10 drugs most recently removed from the market were done so because of unanticipated side effects on women, Templeton said.

One notable example is the sleep drug Ambien, known generically as zolpidem. When it first came on the market, the dose recommendation for men and women was the same. It was only after a significant number of women started getting into motor vehicle accidents the morning after they took the drug that researchers realized the effect was much stronger for women.

“That wasn’t a hormone thing. That is the different pharmacokinetics and pharmacodynamics in women,” Templeton said.

More Than “Bikini Medicine”

In addition to being historically excluded from clinical trials of all kinds, conditions that specifically affect women are understudied, said Courtney Marsh, associate professor of obstetrics and gynecology and division director for reproductive endocrinology at KU Medical Center.

“It’s always felt taboo,” Marsh said. “Even during COVID, there weren’t enough studies done on vaccines for pregnant people. There just isn’t enough focus on women in any area.”

Endometriosis is one example of an understudied chronic condition. It effects roughly 10% of women worldwide and 50% of women who are infertile, but research searching for a cure is underfunded compared to its disease burden — a measure of how much death and disability it causes. Conditions that disproportionately impact men, such as HIV/AIDS or substance abuse, are conversely often overfunded compared to their disease burdens.

Marsh, whose research has spanned from polycystic ovary syndrome to fertility drug trials to the differences in how the sexes perceive pain, entered the field of obstetrics and gynecology because she wanted to change that.

“Some of these things are a challenge to study. Miscarriage, for example, is classically hard to study because it’s just difficult to get a good model of what’s going on inside the uterus,” Marsh said. “But things have come so far now. We have things like 3-D organelles and different models you can use to actually see attachment and implantation. It’s just so exciting how far we’ve come.”

Marsh’s research is most often inspired by problems her patients bring to her, she said. Most recently, she has been looking into ways transgender men can preserve their fertility. Like cisgender women, transgender men have been historically excluded from research. Research into transgender issues is also chronically underfunded, Marsh said. 

“The egg freezing process has become kind of touted as the standard, but it’s a rough process to go through. The barriers are really high — it’s expensive and typically not covered by insurance, you have to be off gender-affirming hormones and given hormones that are not gender affirming, go thought potentially invasive procedures that can cause dysphoria — all for something you don’t know if you’re going to use in the future,” Marsh said.

Marsh wanted to investigate methods that would not interrupt a patient’s gender care because she saw such a need for it in her patients, and such a lack of information on how to improve care.

“A lot of trans men undergo ovariectomies as part of their gender affirming care. So, we wondered if there was a way, when we’re taking the ovaries out, to be able to grow eggs off of the ovary, mature them outside of the body, and freeze them that way,” Marsh said. “It’s still very early. But everything we do stems from a place of how can we make this process better?”

But there are still many areas, such as infertility, polycystic ovary syndrome and endometriosis, that Marsh said need to be bolstered before medicine truly understands reproductive health for women.

“Some of the problem lies in how we think about research. Many people think of mice in a lab — and that level of research has a very specific role for reproductive medicine because there are biologic things that we don’t understand yet that we need better science for,” Marsh said. “But there’s also much broader research that needs to be done on social awareness, access to fertility care and how we can make it more normal to seek care and talk about the issues some people have with getting pregnant.”

Solving the Problem

While she emphasizes how important it is for women to be included in clinical trials, Templeton said it would be unrealistic to repeat every trial done exclusively on male subjects. Not only would that endeavor be prohibitively expensive, it would not provide the insight researchers need to create a more equitable health care system.

“We don’t want to go from a time where all research subjects are men to a time where all research subjects are women,” Templeton said. “We need both so we can properly compare them.”

Rather than focusing on individual trials that might need to be repeated, researchers like Judith Regensteiner, director of the Ludeman Family Center for Women's Health Research and professor of medicine internal medicine and cardiology at the University of Colorado Anschutz Medical Campus, want to see more sex-specific clinical practice guidelines that take into account how women’s bodies are different.

“The model of health care was based on men, and women are treated just like men,” Regensteiner said. “It is pretty clear now that is not appropriate.”

The Sex and Gender Equity of Research guidelines, originally published in 2016, are the most well-known and widely used guidelines for incorporating gender analysis into research, Templeton said. The World Health Organization adopted the guidelines in 2023 in an effort to make sex and gender reporting less sporadic in research on an international scale.

Taking a more detailed look at sex differences would not just provide insight into women’s health, but it could improve research into men’s health as well, Regensteiner said.

“We want the best health care for everybody. But men are treated according to these same guidelines, some of which were developed combined with women, so is that really the sharpest health care for men? Probably not,” Regensteiner said. “We need to be doing careful, sex-specific evaluation of treatment to get better health care for everybody.”

Bolstering the number of women in STEM fields is another central goal of the movement to create more equitable health care for women. Regensteiner is also the co-principal investigator for the NIH's Building Interdisciplinary Research Careers in Women's Health grant, which connects junior faculty to senior faculty with shared research interest in women's health and sex differences research.

“Without a diverse workforce, you are not going to get the work done,” Regensteiner said.

Smith said this workforce building is especially important when it comes to increasing the representation of women of color.

“We still have a dearth of people of color in medicine,” Smith said. “Continuing to recruit people of color to medicine will help, but we also need to recruit more people of color in research. Very few large research grants from the NIH go to women of color. Making a path for that to happen would help a lot.”

As more people of color join the medical field, Smith hopes to see an increase in cultural awareness, as well as more people of color in recruitment roles.

“People need to learn about people of color — what they value, what’s important to them, who they are — before we go and try to answer research questions about them,” Smith said. “We need more people of color at all levels.”

Data May Be the Key

Templeton also wants to see more information in medical school curriculums about the sex differences between men and women. But without the data from research projects first, there is nothing to add to study materials.

“If you don’t have the data, you are still teaching students and residents on a one-sex model,” Templeton said. “You are not asking them to look for differences because you are not talking about those differences.”

A $11.3 million grant awarded to the University of Kansas in May 2024 from the NIH may offer a potential key in unleashing the power of information. The grant will establish a multidisciplinary biomedical center at KU to research big data’s potential to improve women’s health.

“All of the research projects within the center will have a component of using large data sets or machine learning, and an application area related to women's health in some way — especially looking at health disparities that women incur,” said Heather Desaire, Ph.D., he Keith D. Wilner Chair in Chemistry at KU, who will serve as the center’s director. “We are talking about diseases like ovarian cancer, breast cancer, multiple sclerosis and Alzheimer’s disease, which are more prevalent in women.”

By funding research projects, supporting faculty, improving lab facilities and boosting collaboration across scholarly fields, the center will harness complex datasets to tackle biomedical issues vital to women. The new center will also help expand education and training of students in handling complex datasets as well.

Becoming a Priority

While progress on women’s health equity has not come quickly, it is starting to gain national attention. In November 2023, the White House announced its Initiative on Women’s Health Research, led by first lady Jill Biden and backed by $100 million to bolster research into women’s health. Templeton said she sees this initiative as a sign that people are seeing the problem and starting to get on board with the solution.

“We know how to make it better. Do the research and include enough women and men. If you can’t, list that as a limitation. If your study isn’t big enough, get more people on board,” Templeton said. “I realize it’s not all that simple, but it’s not like we don’t know what to do.”

While her national work for women’s health equity spans all areas of medicine, Templeton is working to lead by example in her own specialty. Last year, Templeton gathered a group of orthopedic publishers and editors to figure out how to address the lack of gender equity in research. Together, they are developing guidelines that Templeton hopes will have an impact across her specialty and beyond.

She is also working to set a new standard with clinical guidelines for how women’s care should be different to men’s care following orthopedic surgery because of the inherent differences in the skeletal structure.

“My hope is that orthopedics can serve as a model for how other specialties can work on improving their care for women,” Templeton said.

On The Road To Recovery

After her two years of debilitating stomach pain, today, Cynthia Ward is 90% back to her old self, she said. It took a trip to the Mayo Clinic in Rochester, Minnesota, for her to finally find an answer and a solution to her pain.

Doctors there determined that Ward had developed nerve damage in her stomach, likely from the antibiotic she was prescribed or from the sickness that prompted it. Her physician at the Mayo Clinic told her there was no way to know for sure. But there was an over-the-counter solution she could take for the rest of her life if she needed to that would begin to ease the pain she felt.

“It was just such a relief,” Ward said. “Just to know that at some point, I was going to be functioning and alive again, and that someone finally listened to me and believed my pain. It was life-changing.”