Elaine Frederick

Faculty and students at the School of Medicine are spearheading efforts to integrate sex- and gender-related differences in health into the medical school curriculum, aiming to address educational gaps about sex differences and ultimately to enhance patient outcomes.

Sex and gender affect many aspects of health; differences between men and women can lead to distinct presentations and prognoses of diseases. For example, women suffer more often from Alzheimer’s disease, while men are more susceptible to immune infections due to immune system differences. Unfortunately, traditional medical school curricula have largely overlooked these differences in health and disease, according to Michael Schwartz, the associate director for curriculum at the medical school. By starting with reform of the first-year neuroanatomy course, the team hopes to jumpstart school-wide curricular change.

Yasmin Zakiniaeiz GRD ’18, who took neuroanatomy as a graduate student and subsequently taught the course for two semesters, has been leading the efforts to include sex differences in the brain in the course’s curriculum.

“While I was teaching the neuroanatomy course the first time, I started to notice there was a lack of acknowledgement of these sex differences in the brain, as well as in disease prevalence and symptoms,” Zakiniaeiz said. “The understanding of those differences is important for medical practice. And students, as future clinicians, should be aware of these differences.”

For example, Zakiniaeiz explained, men tend to have larger brains than women — 8 to 13 percent larger in volume on average — which suggests that larger sizes of brain structures in men could be a potential explanation for differences in the prevalence and symptoms of neurological diseases.

Working alongside Director of Women’s Health Research at Yale Carolyn Mazure and Schwartz, the professor of the course, Zakiniaeiz has led a group of students in preparing and integrating sex and gender differences into the course curriculum. This upcoming fall will mark the first administration of the integration, Zakiniaeiz said.

“A greater focus on sex and gender in the curriculum will hopefully lead to improved care and outcomes for all patients, not just women,” said Njeri Thande, a medical school professor and one of the leaders of these initiatives. “Our students need to be aware that various illnesses can have different symptoms for women and men, that medications may need to be given at gender-specific doses and that treatments often need to differ by gender.”

For example, the pathophysiology and mechanism of heart attacks can be very different in men and women, Thande explained. This difference means that women may display more subtle symptoms and hence experience a delay in diagnosis and treatment.

“Sex differences in terms of different disease presentations or in drug regimens have historically not been looked at very carefully,” Schwartz said. “Most of the clinical trials have predominantly been dominated by men and white men in particular.”

Thande similarly emphasized the value of studying male and female differences in laboratory models in basic research studies and of recruiting a diverse population in clinical studies. Scientists and physicians must also study disease states and access to health care for individuals with nonbinary gender identities, she added.

To target the lack of focus on sex differences at the curricular level, Thande began a task force of medical students about a year and a half ago to start developing potential reforms.

Working with Mazure, Thande first conducted an extensive survey-based review of the preclinical curriculum. The survey results prompted them to propose areas to integrate sex and gender content into the curriculum. For example, they recommended greater coverage of the intersectional impact of sex, gender, race and socioeconomic status on health.

“We found that there were few in-depth discussions on gender bias in research design and analysis — an important source of current disparities in health,” Thande said. “Outside of the realm of reproductive health, the predominant focus on the impact of sex and gender was found on citing differences in the prevalence and presentation of disease, but there was little focus on well-established differences in treatment and prognosis.”

The faculty hope to incorporate a focus on sex differences beyond just the preclinical curriculum. Although curriculum changes in hospital training can be more difficult, bringing the conversation into the clinics and clerkships, where students work with patients, is essential, Schwartz explained.

At the moment, the limited number of hours in the medical school curriculum is one of the biggest challenges for the group, Schwartz said.

Still, the faculty interviewed noted the support their efforts have received.

“There’s great enthusiasm among both faculty and students in terms of bringing these areas into the more traditional training of physicians,” Schwartz said. “These differences impact our patients importantly in the treatments that we provide to them, so it’s important to understand these issues to be effective in terms of health care delivery.”

Unfortunately, Zakiniaeiz said, some scientists still do not fully believe that sex differences exist in the brain. These scientists continue to only use male cell lines and male animals and not include females in their clinical research. This pushback may result from the difficulty of securing research funding, she added, as scientists accounting for sex differences must conduct more experiments with additional subjects.

According to Zakiniaeiz, though, including females in research can often be more cost-effective, as researchers may be able to more accurately predict risks of drugs in clinical trials by using females from the start of the drug development pipeline.

“Eight out of 10 drugs that are removed by the FDA from the market for various reasons tend to pose a greater health risk for women than men,” Zakiniaeiz said. “That’s likely because we don’t test drugs in women as much as we should.”

Amy Xiong | amy.xiong@yale.edu

Correction, March 12: Due to an editing error, Yasmin Zakiniaeiz’s class year was mistakenly stated to be 2019. It is in fact 2018.