The Yentl Phenomenon: How the Evidence Base Built on Men Still Costs Women

Dr. Job Mogire, MD, FACP, FACC Board-Certified Cardiologist | Carle Foundation Hospital, Champaign, IL

In 1991, a cardiologist named Bernadine Healy gave a name to a pattern she saw repeatedly: women had to prove they were as sick as men before receiving comparable cardiac care. She called it the Yentl syndrome, after the character who had to disguise herself as a man to be taken seriously. Decades later, the pattern has narrowed but not closed, and its mechanisms are worth stating precisely, because they are structural rather than a matter of individual fault.

The original observation

Healy’s editorial named the phenomenon: once a woman demonstrated disease in the same terms as a man, she was treated similarly, but reaching that threshold of recognition was itself harder for women (Healy, NEJM 1991). 3 / Early The observation was clinical and is now decades old; its persistence is what makes it more than history. This is a sociological diagnosis of a medical system, rated accordingly, and stated as the documented pattern it is.

The mechanisms behind it

Three structural factors compound. 4 / Promising First, the cardiovascular evidence base was built substantially on male participants, so the disease patterns most familiar to clinicians are male patterns. Second, women more often present with the non-obstructive disease, MINOCA, INOCA, and the broader symptom range, that male-derived heuristics handle poorly. Third, the framing of women’s symptoms as atypical encodes the male presentation as the norm and a woman’s as deviation.

The downstream evidence is concrete. Studies have documented that younger patients, particularly younger women, can be more likely to be initially missed in the emergency evaluation of myocardial infarction (Pope et al, NEJM 2000), and the VIRGO study described the symptom presentations and care experiences of young women with MI, including frequent attribution of symptoms to non-cardiac causes.

What closes the gap

The corrective is partly systemic and partly individual. 3 / Early Systemically, sex-specific evidence, sex-aware diagnostic pathways, and access to coronary function testing address the structural causes. Individually, a woman can carry her sex-specific history, ask directly whether her heart has been ruled out, and seek evaluation tuned to women’s disease. The advocacy is not a substitute for system change, but it is a real lever a woman holds now.

The trials that built the evidence base, and who was in them

To understand why the evidence base skews male, you have to look at the trials that created it. The Framingham Heart Study, launched in 1948, enrolled both men and women from the start, which is worth crediting. But the landmark randomized trials of the following decades were far less inclusive. The Physicians’ Health Study, which established aspirin’s role in primary prevention, enrolled 22,071 male physicians and zero women. The Multiple Risk Factor Intervention Trial, known as MRFIT, enrolled more than 12,000 men and no women. Early statin trials, including the landmark 4S trial in 1994, enrolled populations that were roughly 80% male. The CARE trial and the LIPID trial followed similar patterns. 4 / Promising

The practical consequence is not subtle. When a cardiologist’s training, risk calculators, and prescribing thresholds are all derived from male populations, the patterns she recognizes most readily are male patterns. Risk calculators calibrated on men may underestimate risk in women with non-traditional risk factor profiles: those who develop coronary artery disease at a younger age in the setting of autoimmune disease, preeclampsia, or premature menopause. These are not rare conditions. Preeclampsia affects roughly 5-8% of pregnancies and is now recognized as an independent cardiovascular risk factor for the mother’s lifetime, yet it does not appear in the Framingham risk score or most standard risk algorithms.

The NIH Revitalization Act of 1993 required the inclusion of women and minorities in NIH-funded clinical research, and subsequent decades have improved enrollment. But the historical evidence base does not rewrite itself, and clinical practice moves slowly relative to the research that tries to correct it. A clinician trained on guidelines derived from 1980s and 1990s trials is applying, at least in part, a male-derived knowledge structure to patients whose disease behaves differently.

MINOCA and INOCA: the diagnoses the angiogram was not designed to find

Standard coronary angiography is built to detect obstructive coronary artery disease: plaque that narrows the lumen of an epicardial coronary artery by 50% or more. It does this well. The problem is that a substantial proportion of women who have myocardial infarctions, and a larger proportion of women with ischemic symptoms, have disease the angiogram is not looking for.

MINOCA, myocardial infarction with non-obstructive coronary arteries, is defined as MI with troponin elevation in the absence of obstructive disease on angiography. It accounts for roughly 6% of all MI hospitalizations, but women are substantially overrepresented, comprising roughly 40% of MINOCA patients compared to about 25% of obstructive MI patients (Safdar et al, JACC 2018). 4 / Promising The underlying mechanisms are heterogeneous: coronary spasm, spontaneous coronary artery dissection, plaque erosion rather than rupture, and coronary microvascular dysfunction are all potential causes. Identifying which mechanism applies to a given patient requires additional testing beyond the angiogram, and that testing is not uniformly available or uniformly ordered.

INOCA, ischemia with non-obstructive coronary arteries, describes patients with angina and objective evidence of ischemia but no obstructive disease on imaging. Coronary microvascular dysfunction and coronary vasospasm are the dominant mechanisms. Women with INOCA are not well served by the standard post-catheterization discharge, which often amounts to reassurance that the coronaries looked clear. The coronaries looking clear on angiography does not mean the coronary circulation is functioning normally. It means the epicardial vessels are not narrowed, which is one mechanism of coronary disease, not the whole of it.

Coronary reactivity testing during catheterization, measuring the coronary flow reserve and the microvascular resistance index, can characterize the functional status of the coronary microcirculation. This testing is not yet standard practice. The Women’s Ischemia Syndrome Evaluation study, WISE, documented the prevalence of microvascular dysfunction in women with chest pain and non-obstructive coronaries, and its participants had measurably worse outcomes than would be predicted by the absence of obstructive disease alone. The diagnosis, in other words, was not benign just because the angiogram was negative.

The practical implication for a woman who has been told her heart looks fine after a catheterization: a normal angiogram rules out obstructive disease; it does not rule out MINOCA, INOCA, or microvascular dysfunction. Those diagnoses require a different set of questions and, in some cases, a different set of tests.

The symptom vocabulary problem

The description of chest pain in cardiac textbooks is built on the classic anginal triad: substernal pressure or heaviness, radiation to the left arm or jaw, and exertional onset with relief at rest. This description is not wrong. It describes a real pattern. The problem is that this pattern is more consistently present in men with obstructive coronary disease, and it has been treated as the canonical description of cardiac chest pain across all patients.

What women with cardiac ischemia actually report, as documented in studies including WISE and VIRGO, includes chest pain, but also more frequent reports of fatigue, shortness of breath, nausea, jaw pain, back pain, upper abdominal discomfort, and a sense of pressure or heaviness that does not fit the substernal location precisely. The VIRGO study, which enrolled 3,572 patients with acute MI (roughly 2:1 women to men), found that women were more likely than men to report three or more associated symptoms alongside chest pain, and were less likely to present with isolated substernal chest pain as the dominant symptom (Lichtman et al, JAMA Internal Medicine 2015). 4 / Promising

None of these symptoms are absent from men. The difference is distributional. Women, on average, report a broader and more varied symptom constellation, and that variation interacts badly with a clinical decision framework built to recognize the narrower male-typical presentation. When a woman presents with fatigue, shortness of breath, and upper abdominal discomfort, the differential diagnosis in an emergency or primary care setting frequently runs toward anxiety, gastrointestinal disease, or a viral illness before it reaches cardiac ischemia. This is not because any individual clinician is uncaring. It is because the heuristics are calibrated to a different patient.

Fatigue as a cardiac symptom is particularly worth naming directly. Profound, sudden-onset fatigue in the weeks before an MI has been reported by women in retrospective studies, sometimes preceding chest pain or occurring in its absence. This prodromal fatigue is not a feature of most cardiac symptom checklists, and a woman who presents describing it, without chest pain, is unlikely to trigger the cardiac workup that her symptom pattern warrants.

The practical correction requires that both clinicians and patients widen the vocabulary. A woman describing her symptoms should not filter them through what she thinks a heart attack is supposed to feel like. She should describe what is actually happening: where the sensation is, what quality it has, whether it comes with exertion or occurs at rest, what else is happening at the same time, and whether it is new or has changed. The more precise her description, the more material a clinician has to work with.

Takotsubo and SCAD: conditions that belong to women’s cardiac history

Two conditions sit at the intersection of under-recognition and female predominance and are worth naming specifically, because a woman reading this is statistically more likely to encounter them than the textbook MI.

Takotsubo cardiomyopathy, also called stress cardiomyopathy or apical ballooning syndrome, is a reversible cardiomyopathy characterized by sudden left ventricular dysfunction, typically in the setting of a physical or emotional stressor. Roughly 90% of cases occur in women, and the median age at presentation is the postmenopausal decade (Templin et al, NEJM 2015). 5 / Solid It presents with chest pain, electrocardiographic changes, and troponin elevation, meaning it is clinically indistinguishable from MI in the initial evaluation. The angiogram shows no obstructive disease, and the diagnosis is made by the characteristic wall motion pattern on imaging. The condition is more than a curiosity: in-hospital mortality in the largest registries runs around 4-5%, comparable to STEMI, and a subset of patients develop cardiogenic shock requiring mechanical circulatory support.

Takotsubo was first described in 1990 in Japan and was initially considered rare. Registry data have since established that it accounts for roughly 1-2% of all suspected acute coronary syndromes. It remains underdiagnosed in part because the physical stressor precipitant is common in hospitalized patients, and the syndrome may be attributed to the underlying illness rather than recognized as a distinct entity requiring its own management.

Spontaneous coronary artery dissection, SCAD, is a non-atherosclerotic, non-traumatic tear in a coronary artery wall that creates a false lumen compressing the true lumen and reducing blood flow. It accounts for roughly 1-4% of all acute coronary syndromes overall, but in women under 50 presenting with MI, it is the most common cause, accounting for up to 35% of cases in some series (Saw et al, JACC 2016). 4 / Promising Fibromuscular dysplasia, a non-inflammatory arteriopathy affecting medium-sized arteries, is found in approximately 50-75% of SCAD patients who undergo dedicated vascular imaging. Peripartum SCAD, occurring in the weeks surrounding delivery, is a recognized subset with its own risk profile.

The management of SCAD is meaningfully different from the management of atherosclerotic MI. Percutaneous coronary intervention on a SCAD lesion carries a higher complication rate than on an atherosclerotic lesion, because the vessel wall architecture is fundamentally different. Conservative management, with anti-ischemic medications and monitoring, is preferred in the majority of SCAD cases, while PCI is the standard of care for most atherosclerotic MI. A woman with SCAD who is taken to the catheterization laboratory without the diagnosis being considered may receive an intervention designed for a different pathology.

Recognition requires that SCAD be on the differential for any young woman presenting with MI, particularly in the peripartum period or in the setting of connective tissue disease. It also requires attention to the angiographic appearance: SCAD produces a distinctive pattern of haziness, intramural hematoma, or double lumen that differs from atherosclerotic plaque, but the pattern is easy to miss if the operator is not looking for it.

Questions a woman can ask at a cardiology visit

The advocacy argument is not that a patient should do a clinician’s job. It is that knowing the specific gaps in standard evaluation gives a woman standing to ask about them. These are not combative questions; they are precise ones, and a cardiologist who takes them seriously is more useful than one who does not.

Before the visit, it helps to assemble the history that belongs in the room: any pregnancy-related complications including preeclampsia, gestational diabetes, or preterm delivery; any autoimmune diagnosis; family history of heart disease in women (not only men); and the exact character, timing, and associated symptoms of whatever is being evaluated. This history is not always elicited, and offering it proactively fills a gap.

During the evaluation, the following questions are grounded in the clinical gaps described in this paper:

“My symptoms include fatigue and shortness of breath without classic chest pressure. Can you explain why cardiac ischemia is or is not on the differential, given that presentation?” This asks the clinician to address the symptom vocabulary problem directly, rather than pattern-matching to the male presentation and stopping there.

“If the angiogram or stress test is negative, what would that tell us about MINOCA or microvascular dysfunction?” This establishes that a negative standard workup is not the end of the inquiry. If the clinician can explain why MINOCA is not on the differential, that is informative. If the question produces a blank response, it is also informative.

“Given that I am a woman under 50 with these symptoms, should spontaneous coronary artery dissection be considered in my workup?” This is directly relevant for any woman in the age range where SCAD is the predominant cause of MI, and it ensures the question is explicitly raised.

“I had preeclampsia with my second pregnancy. Is that in my cardiac risk calculation, and should it change anything about my evaluation today?” This addresses the risk factor gap: preeclampsia is an independent lifetime cardiovascular risk factor that does not appear in standard risk calculators, and many clinicians do not routinely ask about obstetric history.

“If you rule out obstructive disease, what is the next step, and who follows me for cardiac symptoms going forward?” This addresses the discharge-to-nowhere problem: women with MINOCA or suspected microvascular dysfunction are sometimes told they are fine and sent home, with no follow-up plan for what remains a symptomatic cardiac condition.

None of these questions require a medical degree to ask. They require knowing that the gaps exist. That is what this paper is for.

What this means

The Yentl phenomenon is a documented, decades-old pattern in which a male-derived evidence base and atypical-symptom framing make women’s cardiac disease harder to recognize and slower to treat. Its causes are structural, not a matter of any clinician’s intent, which means the fixes are structural too, plus the advocacy a woman can exercise while the system catches up. Naming the mechanism precisely is the first step toward not being subject to it.