Sex and Gender Reshape Disease Diagnosis: New Evidence Exposes Global Health Gaps

Medicine has long treated diagnosis as a neutral act: a symptom appears, a test is ordered, a result is interpreted. A new collection of research published in Frontiers in Global Women’s Health argues that this apparent neutrality is precisely the problem. An editorial by Elena Marbán-Castro of the University of the Balearic Islands and colleagues, introducing a Research Topic on the impact of sex and gender on disease diagnostics in global health, assembles twelve studies spanning basic immunology, clinical epidemiology, burden modeling, health services research, and community fieldwork. Together, they make a case that is hard to dismiss: ignoring sex and gender at the diagnostic stage is not a passive oversight but an active mechanism that reproduces health inequality.

The distinction at the heart of the collection is deceptively simple. Sex refers to the biological attributes that differ among female, male, and intersex individuals, while gender refers to the socially constructed roles, norms, and relations that vary across societies and shape behavior, access, and expectation. Both influence who becomes ill, how illness manifests, who seeks care, who is tested, and ultimately who is diagnosed and treated. Gender is widely recognized as one of the central social determinants of health, yet the editorial’s authors point out that diagnostic pathways, the moment when a symptom becomes a named condition, remain among the least examined stages of the entire care continuum.

One detail from the editorial is particularly striking for anyone who assumes the scientific literature is systematically organized. Gender does not exist as a standalone MeSH term, the controlled vocabulary used to index biomedical research. The word always appears attached to other concepts, such as gender-affirming care or gender identity. The authors read this absence as telling: even in the architecture of scientific knowledge, gender is treated as a modifier rather than a determinant in its own right. If the indexing system cannot name gender as a driver of health, they suggest, it should not be surprising that diagnostic tools struggle to account for it.

Several contributions trace the biological roots of sex differences that diagnostics routinely overlook. Lodde and colleagues examined how microRNAs encoded on the X chromosome regulate immune responses, offering a mechanistic explanation for the sex disparities observed across infectious and autoimmune diseases. Hong and colleagues reviewed the role of estrogen in bacterial infection, showing how hormonal context can alter susceptibility and, by extension, the interpretation of diagnostic findings. The implication is uncomfortable for standard practice: reference ranges and risk models built on male-default physiology may be contributing to diagnostic inaccuracies in women, because the biological baseline against which results are compared was never representative in the first place.

Cardiovascular disease, long framed in the public imagination as a male problem, emerges as a recurring theme. Dakhil and colleagues argue for rethinking cardiovascular risk prediction in women through precision medicine, challenging diagnostic tools that systematically underestimate the risk women face. López-Ferreruela and colleagues, working with a large Spanish cohort, found that women receive less intensive monitoring and follow-up after acute myocardial infarction, a gap that begins with under-recognition and propagates through every subsequent stage of care. Gao and colleagues added a preventive dimension, analyzing sex-specific associations between dietary carotenoid intake and heart failure risk using data from the United States National Health and Nutrition Examination Survey. The combined message is that closing the cardiovascular gender gap requires intervention at every step, from initial risk estimation to secondary prevention.

Large-scale analyses of chronic conditions reinforce the pattern. Li and colleagues modeled the global burden of polycystic ovary syndrome from 1990 to 2021 with projections to 2035, quantifying a condition whose diagnosis is frequently delayed. Liu and colleagues mapped gender disparities in occupational noise-induced hearing loss, a reminder that occupational exposures and the diagnostic systems that capture them are themselves gendered, shaped by who works in which environments and whose hearing complaints are taken seriously. Faulstich and colleagues identified sex differences in the clinical risk factors for early- and late-onset Alzheimer’s dementia, informing more tailored diagnostic assessment. The editorial highlights a shared methodological strength across these studies: they disaggregate their data by sex rather than statistically adjusting it away, preserving the very differences that conventional analysis tends to erase.

Therapeutics and surgical care are not exempt from the pattern. Hu and colleagues conducted a scoping review of sex- and gender-specific differences in the efficacy and safety of traditional Chinese medicine, an area in which such stratified analyses remain rare despite the enormous populations these treatments serve. Ripoll-Romero and colleagues reported gender differences among patients presenting for hip arthroplasty, showing how clinical presentation and referral patterns can diverge well before a patient ever reaches the operating room. In both cases, the diagnostic encounter, not the treatment itself, appears to be where inequity first enters the pathway.

Two contributions speak directly to the infrastructure and equity of diagnosis in global health settings. Atiomo and colleagues described a study protocol to establish a dedicated women’s health biobank in Dubai, grounded in the recognition that sex- and gender-stratified diagnostics depend on representative biological resources. Gandigbe and colleagues took an intersectional approach, examining how gender and disability interact to shape inequities in communities endemic for neglected tropical diseases in Benin and Côte d’Ivoire. Their work anchors the collection in settings where diagnostic gaps carry the highest cost, and where the compounding of gender with disability, poverty, and geography is not an academic abstraction but a daily determinant of whether someone reaches care at all.

The editorial distills several threads that run across the diverse articles. First, sex and gender operate together rather than in isolation: biology sets differential susceptibility, while gender norms govern whether a person reaches a clinic, is believed when they describe symptoms, and is offered a test. Second, intersectionality matters; gender rarely acts alone, and disability, poverty, and geography compound one another, reinforcing gender’s role as one of the main socioeconomic causes of disparities in health status. Third, the male default persists quietly across reference ranges, risk scores, biobanks, and clinical suspicion, shaping who gets diagnosed, how, and when, without anyone explicitly deciding that it should.

The authors are candid about what the collection does not resolve. Much of the evidence remains observational, and several studies analyze sex and gender as binary variables, leaving the diagnostic experiences of intersex, transgender, and gender-diverse people largely unaddressed. Data from low- and middle-income countries, where diagnostic capacity is scarcest, remain under-represented, and while many studies document disparities, interventions and implementation strategies to close them are areas future work must tackle. Still, the direction is clear: better diagnostics will not come from adding sex and gender as an afterthought, but from designing studies, tools, and health systems that expect difference from the start, with sex- and gender-disaggregated reporting as standard practice, gender-sensitive care pathways, representative biobanks, and diagnostic technologies validated across the populations that will actually use them.

Subject of Research: The influence of sex and gender on disease diagnosis and health equity in global health

Article Title: Editorial: The impact of sex and gender on disease diagnostics in global health

Article References: Editorial: The impact of sex and gender on disease diagnostics in global health. (n.d.). https://doi.org/10.3389/fgwh.2026.1969320

Image Credits: AI Generated

DOI: 10.3389/fgwh.2026.1969320

Keywords: sex differences, gender, diagnostics, global health, health equity, cardiovascular disease, intersectionality, polycystic ovary syndrome, Alzheimer's disease, biobanks, non-communicable diseases, women's health