Time to Dump the Sex/Gender Dichotomy for Science and Society

Abstract

Women have been historically underrepresented in every step of scientific enquiry and, therefore, the knowledge of female bodies is lacking. Now the tide is turning to bring focus on the role of sex and gender in human health and disease. The increasing demands by publishers, funders, and policymakers to pay attention to both sex and gender are commendable. Nevertheless, the premise of the definitions of sex, framed as biological attributes of an individual, contrasting with gender, which is defined through the sociocultural roles, identities, and power structures, carries all pitfalls of the nature–nurture divide, undermining that they are deeply intertwined and interact continuously across the lifespan, shaping physiology and behavior. Current scientific studies rarely disentangle the two for etiological purposes, for their respective contributions to health outcomes. Despite this, there is a push to use both terms appropriately in research and society. This invariably results in the oversimplification of complex processes of sex/gender intertwining, leading to incomplete or misleading causal inferences. Here, I make a case for retiring the sex/gender etiological split in the scientific and public discourse and embracing sex/gender intertwining, rather than minimizing it. This will then enable researchers to focus on how they interact with other variables to produce phenotypes, bringing scientific clarity.

1. Introduction

Sex and gender are commonly thought of as distinct but interacting variables that influence health, behavior, and biological outcomes [1]. Sex term is used for classification of living beings, including humans, based on their chromosomes or external reproductive organs, and is often determined using genetics and observed physiological and anatomical reproductive features. Gender, on the other hand, is mainly used only for humans based on how the individual identifies themselves, influenced by the social roles and norms [2]. Thus, analyses of sex by definition include gender and vice versa [3].

Society and the scientific literature use sex/gender terms interchangeably. Scientists and the scientific literature use sex/gender terms interchangeably [4]. For example, an article demonstrating that monkeys do not prefer ‘masculine’ or ‘feminine’ toys corresponding to their gender when tested singly and not in social groups [5], used the term sex differences, while clearly stating that “the ontogeny, i.e., biological or environmental origins of sex differences is mostly unknown” [5]. Similarly, another recent article again called the differences sex differences while describing sex/gender in the abstract of the article [6]. Thus, scientific studies often use simple, unspecific description of the two terms, creating dualism between men and women [7]. Society also uses the term interchangeably, as scientists are part of society [8]. Ironically, there is more and more push towards using both terms accurately in science and society, as treating them separately is thought to enhance accuracy [9]. In official data, there is an increasing tendency to ask a person for their gender identity rather than their sex. Firstly, many times practically in the forms, this is followed by giving male/female/other to choose from, adding to confusion between sex/gender [10]. Furthermore, this can lead to serious consequences in healthcare, such as missed cancer screenings and mistakes in blood testing [11]. Although sex/gender is embedded in human social consciousness, the sex/gender dichotomy itself is not. This is precisely why the two terms are often used interchangeably in both society and scientific discourse. Thus, the emphasis on distinguishing sex and gender in both science and society results in more conceptual ambiguity and increased essentialist or reductionist interpretations [7]. Gender construction is a social process rather than a biological fact, where our everyday interactions create and maintain the categories male and female [12].

The sex/gender dichotomy is separate from binary sex and gender classification. The sex/gender dichotomy should not be confused with the binary sex/gender classification. Most physiological traits are not sex/gender dimorphic. For example, the human brain is best described as being on a female/male continuum [13,14,15]. Thus, the appeal of dividing the population into two groups of “males” and “females” for various biological processes is rather limited. Hormone levels vary widely within “male” and “female” groups [16]. Similarly, gendered behaviors and attitudes are not binary but continuous and multi-factorial. Accordingly, many health outcomes correlate with specific sex/gender components (e.g., estrogen levels, gendered stress exposure), not with a binary label [7]. There is increasing awareness that using binary sex/gender categories instead of more precise, continuous measures leads to serious problems, including misclassification, reduced statistical power, biased results, and hiding meaningful effects [17].

2. A Long History of Awareness of Sex/Gender Intertwining Across Disciplines

The sex/gender intertwining argument is not new. There is a substantial body of work from many scholars theorizing and empirically demonstrating this entanglement across sociology, anthropology, and gender studies. Gender is continually produced through interaction, classification, and cultural meaning rather than innate difference. Human bodies differ in many ways physiologically, but they are completely transformed by social practices to fit salient categories of a society, the most pervasive of which are male/female or men/women [18]. Science is treated as a neutral, objective enterprise, but scientific knowledge is shaped by cultural assumptions, power relations, and gendered biases. Thus, science is not a detached authority but a socially situated practice whose methods and claims must be examined through the lens of inequality and representation [19]. Anne Fausto-Sterling illustrates how social experience becomes embodied, shaping brain, behavior, and physiology in ways that cannot be distinguished into sex/gender components [20]. Rebecca Jordan-Young invalidates the very premise of the human brain organization theory, i.e., prenatal hormones permanently hardwire male and female brains and thereby explain sex differences in behavior, cognition, and sexuality by arguing that the categories, measures, and interpretations used in sex/gender difference research are saturated with social meanings, making it impossible to treat biology as an independent, pre-social cause [21]. Cordelia Fine demonstrates that social expectations shape behavior, which are then read back as evidence of innate difference through studies on testosterone, risk-taking, and competitiveness, while ignoring that they are deeply entangled with economic, political, and cultural differences [22]. Social science research and feminist movements have a long history of demonstrating that sex and gender are not fixed biological givens, but socially constructed categories shaped by norms.

Until the mid-20th century, sex as a term was used as a unified concept encompassing both biological traits and social roles. The one-sex model framed women as diminished versions of men, treating female anatomy as inverted male organs and positioning the body as a symbolic expression of social gender. By contrast, the two-sex model, dominant after the Enlightenment, asserted that biological sex produces fundamental, oppositional differences between men and women [23]. The medical and legal systems, however, mostly used male bodies as a norm, with an implicit assumption that findings would generalize to all individuals, and gender was rather moral or theological rather than a scientific concern [24]. The distinction between sex and gender began to formalize around the 1950s, when social and psychological aspects of being a male or female were increasingly described using the term gender [25]. The biological male and female distinctions also have an enormous social component [26]. Gender bias in health affects all aspects, including disease manifestation, diagnosis, and treatment. This gap emerges from two fundamental issues: underrepresentation of women at all stages of research and development and male-centered interpretation of symptoms [27]. To correct this gap, the Sex As a Biological Variable (SABV) policy was developed and has had wide implications for science and society over the past decade [10]. The awareness around incorporating sex/gender in research and clinics is growing. Although the intentions behind SABV, i.e., increasing scientific accuracy and clinical relevance, are commendable, the results have failed to deliver, partly due to the oversimplified definition of sex and a persistent neglect of gender as a multifaceted and influential factor in shaping human development, physiology and behavior [4].

3. The Sex/Gender Dichotomy Is an Extension of Nature/Nurture

The nature vs. nurture narrative is one of the most persistent concepts in science, which urgently needs retiring. It is intuitive, but unfortunately is highly misleading as it is not in agreement with the current understanding of biology [28], development [29], and social science [3]. Such a narrative presents a false choice between biology and environment, and distorts the mindset to overinterpret genetic associations, underestimate environmental effects, and ignore gene–environment interactions. Even though nearly every serious researcher knows well that the interactions provide developmental plasticity to shape most traits, including intelligence, mental health, behavior, and disease risk [30].

Unequal social status, economic conditions, and sociodemographic factors contribute to gendered health inequality [31]. The sex/gender dichotomy mirrors the central belief that nature and nurture operate as two distinct and opposing forces. Human biology and culture constantly interact. Bodies influence social experiences, and social environments shape how bodies are developed over time [8]. By treating sex and gender as neatly separable categories, the dichotomy reduces deeply intertwined processes into two rigid boxes [7], with real-world consequences of reinforcing stereotypes, misguiding public policy and misinterpreting health risks.

There is no unique scientific way of defining sex or gender. Sex can be defined using chromosomes (XX, XY, XXY, X0, etc.), or hormones (levels of estrogen, testosterone, etc.) or reproductive anatomy (internal and external reproductive structures), and includes secondary sex characteristics (breast, voice pitch, body hair, fat distribution, etc.). There is enough evidence now that many aspects of what is defined as sex are influenced by environmental factors throughout life. New fathers show reduced prenatal testosterone and vasopressin, which predict greater later paternal investment [32]. Gender, similarly, does not have a unique definition either. It can be defined as gender identity, gender expression, or gender roles and norms.

Furthermore, the sex/gender divide intrinsically holds a fundamentally wrong belief that gender aspects are changeable. The influence of gender on biological traits and health outcomes is therefore mostly ignored or downplayed in scientific research [33], despite sufficient evidence that gender has far-reaching implications on human health [34]. Importantly, many traits essential for survival are not genetically programmed but socially passed down through the generations. Something as essential as breastfeeding success is highly dependent on social learning [35]. Thus, gender traits are also biologically driven and essential. Ironically, with the advent of genetic technologies, genetic modifications might soon be more easily changeable compared to social roles, attitudes and behaviors. Genetics has progressed enormously because of research investment, but the social aspects affecting health remain largely underexplored.

If the main motivation for the sex/gender dichotomy is rather scientific, we would then firstly need a clear, unambiguous definition of sex and gender. Sex and gender are thought to interact at the molecular level, where genes, hormones, and social environments all shape gene expression through epigenetic mechanisms. For example, DNA methylation differences in genes involved in the control of immune response and cellular signaling systems are noted in children raised from birth in institutional care compared to those raised by their biological parents [36]. Interestingly, epigenetic modifiers are classified as gender influence [37], while the epigenetic modifications are classified as sex influence [38]. Thus, doubts are not in scientific findings but interpretations.

4. Ills of Sex/Gender Dichotomy

Sex vs. gender overlaps with innate vs. adaptive, which overlaps with the nature vs. nurture narrative. Scientifically, these distinctions are imprecise. We should go one step further and ask that, even if hypothetically we could find strategies to accurately discern the effect of one from the other, does answering this question really benefit anyone? In regions affected by conflict, men are often on the frontline, while women remain behind, frequently facing severe malnutrition. This will be typically described as a gender difference. These malnourished women will be more likely to give birth to malnourished children, and among these infants, girls tend to have higher survival rates than boys, a pattern typically labeled as sex differences. Over time, this dynamic can produce a population with a higher proportion of physically weaker women than men. This brings us back to the main question: Should we describe this as a sex difference or a gender difference, and will choosing one label over the other help close the social disparity? The evidence is, in fact, the contrary, for science, policy and society.

The misinterpretation of research findings is common as sex/gender interactions are ignored in understanding developmental and disease mechanisms, leading to reduced scientific rigor. Furthermore, traits arise due to multiple influences, apart from sex/gender differences. Our causal reasoning is never purely empirical or value-free, but rather shaped by our judgments and assumptions about what needs explaining, framing effects, and social interests [39]. We should therefore avoid single-cause explanations. SABV policy inadvertently puts an overwhelming focus on sex/gender. Studying it in isolation from all other factors, such as age, ethnicity, education, socio-economic status and other factors, is based on implicit, often unquestioned starting assumptions about the causal primacy of sex relative to other possible factors, in producing outcomes [40]. These assumptions are entrenched at every stage of research design, analysis, publication, and public translation. Studying sex/gender in isolation, overlooking all other sources of diversity, is a doubly missed scientific opportunity [41]. Firstly, without inclusive representation, we fail to fully uncover the biological, environmental, and social factors that contribute to health and disease across different communities. Secondly, it further limits the applicability of the identified sex/gender differences as there is a lower chance of reproducibility. A recent study stratifies health data, showing how sex/gender differences vary within groups depending on socioeconomic and demographic factors [16].

Clinical interventions are beneficial when they target physical and social factors, i.e., combined effects. Sex/gender influences health outcomes in a context and there is plasticity in some of these processes. Instead of studying sex/gender as a sole factor associated with a trait, it is more productive to examine the developmental pathways that shape it over time [42]. For example, women have higher rates of depression than men. Rather than focusing the research on whether this pattern is caused by sex or gender, it is more relevant to ask which pathways (biological, psychological, and socio-cultural) converge to produce this difference. Depression, like many other traits, is not a fixed or static trait. It is dynamic, influenced by life events, stress exposure, coping resources, hormonal changes, cultural norms, and many other interacting factors.

Policy blunders based on a false sex/gender dichotomy are numerous. Even a reputable scientific institute such as NIH, differentiated sex and gender in its poster on how sex and gender influence health and disease [43], unnecessarily and incorrectly separating sex and gender components associated with multiple sex/gender-biased disorders. In the mental health section, it attributes the observation that “women are twice as likely as men to experience depression, with some women experiencing mood symptoms related to hormone changes during puberty, pregnancy and perimenopause” to ‘sex’ differences, while “women are more likely to admit mental health issues and seek treatment” under ‘gender’ differences. There is no scientific justification for calling disease incidence or prevalence a sex difference, while providing potential underlying behavioral differences as gender differences. This confusion does not show ignorance of scientists at NIH. Researchers at NIH are highly unaware that gender has far-reaching impacts on health [34]. It actively encourages inclusion of both sex and gender in research.

Social narratives are reinforced using scientific findings of research on men and women. Researchers often justify funding for their studies by citing the disproportionate prevalence of many disorders across sex/gender categories [2]. Confusing sex/gender terms in the research process, including scientific publications, makes it difficult to ascertain the exact causes of the disparities in incidence, prevalence and manifestation of these conditions [44]. These results in the press and media are, however, presented as if they are inherent differences between men and women. To fully understand causal factors behind health disparities, firstly, other factors such as age, socioeconomic status, education, and geographic location should be considered, together with sex/gender. Indeed, age is a dominant factor in shaping brain gene expression patterns [45], surpassing the effects of sex/gender. This necessitates new analysis workflows using multidimensional, intersectional frameworks that go away from current simplistic analyses to identify precise disease mechanisms and improve health across diverse populations [46]. Though there are a handful of examples of such deep and meaningful research, it is not the bulk of the tide [47].

5. Conclusions

Thus, the analytical separation of biological characteristics (sex) and social roles, expectations, and power structures (gender) in research does not reduce discrimination against women or other marginalized groups. This separation has been used to structure research questions, but a woman is not discriminated against because of her chromosomes. Biology and social meaning interact constantly, leading to sex/gender gaps, such as pregnancy/childbearing (sex) and expectations about caregiving (gender). Diverse sex/gender gaps are interconnected, where economic inequalities (pay gap), unequal care burdens (unpaid care gap), limited political representation (political gap), biased social norms (health gap), and restricted access to leadership (leadership gap) reinforce one another, creating a cycle where disadvantages in one domain deepen vulnerabilities in the next and collectively sustain broader patterns of discrimination. Greater female political representation is associated with better health for everyone and smaller health inequalities [48]. Achieving gender equity requires intersectional and coordinated policies to simultaneously address labor barriers, wage inequalities, cultural norms, and systemic discrimination [49].

The sex/gender dichotomy helps maintain the socio-political status quo. Enormous societal interest in identifying sex/gender differences and publication bias of positive results has resulted in exponential growth in scientific studies identifying differences [2,50]. These so-called ‘scientific’ differences in men and women grab both scientific and public attention, and feed into the narrative that women are inherently different than men. The fact that gender is built upon sex across diverse cultures around the world, by creating a smooth, inseparable intertwining of the two, shaping gendered behavior far beyond biology [26], is sadly not hardwired in the social narrative. Thus, science feeds back into society to widen the male–female divide, despite the research showing the opposite [15]. Deeply rooted cultural norms around gender with binary, polarized expectations produce structural inequalities, social penalties, and psychological strain [49]. Gender-biased norms, including expectations tied to ideal masculinity or femininity, are associated with higher stress, reduced well-being, and social disadvantage [51].

We have a long history of using science to suit the political narrative, including differences in the brain as a ‘scientific justification’ for unjustifiable social hierarchies. Various forms of brain measurements, based on the false idea that some features of the brain (skull size, shape, and brain region differences) are correlated directly with intellectual capacity, were used to ‘prove’ that white Europeans were intellectually and morally superior [52]. Sex/gender divide leaves the diversity unaccounted for, leaving gender non-conforming individuals mostly ignored in research, who already suffer from other social prejudices, including social bias and discrimination [53].

Some Practical Implications of Moving Away from Sex/Gender Dichotomy

In summary, identification of sex/gender differences in disease prevalence is not a good enough justification to dissect differences in male and female physiology. Human bodies vary widely in anatomy, capability, and lived experience, yet descriptions of the body are always shaped by ideas about how men and women are supposed to be [23], or it is impossible to have a purely biological view of male and female anatomy without immediately importing social ideas of gender [54]. While biological differences between males and females exist, they acquire social significance only when cultural practices interpret and organize them into meaningful classifications [18]. Sex/gender identity is used as a proxy for a wide range of specific, measurable biological variables, chromosomes, gonads, hormones, genital anatomy, metabolism, immune function, and body size, thereby limiting our ability to identify the physiological processes at work beyond the simple categories of male/man or female/woman. To better capture biological diversity, research requires direct measures of biological variation that are independent of identity categories [55].

Many methodological solutions have been proposed to account for sex and gender systematically. For example, the EU report Gendered Innovations 2 describes in detail methodological and practical considerations for studying the sex, gender and intersectionality (European Commission, Directorate General for Research and Innovation, 2020). The report, however, still upholds the sex/gender dichotomy, together with intersectionality. Even the most recent NIH strategic plan for research on the health of women (2024–2028) is very thorough and highly relevant, but still intrinsically assumes the false sex/gender dichotomy. The methodologies stated in these documents are not the issue; rather, it is the framing. The scientific formula to capture the Interconnected Sex–Gender (ISG) variable should not be ISG = w_sS + w_gG + w_sg (S·G) but rather ISG = ∑ w_sg·SG_sg, where SG_sg terms encompass a constellation of measurable traits such as chromosomes, hormone profiles, reproductive anatomy, and secondary sex characteristics, alongside not easily measurable dimensions like personal identity, lived experience, cultural expectations, and social roles. SG_sg terms are interdependent and may vary throughout the lifetime of a person. There are several existing attempts to create a score for individual aspects of sex/gender [56,57] or a unified sex/gender score [58].

Interestingly, we apply the sex/gender dichotomy only for humans, so the call to end it also applies to humans. There is no dichotomy used in non-humans, as we are not aware of the gender component of other animals. Thus, one term ‘sex/gender’ for all living species, including humans, will bring humans back to where they belong in the tree of life, correcting the fallacy of the nature–culture divide [59].

Sex/gender is a part of human diversity. Anthropologist Desmond Morris describes how gender is built upon sex across diverse cultures around the world, by creating a smooth, inseparable intertwining of the two, shaping gendered behavior far beyond biology [26]. There are strong parallels with race/ethnicity [60], as both originate from systems of social hierarchy that assign differential value, opportunity, and power to groups based on perceived group membership. However, race has no true biological foundation; it is often misused, and people, including professionals such as scientists and physicians, wrongly assume race as a proxy for genetics and overestimate its value in science and clinic [61]. The mechanisms through which gender and racial discrimination operate overlap in processes of stereotyping, social stratification, and institutionalized inequality, shaping access to resources, influencing social status, and structuring lived experiences.

There is already substantial scholarship demonstrating why the nature/nurture divide is untenable, and the sex/gender distinction inherits the same conceptual problems. The strongest alternative to this narrative is an interactionist or developmental systems perspective, which conceptualizes genes and environments as inseparable, co-acting processes rather than competing causal forces [55]. Sex/gender is a dynamic developmental process. Therefore, understanding it requires attention to both its dynamic form and the static biological constituents on which it draws [62].

Taken together, abandoning the sex/gender dichotomy enhances scientific precision by removing an artificial division that separates phenomena that are deeply interdependent. The unified etiological framework can enhance clarity because it represents the empirical reality that biological and environmental factors are deeply co-constitutive. For the average researcher, this shift will reduce conceptual fragmentation, streamlining theoretical interpretation by preventing the need to artificially force findings into dichotomous categories of sex and gender. Thus, scientific studies measuring physiological variables will not be able to pretend to be studying ‘sex’ differences and thereby implicitly undermine the social component. There is hope, as the narrative around poverty, race and health outcomes is slowly shifting over the last few decades, where effects of poverty are becoming evident in health outcomes, slowly replacing old racial narratives. Similarly, research will move towards unraveling the ways in which the effects of sex/gender gaps (like poverty) will become evident in health outcomes, replacing old sex/gender narratives.