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

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The proposal to abandon the sex/gender dichotomy is not a mere theoretical whim, but a response to evidence showing that both concepts are so intertwined that separating them often proves artificial and limiting.

The manuscript constitutes a valuable attempt to clarify this field and, as the author points out, “the emphasis on distinguishing between sex and gender, both in science and in society, generates greater conceptual ambiguity and an increase in essentialist or reductionist interpretations. Consequently, scientific studies often employ simplistic and nonspecific descriptions of both terms, creating dualisms between men and women” (Hammarström and Annandale, 2012).

However, at a conceptual level, we find the text very confusing. Perhaps its brevity prevents it from delving deeper into the subject. From our point of view, it addresses disparate and unconnected topics that are difficult to integrate into a common theme.

Stereotypical and Inappropriate Examples: The examples provided in lines 58 and 85 are inappropriate. For instance, while defining sex and gender in lines 77-87, the author suddenly introduces hirsutism and its associated social stigma as an example. It is proposed that these examples be replaced with two or three clinical or epidemiological cases where the distinction between sex and gender is inseparable.
Conceptual Framework: The author must adopt a solid conceptual framework (e.g., behavioral epigenetics) that explains the interrelationship between sex and gender. It is not enough to state that they are "entangled"; the biological and social processes by which they are intertwined must be explicitly explained (e.g., discussing epigenetics in the context of Nature vs. Nurture).
Misinterpretation of Sources: The article claims that gender is also a biological variable, citing Scelza (2025): “Something as essential as ‘how to breastfeed a newborn’ is a socially learned behavior.” However, what Scelza actually states is: “Learning to breastfeed is part of the evolutionary legacy of assisted reproduction in humans. Nevertheless, we know little about how social learning facilitates successful breastfeeding.” This is a significant distinction.
The reference to sexual orientation (van Anders, 2015) is irrelevant in this specific context and distracts from the core argument.
Lack of Nuance: Regarding line 165 (“Being at one end of the male-female continuum is disadvantageous both socially and psychologically”), this point must be elaborated upon. Zhang et al. (2021) specifically refer to brain gender and not to other broader aspects.

The author is urged to review the conclusions. The statement regarding the shifting narrative around poverty, race, and health outcomes is noted; however, conclusions must follow directly from the arguments presented in the body of the work, rather than relying on aspirational analogies.

We suggest a reference that could help the author better integrate the content.

Antequera A, Stallings E, Henry RS, Lopez J, Runnels V, Tudiver S, et al. Sex and Gender Appraisal tool for Systematic Reviews-2 (SGAT-SR-2) and Participation-to-Prevalence Ratio: methods to assess to whom the evidence applies in Cochrane sepsis reviews. J Clin Epidemiol. 2022;142:119-32.

In short, we found the article to be highly relevant, but I recommend a major revision before publication. We encourage the author to undertake this revision.

Author Response

I wholeheartedly thank the reviewers for taking time and giving very constructive feedback to
improve the article. The point-wise responses to the reviewers’ concerns are below and the edits
are marked in red color in the revised article. Major rearrangement of the text is done in
revised version according to reviewers’ suggestions. This is not marked in red, ONLY newly
added/edited text is marked in red.

Reviewer 1:
The proposal to abandon the sex/gender dichotomy is not a mere theoretical whim, but a
response to evidence showing that both concepts are so intertwined that separating them often
proves artificial and limiting.
The manuscript constitutes a valuable attempt to clarify this field and, as the author points out,
“the emphasis on distinguishing between sex and gender, both in science and in society,
generates greater conceptual ambiguity and an increase in essentialist or reductionist
interpretations. Consequently, scientific studies often employ simplistic and nonspecific
descriptions of both terms, creating dualisms between men and women” (Hammarström and
Annandale, 2012).
1. The examples provided in lines 58 and 85 are inappropriate. For instance, while defining sex
and gender in lines 77-87, the author suddenly introduces hirsutism and its associated
social stigma as an example. It is proposed that these examples be replaced with two or
three clinical or epidemiological cases where the distinction between sex and gender is
inseparable.
>> Indeed, we thank the review for this. Now sex/gender inseparability is elaborated with more
clear examples.

2. The author must adopt a solid conceptual framework (e.g., behavioral epigenetics) that
explains the interrelationship between sex and gender. It is not enough to state that they are
"entangled"; the biological and social processes by which they are intertwined must be
explicitly explained (e.g., discussing epigenetics in the context of Nature vs. Nurture).
>> Indeed, epigenetics to describe the sex/gender interaction at the modular level is now added
to manuscript.
Sex/gender are thought to interact at molecular level because genes, hormones, and social
environments all shape gene expression through epigenetic mechanisms. 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 (Naumova et al. 2012). Interestingly, epigenetics modifiers are classified as
gender influence (Regitz‑Zagrosek 2012) Figure 1), while the epigenetics modifications as sex
influence (Regitz-Zagrosek and Gebhard 2023) Figure 1).

3. The article claims that gender is also a biological variable, citing Scelza (2025): “Something
as essential as ‘how to breastfeed a newborn’ is a socially learned behavior.” However, what
Scelza actually states is: “Learning to breastfeed is part of the evolutionary legacy of
assisted reproduction in humans. Nevertheless, we know little about how social learning
facilitates successful breastfeeding.
>> Scelza (2025) describe in their article evidence for social learning is critical to breastfeeding
success (including the title of the article). The two lines from the summary of the article cited
above by the reviewer are followed by “Using interviews with rural Namibian women, this
research highlights how learning and support foster proper breastfeeding techniques and help
women to overcome barriers.”. The citation is therefore appropriate in my view. I have now
rewritten the statement “Something as essential as breastfeeding success is highly dependent
on social learning” in line with the title of the citation.

4. The reference to sexual orientation (van Anders, 2015) is irrelevant in this specific context
and distracts from the core argument.
>> Indeed, this is omitted now.

5. Regarding line 165 (“Being at one end of the male-female continuum is disadvantageous
both socially and psychologically”), this point must be elaborated upon. Zhang et al. (2021)
specifically refer to brain gender and not to other broader aspects.
>> Indeed, it is elaborated upon with additional text below.
Deeply rooted cultural norms around gender with binary, polarized expectations produce
structural inequalities, social penalties, and psychological strain (Peralta-Jaramillo 2025).
Gender-biased norms, including expectations tied to ideal masculinity or femininity are
associated with higher stress, reduced wellbeing, and social disadvantage (Heymann et al.
2019).

6. The author is urged to review the conclusions. The statement regarding the shifting narrative
around poverty, race, and health outcomes is noted; however, conclusions must follow
directly from the arguments presented in the body of the work, rather than relying on
aspirational analogies.
>> Indeed, the conclusion section is now expanded extensively.

7. We suggest a reference that could help the author better integrate the content. Antequera A,
Stallings E, Henry RS, Lopez J, Runnels V, Tudiver S, et al. Sex and Gender Appraisal tool for
Systematic Reviews-2 (SGAT-SR-2) and Participation-to-Prevalence Ratio: methods to
assess to whom the evidence applies in Cochrane sepsis reviews. J Clin Epidemiol.
2022;142:119-32.
>> This citation is now included.

In short, we found the article to be highly relevant, but I recommend a major revision before
publication. We encourage the author to undertake this revision.

Reviewer 2 Report

Comments and Suggestions for Authors

please see the file attached

Comments for author File: Comments.pdf

Author Response

I wholeheartedly thank the reviewers for taking time and giving very constructive feedback to
improve the article. The point-wise responses to the reviewers’ concerns are below and the edits
are marked in red color in the revised article. Major rearrangement of the text is done in
revised version according to reviewers’ suggestions. This is not marked in red, ONLY newly
added/edited text is marked in red.
Reviewer 2:
The paper “Time to Dump the Sex/Gender Dichotomy for Science and Society” is very well
written, easy to read, and accessible even to readers with little prior exposure to gender
studies/research. I really like the paper, especially how clearly it describes the shift in
perspective between “sex” and “gender” and the respective implications this has for medical
research, interpretation of the findings, and implications for patients. The findings are well
compiled. To further highlight the value of this contribution, I recommend the following: -
>> I am deeply grateful for the reviewer’s thoughtful feedback below. Your understanding of my
intentions and your suggestion to restructure the article were especially helpful. Revising in
response to the feedback was a rewarding process, and I learned a great deal along the way.

1 In the introduction, please revisit the historical origins of gender studies and the recognition
of the distinction between “sex” and “gender.” Here, it seems to me that the significance of
social science research has not been fully explored, and the distinction between social
movements (feminism) and the establishment of gender studies could be more carefully and
clearly addressed. Here, it might be helpful to mention introductory works such as that by
Judith Lorber.
>> Indeed, thank you for the suggestion. Following section has been added to the historical
originals
“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 (Lorber 1993). Science is treated as a neutral, objective enterprise,
but in reality, scientific knowledge is shaped by cultural assumptions, power relations, and
gendered biases. Thus, science is not as a detached authority but as a socially situated practice
whose methods and claims must be examined through the lens of inequality and representation
(Harding 1986).”
“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, asserts that biological sex
produces fundamental, oppositional differences between men and women (Laqueur 2003). ”

2 One example is the so-called “nature-nurture divide” debate, which is addressed in the
social sciences as the nature/culture dichotomy; here, these reciprocal translations might
be appropriate, though they are not strictly necessary
>> Thank you very much, this fits excellently with reviewer 3, point 5 suggestion. It is now added
with proper context.

3 In Chapter 2, regarding the scientific distinction between sex and gender, reference should
be made to the groundbreaking study by Kessler and McKenna (1978), which also
demonstrates through social experiments that people use different markers to distinguish
between sexes and that there is no biological unambiguity, even though this is often
suggested

>> This citation is added now.
“Gender construction is a social process rather than a biological fact, where our everyday
interactions create and maintain the categories male and female (Kessler and MacKenna 2001).”

4 Starting on page 4, the paper appears to be somewhat less thoroughly developed, though
this is evident only in minor details. For example, I would recommend formatting the heading
“Sex/gender dichotomy has widespread implications” as Chapter 3 and, as in Chapter 2,
writing a brief introduction explaining what the chapter is about.
>> I wholeheartedly thank the reviewer. The manuscript has improved following these highly
specific suggestions. The manuscript is now entirely restructured.

5 On page 6, the chapter finally ends with a question: “This brings us back to the main
question: should we describe this as a sex or gender difference, and will choosing one label
over the other help close the social disparity?” I don’t think it’s wise to end with this
question; it leaves the reader without a clear solution alone. It doesn’t seem to appear that
clearly elsewhere in the paper, but I do consider it absolutely important and groundbreaking.
I would mention it in the introduction, noting that this question arises, and also directly offer
a proposed solution supported by the results presented in sections 2 and 3. In my view, this
can only mean that we need both research perspectives: those that work with “sex” and
those based on “gender”—but both perspectives must always be related to one another (!)
because these are merely pragmatic and analytical distinctions in research. Perhaps the
author has another idea; however, that would be my suggestion.
>> I again thank the reviewer for appreciating the core message. It is now presented on page 4
and next article is edited along those lines as suggested by the reviewer.

6 The conclusion is far too brief; given the ambitious aim to demonstrate that resolving the
sex/gender distinction is absolutely necessary for medical research, the most important
arguments should be summarized here, and next steps should be outlined regarding how to
proceed. - This may mean that the previous chapters need to be shortened; I see particular
potential here in Chapters 2 and 3 to condense certain points.
>> Indeed, the conclusion section has been expanded significantly now with a few steps
suggested on how to proceed. Also, other sections are reduced as suggested.

Reviewer 3 Report

Comments and Suggestions for Authors

This perspective article argues for abandoning the rigid dichotomy between biological sex and sociocultural gender in scientific research. The author contends that these two variables are deeply intertwined and constantly interact to shape human physiology and behavior, making them impossible to fully separate them. Maintaining an artificial split leads to conceptual ambiguity, reinforces stereotypes, and results in misleading causal inferences regarding health outcomes. By moving toward a multidimensional framework, researchers can better understand how environmental factors and biology work together to produce diverse phenotypes. Ultimately, the source advocates for scientific precision by embracing the complexity of the sex/gender continuum rather than relying on oversimplified binary classifications. The author’s premise is interesting and sound encouraging but it is unclear how it would be applied or if/how it could avoid suffering the same limitations as the current dichotomy. More details suggestions are bulleted below.

The parallel to race does not seem appropriate

Race is not a universal construct, like sex. It’s also fully socially constructed, whereas sex/gender has biological aspects, such as reproductive anatomy, experiences and roles.

Some comment on minoritized communities is warranted to assure the proposed framework is sufficiently inclusive of diversity.

More concrete details are needed on the solution that is being proposed. The author’s suggestion of pointing to pathways seems like a reasonable starting place but it’s unclear what this would actually look like or what steps a researcher would take. In fact, the “intertwined” variable was too broad or amorphous, it is difficult to imagine that a researcher would be able to develop a study that would sufficiently elucidate mechanisms along any particular pathways.

While the author argues for "embracing the interconnection of sex/gender, a concrete definition or a specific scientific formula for how to measure this new variable is needed to make it a feasible suggestion.
The author's call to retire the sex/gender dichotomy for all "living beings" lacks a clear logical application for the vast majority of biological research. The sex dichotomy is what applies to most living things and non-human mammals, not gender.
The author may need to offer further clarification that while perhaps sex/gender ought to be merged into a single "intertwined" concept (ie. construct), the variables that might comprise that construct would remain many (ie., chromosomes, hormones, behaviors) if this is in fact what the author intends. Otherwise, a single concept would lose the ability to isolate drivers, potentially obscuring rather than clarifying disease mechanisms.
The author may want to address how "retiring" the current etiological split would affect the scientific community's ability to use historical data.
The author admits that sex and gender are "mostly impossible to properly study" and that both terms are already "saturated with social meanings". They do not explain how combining two "impossible" and "saturated" variables into a more complex, "multidimensional" framework will realistically produce more clarity rather than exponentially more confusion for the average researcher.

Some cites to consider:

Thomas Laqueur (1990), Making Sex: Body and Gender from the Greeks to Freud: The author mentions the mid-20th-century shift in the term "sex" and the long history of using science to justify social hierarchies. Laqueur’s work provides the historical evidence for this, detailing how Western science shifted from a "one-sex" model to the "two-sex" binary we recognize today.

Daphna Joel et al. (2015), "Sex beyond the binary: Celebrating complexity" The author cites Zhang et al. (2021) to argue that the human brain is a continuum rather than dimorphic. However, Daphna Joel’s 2015 paper is the primary scientific source for the "brain mosaic" theory, which statistically proves that most individual brains are a unique mix of "male-leaning" and "female-leaning" features rather than falling into two distinct categories.

Author Response

I wholeheartedly thank the reviewers for taking time and giving very constructive feedback to
improve the article. The point-wise responses to the reviewers’ concerns are below and the edits
are marked in red color in the revised article. Major rearrangement of the text is done in
revised version according to reviewers’ suggestions. This is not marked in red, ONLY newly
added/edited text is marked in red.

Reviewer 3:
This perspective article argues for abandoning the rigid dichotomy between biological
sex and sociocultural gender in scientific research. The author contends that these two
variables are deeply intertwined and constantly interact to shape human physiology and
behavior, making them impossible to fully separate them. Maintaining an artificial split leads
to conceptual ambiguity, reinforces stereotypes, and results in misleading causal
inferences regarding health outcomes. By moving toward a multidimensional framework,
researchers can better understand how environmental factors and biology work together to
produce diverse phenotypes. Ultimately, the source advocates for scientific precision by
embracing the complexity of the sex/gender continuum rather than relying on oversimplified
binary classifications. The author’s premise is interesting and sound encouraging but it is
unclear how it would be applied or if/how it could avoid suffering the same limitations as the
current dichotomy. More details suggestions are bulleted below.

1 The parallel to race does not seem appropriate. Race is not a universal construct, like sex.
It’s also fully socially constructed, whereas sex/gender has biological aspects, such as
reproductive anatomy, experiences and roles.
>> Indeed, this is a very good point. The scope of race and sex/gender analogy is limited. This is
now elaborated in the article.
“There are strong parallels with race/ethnicity (Avila et al. 2019), 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 (Plaisime et al.
2023). Sex/gender on the other hand involve both biological and social dimensions. Despite
these differences in origin, the mechanisms through which gender and racial discrimination
operate overlap in processes of stereotyping, social stratification, and institutionalized
inequality. Both shape access to resources, influence social status, and structure lived
experiences across multiple domains, including employment, education, and political
participation.”

2 Some comment on minoritized communities is warranted to ensure the proposed
framework is sufficiently inclusive of diversity.
>> Indeed, sex/gender dichotomy is harmful to everyone including the minorities. Following is
added to the manuscript
“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 sigma. Gender non-conforming people face social bias and discrimination because their
sex/gender is assumed to be ‘doing’ something to others causing a reaction, rather than letting it
belong to the person (Vaid-Menon 2020).”

3 More concrete details are needed on the solution that is being proposed. The author’s
suggestion of pointing to pathways seems like a reasonable starting place but it’s unclear
what this would actually look like or what steps a researcher would take. In fact, the
“intertwined” variable was too broad or amorphous, it is difficult to imagine that a researcher
would be able to develop a study that would sufficiently elucidate mechanisms along any
particular pathways.
>> Indeed, this aspect is now elaborated in detail in conclusion.

4 While the author argues for "embracing the interconnection of sex/gender, a concrete
definition or a specific scientific formula for how to measure this new variable is needed to
make it a feasible suggestion.
>> This is a very good point. The main aim of this article is to stress that we should stop seeing
sex/gender as two independent aspects. Following is added to conclusion section.
“The exact scientific formula to capture the Interconnected Sex–Gender (ISG) variable
should not be ISG = ?s? + ?g? + ?sg ( ?⋅?) but rather ISG = ∑ ?sg⋅S?sg where S?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.
There are several existing attempts to create a score for individual aspects of sex/gender
(Morgan et al. 2024)table 1, (Smith and Koehoorn 2016) as well as valid attempts to create
such a unified sex/gender score (Kraus et al. 2023). One also needs to be aware that S?sg can
change through the lifetime of a person.”

5 The author's call to retire the sex/gender dichotomy for all "living beings" lacks a clear logical
application for the vast majority of biological research. The sex dichotomy is what applies to
most living things and non-human mammals, not gender.
>> The reviewer is entirely right, and this is now elaborated in the last section.
We apply sex/gender dichotomy ONLY for humans so the call to end it also applies for humans.
As the reviewer correctly points, there is no dichotomy used in non-humans as we are not aware
of the gender component of other animals. Thus, if we use one term ‘sex/gender’ for all living
species including humans, will bring back humans to where the belong in the tree of life,
showing the fallacy of nature-culture divide. Nature–nurture divide contrasts biological
determinants with social/environmental influences, whereas the nature–culture dichotomy
frames human and environment as opposing conceptual domains, though both are deeply
intertwined as each is the implication of the other (Haila 2000).

6 The author may need to offer further clarification that while perhaps sex/gender ought to be
merged into a single "intertwined" concept (ie. construct), the variables that might comprise
that construct would remain many (ie., chromosomes, hormones, behaviors) if this is in fact
what the author intends. Otherwise, a single concept would lose the ability to isolate drivers,
potentially obscuring rather than clarifying disease mechanisms.
>> This again relates to point 4 in the response and indeed, the reviewer is correct in the
interpretation that S?sg terms encompass a constellation of both easily measurable and not so
easily measurable traits.

7 The author may want to address how "retiring" the current etiological split would affect the
scientific community's ability to use historical data.

>> Retiring the split would not impede the scientific community’s use of historical data because
past findings can still be reinterpreted using new conceptual frameworks without loss of
methodological validity. Thus, historical datasets will remain analytically comparable, since the
shift concerns theoretical framing rather than the empirical integrity or applicability of earlier
research.

8 The author admits that sex and gender are "mostly impossible to properly study" and that
both terms are already "saturated with social meanings". They do not explain how combining
two "impossible" and "saturated" variables into a more complex, "multidimensional"
framework will realistically produce more clarity rather than exponentially more confusion
for the average researcher.

>> This is a very good point. Following is added to the conclusions to clarify this.
“The unified etiological framework can enhance clarity because it aligns research practice with
the empirical reality that biological and environmental factors are deeply co-constitutive rather
than separable variables. For the average researcher, this shift will reduce conceptual
fragmentation, streamlining theoretical interpretation by preventing the need to artificially force
findings into dichotomous categories that rarely map onto actual developmental processes.”

9 Some cites to consider:
Thomas Laqueur (1990), Making Sex: Body and Gender from the Greeks to Freud: The author
mentions the mid-20th-century shift in the term "sex" and the long history of using science to
justify social hierarchies. Laqueur’s work provides the historical evidence for this, detailing how
Western science shifted from a "one-sex" model to the "two-sex" binary we recognize today.

>> A very big thank you for this highly relevant citation I missed. It is added in the introduction as
well as I have now explicitly added one-sex, two-sex model in the conclusion section which is
highly relevant.
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, asserts that biological sex
produces fundamental, oppositional differences between men and women (Laqueur 2003).
Thus, be it sex/gender or race, it’s the political and cultural context that determines what we
notice and elevate to the status of a different category. Science may uncover new facts, yet it
ultimately offers them fitting into the current political and social framework rather than a
genuine pathway to women’s emancipation or broader social progress.
Also, any claim about sex as a biological fact already carries cultural assumptions about gender.
In other words, descriptions of the body are always shaped by ideas about how men and women
are supposed to be (Laqueur 2003) or it's impossible to speak of structural differences between
male and female bodies without immediately importing social ideas of gender, that language is
so implicated in gender that it's impossible to have a purely biological view of male and female
anatomy (Butler 1993).

10 Daphna Joel et al. (2015), "Sex beyond the binary: Celebrating complexity" The author cites
Zhang et al. (2021) to argue that the human brain is a continuum rather than dimorphic.
However, Daphna Joel’s 2015 paper is the primary scientific source for the "brain mosaic" theory,
which statistically proves that most individual brains are a unique mix of "male-leaning" and
"female-leaning" features rather than falling into two distinct categories.
>> Indeed, this citation is now added (Joel et al. 2015).
References
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Cognitive Trajectories Vary as a Function of Race/Ethnicity.” Alzheimer’s & Dementia: The
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Kraus, Ute, Katharina Jacke, Lisa Dandolo, et al. 2023. “Operationalization of a Multidimensional
Sex/Gender Concept for Quantitative Environmental Health Research and
Implementation in the KORA Study: Results of the Collaborative Research Project
INGER.” Frontiers in Public Health 11 (April): 1128918.
https://doi.org/10.3389/fpubh.2023.1128918.
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print. Harvard University Press.
Lorber, Judith. 1993. “Believing Is Seeing: Biology as Ideology.” Gender & Society 7 (4): 568–81.
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Gender Dimensions in Biomedical Research.” Biology of Sex Differences 15 (1): 96.
https://doi.org/10.1186/s13293-024-00663-7.
National Institutes of Health. 2024. NIH-Wide Strategic Plan for Research on the Health of
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Naumova, Oksana Yu., Maria Lee, Roman Koposov, Moshe Szyf, Mary Dozier, and Elena L.
Grigorenko. 2012. “Differential Patterns of Whole-Genome DNA Methylation in
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of Policies, Labor Practices, and Social Movements.” Social Sciences 14 (7): 401.
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People Are the Default’: A Qualitative Analysis of Medical Trainees’ Perceptions of
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Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

We are pleased to accept the manuscript in its current form, as all requested changes have been addressed.

Author Response

I wholehearted thank the reviewer for accepting the revision.

Reviewer 3 Report

Comments and Suggestions for Authors

The revised essay is much improved over the initial draft. I expect it will make a strong contribution to the existing literature, pending the author(s) can address one remaining issue from my initial critique. In the revision, the author(s) offer a compelling report as to ways the sex/gender dichotomy is damaging and limited. The piece that remains unaddressed from my initial review is the question of what do the authors' propose as the alternative?

As the authors clearly describe, there is a historical context that shows the consequences of how sex/gender is (or is not defined). In one passage, for example, the authors write:

"Until the mid-20th century, sex 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 1950s where social and psychological aspects of being a male or female were described increasingly using the term gender [25]."

It seems ill-advised to do away with the sex/gender construct, even if the construct is, as the authors' argue, deeply flawed. First, I'm unsure it's feasible to undo something that exists in the social consciousness. Second, assuming deletion of the construct in the absence of an alternative, it opens the door for a group in power to force others (further) into invisability --- similar to the one sex model. For example, in the discontinued use of sex/gender, there would be no pragmatic mechanism to, for example, drive research on childbirth, menapause, or remedy disparities that have been created by historical failings of the construct. In sum, it seems insufficient to argue the flaws of the model without proposing a solution, alternative or other fix. This is one of the major challenges of this topic, and, to my knowledge, there is no clear answer to this issue. The contribution of the current work is weakened without addressing the issue. Stites and Velocci (2024) attempted to address it by proposing a lens that features often embroiled in the sex/gender dichotomy can act as social and structural determinants of experience with social, structural and health consequences. Thus, they can be treated as singular, defined issues rather than the ambiguous idea that constitutes sex/gender.

Stites SD, Velocci B. Sex, gender, sexual orientation, and more: Sexual diversity in Alzheimer's research needs a new lens to achieve inclusive research and generalizable results. Alzheimers Dement (N Y). 2024 Jun 24;10(2):e12476. doi: 10.1002/trc2.12476. PMID: 38915815; PMCID: PMC11194612.

Author Response

As the authors clearly describe, there is a historical context that shows the consequences of how sex/gender is (or is not defined). In one passage, for example, the authors write:

It seems ill-advised to do away with the sex/gender construct, even if the construct is, as the authors' argue, deeply flawed. First, I'm unsure it's feasible to undo something that exists in the social consciousness. Second, assuming deletion of the construct in the absence of an alternative, it opens the door for a group in power to force others (further) into invisibility --- similar to the one sex model. For example, in the discontinued use of sex/gender, there would be no pragmatic mechanism to, for example, drive research on childbirth, menopause, or remedy disparities that have been created by historical failings of the construct. In sum, it seems insufficient to argue the flaws of the model without proposing a solution, alternative or other fix. This is one of the major challenges of this topic, and, to my knowledge, there is no clear answer to this issue. The contribution of the current work is weakened without addressing the issue. Stites and Velocci (2024) attempted to address it by proposing a lens that features often embroiled in the sex/gender dichotomy can act as social and structural determinants of experience with social, structural and health consequences. Thus, they can be treated as singular, defined issues rather than the ambiguous idea that constitutes sex/gender.

>> I sincerely thank the reviewer for the positive feedback on the revised manuscript. The reviewer is correct in noting that I had not explicitly articulated an alternative to the sex/gender narrative. This omission has now been addressed. There is already substantial scholarship demonstrating why the nature/nurture divide is untenable, and the sex/gender distinction inherits the same conceptual problems. Accordingly, the revised manuscript now includes the following clarification:

“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 [1]. 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 [2].”

Second, 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. This clarification has now been incorporated into the revision.

Third, I am grateful for the reviewer’s reference to the historical shift from the one sex to the two sex model. Rejecting the sex/gender dichotomy does not imply a return to the one sex model i.e., treating women as merely smaller or lesser men. Rather, it means acknowledging that sex/gender is a social construct built upon physiological variation. Treating gender as a separate social variable, detached from sex, can obscure the role of social influences in biomedical outcomes [3]. We need to move beyond the sex/gender dichotomy and recognize that all bodies exist along a sex/gender continuum.

Finally, there is no evidence that the sex/gender dichotomy has facilitated research on childbirth, menopause, or the remediation of disparities produced by earlier conceptual failures. The reviewer’s cited reference articulates the core issue with clarity:

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 [3].

In summary, I am deeply appreciative of the reviewer’s insightful feedback and the recommended reference, which aligns closely with and strengthens the central argument developed in the manuscript ([1], section 3).

References:

[1] S. D. Stites and B. Velocci, “Sex, gender, sexual orientation, and more: Sexual diversity in Alzheimer’s research needs a new lens to achieve inclusive research and generalizable results,” Alzheimers Dement. Transl. Res. Clin. Interv., vol. 10, no. 2, p. e12476, Apr. 2024, doi: 10.1002/trc2.12476.

[2] C. Guanghui, “Developmental Systems Theory,” in The ECPH Encyclopedia of Psychology, Z. Kan, Ed., Singapore: Springer Nature Singapore, 2024, pp. 410–412. doi: 10.1007/978-981-97-7874-4_437.

[3] P. Griffiths and K. Stotz, “Developmental Systems Theory as a Process Theory,” in Everything Flows, 1st ed., D. J. Nicholson and J. Dupré, Eds., Oxford University PressOxford, 2018, pp. 225–245. doi: 10.1093/oso/9780198779636.003.0011.