Inclusion of sex and gender in clinical practice guidelines: an umbrella review

Abstract

Background

Clinical practice guidelines (CPGs) are key to standardised, evidence-based and equitable healthcare, and the inclusion of sex and gender considerations in CPGs is increasingly recognised as essential for quality care and health equity. This umbrella review synthesised evidence from reviews examining the extent and quality of sex and gender considerations in CPGs and identified barriers and best practice strategies to support their inclusion.

Methods

Literature searches were conducted across eight databases, identifying systematic reviews and other reviews published between 2000 and 2025 that focused on sex and gender considerations in CPGs. Data extraction and quality appraisal followed Joanna Briggs Institute guidelines. After descriptively summarising the reviews, narrative synthesis was used to summarise how sex and gender considerations were integrated across the included reviews, identifying common issues and recommendations for improving their incorporation into CPGs.

Results

Analysis of the seven included reviews (appraising a total of 784 CPGs) found that despite mention of sex or gender in 69% of CPGs, only 15% incorporated these factors into diagnostic or management recommendations, reflecting inconsistent, conceptually unclear and often superficial application. Major barriers included under-representation of women, limited sex and gender expertise on guideline committees, incomplete translation of sex-specific and gender-specific evidence into recommendations, inconsistent terminology and methodological limitations in guideline development. To address these gaps, the included reviews identified several strategies that could be implemented before, during and after the guideline development process.

Conclusion

Sex and gender inclusion in CPGs remains inconsistent and superficial, with significant implications for health equity. Addressing this requires strengthening sex-informed and gender-informed evidence, ensuring diverse and expert representation in guideline development and adopting systematic approaches that translate evidence into equitable, population-responsive recommendations.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Sex and gender differences contribute to differential health outcomes through biological, social, and structural pathways, and clinical practice guidelines (CPGs) are a key mechanism for promoting evidence-based and equitable care.

WHAT THIS STUDY ADDS

• This umbrella review demonstrates that although sex and/or gender considerations appeared in over half of CPGs examined, their inclusion was often inconsistent and largely superficial. Key barriers to the inclusion of sex and gender considerations in CPGs include limited sex- and gender-disaggregated evidence, lack of guidance for guideline developers and insufficient expertise and training on sex and gender within CPG committees.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Strengthening sex and gender integration in CPGs will require coordinated efforts across research, practice and policy to improve the underlying evidence base and its translation into recommendations. There is a crucial role for research and policy in building capacity, resources and accountability mechanisms to ensure CPGs better reflect the needs of people of all sexes and genders.

Introduction

Sex (biological characteristics) and gender (a dynamic social construct) are key determinants of health, shaping health behaviours, experiences and outcomes.^1–3 They influence how individuals engage with health services and how health systems respond to their needs. Overlooking these sex-related and gender-related differences can contribute to biases within the health system, potentially leading to misdiagnoses, treatment delays, inappropriate treatment, differential care pathways and suboptimal outcomes (eg, adverse drug reactions).^{2 4–6} Evidence has shown that failing to acknowledge and address sex-related and gender-related differences can impact outcomes across a range of conditions including cardiovascular diseases (CVD)^{1 7} and mental disorders⁸ and can reflect and reinforce existing gender inequalities.^{2 9}

To support health equity, health systems need to be underpinned by evidence that acknowledges and considers the impacts of sex and gender differences. Fundamental to this are clinical practice guidelines (CPGs). These are systematically developed, evidence-based documents that provide recommendations to guide clinical decision-making and can aid in addressing or reinforcing these disparities.^{5 10–12} CPGs assist healthcare practitioners for specific conditions, populations or settings.¹¹ By translating research evidence into recommendations, CPGs play a crucial role in standardising care, reducing unwarranted practice variation and optimising patient outcomes across diverse healthcare settings.^{5 11 13}

Including sex and gender considerations in CPGs is, therefore, central to delivering appropriate and equitable care.¹⁰ In response to this need, recent initiatives worldwide have begun to examine how sex and gender are addressed in CPGs. In Europe, the first comprehensive review of internal medicine CPGs assessed the incorporation of sex-related and gender-related evidence to promote health equity.¹⁴ Similarly, in Australia, a government-commissioned review identified major inconsistencies across 80 national CPGs and called for mandatory inclusion of sex and gender considerations, and accurate and consistent use of terminology.⁴ Building on this growing global interest and commitment, this umbrella review aims to synthesise existing reviews of the way sex and gender considerations have been incorporated into CPGs and to identify key barriers and recommendations for best practice.

Methods

This umbrella review was conducted on reviews of CPGs, not primary guideline documents themselves. An umbrella review aims to systematically review existing reviews to provide an overall examination of a body of information that is available for a certain topic.^{15 16} This umbrella review followed the Joanna Briggs Institute (JBI) umbrella review methodology¹⁵ and adhered to principles from published guides for ‘overview of reviews’, the 2022 PRIOR statement (see online supplemental file 1 for completed checklist).¹⁶ The protocol was prospectively registered in PROSPERO (CRD420251117265). While umbrella reviews typically restrict inclusion to systematic reviews only, we broadened our inclusion criteria due to the limited research in this area, enabling a more comprehensive synthesis of available evidence. High-quality narrative and non-specific reviews of sex and gender considerations in CPGs were also included in this umbrella review.

Search strategy and selection criteria

Primary literature searches were conducted between 30 June and 9 July 2025, across eight databases: Medline (via OVID), Scopus, Embase (via OVID), CINAHL (via EBSCOhost), Sociological Abstracts (via ProQuest), The Cochrane Database of Systematic Reviews (via OVID), JBI Evidence Synthesis (via OVID) and Database of Abstracts of Reviews of Effects (via OVID). Search alerts were also set for each database, and screening continued until 14 November 2025. The references of included studies were also screened to identify additional papers. The search was conducted using a three-tiered search strategy that combined terms for CPGs, sex and gender concepts and review types. The search strategy was first developed in Medline and then reviewed by the research team before being applied across all databases (see online supplemental file 2 for the complete search terms). The search was limited to English-language reviews published from January 2000, given that meaningful attention to sex and gender considerations in CPGs has increased in the 21st century. No geographical restrictions were applied.

This review included systematic, scoping and other non-specific reviews that analysed how sex and gender are considered and/or integrated into CPGs, including their development, content or implementation strategies. Primary research studies, editorials, protocols, opinion pieces and guidelines were excluded. No limitations were placed on the type of CPG covered by the included reviews (eg, health outcome, population target or clinical condition, diagnosis vs treatment, geographical context).

Records arising from the search results were imported into Covidence, a web-based tool for conducting reviews.¹⁶ Potential review articles for inclusion were independently screened by two reviewers. Title and abstract screening were conducted by HM and MYS, while full-text screening was conducted by TK and MYS. Discrepancies during the screening process were resolved by two reviewers through discussion and by discussion with a third reviewer if consensus was not achieved.

Data analysis

Data extraction

A standardised data extraction form was developed by MYS in Excel and reviewed by two other authors (TK and JE). The form was then imported into Covidence, and data extraction was conducted by JE and MYS. Data extraction captured citation details (first author’s last name, year), review type, details of CPGs included in the review (number of CPGs, country setting, year, health domain and sources) and key findings regarding sex and gender focus (extent to which sex and gender were considered, issues identified and recommendations for best practices). After independently conducting the data extraction, JE and MYS met to reach consensus on data capture for each review and consolidated a final data information form to proceed, with no notable discrepancies encountered during the process.

Risk of bias assessment

The quality of the included reviews was independently assessed by JE and MYS using the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses.¹⁵ The JBI checklist was selected because it evaluates key aspects of systematic review methodology, including the clarity of the review question, the appropriateness of inclusion criteria and search strategy, the adequacy of study appraisal and data extraction methods and the assessment of publication bias.¹⁵ We applied eight of the 11 JBI appraisal items, excluding three items on study appraisal and publication bias, which are related to guideline quality assessment. These three items were not considered applicable to this study because the included reviews primarily examined the extent to which sex and gender were integrated into CPGs, rather than evaluating the overall methodological quality of the guidelines themselves. We note that there is currently no standardised tool for evaluating the extent of sex and gender integration in CPGs.¹⁷ Following independent assessment, discrepancies between reviewers were discussed and resolved through consensus. Where necessary, the original review was re-examined to ensure consistent interpretation of the appraisal criteria. The overall quality of included reviews with respect to how they considered sex and gender integration was reported narratively, considering their strengths and limitations. Please see online supplemental file 4 for details of the quality appraisal process applied here.

Data synthesis

A descriptive summary was conducted using the information obtained from the data extraction process to present the review type, characteristics of the included CPGs and how sex and gender were considered in these CPGs. Additionally, a narrative synthesis was performed for both quantitative and qualitative findings to summarise how sex and gender considerations were integrated across the included reviews, identifying common issues and recommendations. Quantitative findings on the proportion of guidelines considering sex and gender, and the extent to which these factors were considered, were then descriptively synthesised to illustrate the degree of inclusion across contexts. Finally, qualitative findings were analysed thematically to identify common issues and recommendations for the consideration of sex and gender in CPGs. Information was presented using tables, figures, descriptive statistics and thematic summaries. No meta-analysis was conducted due to the qualitative and conceptual nature of the topic.

Results

Study characteristics

The identification and screening processes are illustrated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram (figure 1). After the removal of duplicates, titles and abstracts of 719 studies were screened. A total of 27 studies underwent full-text screening, and of these, 21 were excluded, while a further two were identified through reference lists or as protocol papers. Reasons for exclusion are provided in online supplemental file 3), with the most common reason being an ineligible study design that did not involve a review of CPGs. In total, seven reviews of CPGs were included in this umbrella review.^18–24

Figure 1. PRISMA diagram of included studies. CPGs, clinical practice guidelines; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

The characteristics of the seven included reviews are presented in table 1. Regarding the scope, five reviews focused on individual countries, including Australia,²⁵ Canada,¹⁸ the Netherlands,¹⁹ Spain²⁰ and the United Kingdom (UK),²¹ while one review examined CPGs across Europe,^{14 22} and one review assessed global CPGs for low back pain.²³ Three reviews did not restrict to any CPG type,^{20 21 25} while Keuken et al focused on four specific health domains (hypertension, depression, osteoporosis and rheumatoid arthritis),¹⁹ Naghipour et al focused on internal medicine and its subspecialties,^{14 22} and Tannenbaum et al focused on non-communicable diseases.¹⁸ The earliest review was published in 2007,¹⁹ and four of the seven reviews were published very recently in 2024–2025.^{20–22 25} Of the seven included reviews, three were explicitly systematic reviews,^{14 18 21} one was a scoping review,²³ while the remaining three did not specify a review type and were classified as non-specific reviews.^{19 20 25} Collectively, the reviews appraised 784 CPGs, with the largest contribution from the European guidelines review (n=325),²² and the smallest from the study of CPGs in the Netherlands (n=7).¹⁹

Table 1. Descriptive summary of included reviews.

Author	Review/article type	Country/ region	Study aim/s	Details of CPGs	Key findings
					Sex and gender incorporation	Identified issues and barriers	Study recommendations
González Ramos20	Non-specific review	Spain	Examine use of sex and gender terms in Spanish CPGs Create methodology to assess sex and gender inclusion	CPGs included: 21 Year: 2018–2022 Health domain: any Sources: Spanish National Health System Programme GuaSalud	76% were text-positive for sex and/or gender terms CPGs related to patients’ conditions contained fewer sex and gender terms compared with those related to technical procedures Women mentioned more often overall, but men appeared more consistently across guidelines	Limited information on sex & gender Evidence and resulting recommendations did not differentiate illness processes between men and women	Integrate sex and gender into PICO question framing Apply manual/guidelines that provide guidance for sex and gender inclusion Train practitioners and developers to use gender markers appropriately and explain benefits of accurate language
Hulme et al21	Systematic Review	United Kingdom	Examine inclusion of sex and gender in UK’s NICE CPGs	CPGs included: 197 Year: 2024 Health domain: any Sources: NICE’s publicly accessible guideline database	61% included information on sex and/or gender, dropping to 41% when excluding pregnancy Of non-pregnancy guidelines, 43% used sex and gender interchangeably 5% included sex and/or gender in clinical scoring systems 35% mentioned the terms superficially; 39% made no mention of sex or gender	No standardised way to include sex and gender evidence Limited data on differences in clinical presentation, investigation or management for women or females Research based on male default, missing evidence for females Sex differences often limited to sexual/reproductive health	Establish robust, standardised processes for embedding sex- & gender-specific evidence Apply standardised terminology, with inclusive definitions Involve more women in guideline committees Avoid assessing sexes differently; adopt a life-course approach that considers intersections of age, sex and gender in health
Keuken et al19	Non-specific review	Netherlands	Examine consideration of sex factors in guideline development Assess how attention to sex-related factors could be improved	CPGs included: 7 Year: 1999–2002 Health domain: hypertension, rheumatoid arthritis, depression, osteoporosis. Sources: NHG and CBO	Sex-specific evidence often included but research questions/search terms not framed around sex-factors Available critical appraisal tools lacked systematic assessment of sex-specific evidence Few sex-specific recommendations (0–16 out of 84 in osteoporosis guidelines)	Low representation of women on guideline committees Limited awareness and expertise among developers on integrating sex considerations Guideline development methods did not systematically account for sex-related factors Lack of relevant evidence on sex-related factors	Incorporate sex-related factors in initial key questions to capture potential differential effects Design search strategies to detect sex-specific evidence Critically appraise validity and reliability of sex-specific findings Consider multiple approaches to incorporate sex-related factors
Kirkman et al25	Non-specific review	Australia	Examine inclusion of sex and gender in Australian clinical guidelines	CPGs included: 80 Year: 2014–2024 Health domain: any Sources: GIN, Google, NHMRC guideline database organisations’ websites	Most CPGs showed low levels of sex and gender inclusion 85% mentioned sex and/or gender, 42% used terms interchangeably, only 5% defined them 81% of CPGs incorporated sex-related factors Only 15% of CPGs addressed gender in depth	Sex and gender terms rarely defined and often used interchangeably Research based on males default, with limited attention to sex- and gender-based differences Few publications consider sex-specific management Guideline tools lack guidance for synthesising sex/gender evidence	Collaborative co-design approaches to integrate sex and gender Explicit guidance for sex and gender evidence synthesis Inclusion of women and gender-diverse individuals on guideline panels Absence of sex or gender evidence should be noted
Naghipour et al22	Systematic review	European Union (EU)	Examine inclusion of sex and gender in European CPGs	CPGs included: 325 Year: 2012–2022 Health domain: 10 subspecialties of internal medicine Sources: official websites of medical organisations and PubMed	74% of EU CPGs contained sex &/or gender terms 4.7% of all CPG recommendations covered sex/gender-related topics Of these recommendations, 83% focused on fertility/reproduction, gynaecology/urology-related aspects and gonosomal variations	Under-representation of women in clinical trials and guideline committees When included, sex and gender terms operationalised as binaries Interchangeable use of sex and gender terms Resistance and perceived barriers among some guideline committees	Identify evidence gaps, context of target population and apply structured implementation frameworks Include broad range of expertise and stakeholders with lived experience Include attention to LMICs Consider AI/machine learning in low resource settings to minimise bias and assist synthesis
Rathbone et al23	Scoping Review	Global	Examine inclusion of sex and gender considerations in low back pain CPGs	CPGs included: 36 Year: 2010–2020 Health domain: lower back pain Sources: Medline, Embase (NICE, TRIP Database, PEDro	42% text-positive for sex and/or gender; none defined terms; 67% used terms interchangeably 33% of text-positive guidelines had sex &/or gender-specific diagnostic &/or management 60% used sex/gender in epidemiology Sex/gender recommendations limited to pregnancy	Research on LBP often overlooks or inconsistently addresses sex and gender Limited knowledge on gender integration in LBP research Interchangeable use of terms risks misapplication of LBP recommendations No CPGs defined sex or gender Little consideration of sex and gender diversity in committees	Integrate sex and gender in LBP diagnosis, prognosis, and management Future research should integrate sex and gender terms across life-course, not only for pregnancy Use inclusive, precise terminology that includes broader gender identities Education for clinicians on differences between sex and gender
Tannenbaum et al18	Systematic Review	Canada	Determine proportion of Canadian CPGs integrating evidence on sex and gender considerations	CPGs included: 118 Year: 2013–2015 Health domain: non-communicable Sources: CMA CPG Infobase, PubMed, territorial and org. websites	66.9% text-positive for sex and/or gender terms 30% recommended different approaches for men and women 35% had sex considerations in screening, diagnosis, management. 41% used sex/gender in epidemiology 35% used sex and gender terms correctly	Lack of sex-disaggregated evidence in CPGs Lack of awareness of guidance for integrating sex/gender in CPGs	Use available frameworks to guide sex and gender inclusion Standardise strategies for sex and gender integration in CPGs Prioritise sex- and gender-responsive interventions in guideline development, medical school curricula and continuing education

AI, artificial intelligence; CBO, The Dutch Institute for Healthcare Improvement; CMA, Canadian Medical Association; CPGs, clinical practice guidelines; GIN, Guidelines International Network; LBP, low back pain; LMICs, low- and middle-income countries; NHG, The Dutch College of General Practitioners; NHMRC, National Health and Medical Research Council; NICE, National Institute for Health and Care Excellence; org, organisation; PEDro, Physiotherapy Evidence Database; PICO, Population, Intervention, Comparison, Outcome; TRIP, Turning Research into Practice Medical Database.

Across the included reviews, the consideration of sex and gender in CPGs was primarily analysed based on the presence of sex-related or gender-related terms, with CPGs classified as text-positive if the main text contained at least one prespecified sex-related or gender-related term (eg, sex, gender, male, female, men, women, boys, girls). Table 1 uses several abbreviations; their full form is provided at the end of the table.

Quality appraisal

Overall, the included reviews were of good quality, with none deemed to be of poor quality (see online supplemental file 4). All three systematic reviews^{14 18 21} and the scoping review²³ demonstrated methodological rigour by fulfilling all JBI criteria for high-quality evidence synthesis. Two non-specific reviews met most of the JBI criteria (75%, and 87.5% of items met),^{19 25} while one non-specific review had moderate quality (62.5% of items met).²⁰ Common aspects not reported across non-specific reviews were methods to minimise data extraction errors and explicit directions for future research. Importantly, given the heterogeneity of review types and the distinct nature of included CPGs (compared with appraising primary empirical studies), the quality assessment results should be interpreted with caution.

Synthesis

Sex and gender incorporation

Overall, 69% (538/784) of the CPGs included sex and/or gender terms in the main text.^{18–23 25} Of the seven included reviews, four analysed how sex and gender terms are used in CPGs (equating to n=235 CPGs). Of these included CPGs, 59% (138/235) used sex and gender terms interchangeably, often using gender terms (women, men, etc) in the context of biological sex (male, female, etc) and vice versa.^{18 21 23 25} Four reviews identified that some text-positive CPGs mentioned sex or gender only in relation to pregnancy and reproductive health,^{18 21–23} noting that sex and gender inclusion in CPGs should extend beyond these contexts.

Three of the reviews further examined text-positive CPGs and assessed the level of sex or gender inclusion (figure 2).^{18 21 23} Excluding pregnancy-related CPGs, this equated to n=206 CPGs. For consistency and comparability, we synthesised and consolidated these findings into three categories (see online supplemental file 5) and found that:

Figure 2. Sex and gender consideration in the text-positive CPGs. CPGs, clinical practice guidelines; LBP, low back pain; NICE, National Institute for Health and Care Excellence.

1. 39% (81/206) of CPGs mentioned sex or gender without integrating these factors into the evidence assessment or recommendations.

2. 46% (94/206) of CPGs addressed sex or gender only in epidemiological and/or laboratory contexts (eg, prevalence or biomarker differences).

3. 15% (31/206) of CPGs incorporated sex or gender within diagnostic and/or management recommendations.

Identified barriers to the inclusion of sex and gender in CPGs

Beyond documenting the extent of sex and gender inclusion, the included reviews also identified key barriers to their incorporation. Four key themes emerged:

1. Lack of diversity in committee representation and expertise

   Two reviews reported limited representation of women on guideline development committees, with Keuken et al reporting that 64%–100% of CPG committee members were men.^{19 22} Four reviews also highlighted limited knowledge and awareness among guideline developers regarding how to incorporate sex and gender.^{19 21 23 25} Naghipour et al further observed that some committees perceived the inclusion of sex and gender considerations as adding complexity to an already time-consuming and resource-intensive guideline development process.²²

2. Evidence and practice gaps

   All reviews highlighted that women are often under-represented in research or clinical trials, resulting in a lack of relevant evidence on sex-related and gender-related factors.^{18–23 25} When evidence of sex differences was available, it was rarely translated into practice or extended to tailored information regarding sex-based patient management or diagnostic approaches.^{18 20 21 25} There was limited acknowledgement of gender-specific evidence, with reviews typically referring to ‘sex and gender’ jointly when discussing evidence gaps.^{18 20–23 25} Hulme et al also noted that sex and gender considerations were often limited to sexual and reproductive health, with little consideration in other health domains.²¹

3. Terminology and conceptual factors

   Sex and gender terms were rarely defined in the CPGs, leading to barriers surrounding correct and distinct use of terms.²⁵ Two reviews similarly noted that sex and gender terms were often used interchangeably in CPGs, a practice that risks misapplication of recommendations.^{22 23} Moreover, sex and gender were generally operationalised in a limited and strictly binary manner.²²

4. Methodological gaps in guideline development

   Three reviews identified that the methodologies commonly used to develop guidelines (eg, AGREE II, GRADE, etc) rarely systematically advised on how to account for sex-related and gender-related factors.^{18 19 21 25} Additionally, tools do not provide standardised procedures for synthesising or applying sex-specific and gender-specific evidence.^{18 19 21 25}

Recommendations to enable sex and gender consideration

Across the reviews, several recommendations were proposed to strengthen the consideration of sex and gender in CPGs. These recommendations outline strategies for each step of the guideline development process as well as cross-cutting implementation strategies and directions for future research and education (as shown in figure 3).

Figure 3. Strategies to enable sex and gender consideration in CPGs. CPGs, clinical practice guidelines; PICO: Population, Intervention, Comparison, Outcome; SAGER, Sex and Gender Equity in Research.

Discussion

This umbrella review synthesised seven reviews to examine how sex and gender considerations are integrated into CPGs. Most CPGs mentioned either or both sex and gender terms (text positive),^{18–23 25} but, in general, these terms were used interchangeably^{18 21 23 25} and only a small proportion incorporated sex or gender into recommendations.^{18–23 25} Text-positive CPGs mostly mentioned sex and gender terms superficially or within the context of epidemiological data but failed to translate them into actionable or evidence-based guidance for clinical practice. Such inclusion risks being tokenistic and perpetuating health inequities, maintaining the appearance of inclusivity without meaningful application in clinical decision-making.

Across included reviews, four recurrent barriers emerged: (1) under-representation of women and sex and gender expertise on guideline committees, (2) limited translation of sex-specific research into recommendations and limited analysis of gender-specific evidence, (3) inconsistent terminology and (4) methodological gaps in guideline development tools. It appears that many guideline development committees are not equipped with the right membership, training and guides to enable them to meaningfully consider sex and gender. Moreover, these barriers risk undermining health equity: guidelines that fail to incorporate sex-specific and gender-specific evidence risk embedding and perpetuating existing biases and disadvantaging women, gender-diverse, intersex and other under-represented groups,¹⁸ while mentioning sex and gender without providing differentiated diagnostic or treatment recommendations leaves clinicians without the guidance needed for equitable care.

Gaps in considering sex and gender in CPGs can have real and significant consequences. This is evidenced in CVD care where the historical predominance of male participants in CVD research, combined with guideline and treatment practices that inadequately address sex-specific symptom profiles and drug responses, has contributed to delayed diagnosis and poorer outcomes for females with CVD.^{1 5 10 24} It is also noteworthy that gender-diverse groups remain largely invisible in CVD guidance despite elevated risks in some groups related to gender-affirming therapy and psychosocial stressors.^{3 5 26} Findings of this review show that this pattern extends well beyond CVD: the persistent use of binary sex and gender categories in most CPGs means that the health needs of intersex, transgender, non-binary and other gender-diverse groups are often overlooked across health domains. Beyond CVD, male-centred research has been documented across a range of non-reproductive clinical domains, contributing to sex-based disparities in evidence and care.²⁷ This includes pain management (where women’s pain is more likely to be undertreated or dismissed),²⁸ pharmacology (where adverse drug reactions occur among women 1.5–1.7 times more frequently than men due to inadequate representation in drug trials),²⁹ and mental health (where diagnostic criteria developed from predominantly male samples have led to underdiagnosis of conditions such as ADHD and autism in women and girls).³⁰

At the same time, the state of evidence differs for sex and gender. Robust sex-disaggregated data are increasingly available in some fields, making sex-based analyses and recommendations a realistic first step, whereas gender—a complex social construct—remains less well measured and reported. Focusing initially on sex-specific considerations in guideline development may, therefore, be a pragmatic approach that can lay essential groundwork for more comprehensive gender-sensitive healthcare as data and methodology evolve.¹⁰ Tannenbaum et al proposed that guideline development groups systematically assess whether evidence and recommendations differ by sex, appoint a sex-a-gender champion to oversee this appraisal and provide sex-specific recommendations supported by data, or explicitly acknowledge uncertainty when evidence is lacking.¹⁰ In the interim, guideline development groups should transparently acknowledge gaps in gender-specific evidence and adopt a stepwise approach that embeds sex-based recommendations for males and females, while building the methodological foundation needed to subsequently incorporate more complex considerations for intersex and gender diverse groups including transgender and non-binary populations in the future.

Integrating sex and gender into CPGs is complex and is shaped by the expertise of guideline developers, the quality and granularity of the evidence base and the methodological tools employed. While some concerns have been expressed about the added complexity of sex and gender considerations in an already resource-intensive process,²² the strategies identified in this umbrella review can be integrated into existing CPG development frameworks rather than requiring complete overhauls, thereby balancing inclusivity with feasibility. Key recommendations include ensuring diverse and expert committee representation, and equipping guideline developers with the training and resources needed to use appropriate terminology and to integrate sex and gender into evidence scoping and synthesis processes; and to translate findings into actionable, sex-informed and gender-informed recommendations. This aligns with recent methodological work by the US Preventive Services Task Force, which emphasises the use of inclusive language in CPG recommendations, clear specification of recommendation applicability by sex and gender and transparent reporting of evidence gaps.¹³

This umbrella review has several strengths and limitations. By synthesising seven reviews covering 784 CPG assessments across multiple countries and domains, it offers a broad view of current CPG practice regarding sex and gender considerations and identifies common challenges. By consolidating different classification schemes into consistent categories and mapping recommendations onto guideline development stages, this umbrella review provides interpretable and actionable findings for guideline developers, researchers and policymakers. However, restriction to English-language, peer-reviewed reviews and a focused search strategy means some relevant work, particularly from regions such as Asia and Africa, may have been missed. Nonetheless, the combination of systematic searching and supplementary search methods strengthens confidence that the included studies sufficiently represent the current evidence landscape of sex and gender inclusion in CPG development. Another strength is that many of the included reviews are very current (with 4/7 published in 2024–2025), which means our review reflects recent evidence in the context of a growing trend towards greater acknowledgement, which may necessitate future updates to this review. While not a limitation of this review, we also note that as an umbrella review of existing reviews, our findings are based on the CPGs examined within included reviews. As such, they do not reflect a comprehensive assessment of all CPGs. This limits our inference to the subset of CPGs that have been subjected to review-level analysis, and this may not represent or capture all clinical domains or other recently published guidelines.

Conclusions

Despite growing recognition of the importance of sex and gender in CPGs, this umbrella review found their inclusion remains inconsistent and often superficial, meaning recommendations may not apply equitably to all patients. This risks perpetuating disadvantages for groups historically under-represented in research and guideline development. Strengthening sex-informed and gender-informed evidence, ensuring diverse and expert representation in guideline development, and adopting more systematic and transparent approaches are critical to producing CPGs that better reflect population diversity and support equitable, evidence-based healthcare.

Data availability statement

Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information.