USPSTF Approach to Addressing Sex and Gender When Making Recommendations for Clinical Preventive Services

Clinical preventive service recommendations from the US Preventive Services Task Force (USPSTF) are based on transparent, systematic, and rigorous methods that consider the certainty of the evidence and magnitude of net benefit. These guidelines aim to address the needs of diverse populations. Biological sex and gender identity are sources of diversity that are not often considered in studies of clinical preventive services that inform the recommendations, resulting in challenges when evaluating the evidence and communicating recommendations for persons in specific gender identification categories (man/woman/gender nonbinary/gender nonconforming/transgender). To advance its methods, the USPSTF reviewed its past recommendations that included the use of sex and gender terms, reviewed the approaches of other guideline-making bodies, and pilot tested strategies to address sex and gender diversity. Based on the findings, the USPSTF intends to use an inclusive approach to identify issues related to sex and gender at the start of the guideline development process; assess the applicability, variability, and quality of evidence as a function of sex and gender; ensure clarity in the use of language regarding sex and gender; and identify evidence gaps related to sex and gender. Evidence reviews will identify the limitations of applying findings to diverse groups from underlying studies that used unclear terminology regarding sex and gender. The USPSTF will use gender-neutral language when appropriate to communicate that recommendations are inclusive of people of any gender and will clearly state when recommendations apply to individuals with specific anatomy associated with biological sex (male/female) or to specific categories of gender identity. The USPSTF recognizes limited evidence to inform the preventive care of populations based on gender identity.

The US Preventive Services Task Force (USPSTF) makes evidence-based recommendations on clinical preventive services, including screening, behavioral counseling, and preventive medications. Frequently, USPSTF recommendations are sex-specific, most commonly based on the biological basis of the preventive service. For example, cervical cancer screening recommendations apply to females (individuals born with a cervix), and prostate cancer screening recommendations apply to males (individuals born with a prostate). However, many people have gender identities that differ from their sex assigned at birth. Transgender people, who were assigned male sex at birth but identify as women, or who were assigned female sex at birth but identify as men, are examples of such individuals, but there are also people with gender nonconforming or nonbinary identities who do not identify as either a man or a woman. A synthesis of data from 12 surveys involving 1 232 667 participants suggested that in the US, about 1 in 250 individuals, or about 1 million people, self-identify as transgender or gender nonconforming.¹ Moreover, in the anonymous Behavioral Risk Factor Surveillance System survey conducted in 2014 among 151 456 US adults, 0.53% of respondents self-identified as transgender. Among these individuals, about 53% self-identified as male-to-female transgender, 31% as female-to-male transgender, and 17% self-identified as gender nonconforming.²

Although data are limited,³ transgender, gender nonconforming, and gender nonbinary people report barriers to health care, including negative experiences in health care settings, and report avoiding health care because of concern about being mistreated.⁴ Moreover, disparities in preventive care, such as cancer screening, have been demonstrated for transgender and gender-nonconforming people.⁵

Therefore, the USPSTF recognizes that the language used in sex-specific recommendations (specifically related to the sex assigned to a person at birth) needs to be clear and consistent so clinicians and patients can effectively and respectfully apply these recommendations in practice. The purpose of this report is to describe the methods that the USPSTF used to identify recommendations that have sex or gender components and clarify the populations for which the recommendations should apply and also to present a proposed approach to making recommendations that are respectful of gender diversity and that identify when biological sex assigned at birth has limitations as a factor for whom should receive recommended services. This report builds on previous USPSTF methods for developing evidence-based recommendations for diverse populations.⁶

It is critical to be able to use terminology with clear definitions. The word sex describes particular biological attributes commonly associated with specific chromosomes, the effect of particular endogenous hormones, and reproductive anatomy. Although individuals can change their hormonal levels and anatomy through medical or surgical approaches, sex is meant to identify those individuals who would likely have been assigned a sex at birth of either female, male, or intersex. Sex is commonly dichotomized into female or male, but this dichotomy is not inclusive of individuals who are intersex—ie, those who have reproductive anatomy that is inconsistent with usual definitions of female or male. For example, an individual with external female genitalia but internal male reproductive organs would be intersex but may by identified by the individual or clinician as male, female, or intersex.

The USPSTF uses gender terms to refer to identities that reflect how individuals generally perceive themselves with regard to social or cultural norms as men, women, gender nonbinary, or gender nonconforming. Gender identity is not specifically confined to a binary categorization and can exist as a continuum; additionally, it can change over time. How individuals identify themselves can differ from how others perceive them based on traditional stereotypes of gender presentation. Assumptions about sex assigned at birth or gender may not be aligned with a person's biology or personal identity. The use of cis- and trans- prefixes are sometimes used to indicate whether an individual has a gender identity that aligns with their biological sex assigned at birth (cisgender) or does not (transgender).

To consider incorporating meaningful sex and gender terminology into its recommendations, the USPSTF created an internal workgroup of USPSTF members, evidence-based practice center (EPC) researchers, and Agency for Healthcare Research and Quality staff supporting the USPSTF program. The workgroup reviewed all USPSTF recommendations published by September 2021 (from September 7, 2015, to September 16, 2021) and identified all USPSTF recommendations with sex- and gender-specific language, performed an environmental scan of how other guideline-making bodies approach the use of the terms describing sex and gender, interviewed experts and leaders in the care of transgender persons, and pilot tested an approach on multiple recommendations to develop a policy to better address sex and gender. Findings from reviews and the cataloging were presented for discussion to the workgroup and the topic experts. The workgroup convened between September 2018 and March 2021 and may continue to meet periodically to further advance its methods around sex and gender.

The USPSTF makes recommendations for specific populations as determined by the evidence, and it pays particular attention to groups that may be underrepresented, underserved, or the target of racism or discrimination. When developing recommendations for specific populations, the USPSTF has 3 general goals. First, USPSTF recommendations must be consistent with the evidence. When the evidence is insufficient to determine the balance of benefits and harms, the USPSTF does not use professional opinion. Instead, the USPSTF either issues an “I” or insufficient evidence statement or does not issue a formal statement, but in both cases makes a call for more research.⁷

Second, the USPSTF strives to be inclusive with recommendations. Clinicians need to know how the evidence about clinical preventive services applies to different groups of people. However, no USPSTF recommendation can address all distinct populations because there is inadequate evidence on the benefits and harms of preventive interventions explicitly addressing every population. When evidence is limited, the USPSTF decides whether evidence from studies in an unselected, general population is applicable to or can be extrapolated to specific populations.⁸ Applying the evidence in this way creates some level of uncertainty. The issue of limited evidence is amplified in transgender, gender nonbinary, gender-nonconforming, and intersex populations, who are not routinely identified or well-represented in studies.⁹

Third, the USPSTF must ensure recommendations are clear so that they are understood and implemented appropriately.^10-12 The current language in many USPSTF recommendations lacks clarity and uses sex and gender terms inconsistently and interchangeably. For example, the USPSTF recommendation statement for breast cancer screening states that it “applies to…women aged 40 years or older.”¹³ However, it is unclear how or whether it applies to transgender, gender nonbinary, or gender nonconforming persons assigned female sex at birth or intersex individuals with breasts.

To catalog USPSTF recommendations, during March of 2021 workgroup members (n = 24) reviewed the current USPSTF recommendations to identify those that included a sex or gender term. The terms used and their intentions were cataloged. Of the 84 topics for which the USPSTF had made recommendations at the time of cataloging, 32 made sex- or gender-specific reference in the recommendation (Figure 1 and Figure 2). The USPSTF most often used gender terms, referring to men or women, instead of the sex terminology of male and female. However, most recommendations were based on sex differences and not gender identity or were for pregnant persons. No recommendation found sufficient evidence to make a specific recommendation for transgender, gender nonbinary, or gender nonconforming populations. One recommendation identified individuals who were not cisgender as a risk factor (preexposure prophylaxis for HIV),²⁸ 2 recommendations called for more evidence in transgender and gender nonbinary persons (preexposure prophylaxis for HIV and behavioral counseling to prevent sexually transmitted infections),^28,39 and 1 recommendation stated that there were no screening data for transgender and gender nonbinary persons.²⁰

Workgroup members reviewed publicly available guidance and methods documents from other national and international guideline bodies to identify (1) approaches to making guidelines based on sex and gender and (2) specific guidelines for transsexual, transgender, and gender nonconforming people. This effort was supplemented with a nonsystematic literature search (August 13, 2013, to August 12, 2018) and interviews with 23 members of the USPSTF partner organizations in an effort to ensure that the workgroup did not miss any approaches or guidelines.⁴⁴

No publicly available documents or statements were identified at that time describing how other guideline bodies handle sex and gender or transgender populations when making recommendations. However, the National Institutes of Health has a website dedicated to the Methods and Measurement in Sexual & Gender Minority Health Research.⁴⁵ Many professional groups identify LGBTQ (lesbian, gay, bisexual, transgender, queer) persons as a specific population and have policies or guidelines reflecting support, the role of the practitioner, and education on the various terms and definitions.^46-56 Several guidelines outlined general medical and prevention approaches to the clinical care of transgender, gender nonbinary, and gender nonconforming persons.^57-59 Many medical professional societies also have policies regarding the use of inclusive language on health care forms, demographic questionnaires, handouts, and paperwork.

Over a series of 6 meetings, the workgroup considered revisions to the USPSTF processes and methods and defined guiding principles to strengthen sex and gender inclusivity when communicating recommendation statements. The EPC and USPSTF members were asked to apply preliminary changes throughout the process of updating 2 recommendations—screening for abdominal aortic aneurysm (AAA) and risk assessment and genetic counseling for BRCA-related cancers.^14,17 Additionally, the EPCs and USPSTF members have prospectively applied the revised approach to subsequent topics to guide further insight and adaptation.

To advance its methods, the USPSTF pilot tested (1) prospectively and explicitly determining whether the preventive service was expected to have a biological (sex) or identity (gender) basis, (2) conducting the evidence review based on the biological or identity basis, (3) identifying whether specific populations based on sex or gender were disproportionately affected by the condition, and (4) developing language to make a clear recommendation for sex and gender. The 2 topics reviewed (AAA screening and BRCA-related cancers) had multiple recommendations that were thought to be based on sex, not gender. However, the primary studies supporting these topics used gender-based language (eg, man, woman) when referring to study populations, without further clarification of these terms.^60,61 For these 2 topics, no studies that addressed transgender, gender nonbinary, gender nonconforming, or intersex populations met inclusion criteria. Thus, when assessing the available evidence, the USPSTF could not determine whether the findings could be applied to these specific populations and could only make recommendations based on sex assigned at birth for both AAA screening and BRCA counseling.

Further, there was no specific evidence for the effect of treatment with gender-conforming therapies (eg, hormonal, surgical) for transgender, gender nonbinary, gender nonconforming, or intersex individuals and its potential effects on the biological basis for these recommendations. For example, for a person assigned female sex at birth who had transitioned during or shortly after puberty to a transgender man and who received maintenance exogenous testosterone, it is unclear whether their risk for AAA or breast cancer would be that of someone born female or male, or if their risk was somewhere on a continuum. Thus, more research is needed to make specific evidence-based recommendations. Still, until such evidence is available, it will be essential to take an inclusive, respectful approach to making preventive service recommendations to avoid further marginalization of these populations.

Very early in the pilot process, the concept emerged of using neutral language in recommendations whenever possible. The first example adopted was using the term “pregnant persons” instead of referring to pregnant women. The USPSTF used this language in several recommendations not included in the planned pilot^15,16 and received no comments, criticisms, or concerns with the transition in the language in their public comment periods or thereafter.

When not possible to use neutral language, the USPSTF decided it was more appropriate to use gender terms throughout the recommendation statement, even when the service was based on biology. However, the USPSTF developed explicit language in the Patient Population Under Consideration section to make the USPSTF intent clear to readers. This addition was first piloted in a 2019 AAA screening recommendation statement in which the recommendation stated, “the recommendations are stratified by “men” and “women,” although the net benefit estimates are driven by biologic sex (ie, male/female) rather than gender identity. Persons should consider their sex at birth to determine which recommendation best applies to them.”¹⁴ Similar language was used for the recommendation statement on BRCA-related cancer.¹⁷ The USPSTF received no comments or feedback, positive or negative, about using this language during the public posting periods for the draft recommendation statement or when the final recommendation statements were published.

The USPSTF is committed to promoting health equity for diverse populations, including based on sex and gender, and ensuring both the specificity and inclusivity of its recommendations. Therefore, the USPSTF will advance its methods and language in every step of its recommendation development process, as outlined in the Box.

Box Section Ref ID

When making a new recommendation or updating an existing recommendation, the USPSTF collaboratively creates a research plan with an EPC. The research plan defines the key questions that need to be answered with evidence for the USPSTF to make a recommendation and defines the types of evidence and populations included in the review. At the outset of this process, the USPSTF will consider whether the preventive service is expected to be applied according to biological or physiologic sex characteristics, gender identity, or potentially both. This consideration will be guided by whether specific populations have a higher prevalence or experience worse outcomes from a condition or if there are unique considerations for risk assessment or service delivery based on sex or gender identity.⁶ If specific sex or gender populations are not called out in the research plan for inclusion or exclusion, the research plan will be considered inclusive of all populations. Once a draft research plan is created, the USPSTF will seek review by transgender, gender nonbinary, gender nonconforming, and intersex individuals and groups with specific expertise in representing these populations, as appropriate. Input will be incorporated into the final research plan.

Based on the research plan, EPC investigators will conduct the systematic review. Each systematic review provides background on the epidemiology across all relevant populations (eg, incidence, prevalence, and mortality); systematically searches the literature for evidence to address each key question in the research plan; conducts data abstraction, critical appraisal, data analysis, and synthesis; and summarizes the evidence in a report. The full systematic review is available and published with each USPSTF recommendation. Throughout this process, EPC investigators will aim to describe the gender of participants from the included studies accurately. They will also note when the terminology used in the underlying evidence is unclear or based on assumptions about gender or the biology of participants. The language will be included in the EPC report to acknowledge the absence or incompleteness of information on gender and biological sex and its implications for the interpretation and applicability of the evidence. EPC investigators also will seek review by transgender, gender nonbinary, and gender nonconforming individuals and groups with specific expertise in representing these populations for services with unique considerations for these communities.

When assessing the evidence to make a recommendation, the USPSTF will consider the sex or gender identity basis of the evidence; applicability of evidence to transgender, gender nonbinary, and gender nonconforming populations and to intersex persons; variability in the quality of evidence based on sex or gender; and whether the net benefit varies based on sex or gender. Consistent with USPSTF methods, letter grade assignments will be based on the certainty and net magnitude of benefits (eg, benefits minus harms) based on the evidence. In many cases, the USPSTF may not have adequate certainty to make a specific letter grade recommendation but may decide that the available evidence applies to transgender, gender nonbinary, gender nonconforming, and intersex persons. In this case, the USPSTF may specifically mention these populations in the Patient Population Under Consideration or Clinical Considerations sections.

Whenever appropriate, the USPSTF will use sex- and gender-neutral terms. The use of gender-neutral language does not seek to deny or diminish the importance of gender in framing personal and social life, nor does it preclude a synthesis of the evidence that recognizes the unique social, economic, and political factors that influence the health risks that accrue to people based on sex and gender. In cases in which the recommendation is to be applied to specific populations based on sex or gender, the USPSTF will make a clear statement to whom the recommendation applies in the Patient Population Under Consideration section. In the Practice Considerations section, the USPSTF will review the evidence supporting the basis for a recommendation focused on a specific population defined by biological sex or gender attributes. When the USPSTF finds important evidence gaps for transgender, gender nonbinary, and gender nonconforming persons, the USPSTF will call for more evidence in the Research Needs and Gaps section of the recommendation.

The USPSTF intends that these new approaches for developing recommendations attuned to sex and gender diversity will improve the clarity of its statements and help clinicians and their patients make informed decisions about preventive care. The USPSTF plans to continue its engagement with individuals and groups with specific expertise in representing these populations to learn how best to formulate recommendations that are gender inclusive, more clearly communicate with regard to sex and gender diversity, and improve understanding of the research gaps. This policy statement should be viewed as a first step in advancing the task force’s methods on these issues. The USPSTF updates its recommendations for each preventive services topic, with a goal of approximately every 5 years. As topics are updated, the approaches outlined above will be applied during the updates. The process is underway or complete for several topics and will continue over the next several years for all others.

It is common for the USPSTF to identify evidence gaps for specific populations of patients—even when there is evidence that these populations are more likely to be diagnosed or experience specific preventable conditions.⁶² The evidence gaps for preventive services are substantial for transgender, gender nonbinary, gender nonconforming, and intersex persons, limiting the ability of the USPSTF to make a specific recommendation. As science and understanding evolve, the USPSTF will remain committed to advancing its processes and methods to further promote equity for all persons regardless of sex or gender. However, until primary studies that inform USPSTF recommendations adopt more nuanced approaches to assessment and reporting on the sex and gender of study participants, there will continue to be gaps in the evidence and challenges to formulating and communicating inclusive clinical recommendations.

Corresponding Author: Carol M. Mangione, MD, MSPH, Department of Medicine, University of California at Los Angeles, 1100 Glendon Ave, Ste 850, Los Angeles, CA 90024 (cmangione@mednet.ucla.edu).

Accepted for Publication: August 31, 2021.

Published Online: October 25, 2021. doi:10.1001/jama.2021.15731

Correction: This article was corrected on December 21, 2021, to fix an error in Figure 1.

Author Contributions: Dr Caughey had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of Interest Disclosures: None reported.

Funding/Support: The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF.

Role of the Funder/Sponsor: AHRQ staff assisted in the writing and preparation of this report and its submission for publication. AHRQ staff had no role in the approval of the final report or the decision to submit for publication.

Disclaimer: The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of the Agency for Healthcare Research and Quality (AHRQ). No statement in this report should be construed as an official position of AHRQ or the US Department of Health and Human Services.

Additional Information: We would like to acknowledge Madeline Deutsch, MD, MPH (University of California San Francisco), Jennifer Potter, MD (Harvard Medical School), and Howard Libman, MD (Harvard Medical School), who provided valuable feedback on early drafts of the USPSTF approach. Martha Duffy, MD, MPH, provided support in cataloging USPSTF recommendations and reviewing guidelines from other organizations and feedback on draft language for recommendations. Drs Deutsch, Potter, Libman, and Duffy did not receive compensation for their contributions to this paper. Amy Cantor, MD, MPH, and Elizabeth O’Connor, PhD, are members of the review teams that support the USPSTF and were involved in pilot testing the approach during systematic reviews. Drs Cantor and O’Connor received compensation through their work as part of the Evidence-based Practice Centers’ (EPC) (Pacific Northwest Evidence-based Practice Center and Kaiser Permanente Evidence-based Practice Center, respectively) support of the USPSTF.