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Statement of Task and Approach

INTRODUCTION

While the health and well-being of a population drives its vibrancy and potential, individuals in the United States suffer from many health problems—both acute and chronic—that hamper the overall population’s ability to most effectively work, care for their families, and contribute to society. At the same time, the United States is a leader in research innovation and health discoveries for basic, clinical, and translational science, leading to breakthrough treatments, such as vaccines, cancer therapies, regenerative medicine, and various community-based initiatives that have improved the health of the population. However, the biomedical and social scientific enterprises have not yielded the anticipated breakthroughs that contribute to improved health and well-being for half the population in the United States—women and girls.¹ This gap appears, in part, attributable to a lack of baseline understanding of basic sex-based differences in physiology and the lack of attention and support for research into conditions and factors specific to, more common among, or that affect women and girls differently.

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¹ The terms “female” and “woman” are used differently according to context and perspective, which may cause confusion. For the purpose of this report, the definition of women goes beyond the sex and gender binary and includes all people who identify as a woman or girl, solely or in addition to other gender identities and regardless of biological sex traits. This inclusive definition recognizes individuals who have been or may be affected by a set of biological or social variables that influence women differently than men across the life course (see later in this chapter for a discussion of report definitions).

Advances in women’s health research (WHR) contribute to overall scientific progress and innovation by unveiling insights that would be relevant to all. However, it is well documented that WHR is inadequate to meet the needs of women and girls (Baird et al., 2021a; IOM, 2001, 2010; NASEM, 2020, 2022a, 2024b; World Economic Forum, 2024). Data that can help advance health are lost when studied in the aggregate or without sex- and gender-specific analyses. Intentionally studying the underlying sex and gender differences and related mechanisms that shape the evolution of disease and disability leads to stronger science. Furthermore, investments in research to better understand the gender-specific health issues and corresponding interventions will benefit the health of the whole population, enhance the economy, and position the United States as a global leader as it is in other areas of research (World Economic Forum, 2024).

The result of inadequate prioritization of and investment in women’s health and sex differences research has perpetuated persistent gaps in our understanding of conditions that are female specific, such as reproductive cancers and fibroids; disproportionately affect women, such as autoimmune disorders and osteoporosis; or affect women differently than men, such as heart disease and diabetes. The inadequate attention paid to women’s health and sex differences has created disparities in the diagnosis, prevention, treatment, and outcomes in many conditions that affect women. Girls, women, families, society, and the economy all pay a price for this gap.

Despite having a longer life expectancy than men, women spend more years living with a disability and in poor health—on average, a woman will spend 9 years in poor health, 25 percent more time relative to men, affecting her quality of life and productivity (World Economic Forum, 2024). Conditions that affect both women and men have disparities in outcomes and treatment success. For example, a lifetime invasive cancer diagnosis is more common among men, but recent declines in cancer incidence and mortality have been larger in men (Siegel et al., 2024). Although women have a lower prevalence of cardiovascular disease (CVD)—4.2 percent versus 7.0 percent in men—they have worse prognoses after an acute cardiovascular event, and research on the underlying pathophysiology of why this occurs is limited (CDC, 2023; Gao et al., 2019).

Starting in adolescence, there are conditions specific to the experiences of women and girls, such as menarche and premenstrual dysphoric disorder (PMDD), and several intersex conditions present during the onset of puberty. Many conditions specific to women, such as endometriosis, polycystic ovary syndrome (PCOS), and cervical and uterine cancers, lead to significant morbidity and mortality. Complications during pregnancy, such as gestational diabetes and preeclampsia, are associated with increased risk of developing chronic conditions, such as diabetes and CVD, later in life (ORWH, 2024). On the other end of the life course, more than 1 million U.S. women experience menopause each year (Peacock et al., 2023), but significant gaps

in knowledge about its health effects—and the health effects of perimenopause—remain (Davis et al., 2023; Moreau and Hildreth, 2014; Samargandy et al., 2022; see Chapters 5 and 7 for more information on research gaps), in large part because of a lack of preclinical research on aging that considers it.² Moreover, less than 15 percent of women receive evidence-based treatment for menopausal symptoms, leading to considerable effects on quality of life. The menopause transition can also increase the risk of certain health conditions, including CVD and osteoporosis (Davis et al., 2023). See Chapters 5 and 7 for more examples of women’s health outcomes.

Women who are racially and ethnically minoritized, are economically disadvantaged, live in rural areas, or identify as belonging to sexual and gender minority groups, experience a disproportionate burden of disease and adverse outcomes over the life course, including autoimmune diseases, cancer, mental illness, maternal morbidity and mortality, and violence (ORWH, 2024). These inequities are in large part a result of structural factors and lack of access to beneficial social determinants of health (SDOH) (see Chapter 6 for a detailed discussion of this topic) (NASEM, 2023; ORWH, 2024). The women in these populations, and the structural and social factors that contribute to their poor health outcomes, remain largely understudied, underrepresented, and underreported in biomedical research (ORWH, 2024). Moreover, the existing data on health outcomes predominantly reflect the experiences of White patients. In many cases, the data lack disaggregation by race, ethnicity, geography, and other relevant factors, leading to the omission of certain populations—such as American Indian and Alaska Native and Native Hawaiian and Pacific Islander individuals—from both data collection and analysis, masking or misrepresenting their health experiences and challenges (NASEM, 2023). Consequently, the findings presented, including those in this report, may not accurately represent the health realities of all demographic groups. This data gap requires alternative methods for analyzing small samples (see NASEM 2023 and 2024b for more information).

Advances in women’s health are absent in many areas, resulting in a lack of prevention, diagnosis, and treatment options for many conditions (Howard et al., 2017; Kuehner, 2017; McHugh et al., 2018; Piccinelli and Wilkinson, 2000):

• Women live longer than men, which is one potential risk factor putting them at double the risk of Alzheimer’s disease (AD)—1 in 5 versus 1 in 10 for men.³ Although women are enrolled at equal rates

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² This sentence was changed after release of the report to update the references cited.

³ This sentence was changed after release of the report to clarify that life-span is not the only risk factor for AD.

• to men in dementia-related clinical trials, the outcomes of those trials infrequently report sex-disaggregated efficacy and safety data (NASEM, 2022b; ORWH, n.d.-a).
• Research on substance misuse and substance use disorders has focused on men, even though sex and gender influence risk, severity, and outcomes (McHugh et al., 2018).
• The cause and risk factors for endometriosis, which can cause severe pain, fatigue, depression, anxiety, and infertility, remain obscure, with little progress over the past 30 years on understanding its pathophysiology (NASEM, 2024b). It has no nonsurgical diagnosis method or cure and frequently recurs even after surgery.
• Fibroids are the leading cause of hysterectomy in the United States, but it takes years from the onset of symptoms to receive a diagnosis (NASEM, 2024b). Although millions are affected by this condition, treatments are limited.
• Eighty percent of people with autoimmune diseases are women, but diagnosis is often delayed due to a lack of understanding of the fundamental mechanisms for most of these diseases (Angum et al., 2020).
• With regard to mental health, research on girls and women for decades has demonstrated that mental health disorders, such as depression and anxiety, are more common than among boys and men. However, limited evidence explains the mechanisms and risk factors producing these gendered differences (Howard et al., 2017; Kuehner, 2017; McHugh et al., 2018; Piccinelli and Wilkinson, 2000).

Data point to a gender disparity in the allocation of National Institutes of Health (NIH) research funding across different diseases, with those that disproportionately affect women underfunded relative to their burden compared to those that disproportionately affect men (see Chapters 4 and 7). Based on an analysis of 2019 NIH funding data and burden of disease data (disability adjusted life-years), one study found that, of 34 conditions that have a disproportionate effect based on gender, 25 are male-favored in that they either disproportionately affect women and are underfunded or disproportionately affect men and are overfunded (Mirin, 2021) (see Figure 1-1). In Figure 1-1, the conditions are arranged by greatest to least burden (panel A) and greatest to least amount of NIH funding (panel B). Disease burden is indicated by the size of the circle representing the condition, and which gender is disproportionately affected is indicated by the circle’s color. HIV/AIDS in the United States, for example, is male dominant and a receives a high level of funding relative to its burden.⁴

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⁴ This sentence was changed after release of the report to clarify that the data are based on the U.S. population.

The funding analysis overseen by this committee identified just 8.8 percent of all NIH spending from fiscal year (FY) 2013–2023 as WHR. It also found that funding for WHR and the number of projects on women’s health have remained flat during this period despite steady increases in the NIH budget and total projects (see Chapter 4 and Appendix A for more on the funding analysis and methodology).

To address the disparities in women’s health outcomes, Congress requested as part of the Consolidated Appropriations Act of 2023⁵ that the National Academies of Sciences, Engineering, and Medicine (National Academies) assemble an ad hoc committee to conduct a study to assess the state of WHR at NIH. The Office of Research on Women’s Health (ORWH) at NIH sponsored the study. Specifically, the committee was asked to assess NIH research on women’s health, including knowledge gaps and the proportion of NIH-funded research on women’s health conditions, including those that are female specific, are more common among women, or affect

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⁵ Consolidated Appropriations Act of 2023, Public Law 117–328, §772, 117th Cong., 2d sess. (December 29, 2022).

women differently. The committee was also asked to capture conditions across the life-span, evaluate both sex differences and racial and ethnic health disparities, determine the appropriate level of funding needed to address the identified gaps, and identify metrics to track progress toward closing these gaps (see Box 1-1 for the full committee statement of task).

In addition, the committee was tasked with making recommendations regarding the following:

• Research priorities for NIH-supported research on women’s health;
• NIH training and education efforts to build, support, and maintain a robust WHR workforce;
• NIH structure (extra- and intramural), systems, and review processes to optimize WHR;
• NIH-wide workforce to effectively solicit, review, and support WHR; and
• Allocation of funding such that NIH women’s health funding reflects the burdens of disease among women.

URGENCY OF ADDRESSING WHR

Improving women’s health through targeted research not only benefits individual women but also has broader societal implications. Healthy women contribute to healthier families, communities, and future generations, and addressing women’s health needs can reduce health care costs associated with undiagnosed or improperly managed conditions. Increased health care costs can stem from misdiagnosis or delayed diagnosis resulting from a lack of knowledge in women’s health, leading to unnecessary tests, treatments, and hospitalizations. In addition, women often respond differently to treatments compared to men because of biological differences. Therefore, research conducted primarily on male subjects can lead to prescribing medications, dosages, or therapies that are less effective or cause more side effects in women. For example, one recent study found that women are at greater risk for implant failure after a total hip replacement, in part because women tend to have smaller joints and bones than men (Inacio et al., 2013). See Chapter 2 for more information on the history of male-focused research.

Women-specific health conditions, such as those related to reproductive health, or female-dominant conditions, such as autoimmune diseases, often require ongoing management—without proper management, women may have higher health care use rates. Recent data suggest that anxiety and depression, both more prevalent in women than men, accelerate the development of cardiometabolic risk factors, such as hypertension and diabetes (Civieri et al., 2024; COVID-19 Mental Disorders Collaborators, 2021; Goodwin et al., 2022). Civieri and colleagues (2024) noted significant age and sex effects—the association was greater in younger women. The McKinsey Health Institute estimates that addressing the women’s health gap could “add years to life and life to years” and that “addressing the 25 percent more time that women spend in ‘poor health’ relative to men not only would improve the health and lives of millions of women but also

could boost the global economy by at least $1 trillion annually by 2040” (World Economic Forum, 2024).

Addressing the women’s health gap could improve the quality of life for women and the health of future generations. The McKinsey report found that sex-specific conditions affect women and girls most frequently between the ages of 15 and 50, so although health conditions affect them over the life course, nearly half of this burden falls during their working years, affecting their ability to earn money and support themselves and their families (World Economic Forum, 2024). The authors also looked at 183 of the most widely used interventions across 64 health conditions (e.g., asthma, lower respiratory infections, diabetes mellitus, stroke, and cardiovascular disease) representing roughly 90 percent of the health burden for women. Of the more than 650 academic papers on these conditions, they found that only 50 percent of the interventions studied reported sex-disaggregated data, and when these were available, 64 percent of the interventions studied were found to put women at a disadvantage resulting from lower efficacy, access, or both; for men, this was the case for only 10 percent of interventions (see Figure 1-2) (World Economic Forum, 2024).

Women’s health issues, such as chronic conditions, can lead to absenteeism from work, reduced productivity, increased health care-related absences, and reduced economic productivity both at the individual and societal levels (Whiteley et al., 2013; World Economic Forum, 2024). Failure to prioritize women’s health can reinforce gender disparities, limiting opportunities for women. Women experiencing poor health may face barriers in accessing education or pursuing career opportunities, affecting their own and their children’s future prospects. Furthermore, when a woman is a caregiver, her

own poor health can strain relationships within her family, affecting emotional well-being and family cohesion (see Chapter 6 for more information) (Caputo et al., 2016; CDC, n.d.; DePasquale et al., 2016, 2019).

Investing in WHR is essential to ensure that health care systems can effectively address the diverse and specific health needs of women, leading to better outcomes, improved quality of life, and the ability to lead healthier and more fulfilling lives, participate fully in economic and social activities, and contribute actively to their families, communities, and societies as a whole.

PAST AND ONGOING EFFORTS IN WHR

A robust history of reports and actionable recommendations aimed at enhancing women’s health was set against an evolving landscape as this report was written. During the development of this report, notable entities, such as NIH, the White House, and Congress, have introduced programs, legislation, and initiatives, and the private sector has published insightful reports and provided funding for innovative initiatives in women’s health. The committee sought to build upon this foundation of work, integrating key insights and initiatives summarized in this section.

Relevant National Academies Reports

This report adds to and builds from numerous past and ongoing efforts to improve women’s health (see Table 1-1). Reports from the National Academies and other organizations have provided important background, evidence, and recommendations to advance women’s health that this report builds on. Several are summarized next.

The 2001 Institute of Medicine (IOM) report Exploring the Biological Contributions to Human Health: Does Sex Matter? explored the knowledge base on and research priorities for animal and cellular models that could be used to determine when sex and gender differences exist and their effect at the cellular, developmental, organ, organismal, and behavioral levels (IOM, 2001). The report concluded that sex and gender differences are an important human variable and recommended considering sex as a biological variable across the life-span in all biomedical and health-related research and promoting research across different life stages to understand the effect of sex differences on health, illness, and longevity.

Building on that 2001 report, in 2010, IOM released Women’s Health Research: Progress, Pitfalls, and Promise. This report observed that investing in WHR has led to significant advancements in treating conditions such as cancer and heart disease, and continued efforts should integrate women’s health into all research while focusing on genetic, behavioral, and social determinants (IOM, 2010). It also concluded there was a lack of accounting for sex and gender differences in the design and analysis

TABLE 1-1 Major Events and Milestones in Federal Women’s Health Research (WHR)

NOTES: ARPA-H = Advanced Research Projects Agency for Health; FDA = Food and Drug Administration; FY = fiscal year; GAO = Government Accountability Office; HHS = Department of Health and Human Services; NIH = National Institutes of Health; ORWH = Office of Research on Women’s Health; RCDC = Research, Condition, and Disease Categorization; WHI = Women’s Health Initiative. Table 1-1 was updated after release of the report to correct the descriptions of four milestones (1986, 2016, 2017, 2019).

SOURCES: Adapted from IOM, 2010; additional information from: FDA, 2024; NASEM, 2022b; ORWH, n.d.-c; Society for Women’s Health Research, n.d.

of studies and of reporting on sex and gender differences, problems that persist in research today. The report discussed how disadvantaged women require targeted research to address their disproportionate health burdens. In addition, it concluded that women’s quality of life needs more attention from researchers, emphasizing wellness and non-mortality outcomes, and recommended that cross-institute NIH initiatives should explore the common factors influencing multiple diseases in women.

Ovarian Cancers: Evolving Paradigms (NASEM, 2016) and Enhancing NIH Research on Autoimmune Disease (NASEM, 2022a) focused on health conditions that are female specific or disproportionately affect women. These two reports concluded that sex differences remain a gap in health research and highlighted the need for more women-centric research. Advancing Research on Chronic Conditions in Women, released in July 2024, reviewed the evidence on select chronic conditions, including female-specific and gynecologic conditions and chronic conditions that predominantly affect women or affect them differently. Referencing many reports on related topics in WHR, it concluded that significant gaps persist across the research continuum, from basic science to population health, and continue to hinder prevention, diagnosis, treatment, and management of chronic conditions in women (NASEM, 2024b).

Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups (NASEM, 2022b) and Advancing Clinical Research with Pregnant and Lactating Populations: Overcoming Real and Perceived Liability Risks (NASEM, 2024a) both highlight the gaps in scientific knowledge about the applicability and effectiveness of medical treatments for women, including pregnant women, resulting from a lack of investment in and inclusion of them in clinical trials. Furthermore, several reports over the past several decades have identified gaps in knowledge about health outcomes, health predictors, and effective translational research for multiple relevant subgroups, such as ethnically minoritized women, lesbian and sexually minoritized women, gender minorities, and intersex populations (IOM, 2001; NASEM, 2020, 2022b,c). These reports, including Understanding the Well-Being of LGBTQI+ Populations; Measuring Sex, Gender Identity, and Sexual Orientation; and Lesbian Health: Current Assessment and Directions for the Future, provide recommendations that highlight the ways sex, gender, and gender identity are relevant to effective population research and indicate multiple gaps in our understanding and financial investment, including parenting and pregnancy, aging, and menopause (IOM, 1999; NASEM, 2020, 2022c).

While the United States has made some progress in addressing the research gaps identified in these reports concerning women’s health, and some of these recommendations have been put into action, both this report and recent others on autoimmune diseases and chronic conditions in women underscore that substantial progress is still required. The historical and

ongoing investment in consensus studies and reports that assess, respond to, and seek to increase WHR provide an important foundation to this report. Moreover, the consistency in their recommendations and calls to action over the years indicate that significant changes are needed to move the needle on increasing and improving science to benefit women’s and girls’ health.

Recent Relevant Actions and Reports by Nonprofits and Research Institutes

Recently, women’s health has garnered a great deal of attention from a variety of organizations. This work has identified research gaps, exploring the depth of the gap in women’s health, analyzing the cost of addressing women’s health needs, and newly funded activities aimed at advancing women’s health.

In 2022, RAND released a series of reports analyzing the effect of increased funding for WHR, focusing on brain health, immune and autoimmune diseases, and CVD (WHAM, n.d.). Using microsimulation models, the study assessed the societal cost of increased funding in rheumatoid arthritis (RA), coronary artery disease (CAD), and AD and AD-related dementias (ADRD) (Baird et al., 2021b,c, 2022). RAND calculated the potential benefits of doubling NIH funding over 30 years, with the assumption that current investments start yielding benefits after 10 years. The reports found that investing in WHR yields higher returns than general research and that small health improvements from increased funding lead to significant savings, such as increased life years, reduced disease years, and enhanced work productivity. It estimates that investing in research in each of these disease areas could generate significant returns in terms of cost savings: $930 million for AD/ADRD, $1.9 billion for CAD, and $10.5 billion for RA (Baird et al., 2021b,c, 2022). The study underscores the potential for significant societal benefits from increased investment in WHR, suggesting that such investments can yield greater gains compared to general research. By using extensive national data on the costs of care and the impact on labor force participation of patients and caregivers and making extremely conservative estimations of the impact of increased investment in research on age prevalence of disease, disease trajectories, and health-related quality of life (a 0.01 percent improvement in each for CAD and ADRD), the study was designed to estimate whether investments in research on women’s health would pay for themselves over 30 years by improving survival, reducing disability, and reducing health care and associated costs. For high-impact diseases, these investments greatly exceed that bar. Choosing to only look at return on investment makes it unlikely that the full benefits of improving women’s health are realized in the analysis and does not take into account women’s other contributions to the economy or the nonmedical costs of these diseases beyond caregiver labor force participation.

The Women’s Health Innovation Opportunity Map 2023, developed by the Bill & Melinda Gates Foundation and NIH, identifies 50 critical opportunities to drive innovation and improve women’s health. The Innovation Equity Forum calls on stakeholders across the research and development ecosystem to act on these opportunities for equitable, high-return innovations (see Box 1-2 for a summary of the recommended research areas) (Bill & Melinda Gates Foundation and NIH, 2023).

The McKinsey report Closing the Women’s Health Gap: A $1 Trillion Opportunity to Improve Lives and Economies highlights the significant disparities in women’s health and outlines the potential economic and social benefits of addressing these gaps (World Economic Forum, 2024). Despite living longer than men, women spend more years in poor health, leading to considerable losses in productivity and quality of life. The report estimates that addressing this gap could boost the global economy by at least $1 trillion annually by 2040. This can be achieved by investing in women-centric research to fill knowledge gaps about conditions specific to women and understanding

sex-based differences in diseases. This report notes that systematic collection and analysis of sex-, ethnicity-, and gender-specific health data are crucial for accurately representing women’s health burdens and evaluating intervention impacts. To enhance access to gender-specific care, the report emphasized that it is essential to improve access to prevention, diagnosis, and treatment tailored to women’s needs. Establishing policies and financial incentives that support women’s health initiatives can further these efforts.

Many organizations are calling for or investing in WHR. In May 2024, for example, the American Cancer Society announced the launch of the largest-ever study of cancer risk and outcomes among Black women, enrolling over 100,000 participants. It will span 30 years and follow Black women aged 25–55 who have not been diagnosed with cancer, aiming to understand the factors contributing to cancer incidence, mortality, and resilience in this high-risk group. The study will survey participants from diverse backgrounds in 20 states about their behavioral, environmental, and lived experiences, without involving medication, clinical testing, treatment, or lifestyle changes. This research is critical because U.S. Black women face the highest cancer death rates and shortest survival times compared to other racial or ethnic groups, with the reasons for these disparities often remaining unclear (American Cancer Society, 2024).

The Commonwealth Fund’s 2024 State Scorecard on Women’s Health and Reproductive Care also highlights wide disparities in women’s health and reproductive care. The report offers an examination of women’s health care across the United States, reviewing each state on health care access, affordability, quality of care, and health outcomes. The report further notes the need for more rigorous collection of self-reported data on race and ethnicity in medical records and additional research on Black, Hispanic, and American Indian and Alaska Native women, which could improve understanding of the disparities in cancer outcomes in underrepresented communities (Collins et al., 2024).

U.S. GOVERNMENT ACTIONS

The WHR gap is gaining significant recognition by the federal government, including Congress, government agencies, and the White House. Several key actions are described next.

Recent White House Initiatives

White House Roundtable on Maternal Health

In December 2023, building on the White House Blueprint for Addressing the Maternal Health Crisis announced the previous year, the Office of the Vice President convened private-sector leaders for a conversation on

improving maternal and infant health. At the roundtable, administration officials and representatives from health start-ups, insurance groups, digital health technology, investors, and others focused on women’s health and maternal mortality, discussing how the private-sector and public–private partnerships could address these issues to advance equity and improve access to high-quality care.

As part of the convening, the Centers for Medicare & Medicaid Services announced a new model, Transforming Maternal Health, to support state Medicaid agencies in developing and implementing a whole-person approach to maternal health for women with Medicaid and Children’s Health Insurance Program coverage. In addition, Department of Health and Human Services (HHS) officials announced a new maternal health collaborative that would build on efforts across HHS, focusing on data-driven quality improvement in maternal morbidity and mortality postpartum. HHS also announced a Notice of Funding Opportunity for the State Maternal Health Innovation Program aimed to reduce maternal mortality and severe maternal morbidity (White House, 2023b).

White House Initiative on Women’s Health Research

In November 2023, the White House launched its Initiative on Women’s Health Research, led by the First Lady and White House Gender Policy Council (GPC), which the White House established in 2021 to coordinate with its other policy councils and across all federal agencies to support a strategic approach to advancing gender equality and equity (White House, 2023a). Recognizing that women have been understudied and underrepresented in health research, the initiative aims to spur investment and innovation in WHR, close research gaps, and improve women’s health. It involves departments, agencies, and offices across the federal government (see Box 1-3). In February 2024, the First Lady announced its first major output, an investment of $100 million from the Advanced Research Projects Agency for Health for its Sprint for Women’s Health, for work from women’s health researchers and start-up companies unable to secure private funding (White House, 2023a).

Executive Order on Advancing Women’s Health Research and Innovation

In March 2024, the president issued an executive order on Advancing Women’s Health Research and Innovation, outlining new mandates for federal agencies. It calls on all agencies to further integrate WHR in federal research programs and prioritize federal investments in it. It calls specifically for ORWH to create and “co-chair a subgroup of the Initiative to promote interagency alignment and consistency in the development of agency research and data standards to enhance the study of women’s health,” in

collaboration with the chair of the initiative and the director of the Office of Management and Budget (OMB) (White House, 2024a).

As part of this work, the executive order directs OMB and GPC to identify gaps in federal funding for WHR and submit recommendations to the White House for additional funding and programming needed to advance this research. OMB is also tasked with annually reporting on progress made on these recommendations and consulting with federal agencies on funding needed for WHR (White House, 2024a).

TABLE 1-2 NIH Actions on Women’s Health Research (WHR) Related to White House Executive Order

NOTE: This table is not comprehensive; it lists only NIH actions on WHR that were announced concurrently with the Executive Order on Advancing Women’s Health Research and Innovation issued in March 2024.

SOURCE: Information from White House, 2024b.

NIH and Other Agency Actions to Advance WHR

Concurrently with the executive order, agencies also announced new actions in support of WHR (Table 1-2 lists actions announced by NIH). To prioritize and increase investments in WHR, NIH is launching an Institute-wide effort to close gaps in WHR across the life course. It will allocate $200 million of existing NIH funding to this effort beginning in FY 2025, noting that it is “a first step towards the transformative central Fund on Women’s Health” at NIH “to advance a cutting-edge, interdisciplinary research agenda and to establish a new nationwide network of research centers of excellence and innovation in women’s health” across the life-span (White House, 2024b). The NIH Office of the Director (OD), ORWH, and directors of multiple other NIH Institutes will cochair this effort, which will allow for interdisciplinary projects that cut across the Institutes and Centers (ICs), including research on the effect of perimenopause and postmenopause on heart, brain, and bone health (White House, 2024b). In addition, NIH has created a “one-stop shop” where researchers can find all of its current, open funding WHR opportunities rather than having to search across all Institutes (White House, 2024b).⁶

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⁶ See https://orwh.od.nih.gov/research/funded-research-and-programs/funding-opportunities-and-notices (accessed July 26, 2024).

To foster innovation and discovery in women’s health, NIH’s Small Business Innovation Research Program and the Small Business Technology Transfer Program⁷ will increase their investments supporting research and development in women’s health by 50 percent, funding proposals that will help “bridge the gap between performance of basic science and commercialization of resulting innovations” (White House, 2024b). Additionally, NIH is launching a new initiative focused on biomarker discovery and validation research that aims to improve the prevention, diagnosis, and treatment of “conditions that affect women uniquely, including endometriosis” (White House, 2024b).

To expand and leverage data collection and analysis related to women’s health, NIH is launching an effort to standardize these data. NIH will bring together data and scientific experts from across the federal government to develop common data elements that will “help researchers share and combine datasets, promote interoperability, and improve the accuracy of datasets when it comes to women’s health” (White House, 2024b).

NIH will also develop a research agenda on menopause. This effort will use its Pathways to Prevention Program to summarize the current state of research of menopause, identify gaps, and devise a path forward. The program identifies research gaps in areas of broad public health importance, holding workshops to advance knowledge in these areas (ODP, n.d.). NIH anticipates this effort “will help guide innovation and investments in menopause-related research and care across the federal government and research community” (White House, 2024b).

Other federal agencies have also directed funding to advancing women’s health issues as part of the White House Initiative. For example, in July 2024, the Substance Abuse and Mental Health Services Administration announced notices of funding opportunities totaling $27.5 million aimed at improving women’s behavioral health. These opportunities include $15 million for the Community-Based Maternal Behavioral Health Services Program, which aims to improve access to evidence-based maternal mental health and substance use treatment. The Women’s Behavioral Health Technical Assistance Center, funded at $12.5 million, works to build the capacity of women’s behavioral health providers, general health care providers, and others involved in the holistic care of women with or at risk for mental health and substance use conditions (HHS, 2024).

Since the White House Women’s Health Initiative and Executive Order on Advancing Women’s Health Research and Innovation were launched at the start of the committee’s work, with concurrent implementation, this report does not build on or assess these efforts, as the administration’s initiatives were in early stages of development.

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⁷ Small Business Innovation Research Program and Small Business Technology Transfer Program are collectively the Small Business Programs. NIH provides funding to early-stage small businesses through these programs. More information can be found at https://seed.nih.gov/small-business-funding/small-business-program-basics/understanding-sbir-sttr.

Recent Congressional Actions

Several recent Congressional actions have also focused on expanding research related to women’s health. For example, in 2021, the House and the Senate appropriations committees requested that NIH develop a conference to assess WHR; Advancing NIH Research on the Health of Women focused on chronic debilitating conditions, maternal morbidity and mortality, and stagnant cervical cancer survival rates as its focus areas related to women’s health (Temkin et al., 2022). The conference report, Perspectives on Advancing NIH Research to Inform and Improve the Health of Women, highlighted the need for clear definitions of chronic debilitating conditions specific to women (ORWH, 2022). It also noted the lack of an NIH Research, Condition, and Disease Categorization (RCDC) code for identifying female-specific research topics in NIH-funded studies. Without a code, it is challenging to quantify research on chronic conditions in women.

The Reproductive Empowerment and Support through Optimal Restoration Act was introduced in June 2024 and is intended to “expand and promote research and data collection on reproductive health conditions” and “provide training opportunities for medical professionals to learn how to diagnose and treat reproductive health conditions.”⁸ The act directs HHS to collect data and issue reports on women’s access to restorative reproductive medicine and infertility care through proper testing, diagnosis, and treatment. It also highlights the use of funding through Title X and the HHS Office of Population Affairs to promote medical training for medical students and professionals to support women with reproductive health conditions and infertility.

In May 2024, 17 senators cosponsored the Advancing Menopause Care and Mid-Life Women’s Health Act,⁹ which authorized $275 million over 5 years to strengthen and expand federal research on menopause, focusing on workforce training, awareness and education, and health promotion and prevention (gillibrand.senate.gov, 2024). The act calls for establishing new RCDC codes for chronic or debilitating conditions related to menopause and midlife women’s health and strengthening coordination within NIH and across HHS to expand research into menopause and midlife women’s health (Murray et al., 2024).

While not directly relevant to women’s health, in May 2024, Senator Bill Cassidy, M.D. (R-LA), ranking member of the Senate Health, Education, Labor, and Pensions Committee, released a white paper with recommendations about how to modernize NIH. The paper recommends that

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⁸ RESTORE Act of 2023, HR 3479, 118th Cong., 1st sess. (May 18, 2023).

⁹ Advancing Menopause Care and Mid-Life Women’s Health Act, S.4246, 118th Congress (2023–2024). [This footnote was changed after release of the report to correct the cited House bill HR6749 to Senate Bill 4246.]

NIH increase its focus on maintaining a balanced portfolio, so all stages of medical research and other public health priorities are funded adequately. This includes “prioritizing work to address diseases of significant unmet need.” The white paper also offers recommendations to improve biomedical research within the agency by streamlining peer review of research, addressing challenges in recruiting and maintaining the biomedical workforce, and expanding collaboration between NIH, other public health institutions, and the private sector (Cassidy, 2024). The paper does not mention women’s health or sex differences research.

In June 2024, House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-WA) also released a proposal to reform NIH that included several policy and structural recommendations (Rodgers, 2024). A key recommendation for structural change was reorganizing the 27 ICs into 15, with a realignment intended to improve coordination around research goals, agendas, and constituencies. This realignment proposes consolidating the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)—which studies certain aspects of pregnancy—with the National Institute on Deafness and Other Communication Disorders into a new Institute for Disability Focused Research, which could significantly impact research on women’s health, in addition to child health and development. The proposal does not mention women’s health or sex differences research. Other policy recommendations include limiting IC leadership terms to 5 years, with two consecutive terms if approved by the NIH director, and limiting grants and awards to primary investigators with no more than three ongoing concurrent NIH engagements.

Summary of Government Actions on Women’s Health

It is encouraging to see increased effort and attention on women’s health in the United States (see Table 1-1). However, such attention has come and gone over time, with many summative reports noting similar conclusions—more research that will expand and improve the knowledge base in women’s and girls’ health is urgently needed. To ensure that current efforts stimulate essential interest and investment in WHR and can create real impact, systemic changes are needed to bring parity to the understanding of and ability to address women’s health with that of men’s health. This report focuses on the pivotal role NIH can play in accomplishing this goal.

WOMEN’S HEALTH AT NIH

The aim of this consensus study was to identify ways NIH could continue to build upon current initiatives and structures and identify needed changes in the interest of optimizing women’s and girls’ health

in the United States. NIH is the largest U.S. government research body, with a budget of $47.1 billion in FY 2024. NIH comprises 27 ICs, each with its own focus and role to advance biomedical research and public health, most of which provide grants to extramural researchers. Though none focuses specifically on WHR, the focus of most ICs includes aspects of women’s health. For example, the National Cancer Institute would have women-specific cancers within its purview. NIH also has Offices that support and coordinate various functions across NIH. Some of these Offices support coordination on specific research topics, and while they do not fund extramural research, they can supplement grants from ICs. (See Chapter 3 for an overview of NIH structure and policies and programs related to women’s health.)¹⁰

In 1990, NIH established ORWH to strengthen research on women’s health conditions, improve representation in clinical trials, and increase the number of women in biomedical careers (Kirschstein, 1991; Pinn, 1992, 1994). Since then, efforts to improve WHR have been ongoing. ORWH continues to be the hub for women’s health at NIH, developing and leading programs and initiatives, such as Building Interdisciplinary Research Careers in Women’s Health and Specialized Centers of Research Excellence on Sex Differences, and overseeing important policies, such as sex as a biological variable (ORWH, n.d.-d). NIH-wide, there is a Strategic Plan for Research on the Health of Women that includes goals such as advancing research on the biological, behavioral, social, structural, and environmental factors affecting women’s health; supporting research on the biology of how sex influences health and disease; and, through training and education, developing a workforce prepared to advance research on women’s health and the science of sex and gender (ORWH, n.d.-b).

THE COMMITTEE’S APPROACH

Definitions and Terms

Terms such as “women,” “sex,” “female,” gender,” and other related concepts are used differently across the population and sometimes misused. Therefore, the committee has defined such terms for the purpose of this report. The definitions for “sex,” “gender,” “women,” “women’s health,” “WHR” (and terms related to these) are discussed next. A full list of report definitions is available in the key terms at the beginning of the report (additional definitions include sexual orientation, sexual and gender minority populations, and structural and social determinants of health).

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¹⁰ This paragraph was updated after release of the report to clarify the scope of NIH ICs.

Sex and Gender

Sex is a multidimensional construct that refers to biological status, based on a cluster of anatomical and physiological traits that include external genitalia, secondary sex characteristics, gonads, chromosomes, and hormones (NASEM, 2022c). It is typically categorized as male, female, or intersex and determined at birth. Some notable characteristics about sex include

• Usually assigned as female or male;
• Most often defined at birth based on visual inspection of external genitalia;
• Traits usually assumed to be unambiguous but may not be;
• Traits usually assumed to correspond to the same sex but may not; and
• Some traits that can change or be altered over time (NASEM, 2022c).

Intersex refers to people whose sex traits do not all correspond to a single sex (NASEM, 2022c).

A female is an individual whose sex traits (see definition of “sex”) include features typically associated with or assigned as female; they typically have any of the following organs or characteristics:

• External genitalia including a vulva, vagina, and/or clitoris; or
• Internal sex organs and gonads including a cervix, uterus, fallopian tubes, or ovaries; or
• Sex chromosome complement that consists of a predominantly X configuration—typically two X chromosomes—in the absence of an active SRY gene.

Female individuals include those who were assigned female at birth and identify as women, men, nonbinary, transgender, genderfluid, and/or Two-Spirit. This definition should not be conflated with that of women; though most women are assigned female at birth, many are not. Furthermore, the definition is not proscriptive, exhaustive, or immutable, as indicated in the definition of sex.

Gender is a multidimensional construct that links gender identity, gender expression, and social and cultural expectations about status, characteristics, and behavior associated with sex traits (NASEM, 2022c). “It influences how people perceive themselves and each other, how they act and interact, and the distribution of power and resources in society. Gender identity is not confined to a binary (girl/woman, boy/man), nor is it static; it exists along a continuum and can change over time. There is considerable diversity in how individuals and groups understand, experience, and express gender through the roles they take on, the expectations placed on them, relations with others, and the complex ways that gender is institutionalized

in society” (CIHR, 2023). Gender identity “refers to a person’s deeply felt, internal and individual experience of gender, which may or may not correspond to the person’s physiology or designated sex at birth” (WHO, n.d.). Gender identities include the following (NASEM, 2022c):

• “Cisgender” (“cis”) refers to a person whose current gender identity aligns with the sex they were assigned at birth.
• “Transgender” (“trans”; not “transgendered”) refers to a person whose current gender identity differs from the sex assigned at birth.
• “Nonbinary” is often used to describe a gender identity that is neither exclusively man nor woman (i.e., outside the gender binary).
• “Genderqueer” describes a person who does not follow gender norms.
• “Genderfluid” describes a person who does not identify with a fixed gender.
• “Two-Spirit” is a placeholder term for specific gender and sexual orientation identities that are centered in Indigenous tribal worldviews, practices, and knowledges.

Gender binary “refers to the concept that there are only two genders, male and female, and that everyone must be one or the other. The concept is also often misused to assert that gender is biologically determined. This concept also reinforces the idea that men and women are opposites and have different roles in society” (NIH Office of Equity, n.d.). Gender expression is how an individual signals gender to others through behavior and appearance, such as clothing and mannerisms. This may be conscious or subconscious and may or may not reflect gender identity or sexual orientation (NASEM, 2022c; NIH Office of Equity, n.d.).

Race and Ethnicity

In discussions of race and ethnicity, this report refers to “racially and ethnically minoritized” individuals and populations rather than “minorities,” recognizing that being minoritized is not about the number of individuals in a population but rather about power and equity (NASEM, 2023).

When referring to specific racial and ethnic populations, this report strives to use language that reflects the preferences of these groups and individuals. However, there is not always consensus on preferred terms, and these preferences may evolve. This report strives to be consistent in its use of the following terms: “American Indian or Alaska Native,” “Asian,” “Black,” “Hispanic or Latino/a/x/e,” “Native Hawaiian or Pacific Islander,” and “White” (NASEM, 2023). When describing data from cited studies, however, terminology from source papers is used, introducing differences in language throughout the report.

Women, Women’s Health, and WHR

As noted, the committee’s definition of women goes beyond the sex and gender binary and includes all people who identify as a woman or girl, solely or in addition to other gender identities, regardless of biological sex traits. This inclusive definition recognizes individuals who have been or may be affected by a set of biological and social variables that influence women differently than men across the life course (NASEM, 2022c, 2024b).

Women’s health includes physical, biological, reproductive, psychological, emotional, cultural/spiritual health and wellness across the life course for more than those identifying as women or girls. It includes the experiences and needs of all people who identify as a woman, girl, female, nonbinary, transgender (men or women), genderfluid, or Two-Spirit or were assigned female at birth (CIHR, 2022).

WHR is the scientific study of the range of and variability in women’s health as defined and the mechanisms and outcomes in disease and nondisease states across the life course. It considers both sex and gender and how these affect women’s health and well-being, disease risk, pathophysiology, symptoms, diagnosis, and treatment. This work also addresses interacting concerns related to women’s bodies and roles and social and structural determinants and systems (CIHR, 2022).

Approach to Recommendations

Given the scope of WHR, the committee could not review every condition that is female specific, is more common in women, or affects women differently. Instead, the committee reviewed a range of women’s health conditions in these categories to identify the types of research gaps across WHR. These examples provided insight into the research enterprise and allowed the committee to identify types of research NIH should prioritize. The committee also leveraged recent evidence-based reports that reviewed the state of WHR and identified gaps, such as the 2022 National Academies report that reviewed autoimmune diseases and the 2024 report on chronic conditions in women (NASEM, 2022a, 2024b). The recommendations were also informed by the committee’s funding analysis of WHR at NIH (see Chapter 4 and Appendix A) and review of the NIH WHR structures, policies, and programs.

Report Guiding Principles

The committee’s makeup reflects a variety of disciplines and perspectives, as does the approach it took to understand the mechanisms that shape women’s health and research. It was guided by a broad range of considerations, including of sex and biology, the sex-gender system, and the role of gender on social position. The gender system and health framework in Figure 1-3 reflects this variety of perspectives the committee brought to its task (Heise et al., 2019).

Heise Framework

The Heise sociological framework on the gender system and health provides a comprehensive conceptualization of the profound hierarchy of sex and gender and how these systems are associated with health inequities and outcomes (Heise et al., 2019). It includes the distinction between health differences arising from biological sex, including sex-linked cancers, such as ovarian versus prostate cancer, compared to health inequities that originate from gender inequity and other social hierarchies, not sex.

Sequentially, the framework begins with the biological basis for sex, including the genetic, hormonal, and phenotypic characteristics with which every human is born (Heise et al., 2019). After birth, humans operate in a gender system that includes interlocking levels of society that socially produce gender. These levels include the family, community, institutions, and structures and policies that both formulate and reflect power and norms in societies. The structural inequities at each of these levels co-occur with the social production of gender and have been similarly characterized in several National Academies reports, such as Communities in Action: Pathways to Health Equity (NASEM, 2017) and Federal Policy to Advance Racial, Ethnic and Tribal Health Equity (NASEM, 2023). These reports describe how structural inequities, biases, and socioeconomic and political drivers impact health equity and SDOH, including education, neighborhood/built environment, social/community context, economic stability, and health care access and quality.

Once gendered, humans are subject to a social position, where intersecting identities such as race, ethnicity, class, sexual orientation and gender identity, age, disability status, immigration status, and sex establish a hierarchy. These gendered social positions produce differential positive and negative exposures leading to health or disease and gendered health behaviors, access to care, health systems, research, institutions, and data collection. These multiple and gendered pathways occur and evolve over the life course and are embodied cumulatively, resulting in poor health and health inequities. Embodiment may refer to the cumulative burden of gender over the life course that may be measured, for example, in the form of stress and allostatic load as a precursor to autoimmune diseases (Krieger, 2001; Mair et al., 2011; Petteway et al., 2019; Rodriquez et al., 2019). The framework also acknowledges the interaction between each of the five main model components and structural and social determinants of health. Each SDOH is gendered, as socioeconomic status, food insecurity, and housing, for example, differentially affect women at the population level, and contribute to health outcomes (WHO, 2008).

The domains detailed in this framework identify the range of women’s health issues and factors affecting women’s health in the United States, provide a road map for the areas of research needing support from NIH, and highlight factors, particularly structural ones, that may affect participation in the scientific workforce.

Sex and Biology

Sex-specific factors, such as genetics, hormones, organs, biology, and physiology, are important contributors to disease. Basic science in this domain would include studying the normal hormonal changes occurring over the life-span across the types of factors the Heise framework details—genes, hormones, genitals, and body features, for example—and associated with puberty, menstruation, perimenopause, and menopause as physiological stages universally affecting approximately half of all humans (see Chapter 5 for more information on hormones over the life course in women). Similarly, fertility-related issues, such as contraception and fecundity, abortion, pregnancy, lactation, biological mechanisms underlying the onset of labor, and breastfeeding, are commonly experienced phenomena among women and contribute to a significant burden of morbidity.

Hormone therapy, including estrogen and testosterone use, and surgical procedures related to transgender health care are crucial dimensions of women’s health. Other important lines of inquiry in this domain include breast, uterine, vaginal, ovarian and cervical cancer, endometriosis, PCOS, vulvodynia, pelvic inflammatory disease, and pregnancy-related conditions, such as preeclampsia, preterm birth, and other contributors to morbidity and mortality in women. In addition to conditions such as these that are primarily sex specific, biological research in this domain includes basic science research on conditions that predominantly affect women or girls, such as myalgic encephalomyelitis and chronic fatigue syndrome, RA, osteoporosis, migraines, and fibromyalgia (Al-Hassany et al., 2020; Alpizar-Rodriguez et al., 2017; Arout et al., 2018; Deumer et al., 2021; Zhang et al., 2024).

The study of sex differences is another aspect of research on the biological components of women’s health (Galea et al., 2020; McCarthy, 2024; Reue, 2024). For example, research has found sex differences in the role of estrogen in neuropsychiatric disorders, diabetes and its complications, physiological responses to cardiovascular pathophysiology, and CVD outcomes (Corbi et al., 2024; Gao et al., 2024; Iqbal et al., 2024; Merone et al., 2022; Ndzie Noah et al., 2021). Research that includes and examines differences between male, female, and intersex populations would help with understanding variations in physiological, epigenetic, and other biological pathways producing differences in health outcomes.

Sex-Gender System

It is important to distinguish between sex and gender in understanding risk factors and precursors to health inequities for women (see Figure 1-4). As noted, sex refers to biology, based on a cluster of anatomical and physiological traits that include external genitalia, secondary sex characteristics, gonads, chromosomes, and hormones (NASEM, 2022c). Gender, on the other hand, refers to the social status and power ascribed to people based

on actual and assumed sex characteristics, including norms, behaviors, and associated roles. Both sex and gender are critical to WHR but play different roles. The locus of power lies with the creation of a hierarchy of gender, and this extends to those who do not ascribe to traditional binary sex-gender identities and expressions. These norms and power structures operate at the family, community, institutional, and structural/policy levels. Marginalization of women and gender minorities needs to be addressed to ultimately improve health. This includes social and structural factors, such as gender-based violence, employment policies/norms, parental and caregiving leave, representation of women in government and leadership, and equal pay.

Gendered Social Position

Intersectionality describes how different dimensions of social status and positioning overlap and interact (see Figure 1-5). Several National Academies reports have relied on intersectionality frameworks to ground an analysis of how the impact of a central social status (in this case, woman or female) on health is impacted by the multiple other social statuses held by a person (NASEM, 2020, 2023). The general concept of intersectionality and what it represents in the United States is rooted in the writings of Black and Chicana feminist activists from the 1970s and 1980s, many of them lesbian identified (Combahee River Collective, 1977; Moraga and Anzaldúa, 1983; Smith, 1983). As an academic term, “intersectionality” was initially coined in critical race studies to describe the position of Black women in U.S. culture and specifically employment settings (Crenshaw, 1989). Intersectionality and similar concepts have been further explicated by multiple authors across several disciplines (Battle and Ashley, 2008; Collins and Moyer, 2008; Comas-Díaz and Greene, 1994). It can be applied across multiple dimensions of social status and positioning, including LGBTQIA+ identity

and status (Agenor et al., 2019; Bowleg, 2012; Lett et al., 2020), disability (Brown and Moloney, 2018; Warner and Brown, 2011), age (Holman and Walker, 2021; Thomas Tobin et al., 2023), weight (Latner et al., 2014; Panza et al., 2020; Reece, 2018; Wilson et al., 2011), and class or socioeconomic status (Homan et al., 2021; Iyer et al., 2008). The concept is an important consideration for women’s health and WHR, since the health of women and female individuals is affected by not only their sex and/or gender but also these other various aspects of social status.

STUDY PROCESS AND REPORT OVERVIEW

Information-Gathering Process

The committee gathered information in a variety of ways (committee biosketches are available in Appendix D). It held five information-gathering sessions between December 2023 and May 2024 (agendas are available in Appendix C; meetings were virtual or hybrid) on a range of topics, including the state of women’s health; an overview of relevant NIH processes,

programs, and structures; the state of the science on several areas of WHR; and workforce issues. In addition, the committee heard from interested members of the public at its meetings (see next section for more information). Proceedings of a workshop in brief were developed for the 2-day information-gathering meetings in January and March 2024 (NASEM, 2024c,d). The study’s online activity page also informed the public about its work.¹¹

The committee examined the literature on WHR to identify research gaps and barriers to such research. The committee was not charged with undertaking a systematic review but to identify research gaps and mechanisms to advance WHR at NIH. The committee conducted a review to gather such information from the peer-reviewed and grey literature (i.e., materials such as government reports, technical reports, white papers), and drew from comprehensive reviews of the evidence and recent National Academies reports. In addition, the committee used data from the NIH RePORTER¹² database to identify funding on WHR at NIH (see Chapter 4 and Appendix A for a description of this process).

Summary of Public Comments

Over the course of the study, the committee received input from patients, clinicians, researchers, advocacy organizations, philanthropies, and others, in both writing and verbal presentations.¹³ The committee solicited public comments via the project website and listserv and heard from individuals at its information-gathering meetings. It asked for input on the following and any other aspect of its charge, with a focus on how NIH could better meet the needs of women, per its purview (see summary of comments received in the next section):

• What does “women’s health” mean to you? What are important considerations for how to define women’s health and WHR?
• What are the knowledge and research gaps in women’s health and WHR? What are the barriers to filling these gaps?
• What should be the most important considerations NIH should use in prioritizing the research on women’s health it supports?
• From an equity perspective, what improvements can be made to NIH processes to advance health and gender equity in its research investments?

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¹¹ See https://www.nationalacademies.org/our-work/assessment-of-nih-research-on-womens-health (accessed June 19, 2024).

¹² See https://reporter.nih.gov/exporter (accessed June 19, 2024).

¹³ Public access materials can be requested from PARO@nas.edu.

• How can NIH training and education systems and programs be improved to build and maintain a robust WHR workforce? What are the barriers and opportunities within the current programs?
• How do the structure, systems, and review processes of NIH affect the type of and level of investments in WHR? How could these systems be strengthened and improved to better support advances in women’s health?

The committee received over 90 written and verbal responses that covered many topics and included background information on the state of women’s health. Many expressed concern about the lack of a clear definition of women’s health, leading to misunderstandings of terms such as “more common among women” or “differently impact women.” Commentors also raised concerns that among conditions that affect both men and women, sex differences are not communicated.

The comments highlighted the gap in knowledge on women’s health, specifically in areas such as major life stages, including puberty, pregnancy, menopause, and aging; perinatal mental health; maternal mortality; endometrial cancer; pelvic floor disorders; menstrual pain; migraines; lung cancer; shifts in estrogen during the life course; postpartum depression; PMDD; vulvodynia; PCOS; endometriosis; and fibroids. Another concern expressed was the underrepresentation of women in clinical trials for certain health conditions, resulting in a lack of gender-specific details in evaluated outcomes. A large proportion of the public comments (39) addressed the lack of funding for WHR. Many expressed that the research gaps will not be resolved if funding levels are not increased.

Commentors also raised critical needs of the women’s health workforce. They discussed how the NIH WHR workforce is not adequately supported, and researchers interested in women’s health are instead turning to other areas of study that have a steadier stream of funding. They also noted the need to increase funding and diversity of the workforce. Regarding the intramural NIH workforce, commentors noted the lack of development internally, lack of training on women’s health and sex differences, and need to hire and retain people with women’s health expertise. An additional highlighted challenge was the lack of alignment between priorities and research needs across Institutes and study sections for women’s health, such as at the National Institute on Aging, NICHD, and National Institute of Diabetes and Digestive and Kidney Diseases. Suggestions to advance the workforce included recruiting more experts in women’s health, particularly in obstetrics, to NIH by expanding fellowship opportunities and ensuring that grant mechanisms prioritize WHR. Others recommended expanding funding and mentorship opportunities for early- and mid-career researchers, integrating research training in postgraduate medical education, and investing in

a physician-scientist workforce specializing in women’s health conditions, such as pelvic floor disorders.

In addition, the committee received many comments regarding the structure of NIH and how to improve it to advance women’s health. Commentors suggested addressing structural barriers, promoting interdisciplinary collaboration, and investing in a dedicated research infrastructure aimed at enhancing research capacity and improving women’s health outcomes. Commentors also suggested NIH’s structure and review processes should better reflect women’s health concerns, including establishing dedicated ICs, transparent funding tracking, and experts who would be better able to appreciate the innovation and methodology in women’s health applications on study sections. Several commentors emphasized the need to address the scientific scope of study sections and their performance to ensure the identification of the most impactful applications.

Many commentors highlighted areas of women’s health that lack funding to meet research needs and have a substantial effect on quality of life. For example, one noted that endometriosis research funding, which affects about 10 percent of females, is $2 per patient for women, girls, and nonbinary individuals, in comparison to diabetes funding, which affects about 3–7 percent of reproductive age women, which is $31 per patient, or 1,500 percent more, for the same peer group (Azeez et al., 2019; Ellis et al., 2022). Another noted that while chronic vulvovaginal pain significantly impacts quality of life of U.S. women and chronic pelvic pain accounts for 10 percent of all gynecology office visits, both are understudied (Carter, 1999). A patient advocate described how, although many “women in the United States will develop chronic vulvovaginal pain in their lifetime, these conditions are understudied, underfunded, and generally misunderstood and ignored by medical research institutions.”

A large proportion of comments highlighted how the knowledge gap on women’s health conditions leads to suffering, noting that a “lack of effective treatment options combined with diagnostic delay takes a toll on our hospital systems when patients show up repeatedly with the same symptoms and their gynecologists aren’t prepared to treat them” and “women’s health has suffered due to historical underinvestment and persistent bias that favored the study of male research subjects.” Many comments were sobering, emphasizing the impact of these conditions and the gaps in knowledge and treatment on the lives of patients. Several of these examples are presented throughout the report.

Report Overview

In this report, the committee reviews the state of WRH and NIH structures, systems, policies, and processes that could be improved to ensure a robust WHR infrastructure; assesses NIH’s investment in WHR over the

past 11 years; and reviews the state of research on women’s health. The committee highlights women’s health research-related activities at NIH throughout the report as examples; however, due to the breadth of its mandate, the report does not attempt to enumerate every relevant funding opportunity, program, or policy.¹⁴ Chapter 2 provides an overview of why research on women’s health is needed. Chapter 3 discusses the NIH structure, policies, and programs that are relevant to WHR, such as the Sex as a Biological Variable policy and peer review process. Next, the committee reviews the process NIH uses to track funding on conditions and diseases and presents the findings of its funding analysis (Chapter 4). The biological basis for women’s health through the lens of chromosomes and hormones is reviewed in Chapter 5, and the structural and social drivers of women’s health outcomes are discussed in Chapter 6. While it was not possible for the committee to review every condition in depth, in Chapter 7, it presents a framework for quantifying and categorizing health conditions that affect women’s morbidity, mortality, and quality of life in different ways and selects exemplars to illustrate pressing needs for further investment in WHR. Chapter 8 provides an overview of the NIH extra- and intramural workforce and discusses barriers and opportunities to growing a robust WHR workforce. The report ends with the committee’s conclusions and recommendations based on its findings in Chapters 2–8 (Chapter 9). The committee identified five steps Congress and NIH should take to advance WHR:

1. Create pathways to facilitate and support innovative and transformative research for women’s health;
2. Strengthen oversight, prioritization, and coordination for women’s health research across NIH;
3. Expand, train, support, and retain the women’s health research workforce;
4. Optimize NIH programs and policies to support women’s health research; and
5. Increase NIH investment in women’s health research.

CONCLUDING OBSERVATIONS

Advancing women’s health has far-reaching benefits for families, communities, and society. Healthy women are pivotal for nurturing strong family units, thriving communities, and economic growth. However, the gaps in WHR underscore the urgent need for a concerted and sustained investment and efforts to advance this research. By prioritizing and investing in WHR and improving our understanding of the chromosomal, hormonal,

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¹⁴ This sentence was added after release of the report to clarify the content of the report.

and gendered impacts on health, better prevention, diagnosis, and treatment interventions to support women’s health and well-being can be offered. This is needed to inform and empower women to make decisions about their health, leading to better outcomes and improved quality of life. This collective action is essential for achieving health equity and ensuring that all individuals, regardless of gender, can thrive and contribute actively to society.

REFERENCES