Advancing Research on Chronic Conditions in Women (2024)

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7 Chronic Conditions in Women and the Structural and Social Determinants of Health STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH As discussed in Chapter 2, health outcomes are the result of an intricate web of interacting and intersecting contributing factors that include a biologic makeup, life experiences, and access to services that can promote health (see Figure 2-1). Chapters 5 and 6 focused mainly on the biology of and clinical research on chronic conditions that are female specific, predominantly impact or affect women differently. This chapter reviews how the structural 1 determinants, most notably sexism, and social determinants of health (SDOH) affect the onset, presentation, and treatment of these conditions. Although research on how the structural and social determinants of health affect health outcomes and can contribute to health disparities is robust (NASEM, 2017, 2019, 2023), the research specifically on chronic conditions in women is uneven. Some chronic conditions, such as fibromyalgia and vulvodynia, have almost no research, others have research on the effects of some of the contributing structural and social determinants of health but not others. Based on the research, the committee found that many of the contributing structural and social determinants of health are similar across conditions. Therefore, the aim of this chapter is to introduce these determinants or factors, demonstrate how they often intersect and can both support and exacerbate chronic conditions in women, and highlight the research gaps across these conditions. Structural Sexism As discussed in Chapter 2, sexism refers to systematic gender inequities among men and women (Kreiger 2003). Structural sexism pertains to institutional discrimination, evident in laws, 1 As stated in Chapter 1, the committee applied the concept of structural determinants of health as the “macrolevel factors, such as laws, policies, institutional practices, governance processes, and social norms that shape the distribution or maldistribution of the social determinants of health, which include housing, income, employment, exposure to environmental toxins, and interpersonal discrimination, across and within social groups” (NASEM, 2023). This chapter addresses structural sexism, other structural determinants are addressed in Chapter 1. PREPUBLICATION COPY: UNCORRECTED PROOFS 

2 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN policies, or rules (Krieger, 2014). Researchers have begun to focus on the impact of structural sexism/gender inequality on health (Homan, 2019). Studies have examined the impact of structural sexism on health, access to health care, use of preventive health care, c-section rates, breastfeeding and disordered eating. One study developed a macro-structural sexism index to characterize gender inequality in major-level social institutions at the state level. Indicators captured political (percent of men in state legislature), economic, cultural, and physical/reproductive (percent of women without abortion access) measures. Study results suggest that exposure to higher macro-structural sexism at the state-level, is associated with chronic conditions, worse self-related health, and worse physical functioning among women (Homan, 2019). Another study examined state-level sexism and health care access and differences by race and ethnicity. Using state administrative data and survey data from the American Medical Colleges’ Consumer Survey of Health Care Access (2014–2019), the study found no association between state-level sexism and access to care for White women, however exposure to higher state-level sexism was associated with more barriers to accessing care for Black and Hispanic women (Rapp et al., 2022). Structural sexism and the use of preventive health care was the focus of another study. Using state-level data and data from the Behavioral Risk Factor Surveillance System (BRFSS), researchers found that women were less likely to seek preventive care in states with more structural sexism, this was also true for men. The finding supports the researcher’s hypothesis that states with higher levels of structural sexism may offer less generous safety-net policies and direct fewer resources to health care, leading to less preventive care use among both men and women (Dore et al., 2024). Researchers have investigated the impact of structural sexism on cesarian sections and breastfeeding. In a study using state level data and 2018 natality data from the National Center for Health Statistics, researchers found that structural sexism was linked to a higher frequency of low-risk c-sections across states. According to the researchers, the study findings support the theory that overmedicalization of birth is a symptom of structural violence and sexism towards women (Nagle and Samari, 2021). In another study, researchers used state-level data and National Survey of Children’s Health data (2016–2021) to examine the impact of structural sexism on the initiation and duration of breastfeeding. Study results showed that children living in states with higher levels of structural sexism had lower odds of being breastfed or breastfed for at least six months (Balistreri, 2024). Disordered eating—chronic dieting, purging, binge eating, and overeating—was the focus of another study evaluating the impact of structural sexism. The study used data from the Growing Up Today study, a cohort of children followed from 1996 to 2016, state-level, and other data sources. Utilizing a subset of data, from 1996 to 2007, the study found that for the total sample of both cisgendered girls/women and boys/men, each added year of living in a high structural sexism state increased the risk of purging, binge eating and overeating, however, the risk increases were larger for girls/women. Further, girls/women who had lived in a high structural sexism state for 4 or more years had an excess risk of chronic dieting, purging, binge eating, and overeating compared to girls/women who had lived in similar states for less than 4 years. Boys/men had an excess risk of binge eating and overeating. These effects were also noted 20 years later at follow-up. One possible explanation suggested for these findings is that in structurally sexist states, experiences of sexual objectification and expectations about appearance may be more common and this may shape how people inhabit and relate to their bodies. Another PREPUBLICATION COPY: UNCORRECTED PROOFS 

STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH 3 explanation suggests that in places where girls/women lack equal political power, access to social and economic resources, and full control over their bodies, they might use beauty to gain social status and this may increase harmful behaviors such as eating restrictions and purging to meet unrealistic standards of beauty (Beccia et al., 2022). Structural Sexism and Health Policy Sexism can significantly influence federal and state health policies including access to care and research funding. The Hyde Amendment is a federal policy that prohibits the use of federal Medicaid funds for abortions except in cases of rape, incest, or life endangerment, however, states can choose to use state Medicaid funds to cover abortions beyond these exceptions (Salganicoff et al., 2020). One study, using national Medicaid population data (2016- 2018), investigated the association of the Hyde Amendment with obstetrical outcomes and found that states with restricted coverage had higher adverse obstetrical outcomes including higher median rates of adolescent, preterm, low birth weight births, and short interpregnancy interval births compared to states providing more comprehensive Medicaid coverage for abortion service (Rodriguez et al., 2023a). In June 2022, the Supreme Court of the United States overturned Roe vs. Wade, which had protected women’s rights to seek an abortion, allowing states to determine if and how to allow abortions. Prior to the decision, some states had already begun to implement more restrictive policies. The Commonwealth Fund conducted a study to assess and compare the status of maternal and infant health in states that had or were likely to have bans or restrictions on access to abortion services with states that were expected to maintain abortion access. Using 2018-2020 data, the study found that states banning or planning to ban or restrict abortion had fewer maternity care providers, more maternity care deserts, higher maternal and infant mortality rates (especially among women of color), higher death rates for women of reproductive age, and greater racial health disparities compared to states where abortion was accessible (Declercq and Zephyrin, 2021). Another study examined the impact of Oregon state’s 2018 policy to expand access to Emergency Medicaid (restricted to non-citizens who qualify for Medicaid) for postpartum care to 60 days postpartum including screenings and care for gestational diabetes. Oregan and South Carolina Medicaid claims data and linked birth certificate data were used to determine postpartum coverage, receipt of a postpartum glucose tolerance test, and new diagnosis of Type 2 diabetes. The study found that Oregon’s expanded postpartum coverage significantly increased the number of immigrant women receiving glucose tolerance tests and being diagnosed with Type 2 diabetes (Rodriguez et al., 2023b). A similar study found that expansion of Emergency Medicaid policy coverage of prenatal and 60 days of postpartum care for immigrant women significantly increased diagnosis and treatment of a perinatal mental health condition (Rodriguez et al., 2024). Structural Sexism and Research Recent studies indicate that gender inequities exist in federal research funding allocations. One study analyzed National Institutes of Health (NIH) funding to assess gender differences in how funds are allocated across diseases. The study found that in cases where a disease mainly affects one gender, funding patterns favored men. Diseases that impact or burden more women tended to be underfunded, while diseases that impact or burden more men tend to be overfunded (Mirin, 2021). Persistent disparities in funding and research resources can lead to PREPUBLICATION COPY: UNCORRECTED PROOFS 

4 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN gaps in the evidence base for screening, diagnosis, and treatment of conditions that are specific to women or disproportionately affect them. There are also impacts to the research and clinical workforce pipeline (Keenan et al., 2023). One study examined the participation trends of women in U.S. based registered clinical trials from 2016 to 2019 in the areas of cardiovascular diseases (CVD), psychiatric diseases, and cancer. Study results showed that although more women now participate in clinical trials, there are still gaps between the trial groups and the patients who will use the drugs or devices studied (Sosinsky et al., 2022). Another study examined the participation of women in clinical guideline panels. It identified 237 guidelines in national general medical journals from Australia, Canada, the United Kingdom, and the United States between June 2014 and June 2021; 3,696 unique guideline panel members participated in the development of the guidelines. Women represented 38 percent of panel members compared to 60 percent men, the gender was unclear in 2 percent of members. Racially minoritized women were even fewer among panel members (Persaud et al., 2022). Exploring gender disparity in authorship of clinical trials and clinical practice guidelines, another study found a persistent gender disparity in the authorship in both (Lohana et al., 2024). The implications of these findings are that women are underrepresented in the clinical trials that contribute to the evidence base used in the development of clinical practice guidelines, further, women’s expertise, perspectives, and insights are underrepresented in the development of clinical practice guidelines that inform the treatment of conditions that are often experienced differently by women than men. Social Determinants of Health Although this chapter discusses the five social determinant of health domains outlined in the Health People 2030 report—economic stability, education access and quality, health care access and quality, neighborhood and built environment, and social and community context— and how as distinct factors they affect chronic conditions in women, these domains do overlap and affect each other. For example, studies have shown that racially and ethnically minoritized women are more likely to have negative interactions with institutions in the prenatal and perinatal periods, and to be underdiagnosed, have poorer psychological well-being, and are less likely to be provided with practical support in terms of lactation, child care, or transportation— these issues span several SDOH (Conteh et al., 2022; Giurgescu et al., 2017; Kemet et al., 2022; Sidebottom et al., 2021). Socioeconomic status, education, gender roles and expectations, and social support can affect the entire spectrum of CVD and stroke from incidence and risk factors to treatment and outcomes (Mehta et al., 2023; Pelletier et al., 2016; Skolarus et al., 2020). Similarly, SDOH affect the risk factors, incidence, and treatment and outcomes of individuals with Human Immunodeficiency Virus (HIV) and substance abuse disorder (SUD) (Cook et al., 2023; van Draanen et al., 2020). Lifestyle and behavior are also shaped by—and cut across—SDOH. For example, studies have demonstrated how factors such as smoking, diet, and lifestyle modify Alzheimer Disease (AD) risk in a sex- and gender-dependent manner (Dhana et al., 2020). This is seen in smoking, which has a stronger association with impaired verbal learning and memory performance in women compared to men (Lewis et al., 2021). A recent systematic review of sex differences in physical activity and incident stroke found a reduced risk with physical activity, with relative risk reductions of 20–40 percent (Madsen et al., 2022). PREPUBLICATION COPY: UNCORRECTED PROOFS 

STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH 5 Economic Stability Economic stability refers to the link between a person’s finances and health and includes such factors as employment, income level, food security and housing stability (HHS). Economic stability can affect chronic conditions in many ways. For example, research has suggested biological and psychological underpinnings as factors behind the association of chronic pain and various aspects of economic stability (Quiton et al., 2020). Based on a systematic review of studies conducted in the United States and other countries, SDOH, such as low socioeconomic status, unemployment, and aspects of social capital such as greater social support, are consistently associated with adverse outcomes in adults with chronic low back pain (Karran et al., 2020). Additional research has shown that individuals who had a low income, more unpaid employment status, and lower education attainment level, and were primarily Black or African American individuals experienced a high severity of pain from chronic lower back issues. Individuals in this group also had worse mental and physical health and were more likely to use prescription analgesics (Huang et al., 2023). Although these effects were experienced differently across racial groups, there were no differences found by sex (Huang et al., 2023). An epidemiological study among aging adults in Baltimore, the Healthy Aging in Neighborhoods of Diversity across the Life Span study, found that sociodemographic factors measured by living in poverty intersect with gender, with women reporting higher pain levels (Quiton et al., 2020). For example, the study found that White women living in poverty were more likely to report pain than White men (Quiton et al., 2020). Research has also shown that socioeconomic status, along with a variety of factors such as racism and health insurance status, is associated with healthcare related disparities for the treatment of headache disorders (Kiarashi et al., 2021). Occupation type is closely linked to both socioeconomic status and the occurrence of pain or injury. Occupational demands from manual labor jobs such as cleaning and construction, where Latina/Latino people represent a large percentage of the U.S. workforce, have increased reporting of pain-inducing injury and experiences of musculoskeletal pain (Bakhshaie et al., 2019; U.S. Bureau of Labor Statistics, 2010; Fernández-Esquer et al., 2020; Tribble et al., 2016; U.S. Bureau of Labor Statistics, 2015). Occupation also presents a challenge to individuals working multiple or off-hour shifts which can affect access to and seeking health care (Meghani et al., 2012). Without a schedule conducive to appointment availability, specialty treatment can be delayed, worsening pain experiences. A handful of studies using data from the Health and Retirement Study have investigated the effects of early and later life socioeconomic status on osteoporosis. One study found that lower levels of childhood and adult socioeconomic status was associated with higher odds of developing osteoporosis (Gough Courtney et al., 2023). “Lower maternal investment,” a term used to describe maternal social capital and that may be linked to childhood behaviors, was linked to greater odds of osteoporosis (Courtney et al., 2023). There is an increased body of evidence that has examined a link between socioeconomic status and menopausal symptoms including vasomotor symptoms (VMS) in women. A recent cross-sectional study enrolled women from various racial and ethnic backgrounds from a telehealth platform who completed an online survey. It found that Black, Hispanic, and American Indian and Alaska Native women with lower socioeconomic status had a greater odds of exhibiting menopausal symptoms compared to White women, the relationship was significant for Black women and the experience of hot flashes (Kochersberger et al., 2024). The Study of Women's Health Across the Nation (SWAN) identified a correlation between VMS associated PREPUBLICATION COPY: UNCORRECTED PROOFS 

6 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN with menopause and various biological factors and SDOH, including income and employment (Gold et al., 2006). For example, stratifying women according to the number of days they reported having VMS identified certain attributes that were significantly correlated with more days of VMS. These attributes included economic factors such as lower income and, unemployment, along with other factors such as less education, smoking status, tobacco smoke exposure, number of premenstrual symptoms, depressive symptoms, anxiety, physical inactivity, higher symptom sensitivity, higher perceived stress, and lower social support (Gold et al., 2006). A secondary analysis of the longitudinal, population-based Coronary Artery Risk Development in Young Adults study identified some of the same early adulthood risk factors as being associated with persistent VMS, including difficulty paying for basic necessities, lower education level, depressive symptoms, and smoking status, as well as others such as migraine (Kim et al., 2024). Overall, more research is needed to understand how race, ethnicity, and access (or lack thereof) to the SDOH confer susceptibilities to VMS severity. Education Access and Quality Access to quality education is associated with general educational attainment, language skill, and literacy factors (CDC, 2023). The relationship between education access and health outcomes is strong and is an important consideration for chronic conditions in women (NASEM, 2017, 2019). For example, in a study including both men and women on the association of educational attainment with chronic disease and mortality in the Kidney Early Evaluation Program, the authors found that higher educational attainment was associated with lower prevalence of several chronic conditions, including hypertension, diabetes, CVD, reduced kidney function, and elevated urine levels of albumin, a sign of kidney disease. Compared with persons who did not graduate from high school, college graduates had a lower odds for each chronic condition, ranging from 11 percent lower odds of reduced kidney function to 37 percent lower odds of CVD (Choi et al., 2011). The Louisiana Osteoporosis Study found that women with a high school degree or some college were 2.68 times more likely to have sarcopenic obesity 2 compared to females with at least a college degree (Jeng et al., 2018). Lower education attainment was also shown to be associated with a greater odds of sarcopenia in the Irish Longitudinal study on Ageing (Swan et al., 2021). One study using data from the National Health Interview Survey examined the effect of education on younger adults and found that women with a General Education Diploma reported higher odds of pain compared to those graduating high school on a standard timeline (Zajacova et al., 2020). A systematic review examining the relationship between education and AD found that lower education was associated with a greater risk of dementia in women; however, only a few studies considered sex differences (Sharp and Gatz, 2011). More recent studies suggest that cognitive reserve may play a larger role. The concept is based on the idea that social and behavioral factors, including education, occupation, physical exercise, and leisure activities or social engagement, contribute to developing more robust neuronal networks (Stern et al., 2020). These networks may help preserve cognitive functions, reduce the risk of dementia, and provide protection even in the presence AD (Nelson et al., 2021; Rawlings et al., 2019). Adverse child events (ACEs) were discussed in Chapter 2 as exposures that can predispose individuals to higher risks for chronic conditions in women. ACEs are briefly noted 2 A combination of obesity and low skeletal muscle mass PREPUBLICATION COPY: UNCORRECTED PROOFS 

STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH 7 here because of the close linkage between ACEs and SDOH, one study using data from the BRFSS found individuals reporting 4 or more ACEs were more likely to report not completing high school (lower education) and household poverty (economic instability). Individuals reporting 3 ACEs or 4 or more ACEs were also more likely to report periods of unemployment (economic instability). Study results were adjusted for sex, but the authors note that ACEs were more prevalent among women than men (Metzler et al., 2017). More recent BRFSS data (2011- 2020) showed ACEs scores greater than 4 to be higher in women (19.2 percent) than in men (15.2 percent) (Swedo et al., 2023). Health Care Access and Quality “…one collected theme…[is] not being listened to enough, not being understood...” –Presenter at Committee Open Session “Gender bias is real… Just remember that impacts women. We have a lot of responsibility on us and we want to live. We want to function.” –Presenter at Committee Open Session Access to health care refers to “the timely use of personal health services to achieve the best health outcomes,” (HHS, 2022; IOM, 1993). Lack of discreet, confidential, and gender- sensitive services keep many women from seeking treatment in the health care system (Adler et al., 2023; Zephyrin et al., 2020). Women may be reluctant to seek care for fear of negative judgment or hostile reactions from service staff. This has been seen for HIV and sexually transmitted infections, where racism, discrimination, and stigma prevent some women from seeking and receiving care (NASEM, 2021; Walcott et al., 2016). Without a diagnosis, women cannot receive timely and appropriate treatment, which can worsen health outcomes. In HIV, for example, this can lead to transmitting the virus to an unborn child or to an uninfected partner if they engage in condomless sexual intercourse or share needles during intravenous drug use. Many women also do not have knowledge of Pre-Exposure Prophylaxis (PrEP). This may be due to their provider lacking awareness to offer PrEP to them, or negative attitudes/stigma from providers about discussing sexual health (Mayer et al., 2020). Mental health conditions and substance use comorbidities also interfere with access to HIV prevention, care, and uptake of and adherence to antiretroviral therapy (ART) and PrEP. Women are more likely than men to experience depression and anxiety symptoms as well as posttraumatic stress disorder and many have experienced intimate partner violence (IPV), factors shown to negatively impact access to HIV testing, access to health care for HIV prevention and treatment, and prescription of and adherence to ART and PrEP (Miller et al., 2021; Waldron et al., 2021). Women with fibromyalgia have also felt misunderstood by health professionals, with difficult experiences navigating health systems with a disorder that is poorly understood and stigmatized (Quintner, 2020). The term “invalidation” can characterize the range of expressions that patients cite, such as denial, rejection, and exaggeration of the symptoms (Galvez-Sánchez and Reyes Del Paso, 2020; Kool et al., 2009). The Illness Invalidation Inventory has been proposed to assess the effect of these negative responses to patients presenting with fibromyalgia (Kool et al., 2014). Gender roles and behaviors may be associated with risk of acute coronary syndrome and major adverse cardiac events in women. One study investigated gender roles measured by gender-related characteristics such as the status of household primary earner, number of hours PREPUBLICATION COPY: UNCORRECTED PROOFS 

8 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN spent doing housework, level of stress at home, and feminine personality traits. Personality traits and social gender roles assigned to women were associated with a greater risk of adverse cardiovascular outcomes in younger women (Pelletier et al., 2016). Women are more likely to underestimate their risk of ischemic heart disease, which can serve as a barrier to seeking care in a timely manner (McSweeney et al., 2016). Delays in seeking care may also arise from a lack of symptom recognition, although a conscious decision to postpone care attributed to female gender behaviors, such as hesitating going to the hospital (Lawesson et al., 2018), and sociocultural influences such as ethnicity, socioeconomic status, and health access (Rosenfeld, 2004), cannot be ruled out (Tisminetzky et al., 2020). Gender roles and behaviors not only contribute to delays in treatment of acute coronary syndrome but may also impact recovery and survival from acute myocardial infarction (Mirzaei et al., 2020). Women are less likely to be referred to cardiac rehabilitation, and when they are, they have lower rates of attendance and completion due to gender roles related to caretaker and single-parent head-of-household, and employment responsibilities (McSweeney et al., 2016). These disparities are more pronounced among racially and ethnically minoritized women. Gender stereotypes contribute to gender biases in clinical practice. These stereotypes influence the biomedical approach of analyzing, interpreting, diagnosing, and treating pain in women. Studies have shown that women’s pain is often underestimated, whereas men’s pain is frequently overestimated and deemed organic (Lloyd et al., 2020; Zhang et al., 2021), the result of health professionals tending to frame women’s pain as amplified by behavior and attitudes considered to be “typical” of women, including heightened emotionality, psychological vulnerability, and dramatization. In clinical settings, this assumption may lead to believing that women are less tolerant of pain and exaggerate their perceptions of it (Colameco et al., 1983; Lloyd et al., 2020). As mentioned in Chapter 2, racial and ethnic discrimination also serves as a structural determinant that results in women of color experiencing inequities. A notable example is perceived pain-related injustices (Aroke et al., 2019; Overstreet et al., 2023). As one research team noted, “pain-related injustice is conceptualized as cognitive appraisals reflecting the externalization of blame and feelings of unfairness about a pain- or injury-related loss, along with the severity and irreparability of the loss,” (Overstreet et al., 2023; Sullivan et al., 2012). Medical injustice against women of color can be traced back centuries (Owens, 2017). Although these medical injustices contribute to a lasting distrust of the medical field, they also inform key, unsubstantiated scripts in modern health care about Black women, such as they have a higher tolerance for pain (Trawalter and Hoffman, 2015). For example, research has shown that clinicians are more likely to prescribe monthly buprenorphine for treating opiate use disorder (OUD) to White women, but refer Black and Hispanic women to daily, mandated, in-person methadone programs (Schiff et al., 2020). The invisibility of pain and its complex pathology may lead to stigmatizing women experiencing chronic pain disorders (De Ruddere and Craig, 2016; Monsivais, 2013). Many of these women report that clinicians did not believe them, and that treatment was delayed or absent (De Ruddere and Craig, 2016; Monsivais, 2013; Samulowitz et al., 2018). Research shows that, compared to men, women receive less intensive and effective pain care, they are less likely to be prescribed opioids and analgesics but more likely to receive antidepressant prescriptions or psychotherapy referrals (Samulowitz et al., 2018; Zhang et al., 2021). Despite the ongoing shift to patient-centered care, Western medicine remains rooted in the theory of biological determinism with strong emphasis on data and statistical evidence to find PREPUBLICATION COPY: UNCORRECTED PROOFS 

STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH 9 answers (Moretti et al., 2023), which can encourage physicians and medical curricula to rely on a highly technical approach that pays insufficient attention to persons with chronic pain, particularly women. In contrast, patient-centered medicine defines pain as a multidimensional experience shaped by several factors, including sex and gender differences, that influence health and the processes of chronic pain (Bartley and Fillingim, 2013; Keogh, 2022). Physicians’ lack of medical training for understanding women’s pain and gender stereotyping contribute to gender biases in treatment (Lloyd et al., 2020; Moretti et al., 2023). Women of color face discrimination in the health care system when diagnosing and treating premenstrual dysphoric disorder (PMDD) (Pilver et al., 2011). Discrimination due to gender and race and the intensity of it each independently increased the chance of PMDD (Pilver et al., 2011). In addition, cost and limitations in insurance coverage for contraceptives, among the first-line treatments for PMDD and premenstrual syndrome, are significant in restricting access to effective treatment (Grady et al., 2015). Black, Hispanic, and sexual minority women are less likely to receive contraception or counseling for it from a healthcare professional (Everett et al., 2019; Grady et al., 2015). These disparities have also been attributed to differences in socioeconomic status and discriminatory practices (Grady et al., 2015). Black, Asian, and Hispanic women are also more likely to report misgivings about the purpose of contraception and negative interactions with health care professionals impacting contraception use (Agénor et al., 2021; Logan et al., 2021; Shih et al., 2011). Given the various types of discrimination women may face and the differential experiences of diverse racial and ethnic groups, it is essential that treatment is tailored to include solutions for structural and health inequities that contribute to PMDD prevalence. Comorbid mental disorders, stigma, discrimination, and the effects of gender-affirming hormone therapy are proposed factors that affect migraine prevalence and treatment in transgender and gender-diverse individuals. Other than a small number of review articles based on limited older data, studies are limited on this topic (Pace et al., 2021). One group showed that many of these same structural and social factors affect women who accessed infertility care. In addition, given the cost associated with infertility treatment discussed in Chapter 5, access to care is a known factor in the inequities seen along the fertility journey (Kelley et al., 2019). Neighborhood and Built Environment As discussed in Chapter 2, the neighborhoods and built environments where women live affect the availability, accessibility, cost, and quality of community goods and services, as well as environmental factors that (NASEM, 2023) affect health outcomes in a number of ways (NASEM, 2023). For example, more disadvantaged neighborhoods was an independent factor associated with PDD in a cross-sectional study using data from Kaiser Permanente Northern California health care system; this association was pronounced in Black individuals and not significant for Hispanic individuals (Onyewuenyi et al., 2023). Residents in predominantly Black, Latino/Latina, and Asian neighborhoods in California 3 were more likely to have chronic conditions including diabetes, obesity, coronary heart disease, and stroke (Li et al., 2023). In addition, a study on the effect of racial segregation found inequitable access to methadone versus buprenorphine treatment, and that methadone treatment programs were more likely to be in 3 Neighborhoods were defined as comprising greater than 50 percent of the three racial and ethnic groups based on census tracts. PREPUBLICATION COPY: UNCORRECTED PROOFS 

10 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN highly segregated African American and Latino/Hispanic communities and facilities providing buprenorphine in predominantly White counties (Goedel et al., 2020). U.S. stroke incidence and mortality also differ by geography, a key social determinant of cerebrovascular disease (Levine et al., 2018). Centers for Disease Control and Prevention data indicate that stroke mortality is approximately 30 percent higher in the region of the United States in the “stroke belt and stroke buckle,” an 11-state region in the southern, southeastern, and midwestern United States (Tsao et al., 2023). Data are limited on chronic conditions in women who live in rural areas. One study showed that parenting women who had a perceived need for SUD treatment and were living in rural counties had a 90 percent lower odds of utilizing treatment compared to those living in urban counties (Ali et al., 2022). Another study showed that rural communities face difficulties accessing headache care because of unequal distribution of headache specialty facilities (Kiarashi et al., 2021). Impoverished neighborhoods contribute to the burden of stressful experiences for both women and men (Maly and Vallerand, 2018) via residents’ decreased feelings and experiences of safety in their environment, limited access to healthy food choices and health care, and physical and social isolation. Research has found that increases in these stressors lead to hypersensitive stress responses over time, adversely affecting chronic pain (Hanley et al., 2011; Hruschak and Cochran, 2017). In addition to the environment’s effect on stress and isolation, living in high- poverty neighborhoods over the life course has been found to have a detrimental impact on physical health in midlife (Yang and South, 2020). Individuals living in poverty have an increased occurrence of pain resulting from the associated physical and economic barriers (Maly and Vallerand, 2018). Impoverished neighborhoods tend to have limited access to specialty pain care and treatment access, compounded by lack of transportation and occupational barriers. The disparity in the experience of chronic pain in individuals of low socioeconomic status living in poverty has been well documented (Tait and Chibnall, 2014). Although opioids are not first-line treatments for chronic pain, minoritized individuals in impoverished urban neighborhoods experience a double burden of disparity regarding opioid access. Even if they are prescribed opioids, pharmacies in zip codes with a predominantly minoritized population report insufficient supplies compared to zip codes with a predominantly non-Hispanic White population (Green et al., 2005). Physical aspects of the environment, such as exposure to air pollution, have been associated with higher likelihood of cognitive impairment and AD (Iaccarino et al., 2021). Certain racial and ethnic groups are disproportionately affected by exposures to harmful pollutants. For example, African American people are more likely to live near particle-emitting facilities in urban areas, which may be a contributing factor to their greater prevalence of Alzheimer’s disease. Research has found that Black women are exposed to more particulate matter than White women and the association between such exposure and AD for Black women was approximately twice as large, even after adjusting for age, region, socioeconomic factors, lifestyle factors, cardiovascular risk factors, and stressful life events (Younan et al., 2022). The authors of this study suggest that the exposure to air pollution caused by neighborhood segregation may be a contributing factor to the increased risk of AD in African American women (Woo et al., 2019; Younan et al., 2022). Several studies have investigated population-level strategies to counter the predisposing effects of built environments on AD. In the Nurses’ Health Study, creating and using more green spaces in urban settings was associated with better cognitive scores and psychomotor speed and attention in a cohort of women. However, as 98 PREPUBLICATION COPY: UNCORRECTED PROOFS 

STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH 11 percent of study participants were White, it is unclear if these findings can be applied to all women (Jimenez et al., 2022). Physical activity is an important lifestyle behavior that is associated with the developing and managing osteoporosis and other chronic conditions in women. Neighborhood environment plays a role in enhancing physical activity levels based on how walkable one’s neighborhood is or amount of green space available (Zhu et al., 2023). One study found that neighborhood factors such as neighborhood socioeconomic status (poverty level), neighborhoods built in 1950-1969, and proximity to business and facilities influence the physical activity levels of postmenopausal women (King, 2005). Another study showed that greater neighborhood walkability and green space in China were associated with fewer fractures; more studies addressing these issues are needed in the United States (Zhu et al., 2023). Social and Community Context Healthy People 2030 notes that “relationships and interactions with family, friends, coworkers, and community members” and “the social support [one needs] where they live, work, learn, and play” are important factors in determining health outcomes (HHS, 2020). In the social and community context, social connection is thought to be a protective factor for depression, either preventing it or contributing to better response to treatment. Being married is associated with better prognosis of depressive symptoms than being single (Buckman et al., 2021). Attachment to family, social connections, and religion are protective against suicidal behaviors as well. Maternity leave has also been reported to reduce the occurrence of postpartum depressive symptoms (Chatterji and Markowitz, 2008; Dagher et al., 2014). The criminal legal system—a component of the community context—also affects health outcomes (Duarte et al., 2020; NASEM, 2017, 2023; Sundaresh et al., 2020). Barriers to SUD and OUD treatment in women are numerous and significantly related to structural and social determinants, with incarceration being an important one. For example, over the past 35 years, total arrests have increased 25 percent for women and decreased 33 percent for men. The rise among women is primarily due to drug-related offenses; during this period, drug-related arrests surged about 216 percent for women, compared to about 48 percent for men. Further, most women are less likely to be able to post bond because their income typically falls below the federal poverty level (Herring, 2020). Drug offenses are the most common reason for woman and maternal incarceration in the United States, yet few women are offered treatment during incarceration or after release (Edwards et al., 2022; Staton et al., 2023). If women progress from prescription opioids to heroin or illicit opioid use or injecting drugs, they become immersed in new, unfamiliar social networks and must rapidly learn how to navigate obtaining drugs, inject them safely, and protect themselves from gender-based violence (Springer et al., 2020). Women in these new environments may be at increased risk for physical and sexual abuse and exploitation, which can further perpetuate drug use and put them at risk for acquiring infectious diseases, and expose them to gender-based violence, trauma, stigma, and laws that punish women who use drugs (Springer et al., 2020). Additionally, these women may have less awareness and skills of how to access and navigate health care services and treatment (Martin et al., 2022). Support services for women are another critical aspect of the social and community context. For example, these services are absent or inadequate for women with SUD (Farhoudian et al., 2022), who need to arrange childcare to attend treatment and experience threats of child protective services interventions because they have a SUD (SAMHSA, 2021). Although more PREPUBLICATION COPY: UNCORRECTED PROOFS 

12 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN than 70 percent of women in drug treatment have at least one child, only 6 percent of outpatient programs provide child care and 2.6 percent provide ancillary beds for children (SAMHSA, 2019). Furthermore, women are discouraged from seeking treatment because of fear of losing custody of their children and are often punished for treatment noncompliance by child welfare agencies due to a clinic’s inability to meet their child care needs (Springer et al., 2020). Pregnant women report several barriers to entering treatment, including fear of testing positive for illicit substances that could result in losing custody of their newborn or other children or incarceration (Stone, 2015). Trauma and violence are common occurrences in the lives of women with SUD, particularly with OUD, yet only 24 percent of SUD treatment programs offer services for IPV, and 24.0 percent provide specific interventions for sexual abuse (SAMHSA, 2017). Untreated psychological trauma is a major risk factor for relapse, overdose and suicide, yet only 38.3 percent of SUD treatment facilities/programs always or often offer trauma-specific counseling (SAMHSA, 2017). Related to trauma, research has shown that adverse childhood experiences contribute to frequent headaches and a higher odds of migraine compared to episodic tension-type headache, but the study did not stratify findings by sex (Tietjen et al., 2015). Social isolation has clear gender differences, with older women being disproportionately affected by a lack of social support following stroke. This is largely the result of sex differences in age at first stroke and longer life expectancies in women compared with men. Studies have suggested that social isolation and loneliness are linked to worse stroke outcomes and it can also impact cardiovascular and brain health outcomes (Boden-Albala et al., 2005; Cené et al., 2022; Gronewold et al., 2021). Discrimination and gendered norms also play out in the social and community context. For example, studies and meta-analyses indicate that racially and ethnically minoritized groups who experience pain face complex issues related to the structural and social determinants of health that affect women’s experiences of pain (Overstreet et al., 2023). Researchers have begun to explore the unique role of exposure to discrimination as a contributor to pain severity across various racial and ethnic groups (Dugan et al., 2017). SWAN investigated how discrimination affects women from different racial and ethnic groups, including how it relates to pain (Dugan et al., 2017). Longitudinal data spanning over a decade from its cohort measured everyday experiences of discrimination among five groups of middle-aged menopausal women: White, African American, Japanese, Chinese, and Hispanic. The analysis showed that that experiences of discrimination in African American, Chinese, and White women, reported primarily as resulting from bias related to race and ethnicity, gender, or language, were significantly linked to bodily pain (Dugan et al., 2017). Furthermore, in a community-based study of Spanish-speaking Latino/Latina participants recruited from a federally qualified health center primary care setting, in which 88 percent of the participants were women, perceived racial discrimination was found to affect individuals’ anxiety sensitivity4, leading to greater pain intensity and disability (Bakhshaie et al., 2019). Trauma is an important consideration in the social and community context. As discussed in Chapter 5, vulvodynia needs to be approached from a biopsychosocial perspective, trauma from a wide variety of sources can influence the onset of vulvar pain. Thus, issues related to racism, coping mechanisms, or even stressors due to the built environment could be involved in Anxiety sensitivity is the belief that anxiety and anxiety-related sensation have harmful consequences 4 (Bakhshaie et al., 2019). PREPUBLICATION COPY: UNCORRECTED PROOFS 

STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH 13 its pathogenic mechanism. However, no studies have directly assessed how much the SDOH influence the incidence of this condition. Once difficulty is the need for studies within the general population, as such a large proportion of women do not seek care because of its stigmatizing effect and the false belief that vulvar pain during intercourse is normal. RESEARCH GAPS Research gaps regarding the structural and social determinants of health in chronic conditions in women warrant attention because they affect the development, progression, and management of these conditions across the life course. The gaps identified in this chapter are not exhaustive, but they represent the types of research needed to advance the field’s understanding of how the structural and social determinants of health affect chronic conditions that are female- specific, gynecologic, and conditions that predominantly impact or affect women differently. In addition, for many conditions, such as vulvodynia, menopausal symptoms, and myalgic encephalomyelitis/chronic fatigue syndrome, research is lacking on the influence of the SDOH on their incidence. The social and biological mechanisms that underlie associations of the structural and social determinants of health also require further investigation. Women face several barriers to treatment access in the health care system, stigma, bias, and availability of social services, including child care during treatment and physician visits. A broad range of SDOH and barriers to care and strategies to overcome them need to be evaluated. For example, improving infertility evaluation and earlier intervention to reduce barriers resulting from geography and costs would increase the proportion of women who receive successful care. Given disparities in access, stigma, and knowledge barriers, both the true age-specific prevalence of infertility unknown and the size of the population that would benefit from assisted reproductive technology are unknown (Fauser et al., 2024). Although SDOH affect both women and men, they differ by gender in many circumstances. Thus, how they affect health needs to be better understood in the context of social identities, including gender roles and cultural norms to fully understand the effects on various health conditions, such as CVD and stroke in women (Ospel et al., 2022). Research to elucidate gender differences in access to health services is also needed, such as gender differences in access to HIV testing, PrEP and ART. Patients may not know where to access testing, treatment, and prevention services for HIV. Women in particular face challenges, including lack of transportation, poverty, stigma, racism, and child care duties, that affect access to care and retention on PrEP or ART (Nawfal et al., 2024). Studies do not typically address these issues and only report biological outcomes such as viral suppression or adherence to ART or PrEP without understanding the underlying structural and social factors that affect adherence. These issues apply to many of the other conditions discussed in this report. Research that explores modes of treatment and prevention that may be better suited to women versus men, such as telehealth, mobile health units, peer and patient navigators, community health workers, and pharmacy delivery, and that explores the intersectionality of sex, gender, race, ethnicity, geography, health care insurance, and other social factors that influence women’s access to care could advance the development of tailored care that meets the needs of women (Ford et al., 2021; Vohra-Gupta et al., 2023). Although maintaining a healthy lifestyle can benefit women with chronic conditions, the SDOH can make doing so difficult by reducing the options for access to green space, physical activity, healthy food, and clean air (Duarte et al., 2024). Research is needed to better understand PREPUBLICATION COPY: UNCORRECTED PROOFS 

14 ADVANCING RESEARCH ON CHRONIC CONDITIONS IN WOMEN how SDOH limit access to healthy lifestyle behaviors and develop interventions that increase available options for women (Andermann, 2016; Salisbury, 2020). The disparities and structural and social contexts of chronic pain for women need to be better understood. These factors are often complex and challenging to measure (Macgregor 2023). Research for chronic conditions in women needs to study mechanisms of how structural and social determinants affect chronic pain development or clinical presentation, and the experience of discrimination and chronic pain – most studies only measure perceived discrimination. Although the biopsychosocial model of pain—how interactions among biological, psychological, and social factors contribute to pain outcomes (Engel, 1977; Turk and Monarch, 2002)—has become widespread and broadly accepted, the medical field still prioritizes the biomedical view when considering treatment approaches. A critical downside of that dominant narrative is that it minimizes psychosocial factors with a subsequent lack of funding dedicated to biopsychosocial narratives (Letzen et al., 2022). Data and Related Research Needs Data on health outcomes of chronic conditions based on sex and gender are often not available. This is a critical limitation in evaluating impact of potential interventions. For example, multiethnic longitudinal studies in women on the structural and social determinants of health are needed to explore changes in bone mineral density and risk factors among racially and ethnically minoritized groups. A more robust and interconnected data infrastructure is needed for chronic conditions to support evidence-based policies and better identify improved outcomes associated with medical interventions and policy changes regarding chronic conditions among women. Data exist on those who seek health care, but data are also needed on those who do not. It is difficult without data on the structural and social determinants of health to develop interventions for women with chronic conditions and analyze outcomes. SDOH research designs are fraught with methodologic issues. For instance, community- level randomized designs are rare, and existing evidence is not generally sufficient to make causal conclusions. Many interventions focus on persons who have experienced adverse outcomes such as hospitalization, but pre- and post- assessments without a control or comparison suffer from regression from the mean. Lack of comprehensive data for health and social outcomes and differences in unmeasured characteristics between those who participate in social needs interventions and those who do not are also major gaps. Methods for evaluating SDOH are not the same as those for studies that focus on acute treatment and interventions. Most studies are cross-sectional and do not assess long-term outcomes. For example, research has focused predominantly on short-term outcomes for a single condition, but long-term outcomes and longer follow-up periods are typically needed. This is especially true for medically complex populations such as women with multiple chronic conditions or high health care use. Longitudinal studies are needed to address these gaps in knowledge. Furthermore, multiple chronic conditions, which is discussed in the following chapter, is common and has been increasing over the last 25 years, which has implications for public health policy and anticipated health costs (King et al., 2018). Research is needed to assess the effect of interventions on multiple chronic conditions and determine if studies can assess more than one intervention with scientific rigor. It is important to develop standardized characteristics of structural and social determinants of health, and how researchers report race and ethnicity and how they assess sex PREPUBLICATION COPY: UNCORRECTED PROOFS 

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