8
Non-Communicable and Chronic Conditions
Non-communicable and chronic diseases are rising rapidly and pose trillions of dollars in economic burden, especially in LMICs. Women are disproportionately affected, yet underrepresented and underfunded. Prioritizing sex- and gender-specific R&D, redefining women’s health beyond reproduction, and building evidence on differential risks, symptoms, and treatment responses will impact millions of women globally.
Non-communicable and chronic conditions are diseases that are not transmitted between people, persist or recur over time, and are often not curable.
Amid the growing burden of non-communicable and chronic conditions in high-income (HIC) and low- and middle-income (LMIC) countries, researchers must work to develop new medicines and products that can increase women’s life expectancy and quality of life. Globally, non-communicable and chronic conditions are estimated to cost over US$30 trillion between 2010 and 2030. Further, particularly in LMICs, the potential market size for chronic condition medications and diagnostics far outweighs measured market expenditures, indicating an unmet need for affordable and scalable solutions in low-resource settings. All partners should collectively commit to driving sex- and gender-specific approaches to R&D for chronic conditions.
Chronic conditions frequently affect women both differently and disproportionately, yet existing research insufficiently addresses how women experience these conditions, such as biological and hormonal differences; social and structural factors; and biological embedding—which refers to the impact of life experiences, such as gender inequity, on biology.
For example, despite cardiovascular disease (CVD) being the leading cause of global female mortality, women represent just one-third of CVD clinical trial participants, which greatly limits information available about the disease in and appropriate treatments for women. This underrepresentation is even more significant because CVD symptoms and progression present differently in women than men. Additionally, many diseases that disproportionately impact women are historically underfunded. For example, migraines—which disproportionately affect women—received less than 8 percent of the NIH funding that would be commensurate with the burden of disease. Similarly, gynecologic cancers are underfunded compared to prostate cancer in the US based on lethality. Mental health also lags behind physical health in attention, funding, and action. Researchers estimate that 20 to 25 percent of women in LMICs experience perinatal depression; this poses significant and lasting implications for women’s health and well-being.
Inadequate attention to the unique, women-centric attributes and needs in research and policy has enduring downstream effects. Women may delay treatment due to limited awareness of how diseases present differently. Additionally, therapeutic drugs may enter the market without sufficient testing in women, which can compromise efficacy and safety in women. Prioritizing personalized care, including precision medicine, in R&D can bring technologies and products to market that meet the diverse needs of women. A more equitable R&D agenda will require 1) defining women’s health beyond reproductive and maternal health to include the broad array of non-communicable and chronic conditions throughout the life course and 2) building the evidence base for sex and gender differences in disease risks, symptoms, and treatment response.
Overview Non-Communicable and Chronic Conditions
8.1 Cardiometabolic diseases
Ischemic heart disease, which is caused by narrowed heart arteries that limit blood and oxygen flow to the heart, is the leading cause of death among women worldwide and diabetes ranks eight; obesity is contributing factor for both conditions. Multiple studies have documented differences in the incidence, prevalence, morbidity, and mortality related to cardiometabolic conditions between men and women worldwide.
Despite recent strides made in understanding sex and gender differences in cardiometabolic disorder risk factors, more research is needed to explore the mechanisms explaining differences in disease presentation and progression, which could lead to more personalized prediction, prevention, diagnostics, monitoring tools and treatments.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Substantial Progress
0 % Achievement
Solution Strategies
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Leverage ongoing longitudinal studies on cardiometabolic conditions with a consortium-based approach to:
- Share and pool existing data and biospecimens to enable research on life stage onset, preclinical and clinical manifestation of these conditions, risk of long-term complications, protective factors, access to and quality of timely identification of risk factors, diagnosis and healthcare delivery, response to treatment, incidence of fatal and non-fatal events, and additional stratification or cross-country comparisons, including natural experiments on the relationship of these conditions and changes in healthcare and public policies, for example;
- Conduct meta-analyses in instances where data or biospecimen sharing is not possible;
- Stimulate and support the proposal of new studies based on innovative research questions, novel biomarkers, emerging risk factors, implementation science, or underrepresented populations not included in the scope of work of established longitudinal studies; and
- Share best practices and cross-collaborate for establishing long-term and sustainable research programs and research capacity building that respond to local health needs and are supported by local governments and public and private partners.
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Develop an artificial intelligence/machine learning (AI/ML) pilot prototype with the assurance of robust and comprehensive data that represent women from diverse health, personal and social trajectories, and conduct prospective trials to develop, test, and evaluate a clinical decision support tool for diagnosing ischemic heart disease in women.
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Research genotypes and phenotypes utilizing datasets that comprehensively document women’s diverse health, personal and social backgrounds to further understand the risk for developing type 2 diabetes, to enable more precise risk stratification and optimize screening, prevention, diagnosis, monitoring, and treatment regimens.
8.2 Lung, colorectal, gynecological cancers
Understanding sex- and gender-related differences in oncology treatment response is critical to ensuring patients receive therapies with the highest chance of success. Studies of several existing therapies have found significant differences in side effects and outcomes between men and women. For example, although immune checkpoint inhibitors have improved outcomes for patients certain types of melanoma and lung cancer, women are more likely to experience immune-related adverse events than men. Women also experience a higher rate of hematologic toxicity from chemotherapy. For example, women experienced higher rates of anemia and leukopenia than men when receiving a common chemotherapy regimen for lung cancer.
On the other hand, studies have found that certain therapies elicit better outcomes for women than men. One meta-analysis, for example, found that women experienced better responses than their male counterparts to a regimen of anti-programmed cell death protein 1 (anti-PD1) or anti-programmed death-ligand 1 (anti-PD-L1) agents plus chemotherapy compared to anti-PD1 or anti-PD-L1 alone. Additionally, men and women may have distinct risk factors; for example, 15–20 percent of lung cancer cases in men globally are not associated with smoking, while over 50 percent of cases in women are not associated with smoking. Discovering and exploiting these critical differences in disease and treatment response is an opportunity to further personalize oncology treatment and improve the chances of better patient outcomes. A critical factor will include adequate inclusion of women in cancer clinical trials, as data shows women are underrepresented in clinical trials of anti-cancer therapies.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Establish a cross-functional consortium of academic researchers, patient advocacy groups, and oncology research and institutional groups to investigate sex- and gender-related differences in efficacy and safety in the treatment of lung, colorectal, and cervical cancer, as well as new tools for diagnosis and screening of women for lung cancer. Build upon these analyses to produce consensus documents to support a greater understanding of these differences and potential next steps to improve outcomes in women living with these cancers. This includes strategies to ensure that clinical trials in these diseases include women patients across races and ethnicities in representative numbers according to epidemiology.
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Work with real-world evidence platforms that include both national and global data to compare the incidence of adverse events and outcomes (e.g., progression-free survival) due to treatment with PD-1 inhibitors (e.g., pembrolizumab, nivolumab) in the treatment of males vs females with non-small cell lung cancer and advance AI/ML-based prediction models to better identify individuals who are at elevated risk for lung cancer.
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Prioritize research to support the development, evaluation of efficacy, and implementation of self-collection mechanisms for cervical cancer screening to improve screening rates.
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Establish global, multi-organizational collaborations to evaluate sex- and gender-related differences in the microbiome, both before and during the treatment of colorectal cancer. Determine whether any microbiome elements correlate with differences in patient outcomes after treatment.
8.3 Neurological disorders
Women are disproportionately impacted by dementia, migraines, and pain. Women not only have a higher incidence rate of dementia but also experience faster disease progression and cognitive decline. As the population of older adults continues to grow, the market for diagnostic, monitoring, and treatment innovations for dementia and chronic pain will also expand.
The global incidence of migraine is also increasing, having jumped 40 percent between 1990 and 2019. The burden of migraine, dementia, and pain syndromes is significant. Migraine (16.3 percent) and dementia (10.4 percent) alone were the second and third largest contributors of neurological DALYs globally in 2016, with migraine causing more burden in females than males.
Expanding the current evidence base of the mechanisms driving sex and gender differences for these prevalent neurological conditions can enable the development of tools and therapies to improve outcomes for women.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Investigate risk and protective factors for dementia, migraine, and chronic pain, including environmental and social determinants, genetic links to autoimmune disorders, phenotypes at risk, and genetic protections.
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Augment current efforts by existing consortia to include sex and gender considerations in the design of diagnostic, monitoring, and treatment tools, including digital ones, that use novel imaging, biomarkers, and AI strategies for women with dementia and their caregivers.
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Apply research on migraine pathogenesis to the development of innovative treatments and develop affordable tools for diagnosis and monitoring of neurological disorders, such as using a smartphone app for monitoring migraine or pain onset and severity.
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Research nuances in women with migraine with and without aura, specifically measuring hormonal levels across the menstrual cycle (e.g., progesterone, estrogen) to determine the potential impact on pharmacodynamics and
medication efficacy.- Study the biological underpinnings of pharmacokinetics, pharmacodynamics, and pharmacotoxicity of medicines for treatment of migraine and pain as they relate to pregnancy and breastfeeding.
8.4 Mental health disorders
Women are at a higher risk of developing a mental health disorder in their lifetime than men. Researchers attribute higher risk in women to numerous factors, including socio-cultural factors, such as gender inequities leading to limited agency, high workloads, and domestic violence, and biological factors, including the impact of hormones on mood modulation. The perinatal period is a particularly critical time to identify and address mental health concerns in women because prevalence is higher during this period. Due to several biological factors, women and men respond differently to psychotropic drugs, but research into these nuances is nascent. Women in low-income countries face additional barriers to receiving culturally sensitive care, as many interventions are not adapted to their unique contexts. If a broader evidence base can be established, an opportunity exists to develop new therapies or dosing guidelines and context-specific tools to prevent and manage mental health disorders in women.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Research nuances in women receiving psychotropic therapies, specifically measuring hormonal levels across the menstrual cycle (e.g., progesterone, estrogen) and life course to determine the potential impact on pharmacodynamics and medication efficacy.
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Fund local academic and community-based advocacy groups to develop culturally- and gender-sensitive diagnostic and monitoring tools for PTSD, depression, and anxiety for use in low-resource settings by community health workers
or individuals. -
Conduct implementation research on how psychological interventions can be scaled up within a stepped-care approach by engaging with the existing healthcare systems and the communities to address the treatment gap for perinatal depression in resource-limited settings.
8.5 Autoimmune disorders
Women disproportionately bear the burden of autoimmune conditions; approximately 80 percent of people diagnosed with an autoimmune disease are women. Lupus, rheumatoid arthritis, and autoimmune thyroid diseases are highly prevalent among women and have limited availability of screening tools, diagnostics, and treatments. Given the overwhelming predominance of autoimmune and immune-mediated diseases in women, sex- and gender-specific R&D is critical. An opportunity exists to continue expanding investment into autoimmune disease R&D, such as that of the NIH, to support the development of screening, diagnostic, monitoring, and treatment tools and therapies that could reach a market of millions of women.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Extend studies on the impact of sex hormones on autoimmunity to clinical and translational efforts to bring new treatment technologies to market, such as cellular genomic and protein-based technologies currently in development.
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Develop guidelines for early detection of autoimmune diseases in girls and young women with high-risk, familial autoimmune disease history.
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Develop AI/ML tools to serve as a first-line risk assessment strategy for lupus to support patients and doctors in determining whether further testing or monitoring is warranted.
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Design and develop inflammation surveillance and autoimmune disease management monitoring solutions using wearable sensors to capture patient data and wearable devices, such as smartwatches. Developed prototypes could allow for a cost-effective means of monitoring autoimmune conditions in pre-, during-, and post-inflammatory crises.
