A FRAMEWORK FOR THE CONSIDERATION OF CHRONIC DEBILITATING CONDITIONS IN WOMEN

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Background/Overview: With the aging of our population and longer life expectancies compared to men, chronic debilitating conditions pose an increasingly significant burden on the health of women. Chronic conditions include a wide array of diseases and disorders that occur across the lifespan, many of which are sex-specific.1 Although women are now routinely included in clinical research, research is infrequently designed to obtain data on women. Inclusion criteria and study end points are not often centered around the needs of women.2 Sex and gender differences in the prevalence and clinical presentation of chronic conditions have been documented. CMS data (fee-for-service beneficiaries, excluding Medicare Advantage enrollees), disaggregated by sex, notes six conditions that occur more frequently in women: hypertension, arthritis, depression, dementia, asthma, and osteoporosis.3 Lower socioeconomic status and lower educational attainment are additional risk factors for multimorbidity, defined as the simultaneous occurrence of two or more diseases that may or may not share a causal link, that further disadvantage women, with additional disadvantage impacting the health of women who identify with historically underrepresented populations.4, 5 Several evidence gaps in our understanding of chronic debilitating conditions in women have arisen from a historical over-reliance on men in clinical research. Symptoms of chronic conditions experienced by women are often different from men; women have lower response rates to many first-line treatments; and the effects of hormonal transitions, such as menopause, on the natural history of chronic diseases have not been well-described. Further, the broad assumption that women’s health is inexorably linked to reproductive health has limited research on female-specific chronic conditions such as dysmenorrhea, endometriosis, and polycystic ovarian syndrome. Sex differences in the innate and adaptive immune system after puberty may influence the risk for disease (e.g., asthma), autoimmunity, and response to vaccination and cancer therapies.6 Chronic disease risk—including for coronary heart disease, cancers, musculoskeletal conditions, chronic pain, obesity, diabetes, and cognitive impairment—accumulate with age and generally increase after menopause, when reproductive hormone production declines.7, 8 There is a pressing need to understand how aging-related skeletal muscle dysfunction, frailty and bone loss impact or is impacted by chronic conditions in women. Aging-related skeletal muscle function deficit (SMFD) or skeletal muscle dysfunction—including loss of muscle mass (sarcopenia), muscle strength, and muscle function—may negatively impact or be impacted by chronic conditions or chronic debilitating conditions in women. Women more commonly than men have multimorbidity.9 The “networks” of morbidity are different in women, with multimorbidity more likely to cross multiple organ systems compared to men.10 Additionally, the pattern of accumulation of morbidity, meaning what initial chronic conditions are diagnosed and how conditions are additive, differs by sex and gender.11 In women with multimorbidity, the interactions among conditions are poorly understood and often inadequately treated.4 Chronic debilitating conditions were last defined by the US Department of Health and Human Services (HHS) in 2010 as “conditions that last a year or more and require ongoing medical attention and/or limit activities of daily living.”12 However, this and other existing definitions of chronic debilitating conditions do not incorporate sex or gender considerations. Sex and gender influence health; and yet, significant knowledge gaps exist in the evidence base for prevention, diagnosis, and treatment of chronic debilitating diseases amongst women. Task Description: • Review existing literature on chronic conditions specific to women. o Specifically review literature on how the development and accumulation of chronic conditions in women are influenced by factors such as menopause, aging-related skeletal muscle dysfunction (loss of muscle mass, muscle strength, and muscle function), and frailty including the epidemiology and social and economic impact. o Gender, racial, and ethnic differences in clinical presentation and outcomes should be considered. o Prevention, diagnosis, and treatment of female-specific gynecologic conditions should be reviewed and considered • Convene workshop[s] of identified experts. • Assemble evidence-based findings on chronic debilitating conditions in women. o The findings should incorporate the influence of social determinants of health, including but not limited to gender, race and/or ethnicity, socioeconomic status, sexual and gender minorities and underserved rural populations Produce a workshop report that describes current gaps in evidence and provides a suggested research agenda for the future.