OBJECTIVE:To test, among women with natural menopause, whether: infertility, miscarriage, stillbirth, and low parity are associated with a higher risk of osteoporosis; menopause age can partly explain their associations. DESIGN:Pooled analysis of five retrospective and prospective cohorts within the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. SUBJECTS:A total of 141,222 naturally postmenopausal women with data on fertility factors (i.e., infertility, miscarriage, stillbirth, or parity), osteoporosis, and covariates (i.e., race, age at last follow-up, education level, smoking status, alcohol intake, body mass index, physical activity level, and age at menarche). EXPOSURE:The history of infertility, miscarriage, stillbirth, and parity was self-reported. MAIN OUTCOME MEASURES:Osteoporosis was identified through surveys, hospital, death registry, primary care, or pharmaceutical data. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between fertility factors and osteoporosis, taking into account clustering within each cohort. All models were first adjusted for fixed covariates, including race, education level, smoking status, alcohol intake, body mass index, physical activity level, and age at menarche, and then time-varying covariate of age at natural menopause. RESULTS:There was a modestly higher risk of osteoporosis for women with a history of infertility (HR = 1.16, 95% CI: 1.13-1.19), recurrent miscarriages (≥3; HR = 1.17, 95% CI: 1.05-1.30), stillbirth (HR = 1.14, 95% CI: 1.10-1.17), and low parity (no live births: HR = 1.20, 95% CI: 1.15-1.25; 1 live birth: HR = 1.15, 95% CI: 1.14-1.16). These associations were unchanged or only slightly attenuated after additional adjustment for age at natural menopause. CONCLUSION:These female-specific factors could be considered as part of the risk assessment and may inform prevention strategies for osteoporosis.

Purpose To describe physical activity (PA) trajectories across 10 years post-breast cancer diagnosis and examine their association with quality of life (QoL). Methods Participants from the longitudinal Study of Women’s Health Across the Nation who developed incident breast cancer completed the Quality of Life in Adult Cancer Survivors scale (QLACS) which has 12 domains. Breast cancer survivors (BCS) with at least one post-diagnosis measure of the Kaiser Physical Activity Survey (PA) were included ( n = 96). We estimated metabolic equivalents of task minutes per week (MET-min/week) for the two most frequent sport/exercise activities. Group-based trajectory modeling determined PA trajectories over 10 years post-diagnosis. Analysis of covariance assessed associations between PA trajectory group and the three QLACS domains with the worst scores (fatigue, pain, and recurrence-related distress), adjusted for PA and other relevant covariates. Results There were four post-diagnosis PA trajectories: consistently very low/no PA (“inactive,” 11.5%); consistently some, but below aerobic PA guideline (“below guideline,” 48.9%); generally met aerobic PA guideline with a slight decline (“met guideline,” 22.2%); and exceeded aerobic PA guideline (“exceeded guideline,” 18.8%). In adjusted models, the below guideline group reported more fatigue than the met or exceeded groups and more pain than the met guideline group, but there were no group differences in recurrence-related distress. Conclusion The majority of BCS did not meet the aerobic PA guideline over 10 years post diagnosis. BCS who met the aerobic PA guideline reported less fatigue and pain compared to those who did not meet the guideline in adjusted analyses, suggesting a negative association between PA and QoL.

STUDY OBJECTIVES:This study examined whether sleep timing and its regularity are associated with cognitive performance in older women and whether associations vary based on cardiometabolic risk factors. METHODS:The cross-sectional analysis included 1177 community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN) annual visit 15. Sleep timing (mean midpoint from sleep onset to wake-up) and its regularity (standard deviation of midpoint) were assessed using actigraphy. Cognitive measures included immediate and delayed verbal memory, working memory, and processing speed. Cardiometabolic risk measures included central obesity, hypertension, diabetes, and the Atherosclerotic Cardiovascular Disease (ASCVD) risk score. Linear regression models, adjusted for covariates, tested associations between sleep and cognitive measures. RESULTS:After covariate adjustment, early sleep timing was associated with worse delayed verbal memory (β = -0.37; p = .047) and late sleep timing was associated with worse processing speed (β = -1.80; p = .008). Irregular sleep timing was associated with worse immediate (β = -0.29; p = .020) and delayed verbal memory (β = -0.36; p = .006), and better working memory (β = 0.50; p = .004). Associations between early sleep timing and delayed verbal memory strengthened as ASCVD risk increased (interaction β = -8.83, p = .026), and sleep timing irregularity's effect on working memory was stronger among women with hypertension (interaction β = -3.35, p = .039). CONCLUSIONS:Sleep timing and its regularity are concurrently associated with cognitive performance in older women. Cardiovascular disease risk may modify some of these associations. Future longitudinal studies are needed to clarify these relationships.

Background: Women may be vulnerable to elevated depressive symptoms during the menopause transition (MT). Studies generally have not considered premenopausal depressive symptom history or examined symptoms in relation to the final menstrual period (FMP). Objective: To identify specific time points in relation to the FMP when depressive symptoms increase or decrease. Methods: Participants were 1582 multiracial/ethnic women from the longitudinal Study of Women's Health Across the Nation (SWAN). Biological, psychosocial, and depressive symptom data were collected approximately annually. Depressive symptoms were measured by the Center for Epidemiological Studies-Depression (CES-D) scale. Results: Women with high baseline depressive symptoms (CES-D >= 16) declined in symptoms (M = -1.04/yr., 95 % CI = -1.58, -0.50) until 4 years before the FMP, followed by a smaller decrease (M = -0.50/yr., 95 % CI = -0.72, -0.28) until 18 months after the FMP. Depressive symptoms increased (M = 0.21/yr., 95 % CI = 0.11, 0.30) in those with low baseline symptoms until 1 year before the FMP, and decreased (M = -0.06/yr., 95 % CI = -0.11, -0.008) going forward. Greater social support, higher levels of follicle stimulating hormone and estradiol, and less sleep disturbance contributed to greater decline in depressive symptoms among those with high baseline depressive symptoms. Anxiety, experiencing stressful life events, lower body mass index, and poor rolephysical function contributed to an increase in depressive symptoms among those with low baseline symptoms. Limitations: Excluded women had higher baseline CES-D scores. Lacked pre-MT depression for pre/early perimenopausal women at baseline. Conclusion: Accounting for baseline depressive symptom level and focusing on the FMP more precisely characterize depressive symptom change over the MT.

Purpose To examine the differential effect of non- and anthracycline-based chemotherapy on fatigue over 12 months post-diagnosis among breast cancer survivors. Methods This study is based on a prospective Wake Forest NCI Community Oncology Research Program (NCORP) multicenter cohort study (WF-97415) of women with stage I to III breast cancer and non-cancer controls. Analyses compared those: 1) receiving, or 2) not receiving anthracycline chemotherapy, 3) receiving aromatase inhibitors (AIs) without chemotherapy, with 4) a comparator group without a history of cancer. In-person clinic assessments were conducted at: baseline (prior to chemotherapy or start of AI therapy), and 3 and 12 months after baseline. The Functional Assessment of Chronic Illness Therapy-Fatigue scale was the primary outcome. Estimated least squares means by group using mixed models with a random subject effect, fixed effects of time and group, and the interaction between time and group was used to compare groups across time, controlling for age, comorbidities, and treatment variables. Results Among 284 women (mean age = 53.4 years, sd 11.9 years), there was a significant (p < 0.0001) group by time interaction, with a sharp increase in fatigue at 3 months in the two chemotherapy groups in comparison to the non-chemotherapy and non-cancer controls. The two chemotherapy groups did not significantly differ in fatigue at any time point. Conclusion Women with breast cancer who receive non- or anthracycline-based chemotherapy experience similar trends in and levels of fatigue within the first year of treatment and greater fatigue than women receiving AIs alone or women without breast cancer.

To identify distinct trajectories of physical health-related quality of life (HRQoL) in older women over the first two years following breast cancer diagnosis, and to examine characteristics associated with trajectory group membership. A secondary analysis of a longitudinal study of women diagnosed with stage I-III breast cancer who completed surveys within eight months of diagnosis and six, twelve, and eighteen months later that focuses on a subset of women aged ≥ 65 years (N = 145).Physical HRQoL was assessed using the Physical Component Score (PCS) of the SF-36 Health Survey. Finite mixture modeling identified distinct PCS trajectories. Multivariable logistic regression identified variables predictive of low PCS group membership. Two distinct patterns of PCS trajectories were identified. The majority (58

Menopause experiences and care vary widely because of biological, sociodemographic, and sociocultural factors. Treatments for troublesome symptoms are not uniformly available or accessed. Intersectional factors may affect the experience and are poorly understood. Disparities across populations highlight the opportunity for a multifaceted equitable approach that includes patient-centered care, education, and policy change.

Objectives Vasomotor symptoms (VMS), including hot flashes and night sweats, are hallmark symptoms of the menopause transition. Previous research has documented greater frequency, duration, and severity of VMS in Black women compared with women from other racial/ethnic groups, even after accounting for other factors. This analysis examined the association between discrimination and VMS and the extent to which discrimination accounts for the disproportionate burden of VMS in Black women. Methods Using available discrimination and VMS data from the SWAN cohort study (n = 2,377, 48% White, 32% Black, 6% Japanese, 4% Chinese, and 9% Hispanic women) followed approximately yearly in midlife from premenopause (42-52 y) through postmenopause (~20 y), we assessed concurrent associations between discrimination and VMS frequency in the past 2 weeks using weighted generalized mixed models. We also assessed associations between chronic discrimination across first four visits and VMS trajectories from premenopause to postmenopause using weighted multinomial logistic regression. Models were adjusted for known risk factors for VMS. Results Higher levels of discrimination were associated with concurrent reporting of any (odds ratio [OR], 1.57 [1.31-1.89]) and frequent (≥6 d) VMS (OR, 1.55 [1.21-1.99]). After adjustment, associations remained significant for any (OR, 1.30 [1.09-1.54]) but not frequent VMS. For any VMS trajectories, chronic discrimination was associated with “continuously high” (OR, 1.69 [1.03-2.77]) and “high pre-FMP-decline post-FMP” (OR, 1.70 [1.01-2.88]) versus “FMP-onset low” trajectories. After adjusting for discrimination, odds of reporting any, frequent, and of being in the “continuously high” any VMS trajectory remained elevated for Black versus White women. Conclusions Discrimination is associated with greater concurrent risk of any (but not frequent) VMS, and chronic discrimination is associated with a continuously high reporting of any VMS over time, independent of known risk factors. Adjusting for discrimination attenuates but does not eliminate the increased risk of VMS for Black women.

Abstract Introduction: Chemotherapy-associated functional decline is a concern for women with breast cancer. Objective: To assess effects of chemotherapy and age on objectively measured physical performance among women with breast cancer over time. Methods: Analyses utilized the multicenter, longitudinal Understanding and Predicting fatigue, cardiovascular decline, and events after BrEast cAncer sTudy (UPBEAT), a study conducted through the Wake Forest NCORP Research Base (5UG1CA189824). We examined physical performance at baseline and at 3 and 12 months and compared means across time by age group (< 65 years v. 65+ years at baseline) and by cancer/control group. For the latter variable, we had 3 groups of participants: 1) newly diagnosed breast cancer patients with Stage 1-3 breast cancer who received chemotherapy (CC; n= 201); 2) newly diagnosed breast cancer patients receiving no chemotherapy (CNC; n=57); and age-matched healthy controls (HC; n=145). The primary outcome was the Short Physical Performance Battery (SPPB) score (range 0-12, worst to best performance, including chair stands, gait speed, and balance testing). Effects of cancer/control group, age group, and time (treated categorically rather than ordinally) were estimated in a mixed model with a random subject effect and fixed effects of time (baseline, 3 month, 12 month) and cancer/control group. In the model we included all first-order interactions as well as the one second-order interaction between all three predictors. We also used linear contrasts to compare estimated means within groups. Analyses were conducted in SAS 9.4. A two-tailed alpha of 0.05 was used throughout to denote statistical significance. Results: Among 403 patients accrued through the Wake Forest Research Base of NCORP, 201 were in the CC group, and 18.9% of these were aged 65 and older; 57 were in the CNC group, and 33.3% were older; and 145 were in the HC group, and 15.9% were 65 or older. We observed a significant (p< 0.0001) main effect of older age group in our model: across all 3 groups, and all 3 time points, those who were 65 years of age or older had worse SPPB scores than those who were younger. Healthy controls tended to have better mean scores than the other 2 cancer/control groups, though the main effect of group did not achieve statistical significance (p=0.06). We observed no significant interaction terms; in other words, the effect of being older (in terms of association with worse SPPB scores) did not vary by time or group. Within the CC group, both the older and the younger groups declined significantly (p=0.04) in mean SPPB at 3 months compared to baseline, but by 12 months, the means had returned to their starting points. No other groups showed significant changes over time. Conclusions: Chemotherapy was associated with decline in SPPB score over the 12-month time period regardless of age. Older adults, regardless of chemotherapy status and time point, had lower SPPB scores. Citation Format: Shirley Bluethmann, Beverly Levine, Brianna Leitzelar, Katherine Ansley, Alexandra Thomas, Nancy Avis, Gregory Hundley, Heidi Klepin, Kathryn Weaver, Glenn Lesser. How do chemotherapy and age affect physical performance in breast cancer patients over 12 months of treatment? Results from the UPBEAT Study (UPBEAT WF-97415) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-11.

Objective: To examine how (1) partnered sexual activity, and (2) sexual functioning, contribute to global quality of life (QOL) and health-related quality of life (HRQL) among midlife and older women, and whether importance of sex modifies these associations. Materials and Methods: Women in the Study of Women's Health Across the Nation (SWAN), a multiethnic/racial cohort study, aged 42-52 at recruitment, were followed for ∼20 years. The Ladder of Life and Short Form-36 physical component summary (PCS) and mental component summary (MCS) assessed Global QOL (N = 3,263) and HRQL (N = 2,576), respectively. Primary predictors were (1) having partnered sexual activity (yes/no), and (2) sexual functioning among those with partnered sexual activity. Sociodemographic, health, lifestyle, and psychosocial covariates were included. Results: Importance of sex modified covariate-adjusted association of having partnered sexual activity with global QOL. Adjusted associations of partnered sexual activity with PCS and MCS were not statistically significant. Sexual functioning, among women with partnered sexual activity, was positively associated with global QOL (adjusted p = 0.03), regardless of importance of sex; unrelated to PCS; but positively associated with MCS (adjusted p = 0.03), particularly when sex was "very/quite important." Conclusions: Partnered sexual activity and better sexual functioning are related to QOL for mid-aged and older women, and are stronger when sex is considered important. Partnered sexual activity and sexual functioning are less consistently related to HRQL when adjusted for covariates, and importance modifies only the association between sexual functioning and MCS. Understanding the importance of sex to midlife and older women contextualizes the impact of sex on QOL.

OBJECTIVE:The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS:A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS:A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS:We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

To compare breast cancer survivors (BCS) to women without breast cancer (controls) on sleep health risk factors and actigraphy-derived dimensions of sleep (duration, maintenance, timing, and regularity) and examine whether the effect of breast cancer on sleep differs by time since diagnosis. Analyses included data from 68 BCS and 1042 controls who participated in actigraphy and Pink SWAN sub-studies within the Study of Women’s Health Across the Nation. BCS and control characteristics were compared using chi-square, Fisher’s exact, and Wilcoxon rank sum tests. Sleep measures were regressed onto breast cancer status using binomial logistic and linear regression. The interaction between BCS status and years since diagnosis (< 5; ≥ 5) was tested in these models before and after covariate adjustment. There were no overall sleep differences between BCS and controls; both groups experienced poor sleep health on average across multiple dimensions. Physical inactivity, sleep apnea, and vasomotor and depressive symptoms were associated with worse sleep in both groups. Total sleep time was lower among BCS than controls within 5 years of diagnosis (6.13 vs. 6.57 h; p = .03) but did not differ at > 5 years post-diagnosis (6.59 vs. 6.45 h; p = .32). BCS reported greater use of exogenous hormones (p < .0001) and were twice as likely to have initiated anxiolytic use post-diagnosis (p = .03). BCS within 5 years of diagnosis experienced shorter sleep duration than controls but did not differ on other sleep parameters. Both groups experienced poor sleep health. BCS and similarly-aged women experience poor sleep health requiring assessment and treatment.

Abstract Sharing scientific resources is a critical component of contemporary research. Data and specimens from established studies can be used for manuscripts on special topics and research projects from experienced investigators and advanced trainees. Researchers external to a study, however, may find it challenging to identify available resources and to determine the steps required to access them. This presentation will describe the SWAN datasets, specimens and documents that are housed at the NIA Aging Research Biobank. It will review the process for requesting the archived resources, provide tips for successful applications, and explain the data and/or material transfer agreements created for research projects. The SWAN longitudinal cohort study aims to understand variations in the experience of reproductive aging and its impact on midlife and early old age outcomes across multiple racial and ethnic groups. SWAN includes 3302 women aged 42-54 years from 7 sites in the United States and consists of a baseline and 17 follow-up visits. The study has repeated measures of reproductive hormones, menopausal symptoms, sleep, genitourinary and sexual function, physical and cognitive function, cardiometabolic and bone health, psychological well-being and quality of life. Serum, plasma, and urine specimens were collected at each clinic visit, and a substudy obtained daily urine for ≤50 days annually for ≤10 years. An expansive collection of SWAN biospecimens and datasets are available to external investigators and trainees. Understanding the existing resources and processes required to access them provides researchers the opportunity to use these valuable resources to advance academic research.

Purpose This manuscript aims to compare and contrast acceptability and perceived benefits of yoga-skills training (YST) and an empathic listening attention control (AC) in the Pro-You study, a randomized pilot trial of YST vs. AC for adults receiving chemotherapy infusions for gastrointestinal cancer. Methods Participants were invited for a one-on-one interview at week 14 follow-up, after completing all intervention procedures and quantitative assessments. Staff used a semi-structured guide to elicit participants' views on study processes, the intervention they received, and its effects. Qualitative data analysis followed an inductive/deductive approach, inductively identifying themes and deductively guided by social cognitive theory. Results Some barriers (e.g., competing demands, symptoms), facilitators (e.g., interventionist support, the convenience of clinic-based delivery), and benefits (e.g., decreased distress and rumination) were common across groups. YST participants uniquely described the importance of privacy, social support, and self-efficacy for increasing engagement in yoga. Benefits specific to YST included positive emotions and greater improvement in fatigue and other physical symptoms. Both groups described some self-regulatory processes, but through different mechanisms: self-monitoring in AC and the mind-body connection in YST. Conclusions This qualitative analysis demonstrates that participant experiences in a yoga-based intervention or an AC condition reflect social cognitive and mind-body frameworks of self-regulation. Findings can be used to develop yoga interventions that maximize acceptability and effectiveness and to design future research that elucidates the mechanisms by which yoga is efficacious.

BACKGROUND Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease.OBJECTIVES This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy.METHODS Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance.RESULTS BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (b +/- SE: 7.1 +/- 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 +/- 0.07; 95% CI:-0.29 to-0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference +/- SE:-29 +/- 10 m; P = 0.029), LV end-systolic volume (5.8 +/- 1.3 mL; P < 0.001), LV ejection fraction (-3.2% +/- 0.8%; P = 0.002), and LV circumferential strain (2.5% +/- 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes.CONCLUSIONS PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581) (J Am Coll Cardiol CardioOnc 2023;5:641-652) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Importance Women often experience physiological and functional changes in their health during midlife. Identifying women who have clinically important improvements in physical health and function and evaluating the factors associated with these improvements can identify intervention targets at midlife. Objective To identify factors associated with improvements in physical health and function among women during midlife. Design, Setting, and Participants Participants were part of the Study of Women’s Health Across the Nation (SWAN), a diverse cohort of US women early in midlife, and followed up annually for up to 21 years between 1996 and 2017. Analyses were based on visit 8 (2004-2006) through visit 15 (2015-2017). Statistical analysis was conducted from October 2021 to March 2023. Exposures Sociodemographic indicators, health status measures, and comorbidities measured at visit 8. Main Outcomes and Measures The main outcome was a clinically important (≥5 points) improvement in the physical component score (PCS) of the 36-item Short-Form Health Survey between visit 8 and visit 15. Results Of the 1807 women (at visit 8: mean [SD] age, 54.5 [2.7] years; 898 [50%] White participants) in SWAN who qualified for analysis, 265 (15%) experienced a clinically important improvement in PCS over a median of 11.1 years (IQR, 10.9-11.4 years). Factors associated with improvement in PCS included no financial strain (odds ratio [OR], 1.73; 95% CI, 1.18-2.52), no sleep disturbances (OR, 1.43; 95% CI, 1.05-1.96), no osteoarthritis (OR, 1.42; 95% CI, 1.01-1.99), and having a higher physical activity score (OR, 1.17; 95% CI, 1.00-1.37) as assessed at visit 8. Women who had a higher PCS at visit 8 (OR, 0.84; 95% CI, 0.83-0.86), who had a higher body mass index (OR, 0.95; 95% CI, 0.93-0.97), or who were taking more medications (OR, 0.93; 95% CI, 0.88-0.98) had lower odds of an improved PCS. Conclusions and Relevance This cohort study of women in midlife suggests that approximately 15% of women experienced clinically important improvements in health and function over an 11-year period. Several potentially modifiable factors associated with improvements may inform women of variables to target for future interventions.

ObjectivesWomen in mid-life often develop chronic conditions and experience declines in physical health and function. Identifying factors associated with declines provides opportunity for targeted interventions. We derived and externally validated a risk score for clinically important declines over 10 years among women ages 55–65 using the Physical Component Summary Score (PCS) of the SF-36.DesignDerivation and validation of a risk score.SettingTwo longitudinal cohorts from sites in the USA were used.ParticipantsWomen from the Study of Women’s Health Across the Nation (SWAN) and women from the Women’s Health Initiative (WHI) Observational Study and/or clinical trials.Outcome measuresA clinically important decline over 10 years among women ages 55–65 using the PCS of the SF-36 predictors was measured at the beginning of the 10 years of follow-up.ResultsSeven factors—lower educational attainment, smoking, higher body mass index, history of cardiovascular disease, history of osteoarthritis, depressive symptoms and baseline PCS level—were found to be significant predictors of PCS decline among women in SWAN with an area under the curve (AUC)=0.71 and a Brier Score=0.14. The same factors were associated with a decline in PCS in WHI with an AUC=0.64 and a Brier Score=0.18. Regression coefficients from the SWAN analysis were used to estimate risk scores for PCS decline in both cohorts. Using a threshold of a 30% probability of a significant decline, the risk score created a binary test with a specificity between 89%–93% and an accuracy of 73%–79%.ConclusionsSeven clinical variables were used to create a valid risk score for PCS declines that was replicated in an external cohort. The risk score provides a method for identifying women at high risk for a significant mid-life PCS decline.