Marcia L Stefanick

Stanford University | SU · Department of Medicine

Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared to normal BMI without metabolic dysfunction. Postmenopausal women (n=20,593) in the Women’s Health Initiative with baseline metabolic dysfunc...

Background Cutaneous melanoma (CM) and non‐melanoma skin cancer (NMSC) are rising in postmenopausal women. Although high doses of oral vitamin A reduce NMSC risk in high‐risk patients, the role of vitamin A in preventing skin cancer in this group remains unexplored. Objectives To determine the association between total (dietary and supplemental) v...

Objective The American Heart Association’s Life’s Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular dise...

Dietary restriction via a healthy low-fat (HLF) diet or a healthy low-carbohydrate (HLC) diet vary in their effects on adiposity and metabolism. The HLC diet, but not HLF diet, may preferentially reduce visceral adipose tissue (VAT), the major adipose tissue contributing to metabolic deregulation. In a 12-month weight loss trial, DIETFITS (Diet Int...

Using 1998-2022 Women’s Health Initiative (WHI) data, our study provides contemporary fracture data by race and ethnicity, specifically focusing on Hispanic and Asian women. Fractures of interest included any clinical, hip, and major osteoporotic fractures (MOFs). We utilized the updated race and ethnicity information collected in 2003, which inclu...

Introduction: Women experience complex physiological and behavioral fluctuations across the menstrual cycle and have a limited understanding of its impact on physical performance. Measurement over a full menstrual cycle (~28 days) poses challenges due to limitations of either in-lab (e.g., time and cost) or remote monitoring (e.g., battery life, me...

e24007 Background: Prior studies of women with obesity-associated cancers in the Women’s Health Initiative (WHI) showed higher overall and mortality due to cardiovascular disease (CVD) for women with a higher number of cardiometabolic risk factors at baseline. It is unclear if this risk differs from women without cancer. In order to determine if th...

Importance Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women’s Health Initiative (WHI) enrolled 161 808 postmenopausal U...

Background Lower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease. Objectives We evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Rel...

BACKGROUND The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS The study population consisted of 16570 participant...

Background: Premorbid health traits that predispose to a fatal initial presentation of coronary heart disease (CHD) remain poorly characterized. Methods: We followed 148,230 post-menopausal participants in the Women's Health Initiative for a median of 13.3 years. We ascertained the first occurrence of CHD and performed a joint Cox multivariate regr...

Introduction: A healthy low fat (HLF) and healthy low carbohydrate (HLC) diet are common strategies for weight loss that vary in their effects on adiposity and metabolism. Visceral adipose tissue (VAT) is the major contributor to metabolism deregulation, beyond subcutaneous adipose tissue (SAT). Despite strong biological evidence that a HLC diet pr...

Introduction: Venous insufficiency, which can occur with prolonged sedentary behavior, is associated with venous thromboembolism (VTE) risk. Whether accelerometer-measured sedentary behaviors are associated with VTE risk is unknown. Hypothesis: Longer total sitting times, mean sitting bout durations, and time spent in prolonged sitting bouts are as...

Background: Although calcium and vitamin D (CaD) supplementation may affect chronic disease in older women, evidence of long-term effects on health outcomes is limited. Objective: To evaluate long-term health outcomes among postmenopausal women in the Women's Health Initiative CaD trial. Design: Post hoc analysis of long-term postintervention...

Background Postmenopausal women with cancer experience an accelerated physical dysfunction beyond that expected through aging alone due to cancer and its treatments. The aim of this study is to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. Methods This...

Importance Heart failure (HF) prevention is paramount to public health in the 21st century. Objective To examine incident HF and its subtypes with preserved ejection fraction (HFpEF) and reduced EF (HFrEF) according to accelerometer-measured physical activity (PA) and sedentary time. Design, Setting, and Participants This was a prospective cohort...

Purpose Identify the effects of engagement with different intervention delivery channels on physical activity (PA), and the participant subgroups engaging with the different channels, among Women’s Health Initiative Strong and Healthy (WHISH) PA trial participants. Design Secondary analysis of data from WHISH, a pragmatic trial that used passive r...

Purpose To examine the association of a traditional Mexican diet score with risk of total, breast, and colorectal cancer among women of Mexican ethnic descent in the Women’s Health Initiative (WHI). Methods Participants were WHI enrollees who self-identified as being of Mexican descent. Data from food frequency questionnaires self-administered at...

Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportion...

Background: Advancements in medical technology and pharmacologic interventions have drastically improved survival of infants born preterm and low birth weight, but knowledge regarding the long-term health impacts of these individuals is limited and inconsistent. Aim: To investigate whether an individual's birthweight or history of being born pre...

Background: The association between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine survival probabilities to age 90 for various SBP levels among women aged ≥ 65 years with or without BP medication. Methods: We analyzed blood pressure data from participants in the Women's Health Initiative (n=16,570) who w...

Understanding the role of both menopausal hormone therapy (MHT) along with non-hormonal options for the treatment of vasomotor symptoms, sleep disruption, and genitourinary symptoms after menopause is critical to the health of women during middle and later life. Recent updates to the evidence for the treatment of menopausal symptoms pertaining to b...

Objective: To assess the associations among several anthropometric measures, as well as BMI trajectories and CRC risk in older women. Design: Prospective cohort study. Setting: Forty clinical centres in the USA. Participants: 79,034 postmenopausal women in the Women's Health Initiative Observational Study. Results: During an average of 15....

Introduction: Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk since metabolic dysfunction can exist at any BMI. We measured the association of metabolic dysfunction, independent of BMI with risk of ORC. Methods: Study included 60% white and 34% black Women’s Health Initiative participants with available baseline cardiovascul...

Calls-to-action in health research have described a need to improve research on race, ethnicity, and structural racism. Well-established cohort studies typically lack access to novel structural and social determinants of health (SSDOH) or precise race and ethnicity categorization, contributing to a loss of rigor to conduct informative analyses and...

Introduction: Physical activity (PA) is prospectively inversely associated with dementia risk, but few studies examined accelerometer measures of PA and sitting with rigorously-adjudicated mild cognitive impairment (MCI) and dementia risk. Methods: We examined the associations of accelerometer measures (PA and sitting) with incident MCI/probable...

Background: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1β, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. Methods: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluat...

“Race” and “ethnicity” are socially constructed terms, not based on biology - in contrast to biologic ancestry and genetic admixture - and are flexible, contested, and unstable concepts, often driven by power. Although individuals may self-identify with a given race and ethnic group, as multidimensional beings exposed to differential life influenci...

Background A later age at natural menopause (ANM) has been linked to several ageing-associated traits including an increased risk of breast and endometrial cancer and a decreased risk of lung cancer, osteoporosis and Alzheimer disease. However, ANM is also related to several proxies for overall health that may confound these associations. Methods...

Objective: The objective of this study was to assess the effect of menopausal hormone therapy (HT) on blood pressure control in postmenopausal women with hypertension. Methods: The Women's Health Initiative HT clinical trials were double-blinded, randomized, placebo-controlled studies of women aged 50 to 79 years testing the effects of HT (conju...

Objective: The aim of this study was to examine the association between common menopausal symptoms (MS) and long-term cardiovascular disease (CVD) and all-cause mortality. Methods: In an observational cohort of 80,278 postmenopausal women with no known CVD at baseline from the Women's Health Initiative, we assessed individual MS severity (mild v...

Background Asymptomatic atrial fibrillation (AF) is associated with an increased risk of stroke. The yield of serial electrocardiographic (ECG) screening for AF is unknown. Objectives The aim of this study was to determine the frequency of AF detected by serial, 7-day ECG patch screenings in older women identified as having an elevated risk of AF...

Background Prior studies examined associations between Healthy Eating Index (HEI) and chronic disease risk based on self-reported diet without measurement error correction. Objectives Our objective was to test associations between biomarker-calibration of food frequency questionnaire (FFQ)-derived HEI-2010 with incident cardiovascular disease (CVD...

Background Identifying late-life men who might benefit from treatment to prevent fracture is challenging given high mortality. Our objective was to evaluate risks of clinical fracture, hip fracture, and mortality prior to fracture among men ≥80 years. Methods Study participants included 3,145 community-dwelling men (mean [SD] age 83 [2.8] years) f...

The WHI (Women’s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementatio...

The built environment can influence physical activity behavior. Walk Score is a widely used measure of the neighborhood built environment to support walking. However, studies of the association between Walk Score and accelerometer-measured physical activity are equivocal and no studies have examined this relationship among older adults. We analyzed...

Introduction: Resilience—which we define as the “ability to bounce back from stress”—can foster successful aging among older, racially and ethnically diverse women. This study investigated the association between psychological resilience in the Women’s Health Initiative Extension Study (WHI-ES) and three constructs defined by Staudinger’s 2015 mode...

10552 Background: In the WHI DM randomized trial, randomization to the dietary intervention group was associated with a 21% lower breast cancer mortality (P = 0.02) (JCO 2020), and while not an intervention target, with higher physical activity as well. Therefore, we examined whether these lifestyle changes attenuate age-related physical functionin...

Background National guidelines promote physical activity to reduce cardiovascular disease (CVD); yet, no RCT has tested the effectiveness of physical activity as the sole intervention for primary CVD prevention in older adults. The Women's Health Initiative (WHI) Strong and Healthy (WHISH) trial, a pragmatic trial embedded in the WHI-Extension Stud...

Background Aging is generally accompanied by decreasing physical activity, which is associated with a decline in many health parameters, leading to recommendations for older adults to increase or at least maintain physical activity (PA). Methods We determined relationships between social connectedness and decreasing or increasing PA levels during...

Context Whether repeated bone mineral density (BMD) screening improves fracture prediction in men is uncertain. Objective Evaluate whether a second BMD 7 years after the initial BMD improves fracture prediction in older men. Methods 3,651 community-dwelling men (mean age 79.1 years) with total hip BMD at baseline and Year 7 (Y7). Self-reported fr...

Background Recommended systolic blood pressure (SBP) targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities. We examined the relationship of DBP levels to CVD and all-cause...

Longitudinal studies can help us understand the effects of long-term neighborhood changes, as these can capture individual self-appraisal of current and future circumstances. We analyzed the association between neighborhood changes and health-related quality of life (HRQoL) outcomes among older women from the Women's Health Initiative (WHI) study....

Purpose The objective of this manuscript is to identify longitudinal trajectories of change in body mass index (BMI) after menopause and investigate the association of BMI trajectories with risk of diabetes and cardiovascular disease (CVD) among postmenopausal women. Methods Using data from 68,132 participants in the Women's Health Initiative (WHI...

Objective: Research is limited regarding the predictive utility of the RAND-36 questionnaire and physical performance tests in relation to all-cause, cardiovascular disease (CVD), and total-cancer mortality in older women. Methods: Data on the RAND-36 questionnaire, gait speed, and chair stand performance were assessed in 5,534 women aged ≥ 65 y...

Objective To investigate the association of infertility with atherosclerotic cardiovascular disease (ASCVD) among postmenopausal participants in the Women’s Health Initiative (WHI). We hypothesized that nulliparity and pregnancy loss may reveal more extreme phenotypes of infertility, enabling further understanding of the association of infertility...

Rethinking the Association of Physical Performance with Blood Pressure Changes in Older Women: Findings form the Women’s Health Initiative Background: This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods: 5627 women (mean...

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potent...

Background A later age at natural menopause (ANM) has been linked to several aging-associated traits including an increased risk of breast and endometrial cancer and a decreased risk of lung cancer, osteoporosis, and Alzheimer disease. However, ANM is also related to several proxies for overall health that may confound these associations. Methods...

Importance Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs r...

Background In this paper, we argue for Gender as a Sociocultural Variable (GASV) as a complement to Sex as a Biological Variable (SABV). Sex (biology) and gender (sociocultural behaviors and attitudes) interact to influence health and disease processes across the lifespan—which is currently playing out in the COVID-19 pandemic. This study develops...

Background: Urinary incontinence (UI) affects more than 40% of US women with an annual societal cost of over $12 billion and demonstrated associations with depressive symptoms, social isolation and loss of work productivity. Weight has been established as an exposure that increases UI risk and certain dietary components have been associated with UI...

Background This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (yea...

Sheltering-in-place, social distancing, and other strategies to minimize COVID-19 transmission may impact physical activity (PA) and well-being in older adults. To assess self-reported PA changes, well-being, and priorities of older women across the USA early in the COVID-19 pandemic. In May 2020, a 10-question survey was emailed to 5,822 women, ag...

Objective: Reduced functional capacity is a hallmark of early pre-clinical stages of heart failure (HF). The Short Physical Performance Battery (SPPB) is a valid measure of lower extremity physical function, has relatively low implementation burden, and is associated with cardiovascular disease and mortality. However, the SPPB-HF association is un...

Objective To investigate whether dual-energy x-ray absorptiometry (DXA) estimates of adiposity improve risk prediction for cardiometabolic diseases over traditional surrogates, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in older women. Patients and Methods We analyzed up to 9744 postmenopausal women aged 50 to 79...

BACKGROUND The IBIS/Tyrer‐Cuzick model is used clinically to guide breast cancer screening and prevention, but was developed primarily in non‐Hispanic White women. Little is known about its long‐term performance in a racially/ethnically diverse population. METHODS The Women's Health Initiative study enrolled postmenopausal women from 1993‐1998. Wo...

Introduction: Visceral adipose tissue (VAT) is a hypothesized driver of chronic disease. Dual-energy X-ray absorptiometry (DXA) potentially offers a lower cost and more available alternative compared to gold-standard magnetic resonance imaging (MRI) for quantification of abdominal fat sub-compartments, VAT and subcutaneous adipose tissue (SAT). We...

Physical activity improves quality of life and extends independence in older adults. Yet, how to motivate older adults to engage in physical activity is unclear. In the present study, 4108 older women, aged 70–99, reported how they motivated themselves to move when they did not feel like it, and their hours of physical activity and walking each wee...

Background /Objective: Insomnia is common in older women and is associated with higher cardiovascular disease risk (CVD). Nonbenzodiazepine GABA agonists (Z-drugs) are the most commonly prescribed sleep aids. The study objective was to determine whether the use of Z-drugs is associated with the risk of developing CVD and mortality in older women wi...

The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and...

Background Obesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated. Methods We included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women’s Health Initiative. Normal weight was defi...

Background Presence of clonal hematopoiesis of indeterminate potential (CHIP) is associated with a higher risk of atherosclerotic cardiovascular disease, cancer, and mortality. The relationship between a healthy lifestyle and CHIP is unknown. Methods and Results This analysis included 8709 postmenopausal women (mean age, 66.5 years) enrolled in th...

In the Women's Health Initiative (WHI), we investigated associations between baseline DXA appendicular lean mass (ALM) and risk of incident fractures, falls and mortality (separately for each outcome) amongst older postmenopausal women, accounting for bone mineral density (BMD), prior falls and FRAX probability. The WHI is a prospective study of po...

Background: National guidelines promote physical activity to prevent cardiovascular disease (CVD), yet no randomized controlled trial has tested whether physical activity reduces prevent CVD. Methods: The Women's Health Initiative (WHI) Strong and Healthy (WHISH) pragmatic trial used a randomized consent design to assign women for whom cardiovas...

Background Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-repo...

(Abstracted from JAMA 2020;324:369–380) Hormone therapy (HT) for menopausal symptoms and its risk-to-benefit ratio have been a controversial topic within the scientific community for several decades. The complicated benefits and potential adverse events associated with menopausal HT were first reported in 2002 by the Women's Health Initiative (WHI)...

Background/objective: Falls cause significant problems for older adults. Sedentary time is associated with lower physical function and could increase the risk for falls. Design: Prospective study. Setting: Sites across the United States. Participants: Older women (N = 5,545, mean age 79 years) from the Women' Health Initiative Objective Phys...

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk....

Background The 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB’s role in heart failure (HF) is unclear. Methods We studied 80 982 women in the Women’s Health Initiative Observational Study, aged 50 to 79 years, who were without known HF and reported ability to walk ≥1 block unassisted a...

Objective: This study evaluated whether vasomotor symptom (VMS) severity and number of moderate/severe menopausal symptoms (nMS) were associated with health outcomes, and whether calcium and vitamin D (CaD) modified the risks. Methods: The Women's Health Initiative CaD study was a double blind, randomized, placebo-controlled trial, which tested...

The health benefits and risks of menopausal hormone therapy among women aged 50-59 years are examined in the Women's Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy post-...

Few studies have evaluated hypertension incidence in relation to walking, which is a common physical activity among adults. We examined the association between walking and hypertension incidence in 83 435 postmenopausal women who at baseline were aged 50 to 79 years, without known hypertension, heart failure, coronary heart disease, or stroke, and...

This study develops a gender assessment tool for use in clinical and population research, including large-scale health surveys involving diverse Western populations. While analyzing sex as a biological variable is widely mandated, gender as a sociocultural variable is not, largely because the field lacks quantitative tools for analyzing the influen...