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1.  Chronic Exposure to Everyday Discrimination and Sleep in a Multi-Ethnic Sample of Middle-Aged Women 
Researchers have suggested that poor sleep may play a role in the association between discrimination and health, but studies linking experiences of discrimination to sleep are limited. The authors examined associations between reports of everyday discrimination over four years (chronic everyday discrimination) and subjective and objective indicators of poor sleep.
Participants were 368 African-American, Caucasian, and Chinese women from the Study of Women’s Health Across the Nation (SWAN) Sleep Study. Everyday discrimination was assessed each year from baseline through the third follow-up exam via questionnaire with the Everyday Discrimination Scale (Intraclass Correlation Coefficient over four years=.90). Subjective sleep complaints were measured beginning in year 5 with the Pittsburgh Sleep Quality Index. Objective indices of sleep continuity, duration, and architecture were assessed via in-home polysomnography (PSG), beginning in year 5.
In linear regression analyses adjusted for age, race/ethnicity and financial strain, chronic everyday discrimination was associated with more subjective sleep complaints (Estimate =1.52, p<.001) and PSG-assessed wakefulness after sleep onset (Estimate=.19, p<.02), a marker of sleep continuity. Findings did not differ by race/ethnicity and remained significant after adjusting for menopausal status, body mass index, medication use and depressive symptoms.
Experiences of chronic everyday discrimination are independently associated with both subjective and objective indices of poor sleep. Findings add to the growing literature linking discrimination to key markers of biobehavioral health.
PMCID: PMC3654016  PMID: 23088174
Discrimination; depression; polysomnography; sleep; stress; psychological; African-Americans; Chinese
2.  Disruptions in ovarian function are related to depression and cardio-metabolic risk during pre-menopause 
Menopause (New York, N.Y.)  2013;20(6):631-639.
To evaluate the extent to which mild disruptions in ovarian function indexed by changes in menstrual cycle length may relate to cardio-metabolic and psychological health in pre-menopausal women.
Among 804 healthy, regularly-cycling women (ages 25–45, M=35.5 [5.5]), patterns of any change (shortening, lengthening, or increased variability) versus no change in menstrual cycle length were examined in relation to a composite of cardio-metabolic risk and individual risk factors (high-density lipoprotein [HDL], triglycerides, waist circumference, glucose, hypertensive status) as well as in relation to depression indicators (Center for Epidemiologic Studies Depression [CESD] score ≥16 [yes/no], lifetime depression diagnosis [yes/no], lifetime anti-depressant medication use [yes/no]). Models were also explored to test whether changes in menstrual cycle length mediated relations between depression history and cardio-metabolic risk.
In covariate-adjusted models, compared to no change, any change in menstrual cycle length was associated with higher cardio-metabolic risk composite scores and lower HDL (p’s<.05). In addition, compared to no change, any change in menstrual cycle length was associated with a CESD score ≥16, having received a depression diagnosis, and having used an anti-depressant medication (p’s<.05). In exploratory analyses, any change in menstrual cycle length partially mediated the relation between depression history and cardio-metabolic risk (b=0.152, p=.040) which attenuated (b=0.129, p=.083) when any change in menstrual cycle length was covaried.
Findings suggest disruptions in ovarian function marked by subtle changes in menstrual cycle length may relate to aspects of cardio-metabolic, and psychological health among healthy, pre-menopausal women.
PMCID: PMC3657585  PMID: 23715377
ovarian function; menstrual cycle length; depression; cardiovascular risk; cardio-metabolic risk; metabolic syndrome
3.  Does Risk for Anxiety Increase During the Menopausal Transition? Study of Women's Health Across the Nation (SWAN) 
Menopause (New York, N.Y.)  2013;20(5):488-495.
Little is known about the risk of anxiety in women during midlife and the menopausal transition. We examined anxiety as a cluster of 4 symptoms and determined the association between menopausal stage and high anxiety during ten years of follow-up of 2,956 women of multiple race/ethnicities.
This study was a longitudinal analysis of data from the multi-site Study of Women's Health Across the Nation (SWAN), a study of menopause and aging. Women were 42-52 at study entry. The outcome was high anxiety, a score of 4 or greater on the sum of four anxiety symptoms rated according to frequency in the previous 2 weeks from 0 (none) to 4 (daily) (upper 20%). Covariates included sociodemographics, health factors, stressors, and vasomotor symptoms (VMS).
Women with low anxiety at baseline were more likely to report high anxiety symptoms when early or late perimenopausal or postmenopausal compared to when they were premenopausal (odds ratios ranged from 1.56 to 1.61), independent of multiple risk factors, including upsetting life events, financial strain, fair/poor perceived health, and VMS. Women with high anxiety at baseline continued to have high rates of high anxiety throughout the follow-up but odds ratios did not differ by menopausal stage.
Women with high anxiety premenopausally may be chronically anxious and not at increased risk of high anxiety at specific stages of the menopausal transition. In contrast, women with low anxiety premenopausally may be more susceptible to high anxiety during and after the menopausal transition than before.
PMCID: PMC3641149  PMID: 23615639
anxiety; menopausal transition; vasomotor symptoms; longitudinal
4.  Childhood Physical Abuse Is Associated with Incident Metabolic Syndrome in Mid-Life Women 
Previous research has suggested that childhood emotional abuse, physical abuse, and sexual abuse are associated with an increased risk for ischemic heart disease. Our objective was to examine whether childhood abuse predicted incident metabolic syndrome, a precursor to heart disease, in mid-life women.
Participants were 342 (114 Black, 228 White) women from the Pittsburgh site of the Study of Women’s Health Across the Nation (SWAN). SWAN included a baseline assessment of premenopausal or early perimenopausal women in midlife (mean age = 45.7), and women were evaluated for presence of the metabolic syndrome over 7 annual follow-up visits. Women were classified as having metabolic syndrome if they met 3 of the following criteria: waist circumference > 88 cm, triglycerides ≥ 150 mg/dl, HDL < 50 mg/dl, SBP ≥ 130 or DBP ≥ 85 mmHg or on blood pressure medication, and fasting glucose ≥ 110 mg/dl or diabetic. The Childhood Trauma Questionnaire is a standardized measure that retrospectively assesses three domains of abuse in childhood and adolescence: emotional, physical, and sexual abuse.
Approximately 34% of the participants reported a history of abuse. Cox model survival analysis showed that physical abuse was associated with incident metabolic syndrome over the course of seven years (HR = 2.12, p = .02), adjusted for ethnicity, age at baseline, and time-dependent menopausal status. Sexual abuse and emotional abuse were unrelated to the metabolic syndrome.
This is the first study to show that a history of childhood abuse, specifically physical abuse, is related to the development of metabolic syndrome in mid-life women.
PMCID: PMC3641896  PMID: 22775234
childhood abuse; metabolic syndrome; menopause
5.  Progression Rates of Carotid Intima-media Thickness and Adventitial Diameter during the Menopausal Transition 
Menopause (New York, N.Y.)  2013;20(1):8-14.
The authors assessed whether the levels and progression rates of carotid intima-media thickness (IMT) and adventitial diameter (AD) vary by menopausal stage.
249 Women (42–57 years old, premenopausal (49%) or early peri-menopausal (46%)) from the Study of Women’s Health Across the Nation were included in the current analysis. Participants were followed for up to 9 years (median=3.7 years) and had up to 5 carotid scans. Linear mixed models were used for analysis.
The overall rate of change in IMT was 0.007 mm/year. Independent of age and race, progression rate of IMT increased substantially in late peri-menopausal stage (0.017 mm/year) compared to both premenopausal (0.007 mm/year) and early peri-menopausal (0.005 mm/year) stages; (P≤0.05). For AD, while the overall rate of change was negative (−0.009 mm/year), significant positive increases in the rate of change were observed in late peri-menopausal (0.024 mm/year) and postmenopausal (0.018 mm/year) stages compared to premenopausal stage (−0.032 mm/year); (P<0.05). In final models, postmenopausal stage was independently associated with higher levels of IMT and AD (P<0.05) compared to premenopausal stage.
During the menopausal transition, the carotid artery undergoes an adaptation that is reflected in adverse changes in IMT and AD. These changes may impact the vulnerability of the vessel to disease in older women.
PMCID: PMC3528819  PMID: 22990755
atherosclerosis; carotid intima-media thickness; epidemiology; menopause; risk factors
6.  Psychosocial Features Associated with Lifetime Comorbidity of Major Depression and Anxiety Disorders Among a Community Sample of Mid-Life Women: The SWAN Mental Health Study 
Depression and anxiety  2012;29(12):1050-1057.
In clinical samples, comorbidity between depressive and anxiety disorders is associated with greater symptom severity and elevated suicide risk. Less is known, however, regarding the long-term psychosocial impact that a lifetime history of both MDD and one or more anxiety disorders has in community samples. This report evaluates clinical, psychological, social, and stress-related characteristics associated with a lifetime history of MDD and anxiety.
Data from 915 women aged 42–52 who were recruited as part of the the Study of Women's Health Across the Nation Mental Health Study were used to examine clinical and psychosocial features across groups of women with a SCID-diagnosed lifetime history of MDD alone, anxiety alone, both MDD and anxiety, or neither MDD nor anxiety.
As compared with women with a history of either MDD or anxiety alone, women with a comorbid history were more likely to report recurrent MDD, multiple and more severe lifetime anxiety disorders, greater depressive and anxiety symptoms, diminished social support, and more past-year distressing life events. Exploratory analyses indicated that women with a comorbid history also report more childhood abuse/neglect and diminished self-esteem, as compared with women with a history of either disorder alone.
Midlife women with a comorbid history that includes both MDD and anxiety disorders report diminished social support, more symptomatic distress, and a more severe and recurrent psychiatric history. Future research is needed to clarify the biological and psychosocial risk factors associated with this comorobid profile, and to develop targeted interventions for this at-risk group.
PMCID: PMC3592574  PMID: 22930404
major depressive disorder; anxiety disorders; comorbidity; child abuse; social support; stress, psychological
7.  Endogenous Sex Hormones Impact the Progression of Subclinical Atherosclerosis in Women during the Menopausal Transition 
Atherosclerosis  2012;225(1):180-186.
To determine whether endogenous sex hormones (estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and follicle-stimulating hormone (FSH)) are longitudinally associated with progression of atherosclerosis among women at midlife.
249 Pre- or early peri-menopausal women (42–57 years) from the Study of Women’s Health Across the Nation (SWAN) were followed for up to 9 years (median=3.7 years) and had up to 5 repeated measures of common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear mixed models were used for statistical analysis. Final models included age at baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI, insulin resistance index, lipids, C-reactive protein and co-morbidity.
In final models for IMT, each one log unit decrease in SHBG was associated with a 0.005 mm/year increase in IMT progression (P=0.003). E2, T, and FSH were not associated with level or progression of IMT. For AD, each one log unit decrease in E2 was associated with a 0.012 mm/year increase in AD progression (P=0.04) and each one log unit increase in FSH was associated with a 0.016 mm/year increase in AD progression (P=0.003). T and SHBG were not associated with progression or level of AD.
Independent of SBP, BMI, lipids and other covariates, lower E2 and SHBG, and higher FSH were associated with increased subclinical atherosclerosis progression in women at midlife.
PMCID: PMC3478422  PMID: 22981430
subclinical atherosclerosis; sex hormones; women
8.  Association of past and recent major depression and menstrual characteristics in midlife: Study of Women’s Health Across the Nation 
Menopause (New York, N.Y.)  2012;19(9):959-966.
To examine the association of a history of major depression (MD) with menstrual problems in a multi-ethnic sample of midlife women.
Participants were 934 participants in the Study of Women’s Health Across the Nation (SWAN), a multi-site study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms (PMS) in the year prior to study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders (SCID) was conducted to determine recent and past psychiatric diagnoses. Covariates included socio-demographics, behavioral, and gynecological factors.
One-third reported heavy bleeding, 20% other abnormal bleeding and 18% premenstrual symptoms. One-third had past; and 11% recent MD. Past MD was associated with an increased likelihood of heavy bleeding (Odds Ratio 1.89; 95% confidence interval: 1.25, 2.85) adjusting for recent MD, menopausal status and other covariates. Past MD was not associated with other abnormal bleeding or PMS in the final analysis that adjusted for recent MD.
Midlife women with a past history of MD are more likely to report heavy bleeding.
PMCID: PMC3404212  PMID: 22510936
major depression; bleeding; menstrual cycle; midlife
9.  Mood Symptoms After Natural Menopause and Hysterectomy With and Without Bilateral Oophorectomy Among Women in Midlife 
Obstetrics and Gynecology  2012;119(5):935-941.
To examine whether mood symptoms increased more for women in the years after hysterectomy with or without bilateral oophorectomy relative to natural menopause.
Using data from the Study of Women’s Health Across the Nation (n=1,970), depression and anxiety symptoms were assessed annually for up to 10 years with the Center for Epidemiological Studies Depression Index and four anxiety questions, respectively. Piecewise hierarchical growth models were used to relate natural menopause, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy to trajectories of mood symptoms before and after the final menstrual period or surgery. Covariates included educational attainment, race, menopausal status, age the year prior to final menstrual period or surgery, and time-varying body mass index, self-rated health, hormone therapy, and antidepressant use.
By the 10th annual visit, 1,793 (90.9%) women reached natural menopause, 76 (3.9%) reported hysterectomy with ovarian conservation, and 101 (5.2%) reported hysterectomy with bilateral oophorectomy. For all women, depressive and anxiety symptoms decreased in the years after final menstrual period or surgery. These trajectories did not significantly differ by hysterectomy or oophorectomy status. The Center for Epidemiological Studies Depression Index means were .72 standard deviations lower, and anxiety symptoms .67 standard deviations lower, five years after final menstrual period or surgery.
In this study, mood symptoms continued to improve after the final menstrual period or hysterectomy for all women. Women who undergo a hysterectomy with or without bilateral oophorectomy in midlife do not experience more negative mood symptoms in the years after surgery.
PMCID: PMC3339661  PMID: 22525904
10.  Role Stress, Role Reward, and Mental Health in a Multiethnic Sample of Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN) 
Journal of Women's Health  2012;21(5):481-489.
Little is known about the independent associations of reward and stress within specific roles with multiple measures of mental health in an ethnically diverse community sample of midlife women. The objective of this study is to examine if (1) role reward (within each role and across roles) contributes directly to mental health and buffers the negative impact of role stress and (2) associations among role occupancy, role stress, and role reward and mental health vary by race/ethnicity.
With separate logistic regression analysis, we investigated cross-sectional relationships between role stress and role reward with presence/absence of high depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D≥16]), anxiety symptoms (feeling tense or nervous, irritable or grouchy, fearful for no reason, and heart pounding or racing total score≥4), or low social functioning (bottom 25th percentile of the Short-Form-36 [SF-36] social functioning subscale) in 2549 women participating in the third visit of the Study of Women's Health Across the Nation (SWAN), a longitudinal population-based study of menopause.
High reward across roles attenuated the negative impact of role stress on social functioning but not on anxiety or depression. High reward marriage buffered the impact of marital stress on depression, and high reward mothering buffered the effect of maternal stress on depression and social functioning. Compared to Caucasians, Hispanics and Chinese with high stress across roles had better social functioning, and African American mothers had lower odds of high depressive symptoms.
Role reward buffers the negative impact of stress on social functioning and depression, but not on anxiety. Minorities may respond to role stress by seeking social support.
PMCID: PMC3353828  PMID: 22360697
11.  Lifetime History of Depression and Anxiety Disorders Predicts Low Quality-of-Life in Midlife Women in the Absence of Current Illness Episodes 
Archives of general psychiatry  2012;69(5):484-492.
It is unknown whether a previous history of depression, anxiety disorders, or comorbid depression and anxiety influences subsequent health-related quality-of-life (HRQL) during midlife in women when vasomotor symptoms (VMS) and sleep disturbance commonly disrupt quality-of-life.
We evaluated whether prior affective illness is associated with low HRQL during midlife in the absence of current illness episodes, and whether low HRQL is explained by VMS or sleep disruption.
Longitudinal, community-based.
Western Pennsylvania.
425 midlife women in the Study of Women’s Health Across the Nation who completed the SCID and SF-36 annually during 6-years of follow-up.
Outcome Measures
SF-36 scales of social functioning (SF), role-emotional (RE), role-physical (RP), body pain (BP), and vitality.
97 (22.8%) women had comorbid affective illness histories, 162 (38.1%) had prior depression only, and 21 (4.9%) had prior anxiety only. Those with comorbid illness histories and depression alone were more likely to report low HRQL on SF, RE, RP, and BP domains (ORs=2.31–3.54 and 1.59–2.28, respectively) than women with neither disorder. After adjustment for VMS and sleep disturbance, the comorbid group continued to have low HRQL on these domains (ORs=2.13–3.07), whereas the association was significant on SF and BP only for the depression-alone group (ORs= 2.08, 1.95, respectively). Compared to women with neither disorder, the anxiety-only group had low HRQL on the RP domain (OR 2.60). Sleep disturbance, but not VMS, was independently associated with low HRQL on all domains except for RE.
A prior history of both depression and anxiety has the most robust negative effect on HRQL in women during midlife, an association not explained by VMS or sleep disturbance. For the depression-alone group, sleep disturbance may partially explain the negative impact of prior affective illness on HRQL. Sleep disturbance remains an independent correlate of low HRQL.
PMCID: PMC3584338  PMID: 22566580
12.  Major Depression During and After the Menopausal Transition: Study of Women’s Health Across the Nation (SWAN) 
Psychological medicine  2011;41(9):1879-1888.
It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to premenopause.
To examine whether the odds of experiencing major depression were greater when women were perimenopausal or postmenopausal compared to when they were premenopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms, serum levels or changes in estradiol, follicular stimulating hormone, or testosterone and relevant confounders.
Participants included the 221 African American and Caucasian women, aged 42–52, who were premenopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women’s Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual, and current major depression at baseline and annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones were obtained annually.
Women were two to four times more likely to experience major depression episode when they were perimenopausal or early postmenopausal. Repeated measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, vasomotor symptoms and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study.
The risk of major depression is greater for women during and immediately after the menopausal transition than when they are premenopausal.
PMCID: PMC3584692  PMID: 21306662
13.  Negative Affect and Vasomotor Symptoms in the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study 
Menopause (New York, N.Y.)  2011;18(12):1270-1277.
Vasomotor symptoms (VMS) are common during the menopausal transition. Negative affect is consistently associated with self-reported VMS, but interpretation of this relationship is limited by infrequent measurement and retrospective recall of VMS. Using prospective data from daily diaries, we examined the daily association between negative affect and reported VMS, as well as temporal associations between negative affect and next day VMS, and VMS and next day negative affect.
Data were derived from the third wave of the Daily Hormone Study (DHS) (n=625). DHS is a substudy of the Study of Women's Health Across the Nation (SWAN), a multi-site community-based prospective cohort study of the menopausal transition. Participants reported VMS and affect in daily diaries for 12–50 days. Multilevel mixed models were used to determine the associations between reported VMS and negative affect, adjusted by antidepressant use, age, education, menopausal status, self-reported health, and race/ethnicity drawn from annual SWAN visits.
VMS were reported by 327 women (52.3%). Negative affect was positively associated with VMS (OR 1.76, 95% CI 1.43–2.17, p<.001) in cross-sectional analyses. Negative affect, adjusted by same day VMS, was not predictive of next day VMS (OR 1.11, 95% CI .85–1.35, p=.55), whereas VMS, adjusted by same day negative affect, was predictive of negative affect the next day (OR 1.27, 95% CI 1.03–1.58, p=.01).
Negative affect was more likely to be reported on the same day and the day after VMS. Potential mechanisms underlying this relationship include negative cognitive appraisal, sleep disruption, and unmeasured third factors.
PMCID: PMC3230697  PMID: 21900850
affect; menopause; vasomotor symptoms
14.  Mood and Menopause: Findings from the Study of Women’s Health Across the Nation (SWAN) over ten years 
Women are twice as likely as men to suffer from depressive symptoms and disorder. Considerable research has focused on the physiological and psychosocial differences between men and women as sources of depression. An important target of study has been the periods of reproductive changes and events that occur at puberty, postpartum and menopause. A controversy has existed regarding the extent to which, if at all, the menopausal transition or postmenopause increases the risk for elevated depressive symptoms and/or disorders. SWAN provided an opportunity to address the issue with the largest, most representative and diverse cohort currently available for study. The current paper presents the findings from analyses conducted on data collected from the larger core SWAN study and an ancillary study on mental health begun in Pittsburgh in 1995. We found, as did four other recent longitudinal studies, that risk for high depressive symptoms and disorder is greater during and possibly after the menopausal transition. Multiple other factors contribute to risk for depression in our SWAN cohort.
PMCID: PMC3197240  PMID: 21961723
menopause; mood; depression; risk factors
15.  The effect of age on clinical outcomes and health status in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial (BARI 2D) 
The objective was to determine the extent to which effectiveness of cardiac and diabetes treatment strategies varies by patient age.
The impact of age on the effectiveness of revascularization and hyperglycemia treatments has not been thoroughly investigated.
In BARI 2D, 2368 patients with documented stable heart disease and type 2 diabetes were randomized to receive prompt revascularization versus initial medical therapy with deferred revascularization and insulin-sensitization versus insulin-provision for hyperglycemia treatment. Patients were followed for an average of 5.3 years. Cox regression and mixed models were used to investigate the effect of age and randomized treatment assignment on clinical and health status outcomes.
The effect of prompt revascularization versus medical therapy did not differ by age for death (interaction p=0.99), major cardiovascular events (interaction p=0.081), angina (interaction p=0.98) or health status outcomes. After intervention, participants of all ages had significant angina and health status improvement. Younger participants experienced a smaller decline in health status during follow-up than older participants (age by time interaction p<0.01). The effect of the randomized glycemia treatment on clinical and health status outcomes was similar for patients of different ages.
Among patients with stable heart disease and type 2 diabetes, relative beneficial effects of a strategy of prompt revascularization versus initial medical therapy, and insulin-sensitizing versus insulin-providing therapy on clinical endpoints, symptom relief, and perceived health status outcomes do not vary by age. Health status improved significantly after treatment for all ages, and this improvement was sustained longer among younger patients.
PMCID: PMC3164969  PMID: 21835316
age; coronary heart disease; diabetes mellitus; revascularization; health status
16.  BMI and Health Status in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial (BARI 2D) 
American heart journal  2011;162(1):184-192.e3.
The longitudinal association between obesity, weight variability and health status outcomes is important for patients with coronary disease and diabetes.
The Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI 2D) was a multi-center randomized clinical trial to evaluate the best treatment strategy for patients with both documented stable ischemic heart disease and type 2 diabetes. We examined BARI 2D participants for four years to study how BMI was associated with health status outcomes. Health status was evaluated by the Duke Activity Status Index (DASI), RAND Energy/fatigue, Health Distress, and Self-rated health. BMI was measured quarterly throughout follow-up years, and health status was assessed at each annual follow-up visit. Variation in BMI measures was separated into between-person and within-person change in longitudinal analysis.
Higher mean BMI over follow-up years (the between-person BMI) was associated with poorer health status outcomes. Decreasing BMI (the within-person BMI change) was associated with better Self-rated health. The relationships between BMI variability and DASI or Energy appeared to be curvilinear, and differed by baseline obesity status. Decreasing BMI was associated with better outcomes if patients were obese at baseline, but was associated with poorer DASI and Energy outcomes if patients were non-obese at baseline.
For patients with stable ischemic heart disease and diabetes, weight gain was associated with poorer health status outcomes, independent of obesity-related comobidities. Weight reduction is associated with better functional capacity and perceived energy for obese patients but not for non-obese patients at baseline.
PMCID: PMC3141323  PMID: 21742107
BMI; obesity; coronary disease; diabetes mellitus; health status
17.  Depressive Symptoms are Related to Progression of Coronary Calcium in Midlife Women: The Study of Women’s Health Across the Nation (SWAN) Heart Study 
American heart journal  2011;161(6):1186-1191.e1.
Major depression and depressive symptoms are associated with cardiovascular disease (CVD), but the impact of depression on early atherogenesis is less well known, particularly in women and minorities. This study examined whether depressive symptoms are associated with progression of coronary artery calcification (CAC) among women at mid-life.
The Study of Women’s Health Across the Nation (SWAN) is a longitudinal, multi-site study assessing health and psychological factors in mid-life women. An ancillary study (SWAN Heart) evaluated subclinical atherosclerosis in women who reported no history of CVD or diabetes. In 346 women, CAC was measured twice by electron beam computed tomography, an average of 2.3 years apart. Progression, defined as an increase by 10 Agatston units or more, was analyzed using relative risk regression. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression (CES-D) Scale.
Progression of CAC was observed in 67 women (19.1%). Each 1–SD higher CES-D score at baseline related to a 25% increased risk of CAC progression [RR 1.25, CI 1.06–1.47, p=0.007], adjusting for age, time between scans, ethnicity, education, menopausal status, and known CVD risk factors. This risk was similar to the risk induced by BMI [RR 1.31, CI 1.11–1.54, p=0.001] and systolic blood pressure [RR 1.28, CI 1.06–1.55, p=0.01].
Depressive symptoms were independently associated with progression of CAC in this cohort of midlife women. Depressive symptoms may represent a risk factor that is potentially modifiable for early prevention of CVD in women.
PMCID: PMC3140211  PMID: 21641367
atherosclerosis; coronary calcium; women; depression; epidemiology
18.  Negative attitudes and affect do not predict elective hysterectomy: A prospective analysis from the Study of Women's Health Across the Nation 
Menopause (New York, N.Y.)  2011;18(5):499-507.
Cross-sectional studies suggest an association between hysterectomy and negative affect. Using prospective data, we examined the associations of negative affect, attitudes toward aging and menopause, premenstrual symptoms and vasomotor symptoms with elective hysterectomy in midlife.
Data were from the Study of Women's Health Across the Nation, a multi-site community-based prospective cohort study of the menopausal transition (n=2,818). Annually reported hysterectomy at visits 2-9 was verified with medical records when available (71%). Anxiety, perceived stress, depressive symptoms, attitudes toward aging and menopause, vasomotor symptoms, and premenstrual symptoms were assessed at baseline using standardized questions. Cox proportional hazards models were used to relate these variables to subsequent elective hysterectomy. Covariates included demographic variables, menstrual bleeding problems, body mass index, hormone levels, and self-rated health, also assessed at baseline.
Elective hysterectomy was reported by 6% of participants (n=168) over an 8-year period. Women with hysterectomy were not higher in negative affect or negative attitudes toward aging and menopause compared to women without hysterectomy. Vasomotor symptoms (HR 1.44, 95% CI 1.03-2.01, p=.03) and positive attitudes toward aging and menopause (HR 1.74, 95% CI 1.04-2.93) at baseline predicted hysterectomy over the 8-year period, controlling for menstrual bleeding problems, site, race/ethnicity, follicle stimulating hormone, age, education, body mass index, and self-rated health. Menstrual bleeding problems at baseline were the strongest predictor of hysterectomy (HR 4.30, 95% CI 2.05-9.05).
In this prospective examination, negative affect and attitudes were not associated with subsequent hysterectomy. Menstrual bleeding problems were the major determinant of elective hysterectomy.
PMCID: PMC3123400  PMID: 21228728
hysterectomy; affect; menopause; vasomotor symptoms
19.  Development of the Barkin Index of Maternal Functioning 
Journal of Women's Health  2010;19(12):2239-2246.
Maternal functional status is important to capture in the 12 months after childbirth, as this period marks a critical window for both mother and child. In most cases, mothers are the primary caregivers and are, therefore, responsible for the majority of the work related to infant care tasks, such as feeding, diaper changes, and doctor's appointments. Additionally, the quality of mother-child interaction in the year after childbirth affects child development. To date, postpartum functioning has exacted scarce coverage, with only one instrument claiming to measure the concept explicitly. This necessitated the development of the Barkin Index of Maternal Functioning (BIMF), which was designed to measure functioning in the year after childbirth.
Three focus groups comprised of 31 new mothers were held to elicit women's concept of functioning in the first postpartum year. Women were asked to discuss the responsibilities associated with new motherhood as well as the circumstances surrounding high and low functioning periods.
The qualitative data produced by the focus groups were coded by emotive tone and content and translated into item construction for the BIMF, a 20-item self-report measure of functioning intended for use in the year after childbirth. Before implementation into the screening study, the BIMF was critiqued by a panel of experts and cross-checked with the literature to ensure that no major contextual domains were absent. Psychometric testing revealed adequate internal reliability and construct validity, and the BIMF has been implemented successfully in clinical settings.
The high level of patient engagement and psychometric properties associated with the BIMF are indicative of its potential to become a valuable tool for assessing maternal wellness.
PMCID: PMC3003914  PMID: 21054183
20.  Physical functioning among mid-life women: associations with trajectory of depressive symptoms 
Social science & medicine (1982)  2010;71(7):1259-1267.
During midlife, physical functioning limitations emerge and depressive symptoms are highly prevalent. We examined the relationship between physical functioning and depressive symptoms in the Michigan Study of Women's Health Across the Nation (SWAN) cohort of midlife women (n=377). Seven performance-based physical functioning measures quantifying strength, balance, coordination, flexibility and range of motion and perceived physical functioning, assessed with the SF-36 physical functioning sub-score, were included. The Center for Epidemiological Studies Depression Scale (CES-D) identified concurrent depressive symptom trajectory from 2000/01 through 2005/06 and history of depressive symptoms from 1996/7 through 1999/00. Longitudinal mixed-effects regression modeling was used to evaluate relationships. Median age of participants was 50 years. As age increased, higher CES-D scores were associated with performance-based functions including slower timed walk sit-to-stand, and stair climb after adjusting for five-year history of depressive symptoms and relevant covariates. As age increased, those with higher CES-D scores were more likely to have perceived limitations in physical functioning, though the association was weak. History of depressive symptoms was not significant in any model. These findings suggest that higher concurrent depressive symptoms are modestly associated with slower movement and a perception of poorer functioning. In contrast, history of depressive symptoms played little or no role in current physical functioning of mid-life women. When evaluating physical function, women's current mental health status should be considered.
PMCID: PMC2937172  PMID: 20692082
physical functioning; depression; women; midlife; USA; age
21.  Recurrent Major Depression Predicts Progression of Coronary Calcification in Healthy Women: Study of Women’s Health across the Nation 
Psychosomatic medicine  2010;72(8):742-747.
Depressive symptoms and major depression are risk factors for clinical coronary heart disease (CHD) among CHD patients and among healthy individuals. It is less clear whether depression is related to the progression of atherosclerosis prior to the onset of CHD events.
Longitudinal cohort study
149 middle-aged healthy women (113 white and 36 African American) who reported no heart disease, stroke, or diabetes were enrolled simultaneously in two ancillary studies of the Study Women’s Health across the Nation (SWAN) at the Pittsburgh site: the Mental Health Study and the SWAN Heart Study. These women were administered psychiatric interviews annually and coronary calcification computed tomography measures (CAC) on two occasions approximately 2¼ years apart.
Women who had recurrent major depression (N = 33) had greater progression of CAC (logged difference scores) than did women with a single or no episodes, b = 0.09 (0.04), p = .01. The other significant covariates were BMI, SBP, initial CAC, and time between scans. Stratified analyses showed that the effect was obtained in those women who had any CAC at the first examination.
Recurrent major depression may be a risk factor for progression of atherosclerosis, especially in those who have at least some initial calcification. Women with a history of depression may be candidates for aggressive cardiovascular risk factor prevention therapy.
PMCID: PMC2950893  PMID: 20668281
Depression; coronary calcification; women; longitudinal
22.  Longitudinal Change in Reproductive Hormones and Depressive Symptoms Across the Menopausal Transition 
Archives of general psychiatry  2010;67(6):598-607.
The contribution of reproductive hormones to mood has been the focus of considerable research. Results from clinical and epidemiological studies have been inconsistent. It remains unclear whether alterations in serum hormone levels across the menopausal transition are linked to depressive symptoms.
To evaluate the relationship between serum hormone levels and high depressive symptoms and whether hormone levels or their change might explain the association of menopausal status with depressive symptoms previously reported in a national sample of midlife women.
A longitudinal, community-based, multisite study of menopause. Data were collected at baseline and annually from December 1995 to January 2008 on a range of factors. Early follicular phase serum samples were assayed for levels of estradiol, follicle-stimulating hormone, testosterone, and dehydroepiandrosterone sulfate.
Seven communities nationwide.
A community-based sample of 3302 multiethnic women, aged 42 to 52 years, still menstruating and not using exogenous reproductive hormones.
Main Outcome Measure
Depressive symptoms assessed with the Center for Epidemiological Studies Depression Scale (CES-D). The primary outcome was a CES-D score of 16 or higher.
In multivariable random-effects logistic regression models, log-transformed testosterone level was significantly positively associated with higher odds of a CES-D score of 16 or higher (odds ratio=1.15; 95% confidence interval, 1.01–1.31) across 8 years, and a larger increase in log-transformed testosterone from baseline to each annual visit was significantly associated with increased odds of a CES-D score of 16 or higher (odds ratio=1.23; 95% confidence interval, 1.04–1.45). Less education, being Hispanic, and vasomotor symptoms, stressful life events, and low social support at each visit were each independently associated with a CES-D score of 16 or higher. No other hormones were associated with a CES-D score of 16 or higher. Being perimenopausal or post-menopausal compared with being premenopausal remained significantly associated with a CES-D score of 16 or higher in all analyses.
Higher testosterone levels may contribute to higher depressive symptoms during the menopausal transition. This association is independent of menopausal status, which remains an independent predictor of higher depressive symptoms.
PMCID: PMC3129620  PMID: 20530009
23.  Childhood Abuse is Associated with Adiposity in Mid-life Women: Possible Pathways through Trait Anger and Reproductive Hormones 
Psychosomatic medicine  2010;72(2):215-223.
To examine the association between childhood abuse/neglect and central adiposity and obesity in a sample of 311 women (106 Black, 205 White) from the Pittsburgh site of the Study of Women's Health Across the Nation (SWAN).
SWAN included a baseline measurement of women in midlife (mean age = 45.7) and 8 follow-up visits during which waist circumference (WC) and body mass index (BMI) were measured. The Childhood Trauma Questionnaire retrospectively assessed emotional, physical, and sexual abuse and emotional and physical neglect in childhood.
ANCOVA analyses showed that women with a history of any abuse/neglect, and specifically physical and sexual abuse, had significantly higher WC and BMI at baseline than women with no abuse history. A significant interaction between abuse and BMI showed that among women with BMI < 30, any abuse/neglect and certain subtypes of abuse predicted greater increases in WC over time. Additional analyses showed that Trait Anger scores and sex hormone-binding globulin (SHBG) attenuated cross-sectional relationships between abuse/neglect and WC and BMI.
This study suggests that abused/neglected women appear to have greater anger and lower levels of SHBG, which are associated with adiposity in mid-life.
PMCID: PMC2832915  PMID: 20064904
abuse; neglect; adiposity; obesity; women; anger
24.  Are there Bi-directional Associations between Depressive Symptoms and C-Reactive Protein in Mid-life Women? 
Brain, behavior, and immunity  2009;24(1):96-101.
To test whether depressive symptoms are related to subsequent C-reactive protein (CRP) levels and/or whether CRP levels are related to subsequent depressive symptoms in mid-life women.
Women enrolled in the Study of Women's Health Across the Nation (SWAN) were followed for seven years and had measures of CES-Depression scores and CRP seven times during the follow-up period. Women were pre- or early peri-menopausal at study entry and were of Caucasian, African American, Hispanic, Japanese, or Chinese race/ethnicity. Analyses were restricted to initially healthy women.
Longitudinal mixed linear regression models adjusting for age, race, site, time between exams, and outcome variable at year X showed that higher CES-D scores predicted higher subsequent CRP levels and vice versa over a 7-year period. Full multivariate models adjusting for body mass index, physical activity, medications, health conditions, and other covariates showed that higher CRP levels at year X predicted higher CES-D scores at year X+1, p = 0.03. Higher depressive symptoms predicted higher subsequent CRP levels at marginally significant levels, p=0.10.
Higher CRP levels led to higher subsequent depressive symptoms, albeit the effect was small. The study demonstrates the importance of considering bi-directional relationships for depression and other psychosocial factors and risk for heart disease.
PMCID: PMC2844108  PMID: 19683568
Depression; inflammation; menopause; women; longitudinal; C-reactive protein
25.  Longitudinal Associations Between Depression and Functioning In Midlife Women 
Maturitas  2009;64(3):145-159.
Associations between depression and impaired functioning are well known and have been documented in numerous clinical, primary care and epidemiological studies. Reviews of this research have focused on the elderly. Recent studies suggest that women become increasingly vulnerable during the menopausal transition to declines in physical and role function and increases in depressive symptoms. The purpose of the current research is to review the literature since 1966 for studies examining the association between depression and physical and psychosocial impairment in midlife women. We selected only longitudinal studies that had the potential to elucidate the nature of the complex relationship between depression and functioning. Results of the review indicate evidence for bi-directional associations between depression and functioning in middle-aged women. However, the studies are only broadly informative. Most adjusted for only a limited group of factors that could be associated with both depression and functioning. None of them directly examined potential moderators or mediators of the relationship between depression and impaired functioning.
PMCID: PMC2791530  PMID: 19854010
Depression; functioning; females; middle-aged; longitudinal

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