Ping G. Tepper

Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition

IMPORTANCE The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS The Study of Womens Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Depressive symptoms in Chinese children and adolescents: Parent, teacher, and self reports

BACKGROUND Most studies of depressive symptoms in children and adolescents have been conducted in Western countries. This study was designed to examine depressive symptoms and age and gender differences in children and adolescents in China. METHODS Participants consisted of two community samples of children and adolescents (n1=4858, n2=1362) in Shandong, China. Child Behavior Checklist (CBCL), Teacher Report Form (TRF) and Youth Self Report (YSR) were used to assess depressive symptoms. RESULTS Using American norms, the prevalence rates of depression in Chinese children and adolescents were 5.9% with self report, 0.9% with parent report, and 0.8% with teacher report. Self and teacher-reported depressive symptoms were significantly increased with age for both boys and girls. Compared with American norms, self-reported depressive scores were significantly higher in Chinese adolescents, while parent and teacher-reported scores were significantly lower in Chinese children. LIMITATIONS Our study lacks clinical assessment of depressive symptoms and the study is comprised of two separate samples where parent and teacher reports and youth reports could not be compared directly. CONCLUSIONS The prevalence of self-reported depressive symptoms in Chinese children and adolescents are much higher than those reported by either parents or teachers. Depressive symptoms are increased with age but do not differ between boys and girls.

Lactation and Maternal Measures of Subclinical Cardiovascular Disease

OBJECTIVE: To examine the relationship between lactation and subclinical cardiovascular disease in a population free of clinical cardiovascular disease. METHODS: We conducted a cross-sectional analysis of 297 women who reported at least one live birth on enrollment in the Study of Women Across the Nation–Heart Study. Participants were mothers aged 45–58 years who were free of clinical cardiovascular disease. History of lactation was self-reported. Electron beam tomography was used to assess coronary and aortic calcification. B-mode ultrasonography was used to assess carotid adventitial diameter, intima–media thickness, and carotid plaque. Multivariable linear and logistic regression models were used to estimate whether lactation was independently associated with markers of subclinical cardiovascular disease. RESULTS: In unadjusted models, compared with mothers who had breastfed all of their children for at least 3 months, mothers who had not breastfed were more likely to have coronary artery calcification (17% compared with 32%), aortic calcification (17% compared with 39%), carotid plaque (10% compared with 18%), and larger carotid adventitial diameters (mean±standard deviation 6.63±0.59 compared with 6.87±0.60 mm). After adjusting for measures of socioeconomic status and lifestyle and family history variables, mothers who had not breastfed remained more likely to have aortic calcification (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.47–10.00) and coronary artery calcification (OR 2.78, 95% CI 1.05–7.14) than mothers who had consistently breastfed. After further adjustment for body mass index and traditional risk factors for cardiovascular disease, mothers who had not breastfed remained more likely to have aortic calcification than mothers who had consistently breastfed (OR 5.26, 95% CI 1.47–20.00). CONCLUSION: Mothers who do not breastfeed their infants seem to be at increased risk of vascular changes associated with future cardiovascular disease. LEVEL OF EVIDENCE: II

Do Changes in Sex Steroid Hormones Precede or Follow Increases in Body Weight during the Menopause Transition? Results from The Study of Women's Health Across the Nation

CONTEXT Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. OBJECTIVE The objective of the study was to characterize the potential reciprocal nature of the associations between sex hormones and their binding protein with waist circumference in midlife women. DESIGN, SETTING, AND PARTICIPANTS The study included 1528 women (mean age 46 yr) with 9 yr of follow-up across the menopause transition from the observational Study of Womens Health Across the Nation. MAIN OUTCOME MEASURES Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. RESULTS Current waist circumference predicted future SHBG, testosterone, and FSH but not vice versa. For each SD higher current waist circumference, at the subsequent visit SHBG was lower by 0.04-0.15 SD, testosterone was higher by 0.08-0.13 SD, and log(2) FSH was lower by 0.15-0.26 SD. Estradiol results were distinct from those above, changing direction across the menopause transition. Estradiol and waist circumference were negatively associated in early menopausal transition stages and positively associated in later transition stages (for each SD higher current waist circumference, future estradiol was lower by 0.15 SD in pre- and early perimenopause and higher by 0.38 SD in late peri- and postmenopause; P for interaction <0.001). In addition, they appeared to be reciprocal, with current waist circumference associated with future estradiol and current estradiol associated with future waist circumference. However, associations in the direction of current waist circumference predicting future estradiol levels were of considerably larger magnitude than the reverse. CONCLUSIONS These Study of Womens Health Across the Nation data suggest that the predominant temporal sequence is that weight gain leads to changes in sex steroids rather than vice versa.

Trajectory Clustering of Estradiol and Follicle-Stimulating Hormone during the Menopausal Transition among Women in the Study of Women's Health across the Nation (SWAN)

CONTEXT Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined. OBJECTIVE The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories. DESIGN The Study of Womens Health Across the Nation is a longitudinal observational study of the menopausal transition. SETTING Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits. PARTICIPANTS Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study. MAIN OUTCOME MEASURES Annual serum E2 and FSH levels anchored to final menstrual period were measured. RESULTS Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories. CONCLUSIONS E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition.

Daily psychological demands are associated with 6-year progression of carotid artery atherosclerosis: the Pittsburgh Healthy Heart Project.

Objective We examine associations between the perception of ongoing psychological demands by ecological momentary assessment (EMA) and 6-year changes in carotid artery atherosclerosis by ultrasonography. Methods A total of 270 initially healthy participants collected ambulatory blood pressure (ABP) and recorded their daily experiences, using electronic diaries, during two 3-day periods. Mean intima-media thickness (IMT) and plaque were assessed in the carotid arteries using B-mode ultrasound at baseline and again during a 6-year follow-up (mean follow-up duration = 73 months). Results Among those who had no exposure to antihypertensive medications during the course of follow-up (n = 192), daily psychological demands were associated with greater progression of IMT as well as plaque, after adjusting for demographic and risk factor covariates. Associations between demands and plaque change were partially accounted for by ABP differences among those reporting high demands. Among those who were employed at baseline (n = 117), 6-year IMT changes were more strongly associated with ratings of daily demands than with traditional measures of occupational stress. Conclusions These data support the role of psychological demands as a correlate of subclinical atherosclerotic progression, they point to ABP as a potential mechanism facilitating these effects, and they highlight the utility of EMA measures for capturing daily psychological demands with potential effects on health. Abbreviations CVD = cardiovascular disease IMT = intima-media thickness ABP = ambulatory blood pressure EMA = ecological momentary assessment BP = blood pressure SBP = systolic blood pressure DBP = diastolic blood pressure JCQ = Job Content Questionnaire PHHP = Pittsburgh Healthy Heart Project

Serum aldosterone is associated with inflammation and aortic stiffness in normotensive overweight and obese young adults

Circulating aldosterone is increased in obesity and is associated with arterial stiffening in hypertensives and older adults. The aim of this article was to determine whether serum aldosterone is associated with pulse wave velocity (PWV), a measure of arterial stiffness, in normotensive overweight and obese adults aged 20–45 years (n = 344). Heart-femoral, femoral-ankle, and brachial-ankle PWV were measured. The sample was 77% female with mean body mass index 32.9 kg/m2 (SD 3.9), median serum aldosterone 106.5 pg/mL (interquartile range 79.9, 155.5), and mean 24-hour urinary sodium excretion 185.9 mEq/day (SD 69.6). Higher serum aldosterone was not significantly correlated with any PWV measure in bivariate analysis. However, in multiple linear regression, adjusting for age, sex, race, height, heart rate, mean arterial pressure, and waist circumference, higher log aldosterone was associated with greater log heart-femoral PWV (β(se) = 0.042(0.021), P = .049). After adjusting for C-reactive protein, this association was no longer significant (β(se) = 0.035(0.021), P = .10). Circulating aldosterone may play an important role in vascular inflammation and aortic stiffening in normotensive overweight and obese adults.

Breastfeeding and Subsequent Maternal Visceral Adiposity

Women gain visceral fat during pregnancy. Studies examining the impact of breastfeeding on maternal body composition are inconclusive. We examined the extent to which breastfeeding was associated with visceral adiposity in a sample of US women. This was a cross‐sectional analysis of 351 women aged 45–58 years, who were free of clinical cardiovascular disease and had not used oral contraceptives or hormone replacement therapy in the 3 months prior to enrollment in the Study of Womens Health Across the Nation (SWAN)‐Heart Study (2001–2003). History of breastfeeding was self‐reported. Computed tomography was used to assess abdominal adiposity. Among premenopausal/early‐peri‐menopausal mothers, those who never breastfed had 28% greater visceral adiposity (95% confidence interval (CI): 11–49, P = 0.001), 4.7% greater waist‐hip ratio (95% CI: 1.9–7.4, P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71–9.26, P < 0.001) than mothers who breastfed all of their children for ≥3 months in models adjusting for study site; age; parity; years since last birth; socioeconomic, lifestyle, and family history variables; early adult BMI; and current BMI. In comparison to women who were nulliparous, mothers who breastfed all of their children for ≥3 months had similar amounts of visceral fat (P > 0.05). In contrast, premenopausal/early‐peri‐menopausal mothers who had never breastfed had significantly greater visceral adiposity (42% (95% CI: 17–70), P < 0.001), waist circumference (6.15 cm (95% CI: 2.75–9.56), P < 0.001), and waist‐hip ratio (3.7% (95% CI: 0.69–6.8), P = 0.02) than nulliparous women. No significant relationships were observed among late peri‐menopausal/postmenopausal women. In conclusion, until menopause, mothers who did not breastfeed all of their children for ≥3 months exhibit significantly greater amounts of metabolically active visceral fat than mothers who had breastfed all of their children for ≥3 months.

Perivascular adipose tissue of the descending thoracic aorta is associated with systemic lupus erythematosus and vascular calcification in women

OBJECTIVE Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Traditional CVD and SLE-disease related risk factors do not fully account for this increased risk. Perivascular adipose tissue (PVAT) is a visceral adipose depot in close proximity to blood vessels possibly influencing CVD. We hypothesized that women with SLE have an increased volume of descending thoracic aortic PVAT (aPVAT) associated with increased vascular calcification. METHODS Using electron beam computed tomography, we quantified the aPVAT in clinically CVD-free SLE women (n = 135) and age-/race-matched healthy controls (HC, n = 152). Coronary artery calcification (CAC) and aortic calcification (AC) were quantified using Agatston scores and the aPVAT was quantified using standard Hounsfield Units (HU) for adipose tissue. RESULTS Women with SLE had greater median aPVAT (32.2 cm(3) vs HC aPVAT 28.6 cm(3), p = 0.0071) and greater median AC (26.0 vs HC AC 6.0, p = 0.0013) than the healthy control women. Total aPVAT (per 25 cm(3)) remained significantly associated with SLE after adjusting for CVD risk factors (Odds Ratio 1.74 [95% Confidence Interval: 1.04-2.9], p = 0.034), but was attenuated when adjusting for circulating inflammatory markers (p = 0.34). In a logistic regression analysis, SLE aPVAT (per 25 cm(3)) was associated with AC (6.78 [2.0-23], p = 0.0019), which remained significant after adjusting for circulating inflammatory markers (p = 0.0074), and CAC (2.66 [1.4-5.0], p = 0.0028). CONCLUSIONS Total aPVAT is greater in clinically CVD-free SLE women than in age-/race-matched controls and is associated with calcification in different vascular beds.

Characterizing the trajectories of vasomotor symptoms across the menopausal transition

Objective:The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women. Methods:The Study of Womens Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling. Results:Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory. Conclusions:These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.