Publications

The North American Menopause Society held the 2019 Pre-Meeting Symposium on September 25, 2019, in Chicago, Illinois, to review the current state of the science related to the physiology of the perimenopause and to address management of the most prevalent and pressing clinical issues. The perimenopause, as defined by the Stages of Reproductive Aging Workshop + 10, encompasses the menopause transition as well as the first year following menopause, the final menstrual period. This phase in the continuum of women's reproductive lives had been one of the least well understood. Fortunately, contributions from a number of prospective, longitudinal, decades-long studies have provided a better understanding of the perimenopause, whereas posing important new questions related to symptom interaction and linkages between symptoms and long-term health. There is now added clarity to distinguish the effects of reproductive hormonal changes from aging. The variation in symptoms, including vasomotor symptoms, among women over time including differences in experiences by ethnicity and race, provides paradigm shifts in clinical perspective. Refinements in understanding the character, timing, and potential predictive markers for menstrual cycles during the transition have emerged. From the perspective of myriad clinical management challenges, significant progress in recommendations for evaluation and therapeutic approaches has been achieved. Finally, recognizing the menopause transition as an opportunity to initiate positive lifestyle changes to enhance future health was emphasized.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial.

METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review.

RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P<0.001). The number of serious errors unitwide were likewise higher during the intervention schedules (181.3 vs. 131.5 per 1000 patient-days; relative risk, 1.56; 95% CI, 1.43 to 1.71). There was wide variability among sites, however; errors were lower during intervention schedules than during control schedules at one site, rates were similar during the two schedules at two sites, and rates were higher during intervention schedules than during control schedules at three sites. In a secondary analysis that was adjusted for the number of patients per resident physician as a potential confounder, intervention schedules were no longer associated with an increase in errors.

CONCLUSIONS: Contrary to our hypothesis, resident physicians who were randomly assigned to schedules that eliminated extended shifts made more serious errors than resident physicians assigned to schedules with extended shifts, although the effect varied by site. The number of ICU patients cared for by each resident physician was higher during schedules that eliminated extended shifts. (Funded by the National Heart, Lung, and Blood Institute; ROSTERS ClinicalTrials.gov number, NCT02134847.).

OBJECTIVE: Dysregulated responses to experimental stress paradigms may indicate exposure to chronic stress. Vasomotor symptoms (VMS) are linked with diminished quality of life and psychological stress, but induced stress responsivity has received limited investigation. We examined whether women with and without VMS differ in their evoked hypothalamic-pituitary-adrenal axis, subjective, hemodynamic, and thermal stress responses.

METHODS: A total of 37 midlife women (27 VMS+; 10 VMS-) completed 2 experimental stress paradigms: (1) Montreal Imaging Stress Task (MIST; computerized social-evaluative stressor) and (2) Quantitative Sensory Testing (QST; thermal stress task). Responses on a five-domain (range 0-50) Visual Analog Scale, salivary cortisol (hypothalamic-pituitary-adrenal axis), and hemodynamic indices (blood pressure, heart rate) were measured before and after each task to compare within-person change between groups. Thermal sensitivity was assessed on the QST.

RESULTS: On the MIST, the VMS+ group showed a smaller cortisol release (0.01 vs 0.07 μg/dL; P = 0.046; corresponding to 54% vs 83% increases), and subjective stress response (21.2- vs 31.1-point Visual Analog Scale increase, P = 0.05; corresponding to 2427% vs 2863% increases) but no hemodynamic difference, compared to the VMS- group. The QST did not provoke stress responses via cortisol release or subjective report, but the VMS+ group tended to perceive heat at a higher temperature (38.5°C vs 36.4°C, P = 0.08).

CONCLUSIONS: Women with VMS exhibited both diminished cortisol and subjective stress responses to the MIST, and reduced thermal sensitivity on QST compared to women without VMS. Dysregulated stress responsivity provides preliminary evidence suggesting that VMS may represent a chronic stress condition.

OBJECTIVES: The association between sleep and adiposity (indexed by body mass index or waist-to-hip ratio) has typically been evaluated using a single dimension of self-reported sleep. However, other dimensions and behavioral measures of sleep may also be associated with adiposity. This study evaluated whether multidimensional sleep health calculated from actigraphy and self-report was longitudinally associated with adiposity in a sample of midlife women who have a high prevalence of sleep disturbances and adiposity.

DESIGN: Longitudinal study with 11-14 years of follow-up time between the sleep health assessment and body mass index / waist-to-hip ratio measurements.

PARTICIPANTS: Two hundred and twenty-one midlife women enrolled in the Study of Women's Health Across the Nation Sleep Study.

MEASUREMENTS: Multidimensional sleep health was quantified using actigraphy (M[SD] = 29.1[7.2] nights) measures of sleep efficiency, midpoint, duration, regularity, and self-report measures of alertness and satisfaction. Each component was dichotomized and summed; higher values indicated better sleep health. Height, body weight, and waist and hip circumference were measured at the sleep study and at follow-up. Linear regression models were used to assess associations between sleep health and adiposity, adjusting for demographic and menopausal covariates.

RESULTS: There was no substantial within-person change in adiposity over time. Better sleep health was cross-sectionally and longitudinally associated with lower adiposity in unadjusted, but not in adjusted, models. Individual sleep health components were not associated with adiposity after adjustment.

CONCLUSION: We did not observe cross-sectional or longitudinal associations between multidimensional sleep health and adiposity. The sleep-adiposity link may be weaker in midlife adults than in other age groups.

OBJECTIVE: To identify groups of women who share levels and patterns of change in follicle-stimulating hormone (FSH), self-reported sleep maintenance problems, and frequent vasomotor symptoms (VMS) up to 10 years before and after their final menstrual period and to evaluate their premenopausal characteristics.

METHOD: Group-based multi-trajectory modeling grouped 1,407 women from the Study of Women's Health Across the Nation who had an observed natural menopause and did not use hormone therapy, based on repeated measures of FSH, sleep maintenance problems, and frequent VMS relative to final menstrual period. Multivariable analyses assessed race/ethnicity, body mass index, smoking, and depressive symptoms as predictors of group membership.

RESULTS: Women formed five distinct groups: (1) low symptoms (low VMS/sleep problems)/high FSH rise (N = 552; 39.2%); (2) moderate VMS and sleep problems/low FSH rise (N = 169; 12.0%); (3) dominant sleep problems (lower VMS/high sleep problems)/high FSH rise (N = 203; 14.4%); (4) dominant VMS (high VMS/lower sleep problems)/high FSH rise (N = 297; 21.1%)); and (5) high symptoms (high VMS/high sleep problems)/intermediate FSH rise (N = 186; 13.2%)). Multivariate analyses showed that race/ethnicity, premenopausal body mass index and depressive symptoms, and increasing depressive symptoms during the early phase of the transition predicted group membership.

CONCLUSIONS: Women can be classified based on shared levels and patterns of FSH, sleep maintenance problems, and frequent VMS across the menopause transition. Either VMS or sleep maintenance problems can be dominant in the face of high FSH. Experiencing one menopause-related symptom or hormone profile does not automatically imply that another is also being experienced.

The purpose of this study was to examine the potential effect modifying role of the BDNF Val66Met polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas. At enrollment and 2 years later, total heading in the prior 12 months (12-mo.) was estimated using an established self-report instrument and diffusion tensor imaging (DTI) was performed. Generalized Estimating Equations (GEE) logistic regression models were employed to test effect modification by the BDNF Val66Met polymorphism on the association between 12-mo. heading exposure and DTI. We identified a significant interaction of 12-mo heading*BDNF Val66Met genotype on the presence of low Radial Diffusivity, a DTI marker associated with myelination. Only Met (+) players demonstrated significantly reduced odds of low RD [OR (95 % CI): -2.36 (-3.53, -1.19)] associated with the highest vs. lowest quartile of 12-mo heading exposure. BDNF Val66Met (+) soccer players with long-term exposure to high levels of heading exhibit less low Radial Diffusivity, suggesting impaired re-myelination may be a substrate of the previously reported association between heading and poor functional outcomes in soccer players.

Diffusion tensor imaging is a magnetic resonance imaging technique that is uniquely capable of detecting microstructural tissue damage in mild and moderate traumatic brain injuries (TBIs). To date, it remains unknown if two common analytic techniques, region of interest (ROI) versus voxel-wise (VW) analyses, detect injury in similar locations. The purpose of this systematic review and meta-analysis was to directly compare the regions of abnormality elucidated by each method. Twenty-seven ROI and 11 VW studies met our inclusion criteria. Our ROI meta-analysis identified 11 regions, including the splenium of the corpus callosum, where fractional anisotropy (FA) was significantly decreased in TBI patients, compared with controls. Likewise, we identified higher mean diffusivity/apparent diffusivity constant in the genu, body, and splenium of the corpus callosum. Alternatively, our VW analysis identified one region of high FA in the right superior longitudinal fasciculus and seven regions of low FA, with the two largest located in the corpus callosum. High mean diffusivity and high radial diffusivity, both in the right inferior longitudinal fasciculus, also was revealed by our VW analysis. Moreover, we have shown that the magnitude of damage in the corpus callosum revealed by ROI analysis (z = -3.15) is greater than that demonstrated by VW analysis (z = -1.41). Overall, this study indicates that both ROI and VW analytic methods are sensitive to low FA in the corpus callosum; however, the ROI method has more power to detect the full extent of tissue abnormality in the corpus callosum. More research utilizing standardized methods and reporting is essential to fully characterize the extent to which ROI and VW analyses can concordantly detect other locations of pathology in mild and moderate TBI patients.

It is now recognized that repetitive head impacts (RHI) in sport have the potential for long-term neurological impairments. In order to identify targets for intervention and/or pharmacological treatment, it is necessary to characterize the neurobiological mechanisms associated with RHI. This review aims to summarize animal and human studies that specifically address Blood Brain Barrier (BBB) dysfunction, abnormal neuro-metabolic and neuro-inflammatory processes as well as Tau aggregation associated with RHI in collision sports. Additionally, we examine the influence of physical activity and genetics on outcomes of RHI, discuss methodological considerations, and provide suggestions for future directions of this burgeoning area of research.