Menopausal symptoms and cardiometabolic risk factors in middle-aged women: A cross-sectional and longitudinal study with 4-year follow-up.

OBJECTIVE: To study associations of menopausal symptoms with cardiometabolic risk factors. STUDY DESIGN: A cross-sectional and longitudinal study of a representative population sample of 1393 women aged 47-55 years with a sub-sample of 298 followed for four years. The numbers of vasomotor, psychological, somatic or pain, and urogenital menopausal symptoms were ascertained at baseline through self-report. Their associations with cardiometabolic risk factors were studied using linear regression and linear mixed-effect models. Models were adjusted for age, menopausal status, body mass index, the use of hormonal preparations, education, smoking, and alcohol consumption. MAIN OUTCOME MEASURES: Cardiometabolic risk factors included total cholesterol, low-density and high-density lipoprotein cholesterol, blood pressure, glucose, triglycerides, total and android fat mass, and physical activity. RESULTS: All cholesterol and fat mass measures had modest positive associations with menopausal symptoms. The number of vasomotor symptoms, in particular, was associated with total cholesterol (B = 0.13 mmol/l, 95 % CI [0.07, 0.20]; 0.15 mmol/l [0.02, 0.28]) and low-density lipoprotein cholesterol (0.08 mmol/l [0.03, 0.14]; 0.12 mmol/l [0.01, 0.09]) in cross-sectional and longitudinal analyses, respectively. However, these associations disappeared after adjusting for confounders. The number of symptoms was not associated with blood pressure, glucose, triglycerides, and physical activity. Menopausal symptoms at baseline did not predict the changes in the risk factors during the follow-up. CONCLUSIONS: Menopausal symptoms may not be independently associated with cardiometabolic risk, and they do not seem to predict the changes in risk factors during the menopausal transition.

Menopause modulates the circulating metabolome: evidence from a prospective cohort study.

AIMS: We studied the changes in the circulating metabolome and their relation to the menopausal hormonal shift in 17ß-oestradiol and follicle-stimulating hormone levels among women transitioning from perimenopause to early postmenopause. METHODS AND RESULTS: We analysed longitudinal data from 218 Finnish women, 35 of whom started menopausal hormone therapy during the study. The menopausal transition was monitored with menstrual diaries and serum hormone measurements. The median follow-up was 14 months (interquartile range: 8-20). Serum metabolites were quantified with targeted nuclear magnetic resonance metabolomics. The model results were adjusted for age, follow-up duration, education, lifestyle, and multiple comparisons. Menopause was associated with 85 metabolite measures. The concentration of apoB (0.17 standard deviation [SD], 99.5% confidence interval [CI] 0.03-0.31), very-low-density lipoprotein triglycerides (0.25 SD, CI 0.05-0.45) and particles (0.21 SD, CI 0.05-0.36), low-density lipoprotein (LDL) cholesterol (0.17 SD, CI 0.01-0.34) and particles (0.17 SD, CI 0.03-0.31), high-density lipoprotein (HDL) triglycerides (0.24 SD, CI 0.02-0.46), glycerol (0.32 SD, CI 0.07-0.58) and leucine increased (0.25 SD, CI 0.02-0.49). Citrate (-0.36 SD, CI -0.57 to -0.14) and 3-hydroxybutyrate concentrations decreased (-0.46 SD, CI -0.75 to -0.17). Most metabolite changes were associated with the menopausal hormonal shift. This explained 11% and 9% of the LDL cholesterol and particle concentration increase, respectively. Menopausal hormone therapy was associated with increased medium-to-large HDL particle count and decreased small-to-medium LDL particle and glycine concentration. CONCLUSIONS: Menopause is associated with proatherogenic circulating metabolome alterations. Female sex hormones levels are connected to the alterations, highlighting their impact on women's cardiovascular health.

Total and regional body adiposity increases during menopause-evidence from a follow-up study.

For women, menopausal transition is a time of significant hormonal changes, which may contribute to altered body composition and regional adipose tissue accumulation. Excess adiposity, and especially adipose tissue accumulation in the central body region, increases women's risk of cardiovascular and metabolic conditions and affects physical functioning. We investigated the associations between menopausal progression and total and regional body adiposity measured with dual-energy X-ray absorptiometry and computed tomography in two longitudinal cohort studies of women aged 47-55 (n = 230 and 148, mean follow-up times 1.3 ± 0.7 and 3.9 ± 0.2 years, mean baseline BMI 25.5 kg/m2 ). We also examined associations between menopausal progression and skeletal muscle fiber characteristics, as well as adipose tissue-derived adipokines. Relative increases of 2%-14% were observed in regional and total body adiposity measures, with a pronounced fat mass increase in the android area (4% and 14% during short- and long-term follow-ups). Muscle fiber oxidative and glycolytic capacities and intracellular adiposity were not affected by menopause, but were differentially correlated with total and regional body adiposity at different menopausal stages. Menopausal progression and regional adipose tissue masses were positively associated with serum adiponectin and leptin, and negatively associated with resistin levels. Higher diet quality and physical activity level were also inversely associated with several body adiposity measures. Therefore, healthy lifestyle habits before and during menopause might delay the onset of severe metabolic conditions in women.

Metabolic health, menopause, and physical activity-a 4-year follow-up study.

BACKGROUND: In women, metabolic health deteriorates after menopause, and the role of physical activity (PA) in mitigating the change is not completely understood. This study investigates the changes in indicators of metabolic health around menopause and evaluates whether PA modulates these changes. METHODS: Longitudinal data of 298 women aged 48-55 years at baseline participating in the ERMA and EsmiRs studies was used. Mean follow-up time was 3.8 (SD 0.1) years. Studied indicators of metabolic health were total and android fat mass, waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, serum total cholesterol, and high- (HDL-C) and low-density (LDL-C) lipoprotein cholesterol. PA was assessed by accelerometers and questionnaires. The participants were categorized into three menopausal groups: PRE-PRE (pre- or perimenopausal at both timepoints, n = 56), PRE-POST (pre- or perimenopausal at baseline, postmenopausal at follow-up, n = 149), and POST-POST (postmenopausal at both timepoints, n = 93). Analyses were carried out using linear and Poisson mixed-effect models. RESULTS: At baseline, PA associated directly with HDL-C and inversely with LDL-C and all body adiposity variables. An increase was observed in total (B = 1.72, 95% CI [0.16, 3.28]) and android fat mass (0.26, [0.06, 0.46]), SBP (9.37, [3.34, 15.39]), and in all blood-based biomarkers in the PRE-POST group during the follow-up. The increase tended to be smaller in the PRE-PRE and POST-POST groups compared to the PRE-POST group, except for SBP. The change in PA associated inversely with the change in SBP (-2.40, [-4.34, -0.46]) and directly with the change in WHR (0.72, [0.05, 1.38]). CONCLUSIONS: In middle-aged women, menopause may accelerate the changes in multiple indicators of metabolic health. PA associates with healthier blood lipid profile and body composition in middle-aged women but does not seem to modulate the changes in most of the studied metabolic health indicators during the menopausal transition.

Associations of physical performance and physical activity with mental well-being in middle-aged women.

BACKGROUND: To investigate whether physical performance is independently of physical activity (PA) associated with positive and negative dimensions of mental well-being in middle-aged women. METHODS: Data were drawn from the Estrogenic Regulation of Muscle Apoptosis (ERMA) study in which women 47 to 55 years were randomly selected from the Finnish National Registry. They (n = 909) participated in measurements of physical performance (handgrip force, knee extension force, vertical jumping height, maximal walking speed, and six-minute walking distance). Both mental well-being (the Centre for Epidemiologic Studies Depression Scale, the International Positive and Negative Affect Schedule Short Form and the Satisfaction with Life Scale) and PA were self-reported. Associations between variables were analysed using multivariate linear regression modelling adjusted for body height, fat mass %, menopausal status and symptoms, marital status, parity, employment status, self-reported mental disorders, and use of psycholeptics and psychoanaleptics. PA was then entered into a separate model to explore its role in the associations. RESULTS: In the adjusted models, significant positive associations of six-minute walking distance with positive affectivity (B = 0.12, p = 0.002) and life satisfaction (B = 0.15, p = 0.033) were observed. No significant associations were observed between physical performance and depressive symptoms or negative affectivity. PA was positively associated with positive affectivity and life satisfaction and negatively with depressive symptoms across all the physical performance variables. CONCLUSIONS: Of the physical performance dimensions, aerobic component was associated with positive mental well-being independently of PA level. In relation to other physical performance components, the results point to the benefits of physical activity for mental well-being.

Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning.

The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23-69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package 'MEAT'. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617-0.824) than in muscle (r = 0.523-0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath's clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.

Perimenopausal women show modulation of excitatory and inhibitory neuromuscular mechanisms.

BACKGROUND: Menopausal transition exposes women to an early decline in muscle force and motor function. Changes in muscle quality and function, especially in lower limbs, are crucial, as they expose individuals to increased risk of falls. To elucidate some of the related neuromuscular mechanisms, we investigated cortical inhibition and peripheral muscle twitch force potentiation in women during the early and late stages of perimenopause. METHODS: Participants were 63 women aged 48-55 years categorized as early (EP, n = 25) or late (LP, n = 38) perimenopausal according to serum follicle-stimulating hormone (FSH) levels and menstrual diaries. EP women had an irregular menstrual cycle and FSH < 25 IU/L, while LP women had an irregular cycle and > 25 IU/L. We examined motor evoked potential (MEP) and silent period (SP) elicited by transcranial magnetic stimulation (TMS), in the tibialis anterior muscle at 20%, 40%, and 60% of maximal voluntary contraction (MVC) levels, and twitch force potentiation in plantar flexors. RESULTS: EP group showed a longer SP duration in 40% MVC condition and larger motor evoked potential amplitude in 20% MVC condition compared to the LP group. No group difference was detected in twitch force potentiation; however, it correlated negatively with FSH levels. Other factors, such as age, height, body mass index, or physical activity did not explain group differences. CONCLUSIONS: Our preliminary results indicate subtle modulation in both TMS-induced inhibitory and excitatory mechanisms and twitch force potentiation in women already in the late perimenopausal stage. This suggests that the reduction of estrogens may have an accelerating role in the aging process of neuromuscular control.

Predicting the age at natural menopause in middle-aged women.

OBJECTIVE: To predict the age at natural menopause (ANM). METHODS: Cox models with time-dependent covariates were utilized for ANM prediction using longitudinal data from 47 to 55-year-old women (n = 279) participating in the Estrogenic Regulation of Muscle Apoptosis study. The ANM was assessed retrospectively for 105 women using bleeding diaries. The predictors were chosen from the set of 32 covariates by using the lasso regression (model 1). Another easy-to-access model (model 2) was created by using a subset of 16 self-reported covariates. The predictive performance was quantified with c-indices and by studying the means and standard deviations of absolute errors (MAE ±â€ŠSD) between the predicted and observed ANM. RESULTS: Both models included alcohol consumption, vasomotor symptoms, self-reported physical activity, and relationship status as predictors. Model 1 also included estradiol and follicle-stimulating hormone levels as well as SD of menstrual cycle length, while model 2 included smoking, education, and the use of hormonal contraception as additional predictors. The mean c-indices of 0.76 (95% CI 0.71-0.81) for model 1 and 0.70 (95% CI 0.65-0.75) for model 2 indicated good concordance between the predicted and observed values. MAEs of 0.56 ±â€Š0.49 and 0.62 ±â€Š0.54 years respectively for model 1 and 2 were clearly smaller than the MAE for predicted sample mean (1.58 ±â€Š1.02). CONCLUSIONS: In addition to sex hormone levels, irregularity of menstrual cycle, and menopausal symptoms, also life habits and socioeconomic factors may provide useful information for ANM prediction. The suggested approach could add value for clinicians' decision making related to the use of contraception and treatments for menopausal symptoms in perimenopausal women.

Video Summary:http://links.lww.com/MENO/A743 .

Physical Performance During the Menopausal Transition and the Role of Physical Activity.

BACKGROUND: To examine longitudinal changes in physical performance during the menopausal transition and the role of physical activity (PA) in these changes. METHODS: Based on follicle-stimulating hormone levels and bleeding diaries, women (47-55 years) were classified as early (n = 89) and late perimenopausal (n = 143) and followed prospectively until postmenopausal status, with mean duration of 17.5 and 13.8 months, respectively. Physical performance was measured by handgrip force, knee extension torque, vertical jumping height, maximal walking speed, and 6-minute walking distance. Physical activity was self-reported and categorized as inactive, low, medium, and high. Longitudinal associations of menopausal status, physical performance, and related changes with PA level were analyzed using generalized estimation equations adjusted for duration of hormonal therapy. RESULTS: A significant decline over the menopausal transition in handgrip force (-2.1%, 95% CI -3.8 to -0.4), knee extension torque (-2.6%, 95% CI -4.5 to -0.8), and vertical jumping height (-2.6%, 95% CI -4.2 to -1.1) and a significant increase in 6-minute walking distance (2.1%, 95% CI 1.4 to 2.7) were observed in the total sample. A significant interaction of PA by time was observed in handgrip force and in vertical jumping height. High PA women had greater increase in handgrip strength but greater decline in vertical jumping height than medium, low, and inactive women (all p ≤ .001). CONCLUSIONS: Both early and late perimenopausal women show decline in muscle strength and power during the transition to postmenopause. Physical activity seems to influence physical performance during the menopausal transition but understanding the benefits of PA requires interventional studies.

Adolescent Sport Participation and Age at Menarche in Relation to Midlife Body Composition, Bone Mineral Density, Fitness, and Physical Activity.

This study aimed to investigate the associations of competitive sport participation in adolescence and age at menarche (AAM) with body composition, femoral neck bone mineral density (BMD), physical performance, and physical activity (PA) in middle-aged women. 1098 women aged 47-55 years formed the sample of this retrospective study. Participants self-reported their PA level at age 13-16 years and AAM. The protocol also included dual-energy X-ray absorptiometry, physical performance tests, and accelerometer-measured PA. Participants were divided into three groups according to their PA level at the age of 13-16 (no exercise, regular PA, and competitive sport) and according to their AAM (≤12, 13, and ≥14 years). After adjusting for potential confounding factors, participation in competitive sport at age 13-16 was associated with higher midlife lean mass and BMD, and better physical performance compared to groups with no exercise or regular PA. Individuals with AAM ≥ 14 years had lower midlife BMI and fat mass than participants in the other AAM groups and pre- and perimenopausal women with AAM ≥ 14 years had lower BMD than those with AAM ≤ 12. The findings indicate that participation in competitive sport in adolescence is associated with healthier body composition, higher BMD, and better physical performance in midlife, but BMD might be impaired if menarche occurs late.

Accelerometer-measured and self-reported physical activity in relation to extraversion and neuroticism: a cross-sectional analysis of two studies.

BACKGROUND: Personality reflects relatively stable and pervasive tendencies in feeling, thinking and behaving. While previous studies have found higher extraversion and lower neuroticism to be linked to higher self-reported physical activity levels, larger studies using accelerometer-measured physical activity are lacking. This study investigated the cross-sectional associations of extraversion and neuroticism with both accelerometer-measured and self-reported physical activity and the role of these personality traits in possible discrepancies between these two measures of physical activity among Finnish adults. METHODS: Two community-dwelling samples were used in this study: a) 47-55-yr-old women (n = 1098) and b) 70-85-yr-old women and men (n = 314). In both samples, extraversion and neuroticism were assessed by the 19-item short form of the Eysenck Personality Inventory. Physical activity was assessed with hip-worn tri-axial accelerometers and self-reported questions. Regression analyses were adjusted by age, BMI and education. RESULTS: In the middle-aged women, neuroticism was negatively associated with accelerometer-measured leisure time moderate-to-vigorous physical activity (ß = -.07, p = .036) and with self-reported physical activity (ß = -.08, p = .021), while extraversion was positively associated with self-reported physical activity (ß = .10, p = .005). No associations of extraversion or neuroticism with physical activity were found in the older men and women. Older adults who scored high in neuroticism reported less physical activity than what was measured by accelerometers (ß = -.12, p = .039). Extraversion was not associated with discrepancy between self-reported and accelerometer-measured leisure time physical activity in either sample. CONCLUSIONS: Neuroticism was associated with lower leisure-time physical activity levels and extraversion with higher self-reported physical activity among middle-aged women. Neuroticism and extraversion were unrelated to physical activity among older adults, but older adults with high neuroticism seemed to underreport their physical activity level. The role of personality in the discrepancy between self-reported and device-based physical activity warrants further research.

Effects of military training on plasma amino acid concentrations and their associations with overreaching.

IMPACT STATEMENT: The diagnosis of overtraining syndrome and overreaching poses a great challenge. Military training aims at improving the physical performance of the conscripts, but an excessive training load could also lead to overreaching. This study of Finnish conscripts provides new insights into the pathophysiology of overreaching and overtraining through amino acids concentrations. In addition to confirming the possible use of plasma glutamine/glutamate concentration to indicate and predict overreaching, we made a novel finding, i.e. low alanine and arginine concentrations might have a role in performance decrement and fatigue related to overreaching. Moreover, this study is the first to show the possible association between amino acids with putative neuronal properties and overreaching. Thus, the present findings might help to detect and prevent overreaching and offer a reliable diagnostic approach. In order to avoid overreaching, military training should be planned more periodically and individually, especially during the first four weeks of military service.

Role of Menopausal Transition and Physical Activity in Loss of Lean and Muscle Mass: A Follow-Up Study in Middle-Aged Finnish Women.

In midlife, women experience hormonal changes due to menopausal transition. A decrease especially in estradiol has been hypothesized to cause loss of muscle mass. This study investigated the effect of menopausal transition on changes in lean and muscle mass, from the total body to the muscle fiber level, among 47-55-year-old women. Data were used from the Estrogenic Regulation of Muscle Apoptosis (ERMA) study, where 234 women were followed from perimenopause to early postmenopause. Hormone levels (estradiol and follicle stimulating hormone), total and regional body composition (dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) scans), physical activity level (self-reported and accelerometer-measured) and muscle fiber properties (muscle biopsy) were assessed at baseline and at early postmenopause. Significant decreases were seen in lean body mass (LBM), lean body mass index (LBMI), appendicular lean mass (ALM), appendicular lean mass index (ALMI), leg lean mass and thigh muscle cross-sectional area (CSA). Menopausal status was a significant predictor for all tested muscle mass variables, while physical activity was an additional significant contributor for LBM, ALM, ALMI, leg lean mass and relative muscle CSA. Menopausal transition was associated with loss of muscle mass at multiple anatomical levels, while physical activity was beneficial for the maintenance of skeletal muscle mass.

The role of physical activity in the link between menopausal status and mental well-being.

OBJECTIVE: To examine the relationship between menopausal status and mental well-being, and whether this relationship varies as a function of physical activity (PA). METHODS: Based on a hormonal analysis and bleeding diary, women aged 47 to 55 were categorized as pre (n = 304), early peri (n = 198), late peri (n = 209), or postmenopausal (n = 387). Mental well-being was assessed using the Centre for Epidemiologic Studies Depression Scale, the International Positive and Negative Affect Schedule Short Form, and the Satisfaction with Life Scale. PA was self-reported and categorized as low, medium, and high. Associations between variables were analyzed using multivariate linear regression adjusted for age, marital and employment status, parity, self-reported mental disorder, use of psycholeptics and psychoanaleptics, and menopausal symptoms. RESULTS: Depressive symptoms were lower amongst the pre than postmenopausal women (B = 0.07, confidence interval 0.01-0.13). Menopausal symptoms attenuated these associations. Menopausal status showed no associations with life satisfaction, or with positive or negative affectivity.Women with high PA scored higher on positive affectivity, and the pre, early peri, and postmenopausal women scored higher on life satisfaction (B = 0.79, P < 0.001; B = 0.63, P = 0.009; B = 0.42, P = 0.009, respectively) and scored lower on depressive symptoms (B = -0.13, P = 0.039; B = -0.18, P = 0.034; and B = -0.20, P < 0.001, respectively) than their low PA counterparts. The pre and postmenopausal women with medium PA scored higher on life satisfaction (B = 0.54, P = 0.001; B = 0.038, P = 0.004, respectively) than those with low PA. CONCLUSIONS: Postmenopausal women reported marginally higher depressive symptoms scores compared with premenopausal women, but menopause was not associated with positive mental well-being. However, this association varies with the level of PA. : Video Summary:http://links.lww.com/MENO/A520.

Muscle and bone mass in middle-aged women: role of menopausal status and physical activity.

BACKGROUND: Women experience drastic hormonal changes during midlife due to the menopausal transition. Menopausal hormonal changes are known to lead to bone loss and potentially also to loss of lean mass. The loss of muscle and bone tissue coincide due to the functional relationship and interaction between these tissues. If and how physical activity counteracts deterioration in muscle and bone during the menopausal transition remains partly unresolved. This study investigated differences between premenopausal, early perimenopausal, late perimenopausal, and postmenopausal women in appendicular lean mass (ALM), appendicular lean mass index (ALMI), femoral neck bone mineral density (BMD) and T score. Furthermore, we investigated the simultaneous associations of ALM and BMD with physical activity in the above-mentioned menopausal groups. METHODS: Data from the Estrogen Regulation of Muscle Apoptosis study were utilized. In total, 1393 women aged 47-55 years were assigned to premenopausal, early perimenopausal, late perimenopausal, and postmenopausal groups based on follicle-stimulating hormone concentration and bleeding diaries. Of them, 897 were scanned for ALM and femoral neck BMD by dual-energy X-ray absorptiometry and ALMI (ALM/height2 ) and neck T scores calculated. Current level of leisure-time physical activity was estimated by a validated self-report questionnaire and categorized as sedentary, low, medium, and high. RESULTS: Appendicular lean mass, appendicular lean mass index, femoral neck bone mineral density, and and T score showed a significant linear declining trend across all four menopausal groups. Compared with the postmenopausal women, the premenopausal women showed greater ALM (18.2, SD 2.2 vs. 17.8, SD 2.1, P < 0.001), ALMI (6.73, SD 0.64 vs. 6.52, SD 0.62, P < 0.001), neck BMD (0.969, SD 0.117 vs. 0.925, SD 0.108, P < 0.001), and T score (-0.093, SD 0.977 vs -0.459, SD 0.902, P < 0.001). After adjusting for potential confounding pathways, a higher level of physical activity was associated with greater ALM among the premenopausal [ß = 0.171; confidence interval (CI) 95% 0.063-0.280], late perimenopausal (ß = 0.289; CI 95% 0.174-0.403), and postmenopausal (ß=0.278; CI 95% 0.179-0.376) women. The positive association between femoral neck BMD and level of physical activity was significant only among the late perimenopausal women (ß = 0.227; CI 95% 0.097-0.356). CONCLUSIONS: Skeletal muscle and bone losses were associated with the menopausal transition. A higher level of physical activity during the different menopausal phases was beneficial, especially for skeletal muscle. Menopause-related hormonal changes predispose women to sarcopenia and osteoporosis and further to mobility disability and fall-related fractures in later life. New strategies are needed to promote physical activity among middle-aged women. Longitudinal studies are needed to confirm these results.

Validity and Reliability of a Single Question for Leisure-Time Physical Activity Assessment in Middle-Aged Women.

PURPOSE: To investigate the validity and test-retest reliability of a single seven-level scale physical activity assessment question (SR-PA L7) and its three-level categorization (SR-PA C3). METHODS: The associations of SR-PA L7 and C3 with accelerometer-measured leisure-time physical activity (ACC-LTPA) and with the results of four different physical performance tests (6-min walk [n = 733], knee extension [n = 695], vertical jump [n = 731], and grip force [n = 780]) were investigated among women aged 47-55 years participating in the Estrogenic Regulation of Muscle Apoptosis study (n = 795). The reliability was studied using Spearman correlations with 4-month test-retest period (n = 152). RESULTS: SR-PA L7 and C3 had low correlations with ACC-LTPA (rs = .105-.337). SR-PA L7, SR-PA C3, and ACC-LTPA explained comparable but small amount of variance of the physical performance test results. The reliability analysis provided moderate agreement (rs = .707 and .622 for SR-PA L7 and C3, respectively). CONCLUSIONS: SR-PA L7 and C3 demonstrated limited validity and reasonable repeatability.

Menopausal Status and Physical Activity Are Independently Associated With Cardiovascular Risk Factors of Healthy Middle-Aged Women: Cross-Sectional and Longitudinal Evidence.

Cardiovascular disease (CVD) is the primary cause of mortality in women in developed countries. CVD risk rises with age, yet for women there is a rapid increase in CVD risk that occurs after the onset of menopause. This observation suggests the presence of factors in the middle-aged women that accelerate the progression of CVD independent of chronological aging. Leisure time physical activity (LTPA) is a well-established protective factor against CVD. However, its role in attenuating atherogenic lipid profile changes and CVD risk in post-menopausal women has not been well-established. The present study is part of the Estrogenic Regulation of Muscle Apoptosis (ERMA) study, a population-based cohort study in which middle-aged Caucasian women (47-55) were classified into pre-menopausal, peri-menopausal, and post-menopausal groups based on follicle stimulating hormone levels and bleeding patterns. Comprehensive questionnaires, laboratory visits, anthropometric measurements, and physical activity monitoring by accelerometers were used to characterize the menopausal groups and serum lipid profiles were analyzed to quantify CV (cardiovascular) risk factors. Based on our findings, LTPA may attenuate menopause-associated atherogenic changes in the serum CV risk factors of healthy middle-aged women. However, LTPA does not seem to entirely offset the lipid profile changes associated with the menopausal transition.

The Older Finnish Twin Cohort - 45 Years of Follow-up.

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Influence of Oral Contraceptive Use on Adaptations to Resistance Training.

Introduction: The majority of young women use oral contraceptives (OCs). Use of OCs has been associated with lower myofibrillar protein and tendon collagen synthesis rates, but it is unknown whether OCs will limit the adaptive response of myotendinous tissue to resistance training. Design and Methods: Fourteen healthy untrained young regular OC users (24 ± 1 years, fat% 32 ± 1, 35 ± 2 ml⋅min-1⋅kg-1) and 14 NOC users (non-OC, controls) (24 ± 1 years, fat% 32 ± 2, 34 ± 2 ml⋅min-1⋅kg-1) performed a 10-week supervised lower extremity progressive resistance training program. Before and after the intervention biopsies from the vastus lateralis muscle and the patellar tendon were obtained. Muscle (quadriceps) and tendon cross-sectional area (CSA) was determined by magnetic resonance imaging (MRI) scans, and muscle fiber CSA was determined by histochemistry. Maximal isometric knee extension strength was assessed by dynamometry while 1 repetition maximum (RM) was determined during knee extension. Results: Training enhanced CSA in both muscle (p < 0.001) and tendon (p < 0.01). A trend toward a greater increase in muscle CSA was observed for OC (11%) compared to NOC (8%) (interaction p = 0.06). Analysis of mean muscle fiber type CSA showed a trend toward an increase in type II muscle fiber area in both groups (p = 0.11, interaction p = 0.98), whereas type I muscle fiber CSA increased in the OC group (n = 9, 3821 ± 197 to 4490 ± 313 mm2, p < 0.05), but not in NOC (n = 7, 4020 ± 348 to 3777 ± 354 mm2, p = 0.40) (interaction p < 0.05). Post hoc analyses indicated that the effect of OCs on muscle mass increase was induced by the OC-users (n = 7), who used OCs containing 30 µg ethinyl estradiol (EE), whereas the response in users taking OCs with 20 µg EE (n = 7) did not differ from NOC. Both the OC and NOC group experienced an increase in maximal knee strength (p < 0.001) and 1RM leg extension (p < 0.001) after the training period with no difference between groups. Conclusion: Use of OCs during a 10-week supervised progressive resistance training program was associated with a trend toward a greater increase in muscle mass and a significantly greater increase in type I muscle fiber area compared to controls. Yet, use of OCs did not influence the overall increase in muscle strength related to training.

Estrogen Regulates the Satellite Cell Compartment in Females.

Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17ß-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri- to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females.