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.

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.

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.

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.

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.

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.

Biological clocks and physical functioning in monozygotic female twins.

BACKGROUND: Biomarkers of biological aging - DNA methylation age (DNAm age) and leukocyte telomere length (LTL)- correlate strongly with chronological age across the life course. It is, however, unclear how these measures of cellular wear and tear are associated with muscle strength and functional capacity, which are known to decline with older age and are associated with mortality. We investigated if DNAm age and LTL were associated with body composition and physical functioning by examining 48 monozygotic twin sisters. METHODS: White blood cell DNAm age (predicted years) was calculated from Illumina 450 k BeadChip methylation data using an online calculator. DNAm age acceleration was defined from the residuals derived from a linear regression model of DNAm age on chronological age. LTL was measured by qPCR. Total body percentage of fat and lean mass were estimated using bioimpedance. Physical functioning was measured by grip strength, knee extension strength and by 10 m maximal walking speed test. RESULTS: In all participants, DNAm age (58.4 ± 6.6) was lower than chronological age (61.3 ± 5.9 years). Pairwise correlations of monozygotic co-twins were high for DNAm age (0.88, 95% CI 0.79, 0.97), age acceleration (0.68, 95% CI 0.30, 0.85) and LTL (0.77, 95% CI 0.60, 0.94). Increased age acceleration i.e. faster epigenetic aging compared to chronological age was associated with lower grip strength (ß = - 5.3 SE 1.9 p = 0.011), but not with other measures of physical functioning or body composition. LTL was not associated with body composition or physical functioning. CONCLUSIONS: To conclude, accelerated DNAm age is associated with lower grip strength, a biomarker known to be associated with physiological aging, and which predicts decline in physical functioning and mortality. Further studies may clarify whether epigenetic aging explains the decline in muscle strength with aging or whether DNAm age just illustrates the progress of aging.

Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy.

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 = 0.30, p = .030), percentage total body (r 2 = 0.43, p = .014), and thigh (r 2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r 2 = 0.27, p = .020) and thigh muscle area (r 2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.

Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass.

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.

Long-term leisure-time physical activity and serum metabolome.

BACKGROUND: Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. METHODS AND RESULTS: Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31-52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins and in matched pairs in the cohorts, and by meta-analysis over all substudies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all 3 population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very-low-density lipoprotein (P<0.001) and higher large and very large high-density lipoprotein (P<0.001) particle concentrations. The findings persisted after adjustment for body mass index. CONCLUSIONS: The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals.

The role of cardiorespiratory fitness and body composition in the association between physical activity and menopausal symptoms.

OBJECTIVE: The aim of the study was to conduct exploratory analyses on the role of cardiorespiratory fitness (CRF) and body composition in the association between physical activity and menopausal symptoms. METHODS: This was a cross-sectional (N = 298) study of women aged 51-59 years including a subsample of 82 women followed for 4 years. The severity of menopausal symptoms was assessed with the Menopause Rating Scale in total symptoms as well as using the somato-vegetative, psychological, and urogenital subscales. Physical activity was assessed with accelerometers and self-reports, body composition with dual-energy x-ray absorptiometry, and CRF with a custom-made prediction model based on the six-minute walking distance and spiroergometry. The associations of interest were studied using unstandardized regression coefficients derived from multiple linear regression models with the severity of menopausal symptoms as the outcome. RESULTS: Higher total body and fat mass (kg) were associated with more severe total symptoms (B = 0.06 [95% CI, 0.01 to 0.12] and 0.07 [0.01 to 0.14], respectively) as well as somato-vegetative (0.03 [0.01 to 0.05]; 0.04 [0.01 to 0.06]) and psychological symptoms (0.03 [0.00 to 0.05]; 0.03 [0.00 to 0.06]) in cross-sectional design. Total and lean body mass interacted with physical activity in total and psychological symptoms with stronger indirect associations being observed in participants with lower total and lean body mass. CRF was not associated with menopausal symptoms and did not interact with physical activity. CONCLUSIONS: Maintaining a healthy weight is associated with less severe menopausal symptoms in middle-aged women. The association between physical activity and the severity of menopausal symptoms varied based on the differences in total and lean body mass.

Fracture mechanics of collagen fibrils: influence of natural cross-links.

Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an important factor that has been shown to influence mechanical behavior of the tendons. To improve our understanding of how molecular bonds translate into tendon mechanics, we used an atomic force microscopy technique to measure the mechanical behavior of individual collagen fibrils loaded to failure. Fibrils from human patellar tendons, rat-tail tendons (RTTs), NaBH4 reduced RTTs, and tail tendons of Zucker diabetic fat rats were tested. We found a characteristic three-phase stress-strain behavior in the human collagen fibrils. There was an initial rise in modulus followed by a plateau with reduced modulus, which was finally followed by an even greater increase in stress and modulus before failure. The RTTs also displayed the initial increase and plateau phase, but the third region was virtually absent and the plateau continued until failure. The importance of cross-link lability was investigated by NaBH4 reduction of the rat-tail fibrils, which did not alter their behavior. These findings shed light on the function of cross-links at the fibril level, but further studies will be required to establish the underlying mechanisms.

Hormone replacement therapy improves contractile function and myonuclear organization of single muscle fibres from postmenopausal monozygotic female twin pairs.

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55-59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fibres expressing the type I but not the IIa myosin heavy chain (MyHC) isoform. In comparison to non-users, higher specific force was recorded in HRT users both in muscle fibres expressing type I (∼27%; P < 0.05) and type IIa (∼23%; P < 0.05) MyHC isoforms. These differences were fibre-type dependent, i.e. the higher specific force in fast-twitch muscle fibres was primarily caused by higher force per cross-bridge while slow-twitch fibres relied on both a higher number and force per cross-bridge. HRT use had no effect on fibre cross-sectional area (CSA), velocity of unloaded shortening (V0) and relative proportion of MyHC isoforms. In conclusion, HRT appears to have significant positive effects on both regulation of muscle contraction and myonuclei organization in postmenopausal women.

Sex hormones and skeletal muscle weakness.

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

Circulating levels of adipokines and IGF-1 are associated with skeletal muscle strength of young and old healthy subjects.

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18-30 years and 260 subjects aged 69-81 years) recruited within the framework of the European research network project "Myoage". The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.

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.

Muscle function in monozygotic female twin pairs discordant for hormone replacement therapy.

INTRODUCTION: Postmenopausal monozygotic twin pairs discordant for hormone replacement therapy (HRT) provide an advantageous study design controlling for genetic background for elucidating the relationships between aging, sex hormone levels, muscle strength, contractile capacity, and fatigability. METHODS: Thirteen postmenopausal monozygotic twin pairs discordant for HRT were measured for maximal voluntary torque (MVC) and twitch characteristics using electrical stimulation before and after intermittent dynamic plantarflexor exercise until exhaustion. RESULTS: Peak twitch torque was 32% higher in HRT users than in their non-HRT, genetically identical sisters (P = 0.002), but MVC did not differ. There were no differences in the activation level or twitch time characteristics between the co-twins. Fatigue caused decreases in MVC (P = 0.001), twitch torque (P = 0.001), time to peak (P = 0.013), and half-relaxation time (P = 0.001) similarly in HRT users and non-HRT users. CONCLUSION: In early postmenopausal women, involuntary but not voluntary force-generating mechanisms of the plantarflexors are augmented by the use of HRT.

Recovery after heavy resistance exercise and skeletal muscle androgen receptor and insulin-like growth factor-I isoform expression in strength trained men.

The effects of heavy resistance exercise on skeletal muscle androgen receptor (AR) protein concentration and mRNAs of AR, insulin-like growth factor-I (IGF)-IEa, and mechano growth factor (MGF) expression were examined from biopsies of vastus lateralis (VL) muscle before and 48 hours after heavy resistance exercise (5 × 10 repetition maximum [RM] leg press and 4 × 10RM squats) in 8 adult strength trained men. The present exercise induced an acute decrease in maximal isometric force and increased serum total testosterone (T) and free testosterone (FT) concentrations. During 2 recovery days, maximal isometric force and subjective perception of physical fitness remained significantly lowered, whereas serum creatine kinase activity, subjective muscle soreness, and muscle swelling (i.e., thickness of VL by ultrasound) were significantly increased compared to pre-exercise values. Subjective perception of physical fitness was followed up to 7 days, and by 6 days postexercise, it was elevated above the pre-exercise level. Basal T and FT concentrations remained unaltered after the exercise. No statistically significant changes were observed in AR protein or mRNA expression, but IGF-IEa (p < 0.05) and MGF (p < 0.05) mRNA expression were increased compared to pre-exercise levels. These findings indicate that IGF-IEa and MGF responses may be related to acute regenerative processes in muscle because of exercise and may contribute to muscular adaptation to resistance exercise. Subjective perception of physical fitness suggests that recovery over a pre-exercise level of the present type of heavy resistance exercise can take approximately 6 days.