Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Circulating miRNA Signature Predicts Cancer Incidence in Lynch Syndrome-A Pilot Study.

Lynch syndrome (LS) is the most common autosomal dominant cancer syndrome and is characterized by high genetic cancer risk modified by lifestyle factors. This study explored whether a circulating miRNA (c-miR) signature predicts LS cancer incidence within a 4-year prospective surveillance period. To gain insight how lifestyle behavior could affect LS cancer risk, we investigated whether the cancer-predicting c-miR signature correlates with known risk-reducing factors such as physical activity, body mass index (BMI), dietary fiber, or NSAID usage. The study included 110 c-miR samples from LS carriers, 18 of whom were diagnosed with cancer during a 4-year prospective surveillance period. Lasso regression was utilized to find c-miRs associated with cancer risk. Individual risk sum derived from the chosen c-miRs was used to develop a model to predict LS cancer incidence. This model was validated using 5-fold cross-validation. Correlation and pathway analyses were applied to inspect biological functions of c-miRs. Pearson correlation was used to examine the associations of c-miR risk sum and lifestyle factors. hsa-miR-10b-5p, hsa-miR-125b-5p, hsa-miR-200a-3p, hsa-miR-3613-5p, and hsa-miR-3615 were identified as cancer predictors by Lasso, and their risk sum score associated with higher likelihood of cancer incidence (HR 2.72, 95% confidence interval: 1.64-4.52, C-index = 0.72). In cross-validation, the model indicated good concordance with the average C-index of 0.75 (0.6-1.0). Coregulated hsa-miR-10b-5p, hsa-miR-125b-5p, and hsa-miR-200a-3p targeted genes involved in cancer-associated biological pathways. The c-miR risk sum score correlated with BMI (r = 0.23, P < 0.01). In summary, BMI-associated c-miRs predict LS cancer incidence within 4 years, although further validation is required. PREVENTION RELEVANCE: The development of cancer risk prediction models is key to improving the survival of patients with LS. This pilot study describes a serum miRNA signature-based risk prediction model that predicts LS cancer incidence within 4 years, although further validation is required.

Associations of menopausal status and eating behaviour with subjective measures of sleep.

Eating and sleeping behaviour are known to interact with each other, yet research is limited in the context of menopausal women. The aim of this study was to examine whether menopausal status is associated with perceived problems in sleeping. Furthermore, we studied different aspects of eating behaviour as potential risk factors for poor sleep in menopausal women. The present study is exploratory in nature, thus the results should be interpreted as hypothesis-generating. We analysed the sleeping and eating behaviour of 1098 women aged 47-55 years and represented different menopausal statuses with regression analyses. Over 20% of them reported fairly poor or poor perceived sleep quality. A higher number of postmenopausal women reported experiencing at least fairly poor sleep quality compared with the other menopausal groups. However, in regression models controlled for several confounding factors menopausal status was not associated with measures of sleep. Women who reported more snacking-type eating behaviour were more likely to report shorter sleep duration, and more daytime tiredness. Externally cued eating was associated with shorter sleep duration and emotional eating was associated with experiencing daytime tiredness. However, after adjusting for multiple testing, it appears that eating behaviour is associated only with daytime tiredness. Menopausal women with sleeping problems may benefit from nutritional interventions targeting eating behaviour.

Circulating metabolome landscape in Lynch syndrome.

Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome.This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape.This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.

Metabolic syndrome and epigenetic aging: a twin study.

BACKGROUND: Metabolic syndrome (MetS) is associated with premature aging, but whether this association is driven by genetic or lifestyle factors remains unclear. METHODS: Two independent discovery cohorts, consisting of twins and unrelated individuals, were examined (N = 268, aged 23-69 years). The findings were replicated in two cohorts from the same base population. One consisted of unrelated individuals (N = 1 564), and the other of twins (N = 293). Participants' epigenetic age, estimated using blood DNA methylation data, was determined using the epigenetic clocks GrimAge and DunedinPACE. The individual-level linear regression models for investigating the associations of MetS and its components with epigenetic aging were followed by within-twin-pair analyses using fixed-effects regression models to account for genetic factors. RESULTS: In individual-level analyses, GrimAge age acceleration was higher among participants with MetS (N = 56) compared to participants without MetS (N = 212) (mean 2.078 [95% CI = 0.996,3.160] years vs. -0.549 [-1.053,-0.045] years, between-group p = 3.5E-5). Likewise, the DunedinPACE estimate was higher among the participants with MetS compared to the participants without MetS (1.032 [1.002,1.063] years/calendar year vs. 0.911 [0.896,0.927] years/calendar year, p = 4.8E-11). An adverse profile in terms of specific MetS components was associated with accelerated aging. However, adjustments for lifestyle attenuated these associations; nevertheless, for DunedinPACE, they remained statistically significant. The within-twin-pair analyses suggested that genetics explains these associations fully for GrimAge and partly for DunedinPACE. The replication analyses provided additional evidence that the association between MetS components and accelerated aging is independent of the lifestyle factors considered in this study, however, suggesting that genetics is a significant confounder in this association. CONCLUSIONS: The results of this study suggests that MetS is associated with accelerated epigenetic aging, independent of physical activity, smoking or alcohol consumption, and that the association may be explained by genetics.

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.

Age But Not Menopausal Status Is Linked to Lower Resting Energy Expenditure.

CONTEXT: It remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj). OBJECTIVES: We investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and FSH concentrations explain REEadj in midlife. METHODS: We divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17 to 21, group II (n = 35) of those aged 22 to 38, and group III (n = 59) of those aged 41 to 58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30), or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry, and hormones using immunoassays. RESULTS: The REEadj of group I was 126 kcal/day [95% confidence interval (CI): 93-160] higher than that of group III, and the REEadj of group II was 88 kcal/day (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/day (95% CI: 63-138 kcal/day) higher REEadj than their middle-aged mothers (all P < .001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations. CONCLUSIONS: We demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline.

Extracellular vesicles and high-density lipoproteins: Exercise and oestrogen-responsive small RNA carriers.

Decreased systemic oestrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both oestrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signalling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that oestrogen-based hormonal therapy (HT) allows the acute exercise-induced miR-response to occur in both EV and HDL particles in postmenopausal women, while the response was absent in nonusers.

Early adulthood and current physical activity and their association with symptoms of pelvic floor disorders in middle-aged women: An observational study with retrospective physical activity assessment.

OBJECTIVE: To investigate associations of early and middle adulthood physical activity (PA) with symptoms of pelvic floor disorders (PFDs), i.e. stress urinary incontinence (SUI), urge urinary incontinence (UUI), faecal incontinence (FI), constipation or defecation difficulties (CDDs) and feeling of pelvic organ prolapse (POP) among middle-aged women. DESIGN: A cross-sectional, observational study with retrospective PA assessment. SETTING: University Research Laboratory. SAMPLE: A random population sample of 1098 Finnish women aged 47-55 years. METHODS: Early adulthood PA, current PA, and demographic and gynaecological variables were assessed using self-report questionnaires. Logistic regression analyses were applied to study associations of PA variables with symptoms of PFDs. Potential confounding effects of demographic and gynaecological variables were controlled in multiple logistic regression models. MAIN OUTCOME MEASURES: Structured questionnaire-assessed retrospective PA assessment at the age of 17-29 years, current PA at middle age, and prevalence of symptoms of CDD, FI, POP, SUI and UUI. RESULTS: Current PA was not independently associated with the occurrence of the symptoms of PFDs. Middle-aged women with an early adulthood history of competitive sports were more likely to experience symptoms of UUI (OR 2.16, 95% CI 1.10-4.24, p = 0.025) but not symptoms of SUI, FI, CDD or POP, whereas women with a history of regular PA were more likely to experience symptoms of FI (OR 4.41, 95% CI 1.05-18.49, p = 0.043) but no other symptoms of PFDs. CONCLUSIONS: Competitive sports during early adulthood may increase the risk of UUI in middle age. Regular PA during early adulthood may increase the risk of FI.

Systemic circulating microRNA landscape in Lynch syndrome.

Circulating microRNAs (c-miRs) are small noncoding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management.

Associations of cardiorespiratory fitness, body composition, and blood pressure with arterial stiffness in adolescent, young adult, and middle-aged women.

Few studies have investigated whether higher cardiorespiratory fitness (CRF) or favourable body composition are related to lower arterial stiffness in women. We therefore investigated the associations of CRF, body fat percentage (BF%), fat free mass index (FFMI), and mean arterial pressure (MAP) with arterial stiffness in 146 women aged 16-58 years. CRF was assessed by a maximal exercise test with respiratory gas analysis either on a cycle ergometer or a treadmill. Aortic pulse wave velocity (PWVao), augmentation index (AIx%), and MAP were assessed by a non-invasive oscillometric device and BF% and FFMI by a bioelectrical impedance or DXA device. CRF was inversely associated with PWVao (ß = - 0.004, 95% CI - 0.005 to - 0.002) and AIx% (ß = - 0.075, 95% CI - 0.102 to - 0.048) and these associations remained similar after adjustment for BF% or MAP, but not after the adjustment for age. FFMI was inversely associated with PWVao (ß = - 0.010, 95% CI - 0.019 to - 0.002) and MAP directly associated with PWVao (ß = 0.005, 95% CI 0.003 to 0.006) and AIx% (ß = 0.092, 95% CI 0.069 to 0.116) and the associations with PWVao also remained after further adjustments for BF% and age. In conclusion, a higher FFMI and a lower MAP were independently associated with lower arterial stiffness.

Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues.

Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas ∼30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues.

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.

Associations of resting and peak fat oxidation with sex hormone profile and blood glucose control in middle-aged women.

BACKGROUND AND AIMS: Menopause may reduce fat oxidation. We investigated whether sex hormone profile explains resting fat oxidation (RFO) or peak fat oxidation (PFO) during incremental cycling in middle-aged women. Secondarily, we studied associations of RFO and PFO with glucose regulation. METHOD AND RESULTS: We measured RFO and PFO of 42 women (age 52-58 years) with indirect calorimetry. Seven participants were pre- or perimenopausal, 26 were postmenopausal, and nine were postmenopausal hormone therapy users. Serum estradiol (E2), follicle-stimulating hormone, progesterone, and testosterone levels were quantified with immunoassays. Insulin sensitivity (Matsuda index) and glucose tolerance (area under the curve) were determined by glucose tolerance testing. Body composition was assessed with dual-energy X-ray absorptiometry; physical activity with self-report and accelerometry; and diet, with food diaries. Menopausal status or sex hormone levels were not associated with the fat oxidation outcomes. RFO determinants were fat mass (ß = 0.44, P = 0.006) and preceding energy intake (ß = -0.40, P = 0.019). Cardiorespiratory fitness (ß = 0.59, P = 0.002), lean mass (ß = 0.49, P = 0.002) and physical activity (self-reported ß = 0.37, P = 0.020; accelerometer-measured ß = 0.35, P = 0.024) explained PFO. RFO and PFO were not related to insulin sensitivity. Higher RFO was associated with poorer glucose tolerance (ß = 0.52, P = 0.002). CONCLUSION: Among studied middle-aged women, sex hormone profile did not explain RFO or PFO, and higher fat oxidation capacity did not indicate better glucose control.

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.

Do Epigenetic Clocks Provide Explanations for Sex Differences in Life Span? A Cross-Sectional Twin Study.

BACKGROUND: The sex gap in life expectancy has been narrowing in Finland over the past 4-5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults. METHODS: Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, education, body mass index, smoking, alcohol use, and physical activity. RESULTS: In comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins. CONCLUSIONS: Previously reported sex differences in life span are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations.

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 Sex Hormones and Hormonal Status With Arterial Stiffness in a Female Sample From Reproductive Years to Menopause.

Objective: Loss of sex hormones has been suggested to underlie menopause-associated increment in cardiovascular risk. We investigated associations of sex hormones with arterial stiffness in 19-58-years-old women. We also studied associations of specific hormonal stages, including natural menstrual cycle, cycle with combined oral contraceptives (COC) and menopausal status with or without hormone therapy (HT), with arterial stiffness. Methods: This study includes repeated measurements of 65 healthy women representing reproductive (n=16 natural, n=10 COC-users) and menopause (n=5 perimenopausal, n=26 postmenopausal, n=8 HT-users) stages. Arterial stiffness outcomes were aortic pulse wave velocity (PWVao) and augmentation index (AIx%) assessed using Arteriograph-device. Generalized estimating equation models were constructed to investigate associations of each hormone (wide age-range models) or hormonal stage (age-group focused models) with arterial stiffness. PWVao models with cross-sectional approach, were adjusted for age, relative fitness, fat mass and mean arterial pressure, while models with longitudinal approach were adjusted for mean arterial pressure. AIx% models used the same approach for adjustments and were also adjusted for heart rate. Results: Negative and positive associations with arterial stiffness variables were observed for estradiol and follicle-stimulating hormone, respectively, until adjustment for confounding effect of age. In naturally menstruating women, AIx% was higher at ovulation (B=3.63, p<0.001) compared to the early follicular phase. In COC-users, PWVao was lower during active (B=-0.33 - -0.57, p<0.05) than inactive pills. In menopausal women, HT-users had higher PWVao (B=1.43, p=0.03) than postmenopausal non-HT-users. Conclusions: When using wide age-range assessments covering reproductive to menopausal lifespan it is difficult to differentiate age- and hormone-mediated associations, because age-mediated influence on arterial stiffness seemed to overrule potential hormone-mediated influences. However, hormonal status associated differentially with arterial stiffness in age-group focused analyses. Thus, the role of sex hormones cannot be excluded. Further research is warranted to resolve potential hormone-mediated mechanisms affecting arterial elasticity.

Bidirectional associations between cognitive functions and walking performance among middle-aged women.

OBJECTIVE: This study investigated whether (1) cognitive functions change after the transition from the perimenopausal to the postmenopausal stage, (2) cognitive functions and walking are associated in middle-aged women, and (3) cognitive functions assessed in perimenopause are associated with walking after reaching the postmenopause or vice versa. METHODS: In total, 342 women, categorized as early (n = 158) or late perimenopausal (n = 184), were included in the study and followed up until postmenopausal. Psychomotor speed, executive functions related to set-shifting and updating, working memory, and visual memory were assessed. Walking was assessed with walking speed, walking distance, and dual-task cost in walking speed. Data was analyzed using the paired-samples t test, Wilcoxon signed rank test, multiple linear regression analysis, and structural equation modeling. RESULTS: We found small but significant improvements in psychomotor speed (P = 0.01) and working memory (P < 0.001) among early perimenopausal and in psychomotor speed (P = 0.001), set-shifting (P = 0.02), visual memory (P = 0.002), and working memory (P < 0.001) among late perimenopausal women after the transition from peri- to postmenopause. Walking speed (ß = 0.264, P = 0.001) and dual-task cost (ß = 0.160, P = 0.03) were associated with updating, and walking distance was associated with updating and set-shifting (ß = 0.198, P = 0.02, ß=-0.178 P = 0.04 respectively) among the late perimenopausal women. We found no longitudinal associations between cognitive functions and walking. CONCLUSION: Cognitive performance remained unchanged or improved after reaching postmenopause. Cognitive functions and walking were associated during the late perimenopause, but the association depended on the cognitive process and nature of the physical task. Cognitive performance was not associated with walking after reaching postmenopause or vice versa.

Personality Traits and Changes in Health Behaviors and Depressive Symptoms during the COVID-19 Pandemic: A Longitudinal Analysis from Pre-pandemic to Onset and End of the Initial Emergency Conditions in Finland.

The COVID-19 pandemic and social distancing measures targeting the transmission of the virus impacted everyday life in 2020. This study investigated pre- to in-pandemic changes in health behaviors and depressive symptoms during the COVID-19 pandemic and the role of personality traits in these changes in Finland. Data from a larger population-based cohort study of 51-59-year-old Finnish women were used (n = 358). Self-reported questionnaires gathered information about depressive symptoms, eating behavior, physical activity, and alcohol consumption before the pandemic time, at the onset, and at the end of the COVID-19 emergency conditions. Information about personality traits (extraversion and neuroticism) and sociodemographic factors was available from the pre-pandemic baseline. Women reported more depressive symptoms and unhealthier eating habits at the end of the emergency conditions compared to the pre-pandemic time. An increase in depressive symptoms was associated with changing to unhealthier eating habits. Higher extraversion was associated with a perceived decrease in alcohol consumption and with changing to healthier eating habits. Women with higher neuroticism reported changing to either healthier or unhealthier eating habits. In general, some women reported healthier lifestyle changes while other women reported the opposite. Personality traits help to understand these individual differences in adaptation to the pandemic situation.