Eija Katariina Laakkonen

Background: Urinary incontinence is a prevalent condition among middle-aged women, yet its relationship with activity behaviours remains underexplored. This study aimed to explore the longitudinal associations between objectively measured sedentary behaviour and physical activity intensities with urinary incontinence and its types in middle-aged Finnish women. Methods: A total of 224 women aged 47–55 years at baseline, drawn from the ERMA and EsmiRs studies were included. The prevalence of stress, urgency and mixed urinary incontinence symptoms was assessed using a structured questionnaire. Sedentary behaviour and physical activity were objectively measured using hip-worn accelerometers at baseline and at 4-year follow-up. Logistic generalized estimating equation models were used to analyse the associations between sedentary behaviour and different physical activity intensities with urinary incontinence, adjusting for potential confounders. Results: Higher light-intensity physical activity was associated with slightly increased odds of urinary incontinence (OR = 1.004, 95% CI: 1.000 to 1.008, p = 0.043), specifically stress urinary incontinence (OR = 1.007, 95% CI: 1.002 to 1.0011, p = 0.002). Sedentary behaviour showed an inverse relationship with urinary incontinence and stress urinary incontinence that disappeared when accounting for all activity behaviours. No significant associations were observed for moderate or vigorous physical activity. Conclusions: No consistent harmful or beneficial associations of physical activity or sedentary behaviour with urinary incontinence were found in middle-aged women. The marginal link between light physical activity and stress urinary incontinence may reflect behavioural adaptations among symptomatic women. Future research should investigate how the type of physical behaviour, rather than its intensity, and long-term activity patterns, as opposed to short- or medium-term, may influence urinary incontinence in this population.

This study examined lower‐extremity power using countermovement jump (CMJ) height and estimated peak power across the lifespan with five Finnish datasets. The pooled dataset included 24 804 males and 5413 females aged 6–75 years. CMJ height (cm) was measured on a contact mat from flight time(s), and peak power (W) was estimated using equations for adults and children and expressed also relative to body mass (W/kg). Five‐year age groups were formed for mean comparison. CMJ height and peak power increased throughout childhood and adolescence. From ages 11 to 15, males exhibited greater CMJ height and peak power than females. Based on mean values, CMJ height peaked at ages 16–20 and peak power at 21–25 in males, while both peaked at 21–25 in females. Males maintained their level until 26–30 years, whereas females showed a decline after the peak. Segmented regression models indicated earlier peaks for CMJ height (18 years in males, 17 in females) and slightly later peaks for peak power (21 years in males, 19 in females). Before the peaking age, annual relative increases calculated over 11–15 years were 5.6% versus 3.1% for CMJ height and 4.7%–7.6% vs. 4.0%–7.3% for peak power (males vs. females). After the peaking age, annual declines calculated over 52–58 years were 0.9% for CMJ height and 0.3%–0.7% for peak power in both sexes. The results provide insights into life‐course patterns and the transitional period of late adolescence and early adulthood, when jumping performance peaks and evidence is limited.

Lynch syndrome (LS) carriers face a high cancer risk, especially colorectal cancer. Although physical activity (PA) is known to reduce cancer risk in LS, it remains unclear whether this protective effect varies by sex and which molecular mechanisms underlie it. This study aimed to use an integrated omics approach to examine molecular mechanisms associated with PA in LS, focusing on sex-specific differences and links to cancer-related processes. We profiled serum sample–based circulating microRNAs (c-miRNA) by Illumina sequencing and quantified metabolites using targeted nuclear magnetic resonance–based metabolomics from 93 Finnish LS carriers. PA levels were assessed by questionnaire. Bioinformatics approaches, such as principal coordinates analysis, weighted correlation network analysis, and overrepresentation analysis, identified molecular mechanisms associated with PA and links to cancer-related mechanisms. In addition, a short submaximal exercise bout was conducted to examine acute miRNA responses. We observed sex-based differences in PA-associated c-miRNAs and metabolites. In females, PA was linked to lipid metabolism. In males, miRNAs negatively correlated with PA are associated with distinct cancers, regulating pathways involved in cell growth, apoptosis, transcription, senescence, and the cell cycle. Four PA-associated miRNAs (hsa-miR-885-3p, hsa-miR-483-5p, hsa-miR-374a-5p, and hsa-miR-301a-3p) strongly correlated with metabolites related to lipid and fatty acid metabolism and inflammation, with correlation patterns differing by sex. The expression of these miRNAs changed after acute exercise. Our findings highlight the importance of considering sex as a biological factor in PA-based cancer prevention strategies for LS and provide novel insights into underlying molecular mechanisms. Prevention Relevance: Understanding how protective lifestyle factors, particularly PA, shape molecular responses in LS carriers may reveal new avenues for cancer risk reduction.

Background: Predictors of arterial health impairment from childhood to adolescence remain largely unknown. We investigated associations of childhood cardiometabolic risk factors with several measures of arterial health in adolescence. Methods: Altogether, 222 children were examined at age 7–9 years and eight years later at age 15-17 years. Body fat percentage (BF%), glucose, insulin, lipids, blood pressure (BP), and inflammation biomarkers were measured and homeostatic model assessment for insulin resistance (HOMA-IR), a metabolic syndrome score (MetSscore), and an inflammation score were calculated at baseline. Pulse wave velocity (PWV) and cardio-ankle vascular index (CAVI) were assessed using impedance cardiography and carotid intima-media thickness (cIMT), carotid distensibility (cDIST), Young’s elastic modulus (YEM), and stiffness index (SI) using ultrasonography. Associations of childhood cardiometabolic risk factors with measures of arterial health were analyzed using linear regression models adjusted for childhood age and sex. Results: BF% was positively associated with PWV (standardized regression coefficient β=0.207, p=0.008), CAVI (β=0.171, p=0.031), cIMT (β=0.146, p=0.034), and YEM (β=0.164, p=0.016). HOMA-IR was positively associated with PWV (β=0.242, p=0.001) and CAVI (β=0.216, p=0.004) and inversely with cDIST (β=-0.162, p=0.015). MetSscore was positively associated with PWV (β=0.266, p<0.001), CAVI (β=0.219, p=0.004), and YEM (β=0.141, p=0.032) and inversely with cDIST (β=-0.140, p=0.035). SBP was positively associated with PWV (β=0.257, p<0.001) and YEM (β=0.156, p=0.018) and inversely with cDIST (β=0.169, p=0.012). Conclusion: Increased adiposity, insulin resistance, elevated SBP, and cardiometabolic risk factor clustering in childhood association of arterial stiffness and reduced arterial distensibility in adolescence, emphasizing prevention of cardiovascular diseases since childhood.

Background: Earlier age at menopause and shorter reproductive span (time from menarche to menopause) have been linked to an increased risk of cardiovascular diseases (CVD), presumably because of limited lifetime exposure to endogenous estrogen. Our intention is to determine whether genetic liability to earlier vs later menarche and menopause are associated with risk of common cardiovascular diseases in women. We also aim to investigate effects of exogenous estrogen exposure in the form of systemic hormonal contraceptive and menopausal hormone therapy use. Methods and results: We determined GWAS summary statistics for age at menopause, age at menarche, and length of the reproductive period with data derived from UK Biobank (UKBB) European-ancestry participants. We calculated polygenic scores for women from FinnGen study (N=184 132) that indirectly capture genetic variation in endogenous estrogen exposure: age at menopause, age at menarche, and length of reproductive span. We also investigated exogenous hormone exposure associated with use of menopausal hormone therapy or systemic hormonal contraceptives. We used Cox proportional hazards model to investigate associations between PGSes and exogenous estrogen exposure and risk of hypertension, stroke, and coronary heart disease (CHD) events. Median follow-up time was 25.8 years. During the follow-up 56 143 women experienced hypertension, 18 200 women experienced strokes, and 13 879 women experienced major CHD events. Genetic liability to later menopause and longer reproductive span were weakly associated with a higher risk of stroke: in models adjusted with smoking and BMI, the hazard ratio (HR) per one standard deviation increase in PGS was 1.03 [1.01–1.05] for both. Menopausal hormone therapy use was associated with lower risk of stroke (HR 0.85 [0.82 – 0.89]) and CHD (HR 0.80 [0.76 – 0.84]). Systemic hormonal contraceptive use was associated with lower risk of hypertension (HR 0.96 [0.93 – 0.99]), stroke (HR 0.84 [0.80 – 0.99]) and CHD events (HR 0.83 [0.78–0.89]). Conclusions: Although observational evidence consistently associates a longer reproductive span with lower cardiometabolic risk, the polygenic component of metabolic timing (PGSes for reproductive span and age at menopause) showed the opposite direction of association. This discrepancy likely reflects the fact that these scores capture genetic pathways only partially overlapping with phenotypic lifetime estrogen exposure. Importantly, the observed cardioprotective associations of menopausal hormone therapy and systemic hormonal contraception underscore that genetic predisposition and exogenous hormonal exposure represent distinct biological dimensions relevant to cardiovascular risk in women. Clinical Perspective: What Is New?: We combined genetic data and information of register-based hormone purchases from over 180 000 women to investigate associations between endogenous and exogenous estrogen exposure and cardiovascular diseases. What Are the Clinical Implications?: Our results suggest that genetic predisposition to a later natural menopause and longer reproductive span are not protective towards cardiovascular diseases. Exogenous hormones were associated with lower long-term risk of stroke and coronary heart disease events. This implies that even if the current use of exogenous estrogen may increase stroke risk, the long-term stroke risk may decrease compared to women who never used hormones.

Introduction: Non-communicable diseases are the leading causes of premature mortality worldwide. Both genetic predispositions and environmental exposures affect disease risk. While biobanks have increased understanding of genetic predictors of these diseases, environmental influences are expected to have a greater impact on disease development. Individuals also create their own environments and lifestyles based on genetically regulated preferences, leading to gene–environment interactions that require large datasets to study. Finnish biobanks typically lack sufficient lifestyle and environmental data, which limits their use. We present a protocol for a biobank-recall study (BioRecall) to collect data on lifestyle and environmental exposures and combine these findings with genotypes, biological samples and clinical outcomes. Methods and analysis: All previously genotyped donors from the Central Finland Biobank who have been diagnosed with type 2 diabetes and have consented to recall will be invited to participate in the pilot study. The preliminary feasibility assessment reveals that there are 1580 suitable candidates. Participants will complete an electronic questionnaire on a secure online platform. The questionnaire includes validated questions on lifestyles, anthropometrics, weight loss history, health, symptoms, work characteristics, emotional states and residential environments. Postcode information will facilitate the addition of spatial environmental data. Genotype and related clinical data will be provided in the study in accordance with the Finnish Biobank Act and combined with questionnaire data. Ethics and dissemination: The Human Sciences Ethics Committee of the University of Jyväskylä delivered a favourable statement regarding the study protocol (1671/13.00.04.00/2023). Central Finland Biobank approved the research plan (no: BB24-0333-A01). The data collected will be returned to the Central Finland Biobank for research purposes with the participants’ consent. Permission for data usage can then be applied through standard protocols of the Fingenious service ( https://site.fingenious.fi/en/ ). If successful, the study will be expanded to other donors and Finnish biobanks.

Objectives: This study examined the effects of step-reduction and subsequent step-recovery and exercise rehabilitation on systemic metabolism in older adults. Methods: Participants were 66 eligible participants from the ENDURE randomised controlled trial allocated to an intervention group (n=32; 25 % male) or control group (n=34; 21 % male). The intervention group was instructed to limit their daily steps to a maximum of 2000 for two weeks (Period I), followed by a four-week exercise rehabilitation program (Period II) involving twice-weekly sessions of whole-body resistance and bicycle ergometer-based endurance training. Fasting blood samples were collected at baseline, after Period I, and after Period II. Systemic metabolism was assessed using high-throughput proton nuclear magnetic resonance spectroscopy. Data were normalised using Box-Cox transformation and analysed with linear mixed-effects models including random intercepts. Results: Period I and Period II had largely opposing effects on systemic metabolism. For instance, compared to the control group, Period one led to increases in VLDL-phospholipids (0.54 SD, P = 0.005), VLDL-cholesterols (0.41 SD, P = 0.012) and VLDL-triglycerides (0.79 SD, P = 0.002), and decreases in HDL-phospholipids (−0.31 SD, P = 0.037) and HDL-cholesterols (−0.47 SD, P = 0.011), alongside an increase in HDL-triglycerides (0.64 SD, P = 0.011). These changes reversed during Period II. Glycoprotein acetylation biomarker GlycA levels were unaffected by either intervention. Conclusions: These findings suggest that short-term inactivity does not markedly influence the inflammatory state but adversely affects lipoprotein metabolism and glycolytic pathways; however, these changes are reversible through the resumption of physical activity.

High aerobic fitness is linked to elevated HDL concentration and a shift toward bigger particle sizes, but its effect on the HDL composition is not well understood. For the first time, this study compared HDL lipid and proteomic compositions between two groups with differences in aerobic fitness level and body composition. The findings suggest positive modulations in HDL composition due to regular physical activity associated with better body composition, inflammation status, and serum lipid homeostasis.

Given that menopause affects about half of the world's midlife population, it is crucial to understand its impact beyond traditional menopausal symptomology. For instance, many women, while transitioning through menopause, experience profound changes in body composition. These changes may contribute to postmenopausal reductions in metabolic health. This narrative review explores the influence of menopause on skeletal muscle and adipose tissue, highlighting the decline in muscle mass and strength and the gain and redistribution of adipose tissue, particularly the increase in visceral adiposity. Although menopausal changes in body composition are seemingly extensively studied, the longitudinal studies are not that common, and the precise mechanisms driving body composition changes remain unclear, with uncertainties surrounding the roles of hormonal shifts compared with regular aging, energy balance, and lifestyle factors. Notably, it remains debated whether menopause or estrogen meaningfully influences resting energy expenditure. The review also considers the potential mitigating effects of menopausal hormone therapy and regular exercise. Understanding these changes is essential for developing effective strategies to support women's health during and after menopause.

High-density lipoprotein particles (HDL) possess anti-inflammatory, anti-thrombotic, cytoprotective, and anti-oxidative properties, thus protecting against cardiovascular diseases. Menopause is associated with changes in serum metabolome and HDL size distribution. We analyzed the protein and lipid composition of the HDL particles from pre-, peri-, and postmenopausal women (N=216) with nuclear magnetic resonance and mass spectrometry to get a deeper insight into the composition of HDL in different stages of menopause. Both particle size and composition differed; in perimenopause, the proportion of small HDL particles (8.7 nm on average) was higher, and the proportion of large HDL particles (12.1 nm on average) was lower than in pre- or postmenopause. In perimenopause, each particle size class was enriched with triacylglycerols, and the calculated lipid class ratio of triacylglycerol/cholesteryl ester was the highest within perimenopausal HDL particles. This potentially affects HDL interaction with lipid-modifying enzymes. We also observed directionally opposite associations for HDL cholesteryl ester and unesterified cholesterol with systemic estradiol and follicle-stimulating hormone levels, especially regarding S-sized HDL particles, but not the hormone associations with HDL triacylglycerols. Perimenopausal HDL exhibited a lower proportion of apolipoproteins (apoA-I, apoA-II, apoC-I, apoC-III, apoD and apoE) per particle than premenopausal or postmenopausal HDL. In summary, we found that premenopausal and postmenopausal HDL particles were compositionally similar and differed from perimenopausal ones. We suggest that menopause, and especially the unbalanced hormonal state in perimenopause, are reflected in the lipid and protein compositions of the HDL, which, in turn, may affect the functions of the HDL particle during menopause.