BMI in childhood and adolescence is associated with impaired reproductive function-a population-based cohort study from birth to age 50 years

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Population-based data at ages 31 and 46 show decreased HRQoL and life satisfaction in women with PCOS symptoms.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with decreased health-related quality of life (HRQoL), but longitudinal data beyond the reproductive years are lacking, and the impact of isolated PCOS symptoms is unclear. OBJECTIVE: To study generic HRQoL using 15D, life satisfaction, and self-reported health status in women with PCOS symptoms at ages 31 and 46yr. DESIGN: A longitudinal assessment using the Northern Finland Birth Cohort 1966. SETTING: General community. PARTICIPANTS: The 15D data were available for women reporting isolated oligomenorrhea (OA;at age 31yr:214 and 46yr: 211), isolated hirsutism (H; 31yr:211 and 46yr:216), OA+H (PCOS; 31yr:74 and 46yr:75), or no PCOS symptoms (controls; 31yr:1382 and 46yr:1412). Data for life satisfaction and current health status were available for OA (31yr:329 and 46yr:247), H (31yr:323 and 46yr:238), PCOS (31yr:125 and 46yr:86), control (31yr:2182 and 46yr:1613) groups. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 15D HRQoL, questionnaires on life satisfaction, and self-reported health status. RESULTS: HRQoL was lower at ages 31 and 46 in women with PCOS or H compared with the controls. PCOS was an independent risk factor for low HRQoL, and the decrease in HRQoL in PCOS was comparable to that of women with other chronic conditions, like asthma, migraine, rheumatoid arthritis, and depression. The risk for low HRQoL in PCOS remained significant after adjusting for BMI, hyperandrogenism, and socioeconomic status. Mental distress was the strongest contributing factor to HRQoL. PCOS was also associated with a risk for low life satisfaction and a 4-fold risk for reporting a poor health status. CONCLUSIONS: Women with PCOS present with low HRQoL, decreased life satisfaction, and a poorer self-reported health status up to their late reproductive years. Assessments and interventions aiming to improve HRQoL in PCOS should be targeted beyond fertile age

Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate : a randomized controlled trial

STUDY QUESTION: Does an estradiol-based combined oral contraceptive (COC) have a milder effect on the serum proteome than an ethinylestradiol (EE)-based COC or dienogest (DNG) only?SUMMARY ANSWER: The changes in serum proteome were multifold after the use of a synthetic EE-based COC compared to natural estrogen COC or progestin-only preparation.WHAT IS KNOWN ALREADY: EE-based COCs widely affect metabolism, inflammation, hepatic protein synthesis and blood coagulation. Studies comparing serum proteomes after the use of COCs containing EE and natural estrogens are lacking.STUDY DESIGN, SIZE, DURATION: This was a spin-off from a randomized, controlled, two-center clinical trial. Women (n = 59) were randomized to use either EE thorn DNG, estradiol valerate (EV) thorn DNG or DNG only continuously for 9 weeks.PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were healthy, young, white volunteer women. Serum samples were collected before and after 9 weeks of hormonal exposure. Samples from 44 women were available for analysis (EE thorn DNG n = 14, EV thorn DNG n = 16 and DNG only n = 14). Serum proteins were analyzed by quantitative, discovery-type label-free proteomics.MAIN RESULTS AND THE ROLE OF CHANCE: Altogether, 446 proteins/protein families with two or more unique peptides were detected and quantified. The number of proteins/families that altered over the 9-week period within the study groups was 121 for EE thorn DNG and 5 for EV thorn DNG, while no changes were detected for DNG only. When alterations were compared between the groups, significant differences were detected for 63 proteins/protein families, of which 58 were between the EE thorn DNG and EV thorn DNG groups. The most affected functions during the use of EE thorn DNG were the complement system, acute phase response signaling, metabolism and the coagulation system. The results were validated by fetuin-B and cortisol-binding globulin ELISA and sex hormone-binding globulin immunoassay.LARGE SCALE DATA: Data are available via ProteomeXchange with identifiers PXD033617 (low abundance fraction) and PXD033618 (high abundance fraction).LIMITATIONS, REASONS FOR CAUTION: The power analysis of the trial was not based on the proteomic analysis of this spin-off study. In the future, targeted proteomic analysis with samples from another trial should be carried out in order to confirm the results.WIDER IMPLICATIONS OF THE FINDINGS: The EE-based COC exerted a broader effect on the serum proteome than the EV-based COC or the DNG-only preparation. These results demonstrate that the effects of EE in COCs go far beyond the established endpoint markers of estrogen action, while the EV combination is closer to the progestin-only preparation. The study indicates that EV could provide a preferable option to EE in COCs in the future and signals a need for further studies comparing the clinical health outcomes of COCs containing EE and natural estrogens.Peer reviewe

Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation : A randomized clinical trial

Introduction Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E-2] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. Material and methods We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). Clinical trial registration: NCT02352090. Results Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. Conclusions Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.Peer reviewe

Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation : A randomized clinical trial

Introduction Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E-2] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. Material and methods We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). Clinical trial registration: NCT02352090. Results Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. Conclusions Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.Peer reviewe

Prevalence of protein intake below recommended in community‐dwelling older adults: a meta‐analysis across cohorts from the PROMISS consortium

European Horizon 2020 PROMISS Project ‘PRevention Of Malnutrition In Senior Subjects in the EU’, (grant agreement no. 678732). The content only reflects the author’s view and the commission is not responsible for any use that may be made of the information it contains.Background: Lower protein intake in older adults is associated with loss of muscle mass and strength. The present study aimed to provide a pooled estimate of the overall prevalence of protein intake below recommended (according to different cut-off values) among community-dwelling older adults, both within the general older population and within specific subgroups. Methods: As part of the PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) project, a meta-analysis was performed using data from four cohorts (from the Netherlands, UK, Canada, and USA) and four national surveys [from the Netherlands, Finland (two), and Italy]. Within those studies, data on protein and energy intake of community-dwelling men and women aged ≥55 years were obtained by either a food frequency questionnaire, 24 h recalls administered on 2 or 3 days, or food diaries administered on 3 days. Protein intake below recommended was based on the recommended dietary allowance of 0.8 g/kg body weight (BW)/d, by using adjusted BW (aBW) instead of actual BW. Cut-off values of 1.0 and 1.2 were applied in additional analyses. Prevalences were also examined for subgroups according to sex, age, body mass index (BMI), education level, appetite, living status, and recent weight loss. Results: The study sample comprised 8107 older persons. Mean ± standard deviation protein intake ranged from 64.3 ± 22.3 (UK) to 80.6 ± 23.7 g/d [the Netherlands (cohort)] or from 0.94 ± 0.38 (USA) to 1.17z ± 0.30 g/kg aBW/d (Italy) when related to BW. The overall pooled prevalence of protein intake below recommended was 21.5% (95% confidence interval: 14.0–30.1), 46.7% (38.3–55.3), and 70.8% (65.1–76.3) using the 0.8, 1.0, and 1.2 cut-off value, respectively. A higher prevalence was observed among women, individuals with higher BMI, and individuals with poor appetite. The prevalence differed only marginally by age, education level, living status, and recent weight loss. Conclusions: In community-dwelling older adults, the prevalence of protein intake below the current recommendation of 0.8 g/kg aBW/d is substantial (14–30%) and increases to 65–76% according to a cut-off value of 1.2 g/kg aBW/d. To what extent the protein intakes are below the requirements of these older people warrants further investigation.publishersversionpublishe

Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†

To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF <= 0.40). A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 +/- 11 years) with a mean LVEF of 31 +/- 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component ( <5.7 ln ms(2)) adjusted for clinical variables was 7.0 (95% CI: 2.4-20.3, P <0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7-13.4, P = 0.003) also predicted the primary endpoint. Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AM

Carotenoid Intake and Serum Concentration in Young Finnish Children and Their Relation with Fruit and Vegetable Consumption

Fruit and vegetable intake has been associated with a reduced risk of many chronic diseases. These foods are the main dietary source of carotenoids. The aim of the present study was to evaluate the associations between dietary intake and serum concentrations of alpha- and beta-carotene in a sample of young Finnish children from the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention (DIPP) Study. The current analysis comprised 3-day food records and serum samples from 207 children aged 1, 2 and 3 years. Spearman and partial correlations, as well as a cross-classification analyses, were used to assess the relationship between dietary intake and the corresponding biomarkers. Serum concentrations of alpha- and beta-carotene were significantly higher among the 1-year-old compared to the 3-year-old children. Dietary intakes of alpha- and beta-carotene correlated significantly with their respective serum concentrations in all age groups, the association being highest at the age of 1 year (alpha-carotene r = 0.48; p <0.001 and beta-carotene r = 0.47; p <0.001), and lowest at the age of 3 years (alpha-carotene r = 0.44; p <0.001 and beta-carotene r = 0.30; p <0.001). A cross-classification showed that 72-81% of the participants were correctly classified to the same or adjacent quartile, when comparing the reported dietary intakes and the concentrations of the corresponding carotenoid in serum. The 3-day food record seems to be reasonably valid in the assessment of root vegetable consumption among young Finnish children. Root vegetables were the main dietary source of both carotenoids in all age groups. The high consumption of commercial baby foods among the 1-year-old children was reflected in the relatively high dietary intake and serum concentration of both carotenoids.Peer reviewe