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The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT. © 2022, The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).

This care pathway from the European Menopause and Andropause Society (EMAS) provides an updated pathway for monitoring and guidance of women at midlife, focusing on those approaching the end of the reproductive life-cycle, going through the menopausal transition and beyond. The care pathway is written by professionals involved in women's health and provides a stepwise individualized approach, stratified according to needs, symptoms and reproductive stage. Furthermore, the pathway provides details on screening for chronic diseases related to menopause and ageing. Treatment options for climacteric symptoms range from menopausal hormone therapy to non-hormonal alternatives and lifestyle modifications. Therapy should be tailored to personal needs and wishes. The pathway aims to offer a holistic, balanced approach for monitoring middle-aged women, aiming to control health problems effectively and ensure healthy ageing. © 2022 Elsevier B.V.

The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the methyltetrahydrofolate reductase (MTHFR) gene. This cross-sectional pilot study recruited 48 girls with AN and 10 age-matched control girls with normal menstruation. We recorded anthropometric parameters and obtained blood samples for genotyping and hormonal assessment. Classification of AN was performed according to the DSM-V criteria. Girls with AN had 2.66 times higher odds of carrying at least one genetic polymorphism from the MTHFR panel (C677T and A1298C) compared with girls without AN (OR = 2.660, p-value = 0.041; CI 95% 1.057–6.720). The presence of atypical vs typical AN was associated independently with the presence of any of the assessed MTHFR polymorphisms (C677T, OR = 4.929, 95% CI 1.076–22.579, p-value = 0.040; A1298C, OR = 0.097, 95% CI 0.011–0.866, p-value = 0.037) in age and estrogen adjusted models. The atypical presentation of AN is mainly linked with higher prevalence of the MTHFR C677T and lower prevalence of the A1298C polymorphism. © 2021 Taylor & Francis Group, LLC.

To evaluate the effectiveness of a structured education program on lifestyle habits, which is also incorporating teaching on deep breathing, progressive muscle relaxation, and guided visualization, in the control of various components of the climacteric symptomatology in peri- and postmenopausal women. Sixty-one women aged 40–65 years with varying climacteric and stress symptoms were included in this study. Women were randomly assigned to the intervention group (31) or the control group (30). The intervention group followed an 8-week stress management program. The following parameters were assessed at baseline and at the end of the 8-week follow-up period in both groups: climacteric symptoms (Green Climacteric Scale (GCS)), sleep quality (Pittsburg Sleep Quality Index (PSQI)), mood status (Depression-Anxiety-Stress Scale), self-esteem (Rosenberg Self-esteem Scale), and health-related control (health locus of control (HLC)). A mixed-model ANOVA showed significant time × group × GCS interaction (within subjects: F = 23.830, p value

Background and aims: We aimed to evaluate the impact of perinatal food manipulation on skeletal characteristics and insulin levels of Wistar rats at the age of 1 year. Methods: Sixty-seven first-time pregnant rats were randomized, to either normally fed (Control Diet, CD), food-restricted (FR), or fat-fed (FF), from the 12th gestational day, and gave birth on the 21st day of pregnancy. Pups born to FR-mothers were divided into: fetal growth restricted (FGR) and non-FGR, based on their birth weight. Maternal food manipulation continued through the lactation period. Following delivery, all neonates were cross-fostered until the 25th day postpartum; the offspring of normally-fed mothers were lactated by FR-, FF- or CD-fed mothers. A similar process was followed for the offspring of mothers FF- or FR-during pregnancy. On the 26th day postpartum, all pups were weaned to the diet of their foster mother until one year old. Bone density was assessed by peripheral quantitative computed tomography. Results: FF/FF rats had lower values of total bone density and total/subcortical area compared to CD/CD. FF/FR showed lower subcortical density compared to FF/FF group. FGR/CD showed lower values of all assessed skeletal parameters compared to those receiving CD throughout the experiment. Non-FGR/FF rats had higher values of all assessed skeletal parameters compared to those food restricted postnatally. FGR-pups that were fat-fed postnatally had higher insulin vs rats FF/FR. Similar insulin levels were identified in rats fat-fed postnatally, irrespective of prenatal food-restriction or high-fat diet. Conclusions: Perinatal food manipulation is associated with distinct skeletal acquisition and insulin levels’ profiles in Wistar rats at the first year of life. © 2021 The Authors

Background Accumulating evidence suggests that circulating amyloidβ 1-40 (Aβ1-40), a proatherogenic aging peptide, may serve as a novel biomarker in cardiovascular disease (CVD). We aimed to explore the role of plasma Aβ1-40 and its patterns of change over time in atherosclerosis progression in postmenopausal women, a population with substantial unrecognized CVD risk beyond traditional risk factors (TRFs). Methods In this prospective study, Aβ1-40 was measured in plasma by enzyme-linked immunosorbent assay and atherosclerosis was assessed using carotid high-resolution ultrasonography at baseline and after a median follow-up of 28.2 months in 152 postmenopausal women without history or symptoms of CVD. Results At baseline, high Aβ1-40 was independently associated with higher carotid bulb intima-media thickness (cbIMT) and the sum of maximal wall thickness in all carotid sites (sumWT) (p < 0.05). Aβ1-40 levels increased over time and were associated with decreasing renal function (p < 0.05 for both). Women with a pattern of increasing or persistently high Aβ1-40 levels presented accelerated progression of cbIMT and maximum carotid wall thickness and sumWT (p < 0.05 for all) after adjustment for baseline Aβ1-40 levels, TRFs, and renal function. Conclusion In postmenopausal women, a pattern of increasing or persistently high Aβ1-40 was associated with the rate of progression of subclinical atherosclerosis irrespective of its baseline levels. These findings provide novel insights into a link between Aβ1-40 and atherosclerosis progression in menopause and warrant further research to clarify the clinical value of monitoring its circulating levels as an atherosclerosis biomarker in women without clinically overt CVD. © 2021 Georg Thieme Verlag. All rights reserved.

The impact of physical exercise, as preventative measure, to control the progression of cardiovascular disease in midlife remains under investigation. We aimed to investigate the effect of different levels of intensity of physical activity on metabolic and vascular profile in healthy postmenopausal women. A total of 625 healthy postmenopausal women (mean age 57.7 ± 7.6 years) were evaluated using the short IPAQ questionnaire for quantification of physical activity. The energy expenditure was estimated in metabolic equivalent of energy (MET) hours per week. Pulse wave velocity (PWV) was measured as an index of arterial stiffness. Intima-media thickness of both right and left common carotid artery, carotid bulb and internal carotid artery, and combined carotid IMT were also assessed by non-invasive and well-validated methods. Mean values of PWV decreased linearly with increasing intensity of physical activity (classes of physical activity: sedentary vs walking vs moderate vs vigorous activity: 9.07 ± 1.22 m/s vs 9.12 ± 1.72 m/s vs 8.47 ± 1.31m/s vs 7.94 ± 0.40 m/s, ANOVA P for linear trend.003). In non-obese postmenopausal women, PWV values associated with: (a) the total number of METs (b-coefficient = −0.261, P =.002) as well as with SBP; (b) or with the number of moderate METs (b-coefficient = −0.192, P =.025) as well as with age and SBP. No significant associations were observed between the intensity of physical exercise and arterial stiffness in the overweight-obese group. Physical activity is negatively associated with arterial stiffness in postmenopausal women with normal weight. This association was not observed in overweight or obese women. © 2020 Wiley Periodicals LLC

Objective: To evaluate the association between a personal history of lactation and indices of subclinical atherosclerosis in postmenopausal women. Methods: We evaluated the association between a history of breastfeeding and indices of subclinical atherosclerosis (pulse wave velocity, PWV; intima-media thickness [IMT]; atherosclerotic plaque presence) in 197 parous postmenopausal women with history of breastfeeding. Results: Women who reported breastfeeding ≥6 months when compared with women who reported breastfeeding for 1–5 months exhibited significantly lower values of common carotid artery IMT (Model R2=15.7%, b-coefficient = −0.170, 95% CI: −0.208—0.001, p-value =.019) and lower odds of subclinical atherosclerosis (Model X2=28.127, OR = 0.491, 95% CI 0.318–0.999, p-value =.049), adjusting for traditional cardiovascular risk factors. Conclusions: Postmenopausal women with a history of breastfeeding for at least 6 months have a lower prevalence of subclinical atherosclerosis, independently of traditional cardiovascular risk factors. A longer duration of breastfeeding may have a beneficial effect on subclinical atherosclerosis later in life. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Anti-Müllerian hormone (AMH), which is secreted by granulosa cells of late preantral and small antral follicles, is a marker of ovarian reserve. The association of ovarian reserve with subclinical atherosclerosis in women of reproductive age is currently unknown. We primary investigated whether AMH levels are associated with markers of subclinical atherosclerosis in healthy, normally menstruating women. In this cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima–media thickness (IMT), flow-mediated dilation, carotid–femoral pulse wave velocity and augmentation index. Lipid profile and serum AMH concentrations were also measured. Seventy premenopausal women, aged 32.7 ± 6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and femoral and carotid IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or established cardiovascular (CV) risk factors was found. After multivariable adjustment, the association between AMH concentrations and combined carotid IMT or carotid bulb IMT remained significant. In conclusion, in healthy, normally ovulating women, AMH concentrations are negatively associated with subclinical atherosclerosis indices and TC levels, independently of established CV risk factors. © The Author(s) 2020.

OBJECTIVE: Recent evidence in postmenopausal women suggested lack of association between serum levels of retinol-binding protein 4 (RBP4) and subclinical atherosclerosis; however, associations with arterial stiffness in this population remain unexplored. We evaluated the association among RBP4 and cardiovascular risk factors, including homocysteine, a marker involved in retinoic acid synthesis, and indices of arterial stiffness, in a sample of apparently healthy postmenopausal women. METHODS: This cross-sectional study included 123 healthy postmenopausal women, not on hormone therapy, antihypertensive, or hypolipidemic treatment and with a menopausal age 10 years or less. We performed biochemical/hormonal assessment and sonographic evaluation, including carotid-femoral pulse wave velocity (PWV) and carotid artery stiffness index (SI). RESULTS: Univariate analysis showed that RBP4 values correlated with age, low-density lipoprotein-cholesterol and estradiol levels. There was a trend of association of SI and PWV with homocysteine and triglycerides. RBP4 differed according to PWV, using the median PWV value as cut-off (RBP4, PWV ≤8.1 vs >8.1 m/s: 10.09 ± 2.05 vs 10.85 ± 1.91 ng/mL, analysis of covariance P value 0.014 adjusted for age, menopausal age, estradiol, pulse pressure). Linear regression analysis showed that PWV was independently associated with RBP4, age, and pulse pressure, whereas SI was independently associated with RBP4. An increase of one standard deviation in RBP4 levels (2.54 ng/mL) was associated with an increase of 0.577 m/s in PWV. CONCLUSIONS: RBP4 serum levels are associated with arterial stiffness, in a sample of healthy postmenopausal women. If this association is causative, serum RBP4 levels could serve as a marker of arterial stiffness. Prospective studies are required to investigate the significance of our findings. : Video Summary:http://links.lww.com/MENO/A621. Video Summary:http://links.lww.com/MENO/A621.

Introduction: The present study aimed to assess the association between ovarian volume and demographic and anthropometric parameters, as well as sex hormones and bone mineral density (BMD) in postmenopausal women. Methods: 161 healthy postmenopausal women participated in this cross-sectional study. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Anthropometric parameters included body mass index (BMI) and waist-to-hip ratio (WHR). Ultrasonography was used to estimate the average ovarian volume for each participant. BMD was measured in the femoral neck (FN) and the lumbar spine (LS) using DXA. Results: Mean ovarian volume increased linearly with increasing quartiles of BMI (Q1:0.985±0.25, Q2: 1.11±0.29, Q3: 1.07±0.28, Q4: 1.19±0.38, p-value for linear trend 0.013). Ovarian volume correlated positively with BMI (r=0.128, p-value=0.038), FN BMD (r=0.233, p-value=0.003), FN T-score (r=0.223, p-value=0.004) and FN Z-score (r=0.171, p-value=0.027). Multivariate analysis showed that ovarian volume was predicted by WHR (b-coefficient=0.157, p-value=0.047) and SHBG (b-coefficient= -0.160, p-value=0.042), independently of age and BMI. Finally, FN BMD was predicted by ovarian volume, independently of age, menopausal age and BMI. Conclusion: Ovarian volume was positively and independently associated with adiposity indexes and femoral BMD in postmenopausal women. Lower SHBG levels were associated with higher ovarian volume. Insulin resistance may mediate these results. The significance of these findings should be assessed in larger prospective studies.

Cardiovascular disease is the leading cause of death worldwide. The identification of protective factors against cardiovascular disease is important with regard to public health policies. Lactation has multiple beneficial effects for both mother and child. This review summarizes the evidence on the association between lactation and maternal cardiovascular risk in later life. Lactation may help to reverse the metabolic and cardiovascular changes that take place during pregnancy. Overall, lactation seems to exert a protective effect against the development of hypertension, metabolic syndrome, and diabetes, whilst data on postpartum weight and lipidemic profile are less conclusive. Both subclinical and clinical cardiovascular disease are negatively associated with a history of lactation. Increased energy expenditure and a favorable hormonal and adipokine profile during lactation may explain these associations. © 2019 Elsevier B.V.

Introduction: We aimed to investigate the incidence of hypertension and to identify potential risk factors in healthy, non-diabetic recently postmenopausal Greek women with normal renal function. Patients and methods: This retrospective cohort study evaluated 141 recently postmenopausal women at baseline and annually thereafter (follow-up time: 1 to 8 years). Blood samples were obtained, and ultrasound evaluations were performed at baseline. A detailed medical history, anthropometric parameters, blood pressure and cardiovascular risk factors were recorded for every woman at each visit. Incident hypertension was defined as the first occurrence of office systolic or diastolic blood pressure, measured at 2 different visits within 2 months or history of initiation of antihypertensive medication. Results: Incident hypertension was diagnosed in 30 out of 141 women (21.3%). The median time to incident hypertension was 3.5 years. Adiposity, elevated cholesterol and triglyceride levels, insulin resistance and parity were positively associated with incident hypertension. In multivariate analysis, however, obesity and insulin resistance were the only statistically significant variables associated with more than 3-fold and 2-fold respectively increased risk of incident hypertension (HOMA-IR, O.R = 1.988, p-value =.043; obesity, O.R = 3.746, p-value =.019). Conclusion: A significant proportion of women entering the menopause present incident hypertension and this is mostly associated with obesity and insulin resistance. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R2= 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings. © 2017, Springer-Verlag Italia S.r.l.

The menopause transition is associated with adverse changes in cardiometabolic risk factors. We aimed to examine the association of the metabolic syndrome (MS) and its features with indices of vascular structure and function in a population of asymptomatic postmenopausal women. A total of 473 informed-consenting, nondiabetic postmenopausal women were included in the study. The MS was defined according to the Joint Definition. We evaluated the association between the presence of MS and indices of vascular structure (carotid artery intima-media thickness (IMT); atherosclerotic plaques) and function (flow-mediated dilatation (FMD); pulse wave velocity (PWV)). The mean age of women was 56.4 ± 6.7 and the mean menopausal age was 7.91 ± 6.31. The MS was present in 17.3% of our population. Mean values of PWV increased linearly with the accumulation of features of the MS. IMT was higher in women with the MS compared to women without the MS (0.78 ± 0.12mm vs. 0.74 ± 0.11, p=.003). Multivariate analysis showed that the presence of the MS was independently associated with common carotid artery IMT (b=0.149, p=.001), PWV (b=0.114, p=.012) as well as central systolic and diastolic blood pressure (b=0.293, p

Background: The present study aims to examine the association of the metabolic syndrome (MS) as well as of the triglyceride-glucose index (TyG-Index), a novel marker of insulin resistance, with subclinical atherosclerosis in a cohort of postmenopausal women, stratified according to their body mass index. Methods: A total of 473 informed-consenting, non-diabetic postmenopausal women, without overt cardiovascular disease, were included in this study. We aimed to compare the association between structural and functional indices of subclinical atherosclerosis (i.e. carotid artery intima-media thickness (IMT), flow-mediated dilation of the brachial artery, pulse wave velocity (PWV)) with the TyG-index or MS, separately for lean and overweight/obese women. Results: The TyG-Index correlated significantly with carotid IMT (r = 0.155, p = 0.012) and PWV (r = 0.157, p = 0.013) only in the group of lean women. Multivariate analysis showed that subclinical atherosclerosis was predicted by MS, in the overweight/obese group (OR = 2.517, 95% CI: 1.078–5.878, p = 0.033), and by the TyG-Index the lean group (OR = 3.119, 95% CI: 1.187–8.194, p < 0.001). Using a TyG-Index cut-off value of 8.0 in the lean subpopulation, women above the cut-off had 44.1% prevalence of subclinical atherosclerosis compared to 29.4% in women below the cut-off (p = 0.043). Conclusions: The TyG-Index is associated with carotid atherosclerosis and arterial stiffness mainly in lean postmenopausal women, while the MS serves as a better predictor of subclinical atherosclerosis in overweight/obese women. The TyG-Index may prove a useful marker for identifying high-risk women in the normal-weight postmenopausal population. © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ)

Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS) and the NADH/NADPH oxidase system are related with atherosclerosis in the general population, but their significance in women is not sufficiently assessed. We investigated the potential association between the G894T polymorphism of the NOS3 gene and the C242T polymorphism of the CYBA gene with subclinical vascular disease. Seventy (70) healthy, normally ovulating, premenopausal women were recruited for this study. Venous blood samples were obtained for biochemical/hormonal assessment as well as for genotyping, using real-time PCR. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD), carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3% (38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4% (22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After multivariable adjustment, the hC242T polymorphism was a predictor of both internal carotid IMT (b-coefficient − 0.119, p = 0.011) and combined-IMT (b-coefficient − 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T determined values of FMD (b-coefficient − 1.604, p = 0.034). Concerning the NOS3 G894T polymorphism, carriers of the polymorphic variant had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis. In healthy premenopausal women, the CYBA C242T polymorphism is an independent determinant of endothelial function and subclinical atherosclerosis of the carotid arteries. The NOS3 G894T polymorphic variant also correlated with atherosclerosis, an association probably mediated by the traditional risk factors for CVD. The relevance of these findings in the clinical setting remains to be elucidated. © 2018, Springer Japan KK, part of Springer Nature.

Objective: Aging and menopause are associated with an adverse cardiometabolic profile, predisposing to cardiovascular disease. Diet may also affect their cardiometabolic risk. The aim of this study is to assess dietary habits and patterns of postmenopausal women and their association with adiposity measures, cardiometabolic parameters and subclinical atherosclerosis. Study protocol: The study will include two parts. The first part consists of cross-sectional evaluation of 750 postmenopausal women recruited consecutively from the Menopause Unit of an academic hospital. Dietary intake will be assessed by a food frequency questionnaire. Nutrient and food group intake will be calculated and adherence to the Mediterranean diet and other dietary patterns will be evaluated. A-priori and a-posteriori defined dietary patterns will be tested for associations with major and minor outcome measures. The second part consists of a prospective follow-up of all women recruited at baseline and re-assessment of the same variables after 3 years. Adherence to predefined or a-posteriori defined dietary patterns over these 3 years will be evaluated in association with changes in obesity indices and lipid levels, as well as in the progression of subclinical atherosclerosis. Major outcome measures: Body mass index, lipid profile, carotid and femoral artery intima-media thickness and plaques. Minor outcome measures: Waist circumference, waist-to-hip ratio, abdominal fat layers, incident hypertension and diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), c-reactive protein and markers of subclinical arterial disease, including flow-mediated dilation, pulse wave velocity, augmentation index and ankle-brachial index. Results: The study is expected to complete baseline enrolment by the end of 2018 and follow-up assessment by the end of 2021. The results of the study will address the question of whether dietary patterns and eating habits are associated with cardiometabolic risk as well as with accelerated subclinical arterial disease and arterial aging in postmenopausal women. © 2018 Elsevier B.V.

Vitamin D, a soluble steroid hormone synthesized in the skin after sun exposure, plays a crucial role in calcium metabolism and is also involved in cardiovascular pathophysiology. The aim of this review is to summarize the available evidence (a) on the association between endogenous vitamin D status and cardiovascular disease, and (b) on the effect of vitamin D supplementation on cardiovascular outcomes. Most studies have shown an inverse association between vitamin D levels and cardiovascular outcomes. Randomized controlled trials, however, do not consistently support a beneficial effect of vitamin D administration on cardiovascular health. Population characteristics, comorbid conditions such as diabetes, the overall population prevalence of cardiovascular disease, vitamin D status and the regimen of vitamin D supplementation may account for the conflicting results. © 2018 Elsevier B.V.

Overt or subclinical thyroid dysfunction may affect the risk of fragility fractures. The aim of the present study was to assess the association of thyroid function and autoimmunity with vertebral fractures (VF) in a large sample of Greek postmenopausal women. This cross-sectional study recruited 335 euthyroid postmenopausal women, aged 35–79 years. Euthyroidism was verified by serum thyroid-stimulating hormone (TSH) within the laboratory reference range (0.4–4.5 μIU/mL). VFs were diagnosed by lumbar spine lateral radiographs, according to quantitative procedures. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, as well as levels of anti-thyroglobulin (anti-TG) and thyroid peroxidase antibodies (anti-TPO) were compared according to the presence of VFs. Multivariate logistic regression showed that the presence of VFs was predicted independently by ln-TSH levels (OR = 0.290, p = 0.037) and positive anti-TG antibodies (OR = 3.308, p = 0.026) in models adjusted for age, menopausal age, and ln-HOMA-IR. Stepwise logistic regression analysis showed that the presence of VFs was predicted by menopausal age (OR = 1.120, p = 0.001), ln-TSH (OR = 0.312, p = 0.052), and thyroid autoimmunity (anti-TG and anti-TPO positive: OR = 6.637, p = 0.007) in a model that also included age and ln-HOMA-IR. Women with lower circulating TSH had higher risk of having a VF, independently of age, menopausal age, and insulin resistance. The presence of positive anti-TG/anti-TPO antibodies also indicated an elevated risk of fracture. Levels of thyroid hormones had no apparent effect on the risk of fracture. Further studies are necessary to establish the significance of our findings. © 2016, The Japanese Society for Bone and Mineral Research and Springer Japan.

Postmenopausal women are at increased risk for progression of arteriosclerosis and hypertension. Recent cross-sectional evidence suggests that high normal circulating prolactin levels may accelerate vascular ageing in menopause. Postmenopausal women (n=201) were consecutively recruited from a Menopause Clinic and re-evaluated in at least one follow-up visit within the next 3 years. Baseline circulating prolactin levels were measured while both baseline and follow-up vascular and biochemical measurements were performed. Endothelial function was assessed by flow-mediated dilation (FMD), aortic stiffness by pulse-wave velocity (PWV) and arterial wave reflections by applanation tonometry. Baseline prolactin significantly correlated with lower FMD at follow-up (P=0.005). After multivariable adjustment for age, follow-up time, blood pressure (BP), body mass index, smoking and medication, this correlation remained significant (P=0.003). In addition, baseline circulating prolactin levels were independently associated with changes in mean BP (β=0.131, P=0.021), peripheral diastolic BP (β=0.169, P=0.004) and new-onset hypertension (OR=1.235, P=0.001). Owing to significant interaction between baseline prolactin and age for changes in PWV over time (P=0.036), a subgroup analysis based on median age was performed. This analysis revealed that in women younger than 55 years, prolactin was an independent predictor of changes in PWV over time (P=0.008). In conclusion, high normal circulating prolactin levels predict changes in haemodynamic indices and worsening endothelial function in healthy postmenopausal women. Particularly in young postmenopausal women, prolactin predicts accelerated arterial stiffening. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Objective: Associations of endogenous androgens in menopause with blood pressure (BP) and indices of arterial stiffness are reported, but directional relationships are not clear. Structural equation modeling is a contemporary statistical method, which allows assessment of such relationships and improves pathway understanding. Methods: We recruited 411 consecutive apparently healthy postmenopausal women who underwent noninvasive vascular evaluation. This included pulse wave analysis (aortic pressures and arterial wave reflections [augmentation index]), measurement of aortic stiffness by pulse wave velocity (PWV), stiffness index (SI), and flow-mediated dilatation. A cumulative marker combining PWV and SI (combined local and aortic arterial stiffness [CAS]) was also assessed. Free androgen index (FAI) was calculated from circulating total testosterone and sex hormone-binding globulin. Results: FAI was an independent determinant of systolic BP (SBP) (P=0.032), SI (P=0.042), and PWV (P=0.027). Under structural equation modeling analysis, FAI was a direct predictor for PWV (beta=0.149, P=0.014), SI (beta=0.154, P=0.022), and CAS (beta=0.193, P=0.02), whereas SBP was a parallel mediator of androgen's vascular effects on PWV (beta=0.280, P

Aims: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). Methods: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. Results: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. Conclusions: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121–125, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Cardiovascular disease is the leading cause of death in both women and men. Its pathogenesis is multifactorial, with sex hormones playing an important role. Androgens have both direct and indirect effects on the vasculature. This review summarizes evidence on the association of both endogenous and exogenous androgens with subclinical and overt cardiovascular disease in women and men. Concerning women, both high and low levels of endogenous androgens have been associated with cardiovascular disease, while other studies have reported no association. Adiposity, impaired glucose metabolism, dyslipidemia and estrogen levels may mediate the observed associations. Regarding testosterone therapy in women, there have been no large prospective studies on cardiovascular outcomes. Concerning men, most studies indicate that low levels of circulating testosterone are associated with increased rates of cardiovascular disease in the general population; the causality, however, of this association remains to be proven. Testosterone replacement therapy in men with symptoms of hypogonadism and low serum testosterone merits caution with regard to cardiovascular safety, as evidence is still conflicting. © 2017 Elsevier B.V.

Objective: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women. Methods: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene’s Climacteric scale. Results: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = −0.568, p = 0.009 and b-coefficient = −0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = −0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = −0.558, p = 0.001 and b-coefficient = −0.474, p = 0.005) and HVLT discrimination index (b-coefficient = −0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = −0.457, p = 0.006) and HVLT total (b-coefficient = −0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = −0.593, p < 0.001), BVMT delayed recall (b-coefficient = −0.492, p = 0.002). Conclusion: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory. © 2016 International Menopause Society.

Purpose/Aim of the study: We evaluated possible associations between the severity of multiple sclerosis (MS) and levels of sex hormones as well as biochemical parameters in a sample of ambulatory patients. Material and methods: This cross-sectional study recruited 133 adults (52 men, 66 premenopausal and 15 postmenopausal women), with relapsing-remitting MS. Fasting venous blood samples were drawn for biochemical and hormonal evaluation. These parameters were tested for possible associations with MS severity, assessed using the Expanded Disability Status Scale (EDSS)-scores. Results: Follicle-stimulating hormone correlated with mean EDSS scores (r = −0.369, p = 0.038) in the premenopausal subgroup. However, this association became non-significant in the age-adjusted multivariate analysis (p = 0.141; power = 67%, type α error 0.10). Free androgen exhibited a borderline negative effect on EDSS-scores in the subgroup of men (r = −0.367, p = 0.093), which was lost after adjusting for age and duration of disease (p = 0.192; statistical power = 93%, type α error 0.05). Levels of estradiol tended to affect disability status of postmenopausal women (normal–mild vs. severe impairment: 23.33 ± 11.73pg/mL vs. 14.74 ± 6.30pg/mL, p = 0.095). Levels of sex hormones or indices of glycemic metabolism did not differ between patients presenting with EDSS scores higher or lower than the median value. Conclusion: Sex hormones and indices of glucose metabolism exhibited only a middle effect on EDSS scoring, which was not independent from the presence of confounders like age and duration of MS. The present study highlights the need for additional research, in order to elucidate the role of sex hormones and insulin resistance in the course of MS. © 2015 Taylor and Francis.

This position statement from the European Menopause and Andropause Society (EMAS) provides a care pathway for the maintenance of women's health during and after the menopause. It is designed for use by all those involved in women's health. It covers assessment, screening for diseases in later life, treatment and follow-up. Strategies need to be optimised to maintain postreproductive health, in part because of increased longevity. They encompass optimising diet and lifestyle, menopausal hormone therapy and non-estrogen-based treatment options for climacteric symptoms and skeletal conservation, personalised to individual needs. © 2016 Elsevier Ireland Ltd. All rights reserved.

Background and aims: We aimed to assess the prognostic value of free androgen index (FAI) and its change over time in arterial stiffness progression, endothelial function and hypertension in postmenopausal women. Methods: Postmenopausal women (n = 180) without clinically overt cardiovascular disease or diabetes were consecutively recruited and followed for a median of 29 months. The main outcome measures were changes over time in endothelial function (FMD), reflected waves, localized and systemic (PWV) arterial stiffness and hypertension. Results: Increased baseline FAI was significantly associated with new onset hypertension (OR for each SD, 2.71, 95% CI 1.14-6.41, p = 0.024), deterioration of pulse wave velocity (PWV) (0.414 m/s per SD), flow-mediated dilation (FMD) (-0.42% per SD), systolic (2.5 mmHg per SD) and pulse pressure progression (2.3 mmHg per SD, p < 0.05 for all). Baseline FAI remained an independent predictor of changes in PWV (p = 0.006), FMD (p = 0.02), peripheral pulse pressure (p = 0.028), transition to new onset hypertension (p = 0.001) and higher BP category (p = 0.012), after adjustment for age, changes in systolic blood pressure, traditional risk factors, vasoactive medication or total testosterone. Baseline FAI improved reclassification for the risk of transition into higher BP category (NRI = 47.5 ± 20.3%, p = 0.02) and abnormal PWV (NRI = 53.4 ± 23.2%, p = 0.021). Similarly, in a subgroup of patients with measured FAI at follow-up, its changes over time predicted changes in PWV, peripheral pulse pressure and hypertension status (p < 0.05 for all). Conclusions: In apparently healthy postmenopausal women, FAI could be a novel biomarker superior to total testosterone for accelerated vascular aging and hypertension status. © 2016 Elsevier Ireland Ltd.

Objective This study aims to evaluate the potential effects of renal function variations on vascular structure before the development of hypertension. Methods This pilot study included 141 postmenopausal women without evidence of renal dysfunction or hypertension. Markers of renal function and levels of glomerular filtration rate (GFR) - using standard calculations (GFR based on levels of creatinine [GFR epi ]) and newer creatinine and/or cystatin calculations (GFR based on levels of creatinine and cystatin [GFR cr cystatin ] and GFR based on levels of cystatin [GFR cystatin ]) - were associated with hemodynamic parameters and markers of vascular structure (intima-media thickness [IMT] and presence of atheromatous plaques in carotid and femoral arteries). Results Levels of GFR epi, GFR cr cystatin, and GFR cystatin exhibited a significant negative correlation with femoral artery IMT, whereas levels of GFR epi correlated significantly with mean carotid bulb (CB) IMT. Multivariate analysis showed that CB-IMT was predicted by GFR epi levels and age (β-coefficient = -0.212, P = 0.020), whereas femoral artery IMT was predicted by GFR epi levels (β-coefficient = -0.293, P = 0.001). GFR epi levels lower than the 25th percentile were associated with higher CB-IMT (P = 0.009), femoral artery IMT (P = 0.001), and combined IMT (P = 0.035) compared with higher GFR epi levels. Moreover, GFR epi levels greater than the 25th percentile were associated with lower odds for the presence of atherosclerotic plaques at the CB and carotid arteries combined (CB: odds ratio, 0.146; P = 0.006; combined: odds ratio, 0.249; P = 0.043) compared with lower GFR epi levels. Conclusions A mild decrease in renal function within normal limits of GFR is independently associated with the presence of subclinical atherosclerosis in a sample of apparently healthy young postmenopausal women. Assessment of GFR using creatinine (vs cystatin C) levels is a more sensitive marker of its association with IMT and atherosclerotic plaques in this postmenopausal population. © 2014 by The North American Menopause Society.