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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).

Menopause is often a turning point for women's health worldwide. Increasing knowledge from experimental data and clinical studies indicates that cardiometabolic changes can manifest at the menopausal transition, superimposing the effect of ageing onto the risk of cardiovascular disease. The menopausal transition is associated with an increase in fat mass (predominantly in the truncal region), an increase in insulin resistance, dyslipidaemia, and endothelial dysfunction. Exposure to endogenous oestrogen during the reproductive years provides women with protection against cardiovascular disease, which is lost around 10 years after the onset of menopause. In particular, women with vasomotor symptoms during menopause seem to have an unfavourable cardiometabolic profile. Early management of the traditional risk factors of cardiovascular disease (ie, hypertension, obesity, diabetes, dyslipidaemia, and smoking) is essential; however, it is important to recognise in the reproductive history the female-specific conditions (ie, gestational hypertension or diabetes, premature ovarian insufficiency, some gynaecological diseases such as functional hypothalamic amenorrhoea, and probably others) that could enhance the risk of cardiovascular disease during and after the menopausal transition. In this Review, the first of a Series of two papers, we provide an overview of the literature for understanding cardiometabolic changes and the management of women at midlife (40-65 years) who are at higher risk, focusing on the identification of factors that can predict the occurrence of cardiovascular disease. We also summarise evidence about preventive non-hormonal strategies in the context of cardiometabolic health. Copyright © 2022 Elsevier Ltd. All rights reserved.

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radio-therapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

The cessation of ovarian function is associated with an increase in abdominal adipose tissue, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), which may contribute to the augmented cardiovascular risk observed in postmenopausal women. After ovarian function stops, circulating triglyceride, total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) concentrations increase, whereas high-density lipoprotein-cholesterol (HDL-C) and lipoprotein (Lp(a)) remain essentially unchanged. Similarly, the rates of NAFLD, possibly including the advanced forms of the disease (e.g., hepatic fibrosis), increase in postmenopausal compared with premenopausal women. These effects make menopausal hormone therapy (MHT) an attractive way to restore them. Estrogen per os decreases LDL-C and Lp(a) and increases HDL-C and triglyceride concentrations. The transdermal administration of estrogen has a more neutral effect on triglycerides, albeit a less beneficial effect on LDL-C, HDL-C, and Lp(a). Co-administration of a progestagen diminishes the effect of estrogen on LDL-C, HDL-C, and Lp(a), which, however, remains beneficial. Importantly, the effect may vary with different progestagens, being lesser with natural progesterone and dydrogesterone. Regarding the effect of MHT on NAFLD, though experimental data are currently favorable, clinical evidence is to date limited and controversial. Therefore, there is a need for specifically designed clinical trials, ideally with paired liver biopsies, to demonstrate the effect of different MHT schemes on NAFLD, which is of considerable importance, given that NAFLD is more prevalent after the cessation of ovarian function. © 2022, Hellenic Endocrine Society.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Context: Menopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories. Design: The CoLaus study is a prospective population-based cohort study in Lausanne, Switzerland. Patients: We used data from women at baseline and follow-up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow-up. Measurements: We measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors. Results: We used the data from 1710 women aged 35–75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin-6 and interleukin-1β decreased with advancing age. Conclusion: The current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5-year changes in cardiovascular risk factors may not depend on the reproductive stage. © 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

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.

Immune checkpoint inhibitors (ICIs) are antibodies that target certain immune checkpoints (ICs), such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) or its ligand (PD-L1), and have emerged as a powerful new tool for oncologists. As these immune checkpoints are crucial for immunological self-tolerance, such therapies can trigger autoimmune adverse effects. Endocrine complications are among the most common, including hypophysitis, thyroid dysfunction, diabetes mellitus and primary adrenal insufficiency, while autoimmune polyendocrine syndrome type 2 (APS-2) may also present. The aim of this article is to critically appraise the literature and present (i) the biological role and function of the main ICs, (ii) the use of ICIs in the treatment of various cancer types, (iii) the endocrine complications of cancer immunotherapy with ICIs and (iv) practical recommendations for screening and management of patients with such endocrinopathies in everyday clinical practice. © 2020 The Authors

Introduction: Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. Aim: The aim of this clinical guide is to set out an individualized approach to the management of VVA with topical estrogens and non-hormonal preparations. Materials and methods: Literature review and consensus of expert opinion. Summary recommendations: An individualized approach is required for the management of VVA. Topical low-dose estrogens are effective and also alleviate urinary incontinence and prevent recurrent urinary tract infections. Women should not be denied long-term use of topical estrogens as long as they feel that this treatment is of benefit to them, because the safety data are reassuring. Non-hormonal preparations (lubricants and moisturizers) should be the first-line treatment for VVA in women taking adjuvant endocrine therapies for cancers considered to be hormone-dependent. They can be used over the long term.

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.

Introduction: Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. Aim: The aim of this clinical guide is to set out an individualized approach to the management of VVA with topical estrogens and non-hormonal preparations. Materials and methods: Literature review and consensus of expert opinion. Summary recommendations: An individualized approach is required for the management of VVA. Topical low-dose estrogens are effective and also alleviate urinary incontinence and prevent recurrent urinary tract infections. Women should not be denied long-term use of topical estrogens as long as they feel that this treatment is of benefit to them, because the safety data are reassuring. Non-hormonal preparations (lubricants and moisturizers) should be the first-line treatment for VVA in women taking adjuvant endocrine therapies for cancers considered to be hormone-dependent. They can be used over the long term. © 2021

Introduction: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care. Aim: The aim of this clinical guide is to provide an evidence-based approach to the management of urinary incontinence in postmenopausal women. Materials and methods: Literature review and consensus of expert opinion. Summary recommendations: Healthcare professionals should consider urinary incontinence a clinical priority and develop appropriate diagnostic skills. They should be able to identify and manage any relevant modifiable factors that could alleviate the condition. A wide range of treatment options is available. First-line management includes lifestyle and behavioral modification, pelvic floor exercises and bladder training. Estrogens and other pharmacological interventions are helpful in the treatment of urgency incontinence that does not respond to conservative measures. Third-line therapies (e.g. sacral neuromodulation, intravesical onabotulinum toxin-A injections and posterior tibial nerve stimulation) are useful in selected patients with refractory urge incontinence. Surgery should be considered in postmenopausal women with stress incontinence. Midurethral slings, including retropubic and transobturator approaches, are safe and effective and should be offered. © 2020

Breast cancer is a common malignancy among women. Despite an increase in incidence, breast cancer mortality has drastically dropped over the last 20 years. This change has been attributed to advances in screening, diagnosis, and treatment. This review summarises recent updates in the clinical approach to breast cancer. Advances in genetics have facilitated the stratification of the risk of recurrence in early-stage breast cancer. Advances in biology have led to the development of novel therapies (poly-ADP-ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, HER2 targeted agents). Their combination with endocrine (tamoxifen, aromatase inhibitors, GnRH-analogues, fulvestrant) and systematic therapy (anthracyclines, taxanes) in early and advanced disease have improved clinical outcomes. In the near future, neoadjuvant strategies in specific breast cancer subgroups (triple-negative breast cancers) and novel strategies (immune-modulatory agents) could further improve histopathological responses and survival. Radical mastectomies have been widely replaced by breast-conserving operations, while the traditional axillary dissection is being replaced with sentinel node techniques. Breast cancer therapeutics represents a great challenge due to patients’ heterogeneous molecular and clinical characteristics, while the identification of reliable and easily reproducible predictive factors could further improve individualized treatment. © 2020

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

Menopausal hormone therapy (MHT) is effective in preventing menopause-related bone loss and decreasing vertebral, non-vertebral and hip fracture risk. MHT contains estrogens that exert both antiosteoclastic and osteoanabolic effects. These effects are dose-dependent, as even ultra-low doses preserve or increase bone mineral density. The transdermal route of administration is effective on cancellous and cortical bone, although fracture data are still lacking. Hormone replacement therapy is the treatment of choice to preserve skeletal health in women with premature ovarian insufficiency and early menopause. MHT can be considered in women aged < 60 years or within 10 years since menopause as, in this population, benefits outweigh possible risks, such as breast cancer and cardiovascular events. Despite the ensuing bone loss after MHT discontinuation, a residual antifracture effect persists. However, in women at risk of fracture, subsequent antiosteoporotic therapy may be needed, either with an antiosteoclastic or osteoanabolic agent. In any case, longitudinal data from randomized controlled trials comparing different estrogen doses and routes of administration, as well as designating the optimal treatment strategy after MHT discontinuation, are needed to elucidate these issues further. © 2020, Hellenic Endocrine Society.

Premature ovarian insufficiency (POI) refers to the loss of ovarian activity before the age of 40 years, which leads to hypoestrogenism and amenorrhea. The diagnosis of POI in a young woman has potentially life-changing physical and emotional consequences for both the patient and her family. Therefore, it is very important that the diagnosis is correct and that it is made in a timely manner. Unfortunately, the diagnosis and therefore the effective treatment of POI are often delayed, which underlines the need for education of the broad medical community on the issue. A panel of menopause experts reviewed and critically appraised the literature, and present: (1) the diagnostic approach to POI, (2) the investigation of the etiology of this condition, (3) the therapeutic strategy regarding both hormone replacement therapy and fertility, and (4) the long-term follow-up and management for ensuring quality of life, as well as urogenital, cardiovascular, bone and mental health. The ultimate goal of this article is to provide a complete toolkit for the primary care physician to have easy access to all the information needed for the optimal management of women with POI, in the context of evidence-based and personalized medicine.HIGHLIGHTS Premature ovarian insufficiency occurs in 1% of the female population of reproductive age, yet the diagnosis is often delayed, with severe physical and emotional consequences for the patient. Primary care physicians should be aware of the possibility of premature ovarian insufficiency in young women presenting with menstrual irregularity. Prompt initiation of hormone replacement therapy ensures quality of life and prevents osteoporosis and cardiovascular disease. Women seeking fertility should be referred to specialists to discuss assisted reproduction options. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group and Elsevier B.V.

Premature ovarian insufficiency (POI) is an increasing public health problem with a prevalence now approaching 4%. POI results in adverse effects on the skeleton and central nervous system as well as disturbances of metabolic and cardiological factors that predispose to a major increased risk of cardiovascular disease (CVD). This article reviews the effects of the premature loss of ovarian function on lipids and lipoproteins, glucose and insulin metabolism, body composition, hemostasis and blood pressure, together with effects on the development of metabolic syndrome and diabetes mellitus. The article examines the effects of POI on vascular endothelial function and inflammation that result in arterial disease, and reviews the effects of hormone replacement therapy (HRT) on these various metabolic processes and on cardiovascular outcomes. It is essential that women with POI receive hormonal treatment to help prevent the development of CVD, and that this treatment is continued at least until the normal age of menopause. It appears that HRT has a more favorable effect than the combined oral contraceptive, but larger clinical trials are needed to establish the optimal treatment. Other therapeutic measures may need to be added to correct existing metabolic abnormalities and, in particular, attention to lifestyle factors such as diet and exercise must be encouraged.

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

Fetal brain is extremely plastic and vulnerable to environmental influences that may have long-term impact on health and development of the offspring. Both the Hypothalamic-Pituitary-Adrenal (HPA) and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (TH s), mediate several fundamental processes involved in neurodevelopment. The effects of these hormones on brain development are found to be time and dose-dependent. Regarding THs, the developing fetus depends on maternal supply of hormones, especially in the first half of pregnancy. It is acknowledged that inadequate or excess concentrations of both GCs and THs can separately cause abnormalities in the neuronal and glial structures and functions, with subsequent detrimental effects on postnatal neurocognitive function. Studies are focused on the direct impact of maternal stress and GC excess on growth and neurodevelopment of the offspring. Of particular interest, as results from recent literature data, is building understanding on how chronic stress and alterations of the HPA axis interacts and influences HPT axis and TH production. Animal studies have shown that increased GC concentrations related to maternal stress, most likely reduce maternal and thus fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating hormone levels in fetal microenvironment. The purpose of this review is to provide an update on data regarding maternal stress and its impact on fetal neurodevelopment, giving particular emphasis in the interaction of two axes and the subsequent thyroid dysfunction resulting from such circumstances. © Copyright © 2021 Anifantaki, Pervanidou, Lambrinoudaki, Panoulis, Vlahos and Eleftheriades.

IMPORTANCE: Genitourinary syndrome of menopause (GSM) consists of genitourinary tract symptoms that occur due to physical changes caused by estrogen concentrations decline after menopause. Unlike menopausal symptoms, which subside with time, GSM symptoms persist throughout a woman's life. OBJECTIVE: This article aimed to systematically review the literature to investigate the prevalence of GSM and its treatment. EVIDENCE REVIEW: The search was conducted in the electronic databases PubMed, CENTRAL, and EMBASE until October 2020. Eligible for the systematic review were studies and surveys conducted via questionnaires or medical interviews evaluating the existence of GSM symptoms with or without gynecological examination in postmenopausal women or women >40 years of age. FINDINGS: After the application of predefined inclusion/exclusion criteria, 27 studies were included in the systematic review. The prevalence of GSM-related symptoms, such as vaginal dryness, irritation, itching, and dyspareunia, ranged from 13% to 87%. The use of GSM-specific treatment varied from 13% to 78%. Over-the-counter lubricants and moisturizers were the most popular therapeutic options (24.0%-85.5%), followed by low-dose vaginal estrogens (4.8%-35.0%). Vaginal health is not frequently discussed during doctor visits and awareness about the condition and the number of treatment options is low. Women are concerned about the long-term safety and side effects of hormonal treatment. The majority of women who suffer from genitourinary symptoms are dissatisfied by the treatment they have used. CONCLUSIONS AND RELEVANCE: GSM is a highly prevalent condition among women. Nevertheless, women are frequently not aware of its cause and its treatment options. The findings of this review underline the need for education of patients and healthcare professionals regarding GSM diagnosis and treatment options. Copyright © 2021 by The North American Menopause Society. Video Summary:http://links.lww.com/MENO/A720.

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.

INTRODUCTION: Globally, the total number of people with depression exceeds 300 million, and the incidence rate is 70 % greater in women. The perimenopause is considered to be a time of increased risk for the development of depressive symptoms and major depressive episodes.; AIM: The aim of this position statement is to provide a comprehensive model of care for the management of depressive symptoms in perimenopausal and early menopausal women, including diagnosis, treatment and follow-up. The model integrates the care provided by all those involved in the management of mild or moderate depression in midlife women.; MATERIALS AND METHODS: Literature review and consensus of expert opinion.; SUMMARY RECOMMENDATIONS: Awareness of depressive symptoms, early detection, standardized diagnostic procedures, personalized treatment and a suitable follow-up schedule need to be integrated into healthcare systems worldwide. Recommended treatment comprises antidepressants, psychosocial therapies and lifestyle changes. Alternative and complementary therapies, although widely used, may help with depression, but a stronger evidence base is needed. Although not approved for this indication, menopausal hormone therapy may improve depressive symptoms in peri- but not in postmenopausal women, especially in those with vasomotor symptoms. Copyright © 2019. Published by Elsevier B.V.

Globally, 985 million women are aged 50 and over, leading to increasing concerns about chronic conditions such as cardiovascular disease, osteoporosis, dementia, and cognitive decline, which can adversely affect quality of life and independent living.

Objective: Menopausal transition has been associated with an increased risk of cardiovascular disease (CVD), mainly attributed to atherogenic dyslipidaemia, central obesity and insulin resistance. Whether arterial hypertension (AH) also contributes to menopause-associated CVD is currently unknown. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the association between early menopause (EM) and AH risk. Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases, up to January 20th, 2020. Data were expressed as odds ratio (OR) with 95 % confidence intervals (CI). The I2 index was employed for heterogeneity. Results: Ten studies were included in the quantitative analysis (273,994 postmenopausal women, 76853 cases with AH). Women with EM (age at menopause 45 years) (OR 1.10, 95 % CI 1.01–1.19, p = 0.03; I2 79 %). The direction or the magnitude of this association remained significant when the analysis was restricted to studies including groups matched for potential confounders, such as age, BMI, smoking or the use of menopausal hormone therapy or oral contraceptives. Conclusions: Women with EM have an increased risk for AH compared with those of normal age at menopause. © 2020 Elsevier B.V.

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.