Polymorphisms in genes involved in T-cell co-stimulation are associated with blood pressure in women.

In recent years, conclusive data have emerged on a relationship between immune system, especially the T-cell, and blood pressure (BP). The objective of the present study was to determine the association between BP and four polymorphisms in CD80, CD86, CD28 and CTLA4 genes that code for key proteins in the T-cell co-stimulation process, in a female cohort. To that end, an association study in a cohort of 934 women over 40 years old from two hospitals was done. Raw data showed a significant association between the SNP rs1129055 of CD86 gene and BP. Analyzing this association against inheritance patterns, higher SBP (p  0.000) and DBP (p = 0.005) values were observed in AA than in GG/GA genoty…

Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide

Abstract Introduction Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved. Aims To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines. Materials and methods Literature review and consensus of expert opinion. Results and conclusion The recommended daily intake of calcium varies between 700 and 1200 mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either fro…

Oral administration of pharmacological doses of Vitamins C and E reduces reproductive fitness and impairs the ovarian and uterine functions of female mice

This study aims to ascertain whether oral administration of pharmacological doses of Vitamins C and E has any detrimental effect on reproductive fitness of female mice. We fed hybrid female mice from the first day of weaning a standard diet supplemented or not supplemented with pharmacological doses of Vitamins C and E. At the age of 28 weeks, we individually caged females with a male for the rest of their reproductive life. We performed a series of mating experiments to ascertain the number of oocytes ovulated and the potential for embryo development in vitro to the blastocyst stage and in vivo to Day 12 of gestation. The antioxidant diet decreased the frequency of litters, litter size, to…

Therapeutic dosages of oral or transdermal estradiol did not modify sCD40L levels in postmenopausal women.

The CD40/CD40L system is considered a crucial modulator of the inflammatory process underlying the progression and complication of atheroma plaques. The soluble fraction of CD40L (sCD40L) is a reliable indicator of the CD40/CD40L system. Our purpose was to investigate whether a therapeutic dose of estradiol, by either the oral or the transdermal route, was associated with changes in circulating levels of sCD40L. Forty-seven women completed a 4-week course of treatment with either oral estradiol valerate (2 mg/day, 20 women) or transdermal estradiol (50 microg/day, 27 women). Serum levels of sCD40L were measured by conventional enzyme-linked immunosorbent assay. Oral, but not transdermal est…

Can Integrated Care Help in Meeting the Challenges Posed on Our Health Care Systems by COVID-19? Some Preliminary Lessons Learned from the European VIGOUR Project

The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOUR ("Evidence based Guidance to Scale-up Integrated Care in Europe", funded by the European Union's Health Programme 2014-2020 under Grant Agreement Number 826640).

Mir-661: A key Factor in Embryo-Maternal dialog With Potential Clinical Application to Predict Implantation Outcome?

Implantation resulting in a full-term pregnancy is, by large, more than a passive process in which the developed conceptus is passively glued to the uterus through adhesive molecules. It is the result of a perfectly orchestrated dialog between a viable embryo and a receptive endometrium, through a mixture of paracrine and juxtacrine processes in which many key proteins and growth factors play fundamental roles (Pellicer et al., 2002.) Since their discovery, microRNAs have become prominent regulatory candidates, providing missing links for a few biological pathways in this process, although their exact role in human normal embryo formation and endometrial preparation for pregnancy remains un…

Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women

Abstract In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis. Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women. Data analysis revealed a statistically significant association between the SNP rs884205 and BP press…

The new frontier of bone formation: a breakthrough in postmenopausal osteoporosis?

Osteoporosis is a chronic disease that accelerates after menopause in many women. Most of the pharmacologic attempts to control the disease, such as hormone therapy, have emphasized the constraint of bone resorption. Since recent years have witnessed important advances in the field of bone formation, this review aims to update the present knowledge on the mechanisms affecting osteoblastogenesis and on the therapeutic results achieved by recently approved drugs.We sought peer-reviewed, full-length basic and clinical articles published between 1995 and May 2008 using a PubMed search strategy, with the terms osteoporosis and osteoblast, osteoporosis and strontium ranelate, and osteoporosis and…

Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway

Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene an…

Comments on the USPSTF draft recommendation statement on menopausal hormone therapy: Primary prevention of chronic conditions

Perceptions and experiences of frailty interventions: quantitative and qualitative results from a survey of partners within the European Innovation Partnership on Active and Healthy Ageing (EIP-AHA)

ABSTRACTThe European Innovation Partnership on Active and Healthy Ageing (EIP-AHA) was launched by the European Commission in 2011 to promote innovation in ageing research. This paper explores the experiences of partners delivering frailty interventions within Europe, registering their programmes with the EIP-AHA. Data were collected using an online survey from 21 partners in seven countries. A mixed-method approach was used with inductive thematic analysis of free-text responses to improve data richness. Responses indicated that there was a lack of consistency between EIP-AHA partners in methods of defining, screening and measuring for frailty and pre-frailty. Open responses to survey ques…

Diet to Reduce the Metabolic Syndrome Associated with Menopause. The Logic for Olive Oil

The rates of metabolic syndrome are increasing in parallel with the increasing prevalence of obesity, primarily due to its concomitant insulin resistance. This is particularly concerning for women, as the years around menopause are accompanied by an increase in visceral obesity, a strong determinant of insulin resistance. A fall in estrogens and increase in the androgen/estrogen ratio is attributed a determining role in this process, which has been confirmed in other physiological models, such as polycystic ovary syndrome. A healthy lifestyle, with special emphasis on nutrition, has been recommended as a first-line strategy in consensuses and guidelines. A consistent body of evidence has ac…

Isoflavones and cardiovascular disease

The specific profile of estrogens on cardiovascular risk, with limiting action on atherogenesis but a less clear protection on cardiovascular episodes, might be improved by other agonists of the estrogen receptor, such as isoflavones. By using a systematic search based on the electronic Medline database plus a hand-search of reference lists of selected review papers, we reviewed the rapidly growing body of experimental and clinical data that, on average, follow a pattern of benefit rather similar to estrogens. Experimental models have used endothelial and vascular smooth muscle cells, isolated arteries, and live animals, including monkeys. The clinical evidence arises from studies on the li…

Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells

Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cyt…

Assisted reproductive technology results: Why are live-birth percentages so low?

The present bioessay aims to analyze the impact of parental age, cause of infertility, embryo chromosomal anomalies, assisted reproduction technology (ART) treatments, and environmental and occupational exposures to xenobiotics on ART results, particularly on live-birth percentages per transfer. Special attention is paid to analyzing the effects of these factors on the mitochondrial, genetic, and epigenetic traits of gametes and embryos to ascertain the molecular/cellular mechanisms responsible for the relatively low percentages of live births reported year after year in ART cycles. The bias of age distribution of women attending fertility clinics toward the late thirties and beyond and the…

Estradiol counteracts oxidized LDL-induced asymmetric dimethylarginine production by cultured human endothelial cells.

Objective: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, is a novel cardiovascular risk factor produced by endothelial cells. ADMA levels are mainly regulated by the activity of dimethylarginine dimethylaminohydrolases (DDAH). Endothelial release of ADMA is increased in the presence of oxidized LDL cholesterol (oxLDL), whereas estrogens stimulate NO production by endothelial cells by increasing both expression and activity of NO synthase and by reducing ADMA levels. Thus, the aim of the present study was to evaluate the estradiol effects on the DDAH/ADMA/NO pathway in cultured human umbilical vein endothelial cells (HUVEC) exposed to LDL. Methods…

Invasive ovarian seromucinous carcinoma developed on an endometrioma. The determining role of transvaginal ultrasound

Endometriosis is a chronic inflammatory disease that has been associated with an increased risk of ovarian cancer, especially epithelial tumors. Transvaginal ultrasound is a first-line diagnostic method for the assessment of endometriosis, and of endometriomas, the ovarian cystic form of endometriosis. Endometriomas usually have typical ultrasound features that allow them to be easily diagnosed. When atypical images are observed, such as solid areas with vascular flow, their malignancy should be ruled out, especially in peri-menopausal women. Early diagnosis of these tumors is essential because immediate surgical treatment is crucial for prognosis. Malignant neoplasms associated with endome…

Antioxidant therapy counteracts the disturbing effects of diamide and maternal ageing on meiotic division and chromosomal segregation in mouse oocytes

This study aims (i) to ascertain whether oxidative-stress-induced disturbances in chromosomal distribution in the metaphase-II spindle of mouse oocytes can be counteracted by supplementing culture medium with antioxidants; and (ii) to determine whether supplemental intake of antioxidants neutralizes the disturbing effects of maternal ageing on segregation of chromosomes during the first meiotic division and distribution of chromosomes in the metaphase-II spindle. (i): Germinal vesicle oocytes from unstimulated 10-12 week old mice were matured in vitro in the presence or absence of diamide and/or dithiothreitol. Metaphase-II oocytes were fixed and stained with 4',6-diamidino-2-phenylindole (…

Delayed Fatherhood in Mice Decreases Reproductive Fitness and Longevity of Offspring1

Abstract This study aims to analyze, in mice, the long-term effects of delayed fatherhood on reproductive fitness and longevity of offspring. Hybrid parental-generation (F0) males, at the age of 12, 70, 100, and 120 wk, were individually housed with a randomly selected 12-wk-old hybrid female. The reproductive fitness of first-generation (F1) females was tested from the age of 25 wk until the end of their reproductive life. In F1 males, the testing period ranged from the age of 52 wk until death. Breeding F1 females from the 120-wk group displayed interbirth intervals longer than females from the 12-, 70-, and 100-wk groups. Furthermore, F2 pups begotten by F1 studs exhibited weaning weight…

Changes in sex ratio from fertilization to birth in assisted-reproductive-treatment cycles

Background: In Western gender-neutral countries, the sex ratio at birth is estimated to be approximately 1.06. This ratio is lower than the estimated sex ratio at fertilization which ranges from 1.07 to 1.70 depending on the figures of sex ratio at birth and differential embryo/fetal mortality rates taken into account to perform these estimations. Likewise, little is known about the sex ratio at implantation in natural and assisted-reproduction-treatment (ART) cycles. In this bioessay, we aim to estimate the sex ratio at fertilization and implantation using data from embryos generated by standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in preimplantation gene…

The oxidizing agent tertiary butyl hydroperoxide induces disturbances in spindle organization, c-meiosis, and aneuploidy in mouse oocytes

It has been recently proposed that a concomitant generation of oxidative stress of oocytes with increasing maternal age may be a major factor responsible for the age-related increase in aneuploid conceptions. As a preliminary step in the testing of this hypothesis, we need to confirm that oxidative stress in itself can induce errors in chromosome segregation. In order to achieve this goal, germinal vesicle (GV)-stage mouse oocytes from unstimulated ICR and (C57BL x CBA) F1 hybrid female mice were matured in vitro for 9 h for metaphase I (MI) oocytes or 16 h for metaphase II (MII) oocytes in the presence of varying concentrations of the oxidizing agent tertiary-butyl hydroperoxide (tBH). MII…

Understanding frailty:meanings and beliefs about screening and prevention across key stakeholder groups in Europe

Innovative methods to manage frailty are critical to managing the needs of an ageing population. Evidence suggests there are opportunities to reverse or prevent frailty through early intervention. However, little is known about older adults’, families’ and practitioners’ beliefs about the malleability of frailty. This study examined European stakeholders’ accounts of the acceptability and feasibility of frailty screening and prevention to inform future intervention development. Semi-structured focus groups and individual interviews were conducted in three European Union countries (Italy, Poland and the United Kingdom) with key stakeholders – frail and non-frail older adults, family care-giv…

Postovulatory Aging of Oocytes Decreases Reproductive Fitness and Longevity of Offspring1

We analyzed the long-term effects of postovulatory aging of mouse oocytes on reproductive fitness and longevity of offspring. Hybrid (C57BL/6JIco 3 CBA/JIco) parental generation (F0) females were artificially inseminated at 13 h (;1 h postovulation) or 22 h (;10 h postovulation) after GnRH injection. Reproductive fitness of first generation (F1) females was tested from the age of 28 wk until the end of their reproductive life. In males, the testing period ranged from the age of 2 yr until their natural death. Experimental F1 females exhibited longer between-labor intervals, decreased frequency of litters, and lower total number of litters and offspring born. Experimental second generation (…

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs …

Receptor Activator of Nuclear Factor Kappa B (RANK) and Clinicopathological Variables in Endometrial Cancer: A Study at Protein and Gene Level

The system integrated by the receptor activator of nuclear factor kappa B (RANK) and its ligand, RANKL, modulates the role of hormones in the genesis and progression of breast tumors. We investigated whether the expression of RANK was related with clinicopathological features of primary endometrial tumors. Immunohistochemistry was used in an endometrial cancer tissue array containing samples from 36 tumors. The amount of RANK mRNA was examined in a tissue scan cDNA array containing cDNA from 40 tumors. Normal endometrium was examined for comparison. Immunohistochemical analyses showed that RANK expression was higher in malignant than in normal endometrium (p &lt

Global consensus recommendations on menopause in the workplace: A European Menopause and Andropause Society (EMAS) position statement

Introduction: Worldwide, there are 657 million women aged 45-59 and around half contribute to the labor force during their menopausal years. There is a diversity of experience of menopause in the workplace. It is shaped not only by menopausal symptoms and context but also by the workplace environment. It affects quality of life, engagement, performance, motivation and relations with employers. Aim: To provide recommendations for employers, managers, healthcare professionals and women to make the workplace environment more menopause supportive, and to improve women's wellbeing and their ability to remain in work. Materials and methods: Literature review and consensus of expert opinion. Summa…

Effect of delayed breeding on the reproductive performance of female mice

The aim of the present study was to determine, in the mouse, whether maintaining females as virgins until an advanced reproductive age was associated with decreased reproductive performance and reproductive lifespan compared with females of the same age that were first mated with males at an earlier reproductive age. Randomly selected virgin hybrid (C57BL/6JIco female × CBA/JIco male) female mice were housed individually with a randomly selected 12- to 14-week-old hybrid male either at the age of 28 weeks (normal breeding group; n = 20) or 51 weeks (delayed breeding group; n = 23) for the rest of their reproductive life. Females were checked once daily to determine the day of parturition an…

Raloxifene promotes prostacyclin release in human endothelial cells through a mechanism that involves cyclooxygenase-1 and -2

Objective To examine the effects of raloxifene on prostacyclin production by human umbilical vein endothelial cells (HUVEC) and to shed light on the molecular details of that action. Design Cell culture for 4, 8, 16, 24, and 48 hours. Setting University research laboratory. Patient(s) Source of HUVEC. Intervention(s) Measurement of prostacyclin production and of protein levels and mRNA expression of cyclooxygenase (COX)-1 and -2. Main Outcome Measure(s) Prostacyclin production was measured by enzyme immunoassay, the mRNA expression of COX-1 was measured by quantitative real time-polymerase chain reaction, and the protein levels of COX-1 and -2 were measured by immunoblotting. Result(s) Ralo…

Long-Term Effects of Postovulatory Aging of Mouse Oocytes on Offspring: A Two-Generational Study1

Aims of this study were to analyze the long-term effects of postovulatory aging of mouse oocytes on 1) reproductive traits of parental (F(0)) and first (F(1))-generation females (pregnancy rate, gestation length, litter size, perinatal death, and sex ratio of offspring) and 2) developmental and behavioral variables of F(1) and second-generation (F(2)) offspring (birth weight and weight gain during preweaning development, postnatal day of attainment of immediate righting, spontaneous motor activity, and passive and active conditioned learning ability). Hybrid (C57BL/6JIco x CBA/JIco) females were artificially inseminated at 13 h (control group) or 22 h (oocyte-aged group) after GnRH injectio…

Metabolismo lipídico y aterogénesis femenina: acción de hormonas, SERM y fitoestrógenos

Resumen Objetivo Revisar los efectos de la terapia hormonal sustitutiva, en sus distintas formas, en el metabolismo lipidico Fuentes Bibliografia medica hasta septiembre del ano 2000 a traves de MEDLINE Conclusiones Los estrogenos, combinados o no con progestagenos, inducen un perfil lipoproteico favorable. Buena parte de esa accion se ejerce a traves de modificacion en la cinetica de particulas. Las acciones sobre oxidacion de las lipoproteinas de baja densidad (LDL), o el tamano de sus particulas, son motivo de polemica. Nuevos preparados, con capacidad de activar receptores estrogenicos, tambien demuestran ejercer acciones selectivas sobre el metabolismo lipidico

Delayed Motherhood Decreases Life Expectancy of Mouse Offspring1

Abstract This study analyzes the long-term effects of delayed motherhood on reproductive fitness and life expectancy of offspring in the mouse. Hybrid (C57BL/6JIco × CBA/JIco) first-generation (F1) females, either at the age of 10 or 51 wk, were individually housed with a randomly selected 12- to 14-wk-old hybrid male following a breeding pen system until females reached the end of their reproductive life. Reproductive fitness of second-generation (F2) females was tested from the age of 25 wk until the end of their reproductive life. In F2 males, the testing period ranged from the age of 52 wk until their natural death. Delayed motherhood of hybrid F1 female mice was associated with a decre…

Correction to: a predictive model for women's assisted fecundity before starting the first IVF/ICSI treatment cycle.

PURPOSE: To introduce a prognostic model for women’s assisted fecundity before starting the first IVF/ICSI treatment cycle. METHODS: In contrast to previous predictive models, we analyze two groups of women at the extremes of prognosis. Specifically, 708 infertile women that had either a live birth (LB) event in the first autologous IVF/ICSI cycle (“high-assisted-fecundity women”, n = 458) or did not succeed in having a LB event after completing three autologous IVF/ICSI cycles (“low-assisted-fecundity women”, n = 250). The initial sample of 708 women was split into two sets in order to develop (n = 531) and internally validate (n = 177) a predictive logistic regression model using a forwar…

Bazedoxifene increases the proliferation of human arterial endothelial cells but does not affect the expression of cyclins A, B, and D1 and of p27Kip1

Endothelial dysfunction and denudation are considered a first step in atherosclerosis. Endothelial proliferation is key for cellular repair. The effect of bazedoxifene on the vascular endothelium h...

Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density

El pdf del artículo es el manuscrito de autor (PMCID: PMC3682472).-- et al.

Cardiovascular Disease and SERMs

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to t…

Management of Osteoporosis in Postmenopausal Women

Osteoporosis is a noncommunicable disease with increasing incidence at a global level. The burden of the disease particularly concerns women. A drastic and rapid decline in the circulating levels of estrogens, a key regulator of bone metabolism, is responsible for the increase in bone loss after menopause. Cells with a role in bone metabolism, osteoblasts, osteoclasts and osteocytes, have estrogen receptors. The fall in estrogens increases the differentiation of osteoclasts from progenitors in the bone marrow. A significant expansion in the resorption process follows.

Noninvasive Monitoring of Lesion Size in a Heterologous Mouse Model of Endometriosis

Here, we describe a protocol for the implementation of a heterologous mouse model in which progression of endometriosis can be assessed in real time through noninvasive monitoring of fluorescence emitted by implanted ectopic human endometrial tissue. For this purpose, biopsies of human endometrium are obtained from donor women ongoing oocyte donation. Human endometrial fragments are cultured in the presence of adenoviruses engineered to express cDNA for the reporter fluorescent protein mCherry. Upon visualization, labeled tissues with an optimal rate of fluorescence after infection are subsequently chosen for the implantation in recipient mice. One week prior to the implantation surgery, re…

Effectiveness of the interventions in preventing the progression of pre-frailty and frailty in older adults: a systematic review protocol

REVIEW QUESTION / OBJECTIVE : The objective of this review is to identify the effectiveness of the interventions in preventing progression of pre-frailty and frailty in older adults. More specifically, the review questions are: - What is the effectiveness of interventions in preventing or reducing frailty in older adults? - How does effectiveness vary with degree of frailty? - Are there factors that influence the effectiveness of interventions? - What is the economic feasibility of interventions for pre-frailty and frailty? INCLUSION CRITERIA : Types of participants This review will consider studies that include older adults (female and male) aged 65 years and over, explicitly identified as…

Predicting risk and outcomes for frail older adults: an umbrella review of frailty screening tools

EXECUTIVE SUMMARY Background A scoping search identified systematic reviews on diagnostic accuracy and predictive ability of frailty measures in older adults. In most cases, research was confined to specific assessment measures related to a specific clinical model. Objectives To summarize the best available evidence from systematic reviews in relation to reliability, validity, diagnostic accuracy and predictive ability of frailty measures in older adults. Inclusion criteria Population Older adults aged 60 years or older recruited from community, primary care, long-term residential care and hospitals. Index test Available frailty measures in older adults. Reference test Cardiovascular Health…

MOESM3 of Interventions to prevent, delay or reverse frailty in older people: a journey towards clinical guidelines

Additional file 3: Table S1. Table that describes the members of the FOCUS Guideline Panel and their role in the development of the guidelines.

Long-Term Effects of Delayed Fatherhood in Mice on Postnatal Development and Behavioral Traits of Offspring1

This study aims to analyze, in mice, the long-term effects of delayed fatherhood on postnatal development, spontaneous motor activity, and learning capacity of offspring. Hybrid parental-generation (F 0 ) males, at the age of 12, 70, 100, and 120 wk, were individually housed with a randomly selected 12wk-old hybrid female. The resulting first-generation (F 1 ) offspring were tested for several developmental and behavioral variables. Cumulative percentage of F 1 pups that attained immediate righting in the 120-wk group was lower than that found in the 12-, 70-, and 100-wk groups. Furthermore, the postnatal day of attaining immediate righting was higher in pups from the 120-wk group when comp…

A Reassessment of the Therapeutic Potential of a Dopamine Receptor 2 Agonist (D2-AG) in Endometriosis by Comparison against a Standardized Antiangiogenic Treatment

Dopamine receptor 2 agonists (D2-ags) have been shown to reduce the size of tumors by targeting aberrant angiogenesis in pathological tissue. Because of this, the use of a D2-ag was inferred for endometriosis treatment. When assayed in mouse models however, D2-ags have been shown to cause a shift of the immature vessels towards a more mature phenotype but not a significant reduction in the amount of vascularization and size of lesions. These has raised concerns on whether the antiangiogenic effects of these compounds confer a therapeutic value for endometriosis. In the belief that antiangiogenic effects of D2-ags in endometriosis were masked due to non-optimal timing of pharmacological inte…

Cellular and Morphological Traits of Oocytes Retrieved from Aging Mice after Exogenous Ovarian Stimulation1

The present study aims to shed light on the origin of abnormal oocytes ovulated by aged females. In order to reach this goal, cellular and morphological traits of ovulated oocytes from hybrid (C57Bl/6JIco female x CBA/JIco male) female mice retrieved after exogenous ovarian stimulation at the age of 12, 40-42, 50-52, or 57-62 wk were analyzed. Aging of female mice was associated with 1) decreased number of ovulated oocytes; 2) increased percentage of cumulus-free oocytes; 3) raised percentage of oocytes with intracellular mitochondrial aggregates; 4) reduced percentage of oocytes displaying a normal distribution of chromosomes in the metaphase-II plate; 5) increased percentage of normal ooc…

Absence of long-term effects of reproduction on longevity in the mouse model.

Background Most human demographic data, particularly those on natural fertility populations, find no relationship or even a positive association between fertility and longevity. The present study aims to ascertain whether there is a trade-off between fertility and longevity in the mouse model. Methods The study was focused on the first litter produced by 10- to 14-wk-old hybrid (C57BL/6JIco female X CBA/JIco male) mice. A single female/male per litter was individually housed with a male/female at the age of 25 and 52 wk, respectively, until the end of reproductive life in females or natural death in males under controlled housing conditions. Post-reproductive females and virgin mice were re…

Selective estrogen receptor modulators and risk for coronary heart disease.

Coronary heart disease (CHD) is the leading cause of death in women in most countries. Atherosclerosis is the main biological process determining CHD. Clinical data support the notion that CHD is sensitive to estrogens, but debate exists concerning the effects of the hormone on atherosclerosis and its complications. Selective estrogen receptor modulators (SERMs) are compounds capable of binding the estrogen receptor to induce a functional profile distinct from estrogens. The possibility that SERMs may shift the estrogenic balance on cardiovascular risk towards a more beneficial profile has generated interest in recent years. There is considerable information on the effects of SERMs on disti…

Regulación de las modificaciones óseas en la madre durante la gestación

El embarazo constituye un modelo donde se produce el desarrollo del esqueleto fetal en un corto lapso de tiempo. Este logro se lleva a cabo bajo la tutela del propio feto, que gobierna este proceso a través de las señales generadas en la denominada unidad feto-placentaria. El organismo materno sufre un proceso de adaptación donde se produce un drástico reajuste en mecanismos implicados en el recambio óseo. Entre los cambios más evidentes detectables en sangre materna están los incrementos con la edad gestacional de los niveles de calcitriol, de la hormona de crecimiento de origen placentario, del factor de crecimiento similar a la insulina tipo I (IGF-1), de estrógenos, y de prolactina. Tam…

Predictive variables of in vitro fertilization and pre-implantation embryo development in the mouse

The present study aims to analyze the cause-effect relationships among several in-vitro fertilization and pre-implantation embryo development variables in the mouse. Superovulation of hybrid (C57Bl/6JIco female X CBA/JIco male) female mice of 4-6 weeks of age was induced by a priming injection of pregnant mare's serum gonadotropin at the estrus stage of the estrous cycle followed after a 48-hr interval by human chrorionic gonadotropin. Ovulated cumulus-enclosed oocytes were inseminated with sperm from hybrid males of 12-16 weeks of age. The multiple linear regression analyses performed indicated that (a) total number of ovulated oocytes is a good predictor of both fertilization frequency an…

Management of depressive symptoms in peri- and postmenopausal women: EMAS position statement.

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. Summa…

Cystic degeneration of uterine leiomyoma during ulipristal acetate treatment

Degenerative cyst formation  is a rare phenomenon in-between uterine leiomyomas, however, both patients and physicians have to be aware of this possibility when using ullipristal acetate as this event may guide to the inaccurate diagnosis of an adnexal malignant pathology.

Personalized health care for midlife and beyond

Long-term effects of delayed parenthood.

The present study aims to define, characterize and compare the long-term effects on offspring of delayed parenthood. Data published so far on this topic show that maternal and paternal ageing may affect offspring by different mechanisms. Delayed motherhood is characterized by increased probability of obstetric complications and/or fetal and perinatal problems which, in turn, may increase the risks of mortality and morbidity in newborns and later life. Furthermore, maternal ageing is distinguished by a decreased ratio of male to female infants and higher odds of conceiving a trisomic child and/or an individual suffering from mitochondrial DNA disorders. In contrast, delayed fatherhood is ass…

Note of clarification: Potential risks to offspring of intrauterine exposure to maternal age-related obstetric complications

Several hypotheses have been proposed to explain the negative effects of delayed motherhood on an offspring’s morbidity later in life. However, these hypotheses are not supported by clinical and epidemiological evidence. Because advanced maternal age is associated with increased risk of obstetric complications, the aim of the present study was to ascertain whether the negative effects on offspring of intrauterine exposure to maternal age-related obstetric complications may explain the reported negative effects of delayed motherhood on offspring. To this end, a literature search was performed to identify relevant publications up to March 2016 on PubMed; references cited in relevant articles …

Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.

Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To date, epidemiological studies of rs10046 have been performed in different populations with contradictory results. In the present study, we have conducted a case-control analysis (522 cases and 1221 …

Benefits of physical exercise in postmenopausal women

Physical inactivity not only places women's health at risk during menopause, but also increases menopausal problems. Abundant evidence links habitual physical exercise (PE) to a better status on numerous health indicators and better quality of life and to the prevention and treatment of the ailments that typically occur from mid-life onwards. We can infer that PE is something more than a lifestyle: it constitutes a form of therapy in itself. A panel of experts from various Spanish scientific societies related to PE and menopause (Spanish Menopause Society, Spanish Cardiology Society, Spanish Federation of Sports Medicine) met to reach a consensus on these issues and to decide the optimal ti…

Unpredicted ovulations and conceptions during early pregnancy: an explanatory mechanism of human superfetation

In this bioessay, a literature review on human superfetation was performed in order to find epidemiological variables associated with this phenomenon. Thereafter, an explanatory mechanism of superfetation compatible with the endocrinological, histological and physiological changes undergone by women during early pregnancy is proposed. Superfetation can be defined as the ovulation, fertilisation and implantation of a second or additional embryo(s) during pregnancy. The literature review evidences a small discordance in gestational age between dizygotic twins in humans (range: 2–4 weeks; mean ± s.e.m.: 3.3 ± 0.3 weeks). This difference is compatible with a luteal out-of-phase (LOOP; i.e. atyp…

Pure anti-oestrogens

Pure anti-oestrogens are a group of at least five new compounds which are able to antagonize the effects of oestrogen in all tissues and species studied. The mechanism by which the pure anti-oestrogens produce their effects remains in question, but all of them are competitive antagonists of the oestrogen receptors and, moreover, have been proposed to block the shuttling of oestrogen receptors into the cell nucleus. When studied in vitro, these compounds are able to block the oestrogen-stimulated growth of breast cancer cells. In animals, their ability to block the effects of oestrogen on breast, uterus, bone, cardiovascular system and other reproductive-associated tissues has been demonstra…

Transdermal estrogens do not appear to modify the extent of lesional areas of aortic atherosclerosis in oophorectomized rabbits on a cholesterol-rich diet.

Cardiovascular disease (CVD) is the leading cause of death in older women in industrialised countries. It has been suggested that it is the cessation of estrogen production by the ovaries that puts postmenopausal women at increased risk of CVD. Estrogen therapy has demonstrated a protective effect against CVD and several reports suggest that diverse mechanisms may be involved. Oral estrogen appears to be associated with a better lipid profile than the use of transdermal estrogens; however, it is assumed that estrogens, oral and non-oral, have direct actions on the blood vessels that may exert an important role in cardiovascular disease prevention. To investigate the effect of transdermal es…

EMAS position statement: Predictors of premature and early natural menopause.

Simoncini, Tommaso/0000-0002-2971-0079; Chung, Hsin-Fang/0000-0003-3261-5942; Mishra, Gita/0000-0001-9610-5904 WOS:000468709100014 PubMed ID: 31027683 Introduction: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (< 40 years) or early natural menopause (40-45 years). Aim: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. Materials and methods…

Effectiveness and quality of life 10 years after transobturator suburethral tape surgery for stress urinary incontinence

AIM We aimed to measure the effectiveness and quality of life (QoL) 10 years after transobturator suburethral tape surgery. METHODS We carried out a prospective observational study of 42 women assessed 10 years after surgical intervention with the transobturator technique. The main outcome measures were subjective and objective cure or improvement, complications, and changes in QoL. RESULTS The median abdominal leak point pressure had been 92 (82-113) mL H2 O prior to surgery. Thirty-six women (85.7%) remained cured (negative cough test) and 13 (31%) reported urine leakage during physical activity, percentages which were similar to those at a previous assessment at the 5th year. Urgency uri…

Are the serum levels of sCD40L modified by raloxifene in postmenopausal women?

Isopropanolic Cimicifuga racemosa is favorable on bone markers but neutral on an osteoblastic cell line

Postmenopausal women treated with an isopropanolic extract of Cimicifuga racemosa underwent a decrease in the urinary concentration of N-telopeptides, a marker of bone resorption, and an increase in alkaline phosphatase, a marker of bone formation, at the third month of therapy. Serum from treated women did not modify the activity of alkaline phosphatase or the expression of three genes, runt-related transcription factor-2 (Runx-2), alkaline phosphatase, and osteocalcin, when added to the MC3T3-E1 osteoblastic cell line.

The mechanisms of thrombotic risk induced by hormone replacement therapy.

Abstract Objective : To review the available information on the action of hormones on the mechanisms involved in thrombotic risk. Results and Conclusions : Thrombosis plays a crucial role in the genesis and progression of both coronary heart disease (CHD) and venous thromboembolic disease (VTED), the two main forms of cardiovascular disease. Two main determinants of the thromboembolic phenotype, hypercoagulable state and altered endothelium, accumulate much of the work performed on the influence of hormones on thrombosis. Information has accumulated mainly for oestrogens, but increasing evidences support a role for progestogens. The sensitivity of each of the three components of the hemosta…

The impact of coffee on health

Abstract Objective Coffee is a beverage used worldwide. It includes a wide array of components that can have potential implication on health. We have reviewed publications on the impact of coffee on a series of health outcomes. Methods Articles published between January 1990 and December 2012 were selected after crossing coffee or caffeine with a list of keywords representative of the most relevant health areas potentially affected by coffee intake. Results Caffeine, chlorogenic acids and diterpenes are important components of coffee. Tolerance often acts as a modulator of the biological actions of coffee. There is a significant impact of coffee on the cardiovascular system, and on the meta…

The effect of hormone replacement therapy on Ca2+ mobilization and P-selectin (CD62P) expression in platelets examined under flow cytometry.

A series of events, such as increase of cytoplasmic free calcium (Ca 2+ ) and expression of P-selectin (CD62P), an adhesion molecule, on the platelet surface, are significant indicators of platelet activation. We have used flow cytometry to examine Ca 2+ mobilization and CD62P expression in platelets in whole blood obtained in women prior to, and after, different forms of hormone replacement therapy. Thirty-two women completed a protocol consisting of two consecutive 1-month periods under oestradlol (E 2 ), administered orally (2 mg/day) or transdermally (50 μg/day) in random order, followed by a 4-week transdermal sequential regime, in which, during the last 14 days, either progesterone (3…

Effect of dietary supplementation with a mixture of Vitamins C and E on fertilization of tertiary butyl hydroperoxide-treated oocytes and parthenogenetic activation in the mouse.

The present study aims to analyze the effect of dietary supplementation with a mixture of Vitamins C and E on fertilization and later development of tertiary butyl hydroperoxide (tBH)-treated mouse oocytes and on parthenogenetic activation of freshly ovulated mouse oocytes. We fed hybrid mice a standard diet supplemented or not supplemented with Vitamins C and E from the first day of weaning until the age of 12 weeks. We noted no significant effect of diet on fertilization rate, percentage of total and hatching blastocysts, total number of cells, mitotic index and percentage of apoptotic nuclei at 120 h post-insemination of oocytes incubated for 15 min in the presence of 0, 1, 5 and 10 micr…

Phytoestrogens increase the capacity of serum to stimulate prostacyclin release in human endothelial cells

Both the estrogen receptor (ER) alpha and beta isoforms are expressed in the endothelium. The ER beta has been assigned a crucial role in normal vascular wall function. Prostacyclin has been ascribed a beneficial effect on vessel wall physiology. Isoflavones bind with higher affinity to ER beta. We investigated the hypothesis that their administration to postmenopausal women can promote endothelial prostacyclin production.Twenty-five healthy postmenopausal women with mild climacteric symptoms received capsules containing 55 mg/day isoflavones derived from soy and red clover for 6 months. Cultured human umbilical vein endothelial cells (HUVECs) were exposed for 24 h to serum collected before…

Acute abdomen due to endometriosis in a premenopausal woman taking tamoxifen.

Tamoxifen exhibits agonistic properties on the uterus. We describe a premenopausal woman who, while having tamoxifen due to a diagnosis of in situ ductal carcinoma, developed endometriosis requiring surgery.

Spanish Menopause Society position statement: Use of denosumab in postmenopausal women

Denosumab is a new drug developed for the treatment of osteoporosis. Moreover, increasing evidences link denosumab with benefits in cancer, an area of interest for those in charge of the postmenopausal health. Denosumab has shown efficacy in the control of bone loss associated with hypogonadic states created by chemotherapy in breast and other cancers. Moreover, some studies reveal efficacy in reducing the progression of metastases. A panel of experts from the Spanish Menopause Society has met to develop usage recommendations based on the best available evidence.

The Health Challenges at Menopause and Midlife: Sustainability, ICT Technology and Patient Empowerment

The implementation of lifestyle is a most cost-effective approach to the management of menopause. Physical activity, for example, may be an appropriate measure to reduce the risk of osteoporosis and other non-communicable diseases affected by menopause. The difficulty with physical activity and other lifestyle measures is often the poor long-term adherence. There are several studies addressing the issue and describing the main variables that impact adherence. Both changes in the strategy, activity program, or even behavioural changes supported by psychological techniques, have been demonstrated to have an impact, though still limited.

Activación de la Vía Osteogénica Wnt/Beta-Catenina por Sales de Estroncio en Células de Estirpe Osteoblásticas

Ten-year assessment of a cancer fast-track programme to connect primary care with oncology: reducing time from initial symptoms to diagnosis and treatment initiation.

Background Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation. Patients and methods Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for br…

Menopause symptom management in women with dyslipidemias: An EMAS clinical guide.

Abstract Introduction Dyslipidemias are common and increase the risk of cardiovascular disease. The menopause transition is associated with an atherogenic lipid profile, with an increase in the concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein B (apoB) and potentially lipoprotein (a) [Lp(a)], and a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C). Aim The aim of this clinical guide is to provide an evidence-based approach to management of menopausal symptoms and dyslipidemia in postmenopausal women. The guide evaluates the effects on the lipid profile both of menopausal hormone therapy an…

Non-use of information and communication technology as a predictor of frailty in postmenopausal midlife and older women

Frailty is a clinically discernible state in which decreased physiological reserve and function result in a reduced ability to cope with stressors. Information and communication technology (ICT) has been proposed as an aid to help with frailty, yet the use of ICT by older people, particularly women, is an understudied area.To analyze the association between use of ICT (specifically internet functions and social media) and frailty status in postmenopausal midlife and elderly women.A cross-sectional study was designed to investigate whether frailty status is related to ICT use in postmenopausal midlife and older women. Community-dwelling women attending primary health care centers for health …

Relationship between PTH, sex steroid and bone turnover marker measurements and bone density in recently postmenopausal women

Objective: It is conceivable that, since menopause accelerates the continuous bone loss determined by age, a specific configuration of bone mass determinants during the first postmenopausal years occurs. Methods: To establish their value as indicators of bone mass in women with recent natural menopause, we assessed relationships between bone mineral density (BMD) and age, menopausal age, body mass index (BMI), PTH, sex steroid hormones (estradiol and testosterone), and several markers of bone turnover in urine (N-telopeptide and calcium/creatinine ratio) or serum (osteocalcin (OC), total alkaline phosphatase (ALP), total and ionic calcium (iCa), phosphate (P) and magnesium (Mg)) for a group…

On the use and abuse of register studies: The case of menopausal hormone therapy

The impact of chocolate on cardiovascular health

Cardiovascular disease is the leading determinant of mortality and morbidity in women. Functional foods are attracting interest as potential regulators of the susceptibility to disease. Supported by epidemiological evidence, chocolate has emerged as a possible modulator of cardiovascular risk. Chocolate, or cocoa as the natural source, contains flavanols, a subclass of flavonoids. The latter years have witnessed an increasing number of experimental and clinical studies that suggest a protective effect of chocolate against atherogenesis. Oxidative stress, inflammation, and endothelial function define three biological mechanisms that have shown sensitivity to chocolate. Moreover, the consumpt…

Comparative effects of estradiol, raloxifene, and genistein on the uterus of ovariectomized mice.

To explore the uterine effects of administration of compounds that exert their bone-sparing functions through estrogen receptors, we administered 17beta-E2, raloxifene, or genistein to ovariectomized mice and analyzed the uterus weight and histology 4 weeks after beginning the treatments. Results indicated that raloxifene and genistein have partial agonistic properties on the uterus in estrogen-depleted mice, and that genistein induced apoptosis and several atypias in the glandular epithelium of endometrium, as demonstrated in hematoxylin-eosin-stained histological sections.

Menopause: The Concepts and the Biological Background

The exhaustion of the follicular endowment in the ovary defines the biological basis of menopause. The clinical implications are the loss of menses and fertility. Menopause is preceded by a series of clinical phases, reflected in the Staging of Reproductive Aging Workshop (STRAW). STRAW includes the different reproductive stages, with the clinically impacting menopausal transition and the end of the reproductive life, represented by the late post-menopausal period. Epidemiological studies show that the age at menopause, globally considered at around 50 years, undergoes significant differences across the world regions. High socio-economic conditions may prolong the age at menopause, but othe…

Predictors of live birth in women with a history of biochemical pregnancies after assisted reproduction treatment

Abstract Objectives To ascertain whether women with a history of biochemical pregnancies (BPs) in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles have decreased chances of live birth (LB); and (2) to build a predictive model for LB in this particular population of infertile women. Methods In order to achieve the first objective, data from 1536 women that had a LB using autologous fresh or frozen embryos, or dropped out of further IVF/ICSI treatments after completing one to three unsuccessful treatment cycles were retrospectively analyzed. A subpopulation of 90 women that experienced one or more BPs in our assisted reproduction unit were selected to buil…

The risk for cardiovascular disease in women: from estrogens to selective estrogen receptor modulators.

Cardiovascular disease, a generic denomination including coronary heart disease (CHD), stroke, and venous thromboembolic disease (VTED), has shown sensitivity to estrogens. The relative protection of women as compared with men has nourished a debate about a possible protective role for estrogens, but the prejudicial effects detected in clinical trials has created confusion on the risk/benefit ratio induced by hormone administration. The hypothesis that agonists distinct to estrogens might improve the effects associated with estrogens is at the base of the increasing interest on the role of selective estrogen receptor modulators (SERMs). There is a lack of definitive clearcut clinical data o…

Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.

OBJECTIVE Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2. DESIGN Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzy…

Reply to Dal Moro

Efficacy and quality of life after 10 years of transobturator tape surgery for stress urinary incontinence

Influence of the ovary on parameters of LH secretion during the recovery from buserelin-induced desensitization

Abstract This study examined the effect of the ovary on LH pulsatility and on the secretory performance of gonadotrophes during the phase of recovery after treatment with buserelin, a GnRH analogue. We included 12 patients, who received buserelin (1.2 mg/day, intranasally for 3 months) as a reductive therapy for uterine leiomyomatosis prior to hysterectomy. Six patients were oophorectomized and the other 6 patients had their ovaries preserved. LH was measured in samples taken basally up to 36 days after suppression of buserelin. LH pulsatility was studied on day 9 along a 24-h cycle, and the response of the hormone to a double-stimulus GnRH test on days 0, 9, 20, and 34. The concentration o…

The effect of oral hormone replacement therapy on lipoprotein profile, resistance of LDL to oxidation and LDL particle size

Abstract Objectives: To disclose if oral estradiol (E 2 ), alone or in combination with natural progesterone (P) or medroxyprogesterone acetate (MPA), may modify the oxidizability of low density lipoprotein (LDL), and if the effect is achieved at physiological dosages. LDL oxidizability was assessed by the resistance to oxidation by copper and by the particle size profile, since small particles have increased oxidation susceptibility. Methods: Thirty-three women received two consecutive, two-month length doses of 1 and 2 mg/day of oral E 2 . They were then randomly assigned to a fourteen-day treatment of 2 mg/day E 2 plus either 300 mg/day P or 5 mg/day MPA. A parallel group of experiments …

Deficiencies in reporting results of lesbians and gays after donor intrauterine insemination and assisted reproductive technology treatments: a review of the first emerging studies

At a time when increasing numbers of lesbians and gays consider parenthood using reproductive assistance in infertility centers, the present review aims to summarize the results obtained so far by lesbians after intrauterine insemination (IUI) and in-vitro fertilization (IVF) using donor spermatozoa (D-IUI and D-IVF, respectively) and gays entering into gestational-surrogacy programs. Data show that gays display normal semen parameters and lesbians exhibit no specific causes of female infertility except perhaps for polycystic ovary syndrome (PCOS) and some PCOS-related factors. Pair-bonded lesbians entering into D-IUI programs, tend to have higher pregnancy and delivery percentages followin…

Demonstration of P29, an oestrogen receptor-associated tumor marker, in human term placenta.

A Mr29,000 serine phosphoprotein (P29) related to oestradiol receptor was studied in human term placenta with the use of a specific monoclonal antibody (D5). D5 was used with two different methods, immunohistochemistry and immunoradiometry. For immunohistochemistry, an indirect immunoperoxidase method was chosen to detect P29 in methacarn-fixed, wax-embedded sections. P29 was mostly confined to the syncytiotrophoblast surrounding placental villi, staining being positive in both cytoplasm and nuclei. The stroma of villi was negative. Content of P29 was uniformly high in crude placental cytosol, as measured by immunoradiometry assays. Specificity of D5 against P29 in placenta was tested by an…

Respuesta de preosteoblastos a compuestos de estroncio o calcio: proliferación, diferenciación, mineralización y respuesta génica global

Fundamento: Los mecanismos que desencadenan la osteogénesis todavía no están aclarados. El objetivo de este estudio fue valorar el papel de estroncio y calcio, aportados en distinto soporte molecular, como inductores de distintos mecanismos de estímulo osteoblástico, incluyendo proliferación, diferenciación y mineralización de células preosteoblásticas. Se investigó también la respuesta global genómica con la técnica de microarray. Métodos: Se diseñó un estudio experimental con células pre-osteoblásticas murinas MC3T3-E1, que fueron estimuladas durante 3 horas y 7 días. Se realizaron estudios bioquímicos y de expresión génica del genoma de ratón (Affymetrix). Resultados: El estroncio unido …

It Is Premature to Use Postmortem Sperm for Reproductive Purposes: a Data-Driven Opinion

AbstractPostmortem sperm retrieval for reproductive purposes is an assisted reproduction procedure that offers women an opportunity to have a child using sperm retrieved from their deceased partners. The ethical issues of this procedure have been discussed in previous works. However, an assessment of the procedure using a scientific perspective is still lacking. Here, we aim to ascertain, using a biological standpoint, whether postmortem sperm should be rescued for reproductive purposes. Data suggest that it is premature to use postmortem sperm for reproductive purposes. This procedure should not be clinically applied until appropriate and comprehensive analyses have been completed. Such an…

Ovarian sex cord tumor with annular tubules in a woman with premature ovarian failure.

Abstract Objective: To report a case of premature ovarian failure (POF) associated with an ovarian sex cord tumor with annular tubules. Design: Case report. Setting: Reproductive endocrinology unit in a tertiary academic center. Patient(s): A 20-year-old woman with POF. Intervention(s): Biopsy of the rudimentary ovary by laparoscopy. Main Outcome Measure(s): Protocol for POF investigation and histological study of the ovarian sample. Result(s): An ovarian sex cord tumor with annular tubules was detected in the rudimentary right ovary. Conclusion(s): The rare ovarian sex cord tumor with annular tubules, which may be hormonally active, was detected in a case of POF.

Progression in healthy ageing: frailty, cognitive decline and gender in the European Innovation Partnership for Active and Healthy Ageing

ABSTRACT Background and Objectives: Lifespan is getting longer at a global level. More people, therefore, live past 65 years of age. Ageing favors frailty, a condition that makes the body more susceptible to diseases. We present updated information of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), and particularly, the Cognitive Decline (CD) group in Action Group 3 (A3), focused in the prevention of frailty and functional decline. Moreover, details of one of the commitments in CD, which deals with the specificities of women in frailty and ageing (Chronic Ailment Reduction after Menopause, CARMEN), will be presented as well. Objectives of EIPAHA are to increas…

MOESM4 of Interventions to prevent, delay or reverse frailty in older people: a journey towards clinical guidelines

Additional file 4. Example of the output of the voting process using the Evidence to Decision template, as received and processed by the guidelines technical team.

Marcadores bioquímicos de remodelado óseo: aspectos descriptivos

Resumen La osteoporosis posmenopausica es un problema de salud publica mundial, y su principal causa es la deficiencia estrogenica. El metabolismo oseo presenta dos actividades opuestas: la formacion de hueso nuevo por el osteoblasto y la degradacion o resorcion de hueso viejo por el osteoclasto. Dado que estas actividades cursan con el vertido a la circulacion de una serie de productos, los denominados marcadores bioquimicos de remodelado oseo, nosotros podemos estimar la tasa de ambos procesos determinando los valores sericos o urinarios de estos productos en el laboratorio. Estos marcadores son una poderosa herramienta para el ginecologo, ya que su determinacion es facil de realizar, es …

Endocrinology and physiology of pseudocyesis

This literature review on pseudocyesis or false pregnancy aims to find epidemiological, psychiatric/psychologic, gynecological and endocrine traits associated with this condition in order to propose neuroendocrine/endocrine mechanisms leading to the emergence of pseudocyetic traits. Ten women from 5 selected studies were analyzed after applying stringent criteria to discriminate between cases of true pseudocyesis (pseudocyesis vera) versus delusional, simulated or erroneous pseudocyesis. The analysis of the reviewed studies evidenced that pseudocyesis shares many endocrine traits with both polycystic ovarian syndrome and major depressive disorder, although the endocrine traits are more akin…

Oral antioxidants counteract the negative effects of female aging on oocyte quantity and quality in the mouse

This study aims to compare the effect of early and late onset administration of oral antioxidants on number and quality of oocytes retrieved from aged mice after exogenous ovarian stimulation. Control hybrid females were fed a standard diet supplemented or not supplemented with pharmacological doses of vitamins C and E either from the first day of weaning or from the age of 32 weeks until they were autopsied at the age 40-42, 50-52, or 57-62 weeks after exogenous ovarian stimulation. Analysis of chromosomal distribution, DNA organization and cellular morphology was performed in ovulated cumulus-enclosed and -free oocytes, ovarian non-germinal vesicle oocytes enclosed by or free of mucous cu…

Understanding frailty: meanings and beliefs about screening and prevention across key stakeholder groups in Europe

ABSTRACTInnovative methods to manage frailty are critical to managing the needs of an ageing population. Evidence suggests there are opportunities to reverse or prevent frailty through early intervention. However, little is known about older adults’, families’ and practitioners’ beliefs about the malleability of frailty. This study examined European stakeholders’ accounts of the acceptability and feasibility of frailty screening and prevention to inform future intervention development. Semi-structured focus groups and individual interviews were conducted in three European Union countries (Italy, Poland and the United Kingdom) with key stakeholders – frail and non-frail older adults, family …

Antioxidants may protect against infertility.

Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in vitro.

The present study was designed to ascertain whether the negative effects on reproductive potential of post-ovulatory ageing in vitro of oocytes can be prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were aged in vitro for 12 h prior to insemination in the presence of varying concentrations of L-ascorbic acid, 6-methoxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), L-cystine dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta-mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was associated with lower fertilization rate, higher proportion of concepti exhibiting cellular fragmentation at 24 h post-insemination and lower percentage of…

Obstetric and offspring risks of women’s morbid conditions linked to prior anticancer treatments

Background Literature shows the effects of type of cancer and/or anticancer treatment on live birth percentages and/or pregnancy and neonatal complications in female cancer survivors. However, studies analyzing the obstetric and offspring risks of the morbid conditions associated with previous anti-cancer treatments are missing. The present review aims to uncover these risks. Methods A literature search based on publications up to March 2016 identified by PubMed and references cited in relevant articles. Results The morbid conditions associated with prior anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant may induce not only obstet…

Sex Hormones and Healthy Psychological Aging in Women

Besides their key role in reproduction, estrogens have effects in several organs in the body, as confirmed by the identification of estrogen receptors (ER) in multiple tissues. Experimental evidence has shown that estrogens have significant impacts on the central nervous system (CNS), and a key question is to what extent the fall in estrogen levels in the blood that occurs with increasing age, particularly around and following the menopause, has an impact on the cognitive function and psychological health of women, specifically regarding mood. This review will consider direct effects of menopausal changes in estrogens on the brain, including cognitive function and mood. Secondary pathways w…

Perceptions and experiences of frailty interventions:quantitative and qualitative results from a survey of partners within the European Innovation Partnership on Active and Healthy Ageing (EIP-AHA)

The European Innovation Partnership on Active and Healthy Ageing (EIP-AHA) was launched by the European Commission in 2011 to promote innovation in ageing research. This paper explores the experiences of partners delivering frailty interventions within Europe, registering their programmes with the EIP-AHA. Data were collected using an online survey from 21 partners in seven countries. A mixed-method approach was used with inductive thematic analysis of free-text responses to improve data richness. Responses indicated that there was a lack of consistency between EIP-AHA partners in methods of defining, screening and measuring for frailty and pre-frailty. Open responses to survey questions ab…

Long-term effects of delayed motherhood in mice on postnatal development and behavioural traits of offspring

BACKGROUND: Some epidemiological evidence tentatively suggests that children born to older parents may have lower intellectual development and maturity than children whose parents are younger. This study aims to analyse the long-term effects of delayed motherhood in mice on postnatal development and behavioural traits later in life. METHODS: Hybrid females, either at the age of 10 weeks or 51 weeks, were individually housed with a randomly selected 12-14 week old hybrid male. After a postweaning resting period of 1 week, dams were caged again with a new randomly selected 12-14 week old male. This sequence of events was repeated until old females reached the end of their reproductive life. R…

Impacto del metabolismo lipídico en la aterogénesis femenina

Resumen Objetivo Revisar los mecanismos que, ligados al metabolismo lipidico, determinan riesgo vascular en la mujer posmenopausica Fuentes Bibliografia medica hasta septiembre del ano 2000 a traves de MEDLINE Conclusiones Nuevos datos, ligados a la modificacion de particulas por oxidacion o cambios en su tamano, aclaran considerablemente la influencia de los lipidos en los procesos de aterogenesis

Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence

A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of 0.694 in favor of iCR (p<0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort (Hypericum perforatum [HP]) were given ( 1.020 and 0.999, respectively), suggesting a dose-depend- ency. For psychological symptoms, the iCRþHP combination was superior to iCR monotherapy. Efficacy of iCR was c…

Vitamin D levels in Mediterranean breast cancer patients compared with those in healthy women

To evaluate the vitamin D status of postmenopausal women with early estrogen-receptor-positive breast cancer and to compare it with that of healthy postmenopausal women from the same Mediterranean region. STUDY DESIGN AND OUTCOME MEASURES: Data from 691 breast cancer (BC) patients in the B-ABLE cohort were analyzed after recent cancer intervention (recent-BC) or after a minimum of two years since this intervention (long-term-BC). Patients were also stratified by previous chemotherapy exposure (ChT+ and ChT-). Plasma levels of 25-hydroxyvitamin D [25(OH)D] (25(OH)D) were compared with data from 294 healthy women (non-BC) by linear regression to estimate β-coefficients using non-BC participan…

The Mediterranean diet: A historical perspective on food for health.

The Mediterranean diet (MedDiet) represents the crystallisation of the centuries-old cooking legacies of different civilisations. The association of the MedDiet with longevity and low cardiovascular risk prompted the Seven Countries Study, which provided epidemiological evidence on the health effects of diet. This led to further studies, both epidemiological and interventional. Scales to measure adherence as well as studies of food components have consolidated a body of knowledge that is of great interest to institutions and governmental agencies. The recognition of its benefits for health has made the widespread introduction of the MedDiet an urgent challenge. Parallel efforts are being ma…

Endometrial response to concurrent treatment with vaginal progesterone and transdermal estradiol.

ABSTRACT Objective To describe the effect of the intermittent administration of vaginal progesterone and a low-dose estradiol patch on endometrial stability, as assessed by the rate of amenorrhea and endometrial stimulation. Methods This was an open study in which 64 moderately symptomatic, postmenopausal women were treated in the outpatient clinic of our University Hospital for different intervals up to 1 year. The treatment consisted of a combination of patches delivering 25 µg/day estradiol and intravaginal pills containing 100 mg of micronized progesterone. Patches and pills were administered concomitantly in a twice-a-week protocol. The endometrial response was assessed by endovaginal …

Two-year prospective, randomized trial comparing an innovative twice-a-week progestin regimen with a continuous combined regimen as postmenopausal hormone therapy.

Abstract Objective: To compare compliance, symptom control, bleeding patterns, endometrial response, and lipid changes in postmenopausal women treated with transdermal E 2 and a regimen of either intermittent or continuous dosing of progestin. Design: Randomized, prospective study. Setting: Menopausal Outpatient Clinic at an academic tertiary care hospital. Patient(s): One hundred women who had reached menopause naturally and had been amenorrheic for at least 1 year. Fifty women were randomly assigned to receive each regimen. Intervention(s): All patients received 50-μg E 2 patches and medroxyprogesterone acetate, either 5 mg twice per week or 2.5 mg daily. The bleeding pattern was register…

Characteristics of urinary luteinizing hormone (LH) during the induction of LH surges of different magnitude in blood

Urinary luteinizing hormone (LH) testing has been proposed as a reliable method for the prediction of ovulation but its accuracy has been challenged by some studies. To check how accurately the oscillations of urinary LH reflected the plasma changes, surges of LH of different magnitude and duration were artificially induced in plasma and the hormone was measured simultaneously in urine. Post-menopausal women (n = 16) were stimulated during 1 week with a combination of transdermal oestradiol (400 micrograms) and i.m. progesterone (25 mg on day 4, 50 mg on day 5) to obtain an LH discharge comparable with the pre-ovulatory LH peak. A short and moderate peak of LH was induced by the i.v. inject…

Menopause: Women should not suffer in silence

Potential health hazards of assisted human reproduction: Effects of manipulations in vitro of human oocytes and embryos on the birthweight of the resultant babies

The adverse effects of estrogen and selective estrogen receptor modulators on hemostasis and thrombosis.

Agonists of the estrogen receptor include estrogens and selective estrogen receptor modulators (SERMs). Both types of compounds increase the risk for thrombosis in the arterial and the venous tree. The magnitude of the effect is influenced by potency, which depends on the type of compound and the dose. The particulars of the process change in each territory. Atherosclerosis, which creates local inflammatory conditions, may favor thrombogenesis in arteries. A direct effect of estrogen agonists is also well endorsed at both arteries, as suggested from data with high-estrogenic contraceptives, and veins. Dose reduction has been proved to be an effective strategy, but there is debate on whether…

The role of CD40 and CD40L in bone mineral density and in osteoporosis risk: A genetic and functional study.

Compelling data are revealing that the CD40/CD40L system is involved in bone metabolism. Furthermore, we have previously demonstrated that polymorphisms in both genes are associated with bone phenotypes. The aim of this study is to further characterize this association and to identify the causal functional mechanism. We conducted an association study of BMD with 15 SNPs in CD40/CD40L genes in a population of 779 women. In addition, we assessed the functionality of this association through the study of the allele-dependent expression of CD40 and CD40L in peripheral blood leukocytes (PBLs) and in human osteoblasts (OBs) obtained from bone explants by qPCR and by sequencing. When an allelic im…

Estrogen receptor agonists and immune system in ovariectomized mice.

Several data implicate the immune system in bone lost after estrogen deficiency, however, some of the effects on the immune system of estrogen deficiency or of estrogen receptor (ER) modulation are not well established. In this study, the effect of ER agonists on the immune system in ovariectomized mice is analyzed. Mice were ovariectomized and were administered 17β-estradiol (E2), raloxifene (RAL) or genistein (GEN). The effect of a 4-week treatment on bone turnover and on several parameters that reflect the status of the immune system was studied. Results show that ovariectomy provoked both uterine atrophy and thymic hypertrophy. Although RAL corrected thymic hypertrophy, only E2 correct…

Effect of continuous oestradiol-medroxyprogesterone administration on plasma lipids and lipoproteins

Plasma lipids and lipoproteins were measured in 21 post-menopausal women after 4 and 8 months of continuous treatment with an orally administered combination of oestradiol and medroxyprogesterone acetate. The mean concentrations of cholesterol and low-density-lipoprotein (LDL) cholesterol were reduced by 12% (P less than 0.001) and 11% (P less than 0.01), respectively, after 4 months of treatment and by 9% (P less than 0.05) and 12% (P less than 0.05) after 8 months. The mean level of high-density-lipoprotein (HDL) cholesterol showed an initial fall of 5% (P less than 0.05) after 4 months and then increased by 13% (P less than 0.05) after 8 months of treatment. The plasma triglycerides leve…

Re: Infertility Etiologies Are Genetically and Clinically Linked with Other Diseases in Single Meta-Diseases.

The present review aims to ascertain whether different infertility etiologies share particular genes and/or molecular pathways with other pathologies and are associated with distinct and particular risks of later-life morbidity and mortality. In order to reach this aim, we use two different sources of information: (1) a public web server named DiseaseConnect ( http://disease-connect.org ) focused on the analysis of common genes and molecular mechanisms shared by diseases by integrating comprehensive omics and literature data; and (2) a literature search directed to find clinical comorbid relationships of infertility etiologies with only those diseases appearing after infertility is manifest…

Frailty and multimorbidity: Two related yet different concepts.

The extension of life expectancy is a global phenomenon. The growth in the ageing population has created a new health scenario in which there is a higher prevalence of frailty and multimorbidity. The attention received by both conditions derives from their strong association with disability, hospitalization, and death. The aim of the present paper is to conceptualize and differentiate these terms and to discuss their interrelations. We conclude that, yet related, they represent two different clinical conditions. Frailty identifies the increased vulnerability to stressors due to a dynamic, non-linear, and multidimensional depletion of physiological reserve and redundancy, whereas multimorbid…

Gene expression profile induced by ovariectomy in bone marrow of mice: a functional approach to identify new candidate genes associated to osteoporosis risk in women.

Osteoporosis is a multifactorial skeletal pathology with a main genetic component. To date, however, the majority of genes associated with this pathology remain unknown since genes cataloged to date only explain a part of the heritability of bone phenotypes. In the present study, we have used a genome-wide gene expression approach by means of microarrays to identify new candidate genes involved in the physiopathology of osteoporosis, using as a model the ovariectomized (OVX) mice by comparing global bone marrow gene expression of the OVX mice with those of SHAM operated mice. One hundred and eighty transcripts were found to be differentially expressed between groups. The analysis showed 23 …

Consequences on offspring of abnormal function in ageing gametes.

The present review aims to analyse (i) the molecular, biochemical and cellular changes that accompany oocyte and sperm ageing in any of the internal or external environments where they can reside, and (ii) the consequences of the abnormal function in ageing gametes on pre- and post-implantation development and later life of offspring. This review also aims to propose and discuss cellular/molecular mechanisms framed within the 'free radical theory of ageing'. It appears that the ageing of gametes prior to fertilization may affect many molecular, biochemical and cellular pathways that may jeopardize not only pre- and post-implantation embryo/fetal development but also later life of offspring.…

Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA)

Introduction: Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. Aim: To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence abou…

Could institutional clinical trials exist in Europe?

Progestogens and risk of breast cancer: a link between bone and breast?

This article reviews the data supporting the role of receptor activator of the nuclear factor kappa (RANK) and its ligand, RANKL, in progestogen-induced breast cancer. Both experimental and clinical studies have been included. The expression of both RANK and RANKL has been described in epithelial cells of both mice and humans. Experiments of gain and loss of function in mice have shown that RANK/RANKL mediate alveologenesis during pregnancy or the estrous cycle. Moreover, the participation of the RANK/RANKL has been detected in models of breast carcinogenesis associated with progestogens-like medroxyprogesterone acetate. Recent clinical studies have found that the expression of RANK is asso…

Management of urinary incontinence in postmenopausal women: An EMAS clinical guide.

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 a…

MOESM1 of Interventions to prevent, delay or reverse frailty in older people: a journey towards clinical guidelines

Additional file 1. Synthesis of quantitative evidence from the FOCUS systematic review [9], showing the effect of the interventions on frailty as an outcome, adapted from the typical GRADE Summary of Findings table structure, as offered to the guideline panellists.

The mediterranean diet and menopausal health: An EMAS position statement

Introduction: 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.Aim: To evaluate the evidence from observational studies and randomized trials on the effects of the Mediterranean diet on short- and long-term menopausal health: estrogen deficiency symptoms, cardiovascular disease, osteoporosis, cognitive and mental health, breast cancer, and all-cause mortality.Materials and methods: Literature review and consensus of expert opinion.Summary recommendations: The Mediterranean diet is a non-restr…

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

AbstractBiogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we…

Transobturator suburethral tape in the treatment of stress urinary incontinence: efficacy and quality of life after 5 year follow up.

Abstract Objectives Stress urinary incontinence (SUI) is a highly prevalent dysfunction in middle-aged and elderly women. One recent technique places a sub-urethral tape passed through the transobturator foramen. Efficacy and quality of life were assessed after five years of treatment with the transobturator technique in women suffering SUI. This evaluation followed a previous control at the first year post-intervention. Study design Sixty-three women were assessed five years after operation with the transobturator technique. Additionally, twenty-nine women of these women had undergone pelvic floor reconstruction due to different forms of genital prolapse. Quality of life (QoL) was assessed…

Somatometric and clinical cardiovascular risk factors in midlife and older women. A tale of four European countries

P29, an oestrogen receptor-associated protein, is down- regulated by mifepristone in first trimester human placenta and decidua

P29 is an oestrogen receptor-associated protein which acts as a marker of oestrogen action in several systems. The concentration of P29 was measured in placenta and decidua from women following medical termination of pregnancy with the antiprogesterone steroid mifepristone (RU 38,486) and a prostaglandin E1 analogue, and compared with the concentration of P29 found in matched controls undergoing surgical aspiration of pregnancy. Oestrogen receptors were also measured in the same samples. Placental and decidual P29 concentrations (IU/mg protein) in patients treated with mifepristone were 9.6 (4.6-54) and 4.8 (1.3-13.3) (median and range), respectively. These values were significantly lower t…

Acute stress may induce ovulation in women

Abstract Background This study aims to gather information either supporting or rejecting the hypothesis that acute stress may induce ovulation in women. The formulation of this hypothesis is based on 2 facts: 1) estrogen-primed postmenopausal or ovariectomized women display an adrenal-progesterone-induced ovulatory-like luteinizing hormone (LH) surge in response to exogenous adrenocorticotropic hormone (ACTH) administration; and 2) women display multiple follicular waves during an interovulatory interval, and likely during pregnancy and lactation. Thus, acute stress may induce ovulation in women displaying appropriate serum levels of estradiol and one or more follicles large enough to respo…

Progestogens stimulate prostacyclin production by human endothelial cells.

BACKGROUND: The effects of progestogens on endothelial physiology are poorly studied. Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase (COX) in endothelium. We examined the effects of two clinically used progestogens, progesterone and medroxyprogesterone acetate (MPA), on prostacyclin production by cultured human umbilical vein endothelial cells (HUVEC) and the possible role of progesterone receptors and both COX enzymes. METHODS: Cells were exposed to 1-100 nmol/l of either progesterone or MPA and prostacyclin production was measured in culture medium. RESULTS: Both progestogens significantly increased prostacyclin release in a time- and dose-dependent man…

Marcadores bioquímicos de remodelación ósea: su utilidad en el tratamiento de la osteoporosis

Resumen Con la deplecion estrogenica se produce un aumento del remodelado oseo, cuyo grado podemos determinar mediante el analisis de los marcadores bioquimicos de remodelado oseo. En los ultimos anos se ha puesto mucho enfasis en establecer la relacion entre estas tasas de remodelado oseo, determinadas a partir de los valores en los marcadores, con la perdida osea y la posibilidad de fractura y como indicadores reales del beneficio de la terapia antirresortiva. Como comentaremos a continuacion, aunque existen varios estudios que demuestran su capacidad predictora de perdida osea y de posibilidad de fractura, el uso mas establecido en la actualidad es el de monitorizar el tratamiento y esta…

Progestogens reduce thromboxane production by cultured human endothelial cells.

Objectives Progestogens have been poorly studied concerning their roles in endothelial physiology. Prostanoids are vasoactive compounds, such as thromboxane A2, a potent vasoconstrictor, and prostacyclin, a vasodilator. We examined the effects of two progestogens used clinically, progesterone and medroxyprogesterone acetate, on thromboxane A2 production by cultured human umbilical vein endothelial cells (HUVEC) and investigated the role of progesterone receptors and the enzymes involved in production of thromboxane A2 and prostacyclin. Methods Cells were exposed to 1‐100 nmol/l of either progesterone or medroxyprogesterone acetate, and thromboxane A2 production was measured in culture mediu…

Promoting longevity: A global approach

Transient regional osteoporosis.

Transient regional osteoporosis (TRO) is a disease that predisposes to fragility fracture in weight bearing joints of mid-life women and men. Pregnant women may also suffer the process, usually at the hip. The prevalence of TRO is lower than the systemic form, associated with postmenopause and advanced age, but may be falsely diminished by under-diagnosis. The disease may be uni- or bilateral, and may migrate to distinct joints. One main feature of TRO is spontaneous recovery. Pain and progressive limitation in the functionality of the affected joint(s) are key symptoms. In the case of the form associated with pregnancy, difficulties in diagnosis derive from the relatively young age at pres…

Topical estrogens and non-hormonal preparations for postmenopausal vulvovaginal atrophy: An EMAS clinical guide

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. W…

Differential expression of receptor activator of nuclear factor kappa B in healthy endometrium, ovarian endometrioma, and endometrioid ovarian cancer

Ibandronic acid subsequent to raloxifene: Effect on bone metabolism and on cardiovascular risk factors

s / Maturitas 81 (2015) 144–190 161 Materials andmethods: This randomized double-blind clinical trialwas carried out inAhvaz (Iran) fromAugust toDecember 2010. Forty postmenopausal women with symptoms of vaginal atrophy were randomly allocated to two groups to take vaginal suppositories of either 5mg hyaluronic acid sodium salt (n=20) or 1mg vitamin E (n=20) for 8 weeks. The symptoms of vaginal atrophy were evaluated by a self-assessed 4-point scale and the composite score was determined as none, mild, moderate, and severe in four periods. Results: The results showed that the symptoms were relieved significantly in both groups (P<0.001). The relief of symptomswas significantly superior in t…

The effects on offspring of premature parturition

The time of parturition defines the length of the intrauterine period of fetal life, a requisite to achieve adequate adaptation to the external environment. Immaturity, a condition whose severity is inversely related to the length of pregnancy, is the main determinant of the increased morbidity and mortality associated with preterm birth. Despite great advances in medical technology and expertise, mainly after the introduction of the neonatal intensive care units, only one- to two-thirds of infants from the subsets with lower birthweight/gestational age reach survival at discharge. Distinct major neurological and sensorial sequelae, including cerebral palsy, retinopathy of prematurity, and …

The Impact of Estrogen Decline on Other Noncommunicable Diseases

Estrogens have specific receptors spread out in various systems of the organism. The drastic hormonal fall after menopause may be followed by a series of effects, which may be more or less relevant in the different areas of the organism. The bone constitutes a field that clearly reflects that impact, and postmenopausal osteoporosis has received attention in one ad hoc chapter. The present chapter reviews the impact on functions of the central nervous system, particularly cognition and mood, the skeletal system, specifically osteoarthritis, and the cardiovascular system. The obvious interest of the chapter derives from the importance of the selected systems, which may house highly prevalent …

Impact of estrogens on atherosclerosis and bone in the apolipoprotein E-deficient mouse model.

Objective The common inflammatory pathophysiology has nourished the hypothesis of a relationship between osteoporosis and cardiovascular disease. Estrogens are key agents in the modulation of both processes. We investigated whether induction of atherosclerosis affects bone and whether estrogens modulate both processes. Methods Female apolipoprotein E-deficient mice (a well-established model of atherogenesis) were ovariectomized or falsely operated and fed either standard diet or high-fat diet (HFD). Six animals were included in each of the four groups. To clarify mechanisms, we treated preosteoblastic MC3T3-E1 cells with mouse serum. Results Physiological levels of estrogens in falsely oper…

Progesterone increases basal 3',5'-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in human term placenta.

Whether the placenta is a target tissue for estrogens and progesterone, and their putative mechanism of action, is still a controversial question in the literature. The effect of progesterone and estradiol on 3′,5′-cyclic adenosine monophosphate (cAMP) and inositol phosphates generation in human term placenta was investigated. Placental explants were incubated in vitro for up to 48 h in the absence and in the presence of estradiol, progesterone or both steroids (0.1 μmol/l final concentration in all cases), and were stimulated with terbutaline, a β-adrenergic agonist, (0.1 mmol/l) or angiotensin II(1 μmol/l), The cAMP content was measured by a competitive protein binding assay, and the gene…

Stage of the estrous cycle at the time of pregnant mare's serum gonadotropin injection affects pre-implantation embryo development in vitro in the mouse

The present study aims to analyze in the mouse the effect of the stage of the estrous cycle at the time of pregnant mare's serum gonadotropin (PMSG) injection on fertilization of ovulated cumulus-enclosed oocytes and later embryo development in vitro to the blastocyst stage. Quality of blastocysts was evaluated by staining and counting of total number of nuclei, mitotic index, percentage of apoptotic nuclei, and cell allocation to the inner cell mass (ICM) and trophectoderm (TE) lineage. Superovulation of hybrid (C57Bl/6JIco female x CBA/JIco male) female mice of 4-6 weeks of age was induced by a priming injection of PMSG at different stages of the estrous cycle followed after a 48-hr inter…

The action of estrogens and progestogens in the young female breast

Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth fa…

Variants translating reduced expression of the beta estrogen receptor gene were associated with increased carotid intima media thickness : a cross-sectional study in late postmenopausal women

Abstract Background There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and β has not been investigated.Methods We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) assoc…

No effect of Cimicifuga racemosa extract on serum interleukin-6 levels and prostacyclin production by human endothelial cells

Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review

OBJECTIVE: To summarize the best available evidence regarding the effectiveness of interventions for preventing frailty progression in older adults. INTRODUCTION: Frailty is an age-related state of decreased physiological reserves characterized by an increased risk of poor clinical outcomes. Evidence supporting the malleability of frailty, its prevention and treatment, has been presented. INCLUSION CRITERIA: The review considered studies on older adults aged 65 and over, explicitly identified as pre-frail or frail, who had been undergoing interventions focusing on the prevention of frailty progression. Participants selected on the basis of specific illness or with a terminal diagnosis were …

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause

Objective: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). Methods: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). Results: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels w…

Estradiol reduces F2α-isoprostane production in cultured human endothelial cells

Free radical-generated F2α-isoprostanes are a group of compounds with vasoconstrictor properties. To investigate whether estradiol exerts antioxidant actions modifying F2α-isoprostane production, cultured human umbilical vein endothelial cells were exposed to estradiol and other compounds and F2α-isoprostanes were measured in culture medium. Exposure to 1 and 10 nM estradiol for 24 h reduced F2α-isoprostane production by 36 and 49%, respectively ( P &lt; 0.001 vs. control). Exposure to antiestrogens alone (ICI-182780 or EM-652) slightly reduced F2α-isoprostanes ( P &lt; 0.05 vs. control), but much less than exposure to estradiol ( P &lt; 0.05). ICI-182780 reversed the estradiol-induced redu…

The Impact of Hormone Therapy on Health

Hormone therapy (HT) has menopausal symptom control as the main indication. However, and because estrogens have receptors spread over many systems in the body, the use of hormones may have consequences on health. Hormone therapy consists of estrogens essentially, since menopausal symptoms mainly derive from estrogen deprivation at different target tissues. However, the normal ovarian cycle includes the regular secretion of progesterone during the days of the luteal phase. Progesterone has a neutralizing effect over endometrial proliferation, this being the reason for adding progestogens to HT formulations in order to protect endometrium. So, guidelines recommend that women with uterus use e…

Alleles and haplotypes of the estrogen receptor alpha gene are associated with an increased risk of spontaneous abortion.

Objective To investigate whether polymorphisms in estrogen receptor alpha (ERα) or beta (ERβ) genes are associated with a risk of miscarriage. Design A retrospectively analyzed, prospectively obtained database of cases and controls. Setting University hospital menopause unit. Patient(s) 177 women with at least one spontaneous abortion and 442 controls with at least one live birth and no history of miscarriage. Intervention(s) None. Main Outcome Measure(s) Genotype frequencies and odd ratios for abortion risk in cases and controls for four single nucleotide polymorphisms (SNPs) located in intron 1 (C>T and A>G), intron 4 (A>T), and exon 8 (T>C) for the ERα gene, and two SNPs located in intro…

HDlive imaging of cystic uterine leiomyoma degeneration

Stage of the estrous cycle at the time of pregnant mare's serum gonadotropin injection affects the quality of ovulated oocytes in the mouse

The present study aims to analyze the effect of the stage of the estrous cycle at the time of pregnant mare's serum gonadotropin (PMSG) injection on number and quality of mouse oocytes retrieved from oviducts after exogenous ovarian stimulation. Cellular and morphological traits of ovulated oocytes from hybrid (C57Bl/6JIco female X CBA/JIco male) female mice of 12, 40-42, 50-52 or 57-62 weeks of age were analyzed. Superovulation was induced by a priming injection of PMSG at different stages of the estrous cycle followed after a 48-hr interval by human chrorionic gonadotropin. Injection of PMSG at diestrus-1 was associated with: (1) increased percentage of cumulus-free oocytes; (2) raised to…

Positive association of high-density lipoprotein cholesterol with lumbar and femoral neck bone mineral density in postmenopausal women.

Abstract Objective Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women. Design A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone. Main outcome measures Association of BMD at lumbar spine and femoral neck with lipid levels. Results A total o…

Go for it! Exercising makes you happy and strong

Despite it is generally recognized the beneficial role of physical activity, large portion of the population is physically inactive. Very alarmingly, the well-known gender gap in physical activity is constantly increasing. Several barriers obstacle women to perform physical activity although exercising would be of paramount importance for their health in particular during pregnancy and menopause. In addition to physical health benefits, physical activity may influence well-being and resilience, greatly impacting on quality of life. Here we explore the relationship between physical activity resilience and well-being in a group of 1107 female residents in the Metropolitan area of Naples.

Do human concepti have the potential to enter into diapause?

Although there is no direct evidence as to whether human concepti have the potential to enter into diapause before implantation, the possibility that human concepti may be capable of following this developmental pathway if exposed to an appropriate environment cannot be ruled out. Direct evidence remains elusive because of the ethical restraints associated with research activities within this area of knowledge. If conceptus diapause has evolved in primates and persists at the present time despite its apparent limited or no adaptive advantage, artificial induction of diapause in humans may have clinical implications for increasing: (i) the viability of concepti after biopsy, freezing-thawing…

Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-α

Estradiol (E2) acts on the endothelium to promote vasodilatation through the release of several compounds, including prostanoids, which are products of arachidonic acid metabolism. Among these, prostacyclin (PGI2) and thromboxane A2 (TXA2) exert opposite effects on vascular tone. The role of different estrogen receptors (ERs) in the PGI2/TXA2 balance, however, has not been fully elucidated. Our study sought to uncover whether E2 enhances basal production of PGI2 or TXA2 in cultured human umbilical vein endothelial cells (HUVECs), to analyze the enzymatic mechanisms involved, and to evaluate the different roles of both types of ERs (ERα and ERβ). HUVECs were exposed to E2, selective ERα (1,3…

Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain.

The aim of this study was to develop and refine a heterologous mouse model of endometriosis-associated pain in which non-evoked responses, more relevant to the patient experience, were evaluated. Immunodeficient female mice (N = 24) were each implanted with four endometriotic human lesions (N = 12) or control tissue fat (N = 12) on the abdominal wall using tissue glue. Evoked pain responses were measured biweekly using von Frey filaments. Non-evoked responses were recorded weekly for 8 weeks using a home cage analysis (HCA). Endpoints were distance traveled, social proximity, time spent in the center vs. outer areas of the cage, drinking, and climbing. Significant differences between groups…

A simplified method to quantitate atherosclerosis in the rabbit aorta.

A simple method to quantitatively evaluate atherosclerosis in the rabbit aorta by measuring macroscopic lesion areas (%) was attempted in the present study. Ten female New Zealand white rabbits were fed on a cholesterol-rich diet (5/1000 g of food) during 4 months. Five of them were oophorectomized at the beginning and all were sacrificed at the end. Total levels of cholesterol increased from 50.7+/-14.7 mg/dl to 782.8+/-296.0. No significant differences were observed between oophorectomized and intact rabbits. At 4 months, the cholesterol-rich diet caused in both, intact and oophorectomized rabbits, atherosclerotic lesions affecting 17 and 46% of the aortic surface, respectively. This meth…

Current management of pelvic organ prolapse in aging women : EMAS clinical guide

Management of pelvic organ prolapse (POP) is a common and challenging task. Nowadays older women are more active than they were in the past, and the development of POP disrupts quality of life and impairs social and personal activities. The menopausal transition is a time of vulnerability, during which many women start experiencing symptoms and signs of POP. The role of hormonal changes or of hormonal therapies in influencing the development or progression of POP has been explored extensively. The management of POP requires considerable clinical skills. Correct diagnosis and characterization of the prolapse and an identification of the individual woman's most bothersome symptoms are the hal…

Tackling frailty and functional decline: Background of the action group A3 of the European innovation partnership for active and healthy ageing

Ageing populations represent a challenge to the sustainability of current healthcare systems. The need to balance these demographic changes with gains in healthy life years and quality of life (QoL) constitutes an additional challenge. Aware of this, the European Commission (EC) launched the European Innovation Partnership on Active and Healthy Ageing (EIPonAHA) in 2012. The EIPonAHA is an interdisciplinary and cross-sector initiative involving more than 3000 partners with two specific objectives: to increase the healthy life expectancy of Europeans by two years by 2020, while increasing their QoL. The initiatives of the EIPonAHA have been organized according to six thematic action groups (…

Raloxifene increases proliferation of human endothelial cells in association with increased gene expression of cyclins A and B1.

Objective To examine the proliferative effect of of raloxifene on human umbilical-vein endothelial cells (HUVECs), and to investigate whether there is an associated increased expression of some key regulators of the cell cycle. Design Cell culture for different incubation times. Setting University research laboratory. Patient(s) Sources of HUVECs. Intervention(s) Measurement of cell proliferation, of protein levels of cyclin A, cyclin B1, cyclin D1, cyclin-dependent protein kinase (CDK) 2, CDK4, and p27 Kip1 , and of messenger RNA expression of cyclin A, cyclin B1, and p27 Kip1 . Main Outcome Measure(s) Cell proliferation was measured by the 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol…

Beneficial effects of dithiothreitol on relative levels of glutathione S-transferase activity and thiols in oocytes, and cell number, DNA fragmentation and allocation at the blastocyst stage in the mouse.

We analyzed the effect of in vitro aging of mouse oocytes in the presence of dithiothreitol (DTT) on relative levels of glutathione S-transferase (GST) activity and thiols in oocytes, and cell number, DNA fragmentation and cellular allocation to the inner cell mass (ICM) and trophectoderm (TE) lineage at the blastocyst stage. Ovulated oocytes from gonadotropin primed hybrid female mice of 6-8 weeks of age were aged in vitro in the presence of 0, 5, 50, or 500 microM DTT for 6 hr prior to insemination. Relative levels of GST activity and thiols in oocytes were determined by confocal laser scanning microscopy, DNA fragmentation using a single-step TUNEL method, and cell allocation to the ICM …

1624P Impact of the COVID-19 pandemic in the cancer fast-track programme

Background: The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly in making timely cancer diagnosis. Our public health system has been concerned about potential delays leading to a higher proportion of patients with advanced stages. Our cancer diagnosis fast-track program (CFP) in the Clinic-Malvarrosa Health department in Valencia (Spain) is connecting primary care (PC) with different specialists to speed cancer diagnosis and treatment upon well founded suspicion. A 10-year evaluation of our CFP has recently been published. The aim of this analysis was to investigate the impact of the COVID-19 pandemic on the CFP. Methods: We analysed the programme…

PREDICTIVE ACCURACY OF FRAILTY MEASURES: OVERVIEW OF REVIEWS

Frailty is an age-related state of high vulnerability to adverse health outcomes after a stressor event, predisposing individuals to progressive decline in different functional domains. A scoping search identified a large number of relevant systematic reviews (SRs) on predictive ability of frailty measures in older adults. Aiming to summarise this set of evidence an overview of reviews, based on the Joanna Briggs Institute (JBI) methodology, was conducted. This project “664367/FOCUS” was funded under the European Union’s Health Programme (2014–2020). The studies considered as eligible for inclusion were quantitative SRs including older adults aged 60 years or more, recruited from any type o…

Association of female aging with decreased parthenogenetic activation, raised MPF, and MAPKs activities and reduced levels of glutathione S-transferases activity and thiols in mouse oocytes

This study aims to determine in the mouse whether oocytes from reproductively old females exhibit a different susceptibility to be parthenogenetically activated when compared to oocytes from young females. At the age of 10–12 (young-female group) or 60–62 (old-female group) weeks, hybrid female mice were superovulated using pregnant mare's serum gonadotropin (PMSG) followed by human chorionic gonadotropin (hCG) 48 hr later. After removing the cumulus cells, oocytes were exposed to any of two different activating protocols: (a) 6-min exposure to 8% ethanol; and (b) treatment with 200 μM thimerosal for 15 min followed by 8 mM dithiothreitol (DTT) for 30 min. Oocytes from old female mice displ…

The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen

OBJECTIVE To enlighten the early response of endometrium to tamoxifen by assessing the expression of estrogen receptors, progesterone receptors, Ki-67, and the histological response in endometria from normal postmenopausal women treated for 21 days with tamoxifen. DESIGN A total of 40 women, scheduled to undergo vaginal hysterectomy because of uterine prolapse, were randomly assigned to the tamoxifen group (20 mg/day; 20 women) or the control group (20 women). Samples were obtained from the upper and the lower thirds of the uterine cavity. Standard immunohistochemical staining of estrogen and progesterone receptors and of Ki-67 was performed on frozen sections. Staining was assessed using s…

Real-world Adherence and Persistence with Bisphosphonate Therapy in Postmenopausal Women: A Systematic Review

Abstract Purpose Bisphosphonate therapy is a well-established and effective treatment for postmenopausal osteoporosis and the prevention of osteoporotic fracture. However, poor adherence to and poor persistence with bisphosphonate therapy may reduce its benefits. Previous studies have documented the poor rates of adherence and persistence among postmenopausal women with osteoporosis. The objective of this systematic literature review was to evaluate adherence, persistence, and the impact of adherence and persistence on fracture risk in postmenopausal women with diagnosed osteoporosis. Methods Articles eligible for review included observational studies of the real-world use of bisphosphonate…

A realist review to understand the efficacy and outcomes of interventions designed to minimise, reverse or prevent the progression of frailty.

Interventions to minimise, reverse or prevent the progression of frailty in older adults represent a potentially viable route to improving quality of life and care needs in older adults. Intervention methods used across European Innovation Partnership on Active and Healthy Ageing collaborators were analysed, along with findings from literature reviews to determine 'what works for whom in what circumstances'. A realist review of FOCUS study literature reviews, 'real-world' studies and grey literature was conducted according to RAMESES (Realist and Meta-narrative Evidence Synthesis: Evolving Standards), and used to populate a framework analysis of theories of why frailty interventions worked,…

Effects of maternal ageing and dietary antioxidant supplementation on ovulation, fertilisation and embryo development in vitro in the mouse.

The present study aims to ascertain whether dietary supplementation with a mixture of vitamins C and E may prevent the maternal-age-associated decrease in both the number of ovulated oocytes after exogenous ovarian stimulation and embryo development in vitro in the mouse. Experimental females were fed a standard diet supplemented with i) high doses of vitamins C and E from the first day of weaning until 12 or 40 weeks of age; or ii) moderate doses of vitamins C and E from the first day of weaning until 12 weeks of age or from 22 to 33 weeks of age. The age-related reduction in ovulation rate was partially prevented by supplementing diet with high doses of vitamins C and E from the first day…

MOESM5 of Interventions to prevent, delay or reverse frailty in older people: a journey towards clinical guidelines

Additional file 5. Detailed justification for the judgement upon each Evidence to Decision criterion, for each guideline.

Association of ACACB polymorphisms with obesity and diabetes

El pdf del artículo es la versión pre-print.-- et al.

The impact of moderate wine consumption on health

Wine is a traditional beverage that has been associated with both healthy and harmful effects. Conceptions like the so-called "French paradox" or the beneficial impact of the Mediterranean diet suggest benefit. Wine has a complex composition, which is affected by whether it is red or white or by other variables, like the variety of grapes or others. Alcohol and phenolic compounds have been attributed a participation in the benefits ascribed to wine. The case of alcohol has been extensively studied, but the key question is whether wine offers additional benefits. Resveratrol, a non-flavonoid compound, and quercetin, a flavonol, have received particular attention. There is much experimental w…

Therapeutic dosages of raloxifene do not modify myeloperoxidase and F2alpha-isoprostane levels in postmenopausal women.

We investigated the effect of a therapeutic dose of raloxifene on the plasma levels of myeloperoxidase and F2alpha-isoprostanes, two markers of oxidative stress recently described as reliable indicators of coronary heart disease. Contrary to changes described in the literature for estrogens (E), raloxifene did not modify the levels of either myeloproxidase or F2alpha-isoprostanes after 3 or 6 months of treatment.

Predicting risk and outcomes for frail older adults: a protocol for an umbrella review of available frailty screening tools

REVIEW QUESTION / OBJECTIVE  The aim of this systematic review is to comprehensively search the available literature and to summarize the best available evidence from systematic reviews in relation to published screening tools to identify pre-frailty and frailty in older adults, that is: (i) to determine their psychometric proprieties; (ii) to assess their capacity to detect pre-frail and frail conditions against established methods; and (iii) to evaluate their predictive ability. More specifically, the review will focus on the following questions: - What is the reliability and validity of existing screening tools that assess pre-frailty/frailty in older patients? - How sensitive and specif…

Understanding frailty:a qualitative study of European healthcare policy-makers' approaches to frailty screening and management

ObjectiveTo elicit European healthcare policy-makers’ views, understanding and attitudes about the implementation of frailty screening and management strategies and responses to stakeholders’ views.DesignThematic analysis of semistructured qualitative interviews.SettingEuropean healthcare policy departments.ParticipantsSeven European healthcare policy-makers representing the European Union (n=2), UK (n=2), Italy (n=1), Spain (n=1) and Poland (n=1). Participants were sourced through professional networks and the European Commission Authentication Service website and were required to be in an active healthcare policy or decision-making role.ResultsSeven themes were identified. Our findings re…

Physical activity and healthy aging.

Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …

Ovarian steroids and cancer: news on the breast, questions on the reproductive tract

The association between steroid hormones and cancer has been a primary research focus for many years. Reproductive hormones are of particular interest given the fact that several highly prevalent c...

Menopausal Hormone Therapy and breast cancer risk: Individualization is the key to safety

Self-organising maps for the analysis of data from big cohorts. The case of the Spanish CARMEN cohort

Similar efficacy of low and standard doses of transdermal estradiol in controlling bone turnover in postmenopausal women

To investigate the effects of a low transdermal estradiol dose on bone metabolism and to compare it with both the standard dose and absence of treatment.In this study performed in a third-level academic center, 66 healthy postmenopausal women underwent hormone therapy (HT) with patches containing estradiol at standard (0.050 mg/day, HT50, 33 women) or low dosage (0.025 mg/day, HT25, 33 women) and 70 women were without treatment (NT). The values (mean of three samples) of several bone biochemical parameters were compared between groups after adjusting for confounding factors. Bone mineral density (BMD) was assessed (by dual-energy X-ray absorptiometry) in the spine and hip in all cases, and …

Evaluation of the risk factors of asymptomatic vertebral fractures in postmenopausal women with osteopenia at the femoral neck

To identify risk factors of asymptomatic vertebral fracture (aVF) in postmenopausal women with osteopenia at the femoral neck and to evaluate the association between the number of aVFs and the risk of major and hip osteoporotic fracture calculated with the FRAX(®) algorithm.Epidemiological case-series study with data collected transversally.728 postmenopausal women with osteopenia were included: 284 (39.0%) had aVF, of whom 200 (70.4%) had prior fragility fractures (FF). The likelihood of having an osteoporotic fracture in the next 10 years increased significantly with the number of aVF. The percentage of women with height loss, which was assessed as the difference between the greatest heig…

Osteoporosis del embarazo

Resumen Este articulo revisa la asociacion entre embarazo y osteoporosis, asi como las dos presentaciones que se encuentran en la practica clinica. Se trata de un problema escasamente investigado, del cual la informacion procede de casos clinicos aislados o de series de casos. Dos formas, posiblemente relacionadas, se describen en la gestacion: la osteoporosis sistemica y la regional. La primera afecta principalmente al hueso trabecular, mientras que la segunda se concentra sobre territorios de carga, frecuentemente la cadera. La fisiopatologia es desconocida, pero probablemente es distinta en ambos casos. No obstante, hay una base comun de susceptibilidad, con osteopenia o franca osteoporo…

Mediterranean diet and health: A systematic review of epidemiological studies and intervention trials

Diet is a crucial variable for a healthy life. A rapidly growing number of studies in recent years support the hypothesis that the Mediterranean diet (MedDiet) has a beneficial effect on certain body systems, but the highly varied objectives and quality of these publications warrants an updated assessment. In the present review we performed a comprehensive evaluation of current evidence on the impact of the MedDiet on human health, assessing its effect on the incidence or progression of the main non-communicable diseases and their intermediate outcomes and risk factors. We scrutinised the clinical evidence from observational studies and randomised controlled trials. Cardiovascular disease w…

Hormonal contraceptives and breast cancer: Clinical data.

Abstract The endocrine background of breast cancer has raised questions about the increase in risk that might bear the use of hormonal contraceptives. This has been a particular issue in the case of young women, who constitute the population of contraceptive consumers. Observational studies have been the main source of evidence, which has mainly limited to the combined estrogen-progestogen preparations, the popular pill. Studies in the 80′s and 90′s of the past century found a small, around a 20%, increase in risk. The translation in absolute number of excess cases has been exiguous because the prevalence of the disease is relatively small in premenopausal women. Moreover, the risk slowly s…

Potential risks to offspring of intrauterine exposure to maternal age-related obstetric complications

Several hypotheses have been proposed to explain the negative effects of delayed motherhood on an offspring’s morbidity later in life. However, these hypotheses are not supported by clinical and epidemiological evidence. Because advanced maternal age is associated with increased risk of obstetric complications, the aim of the present study was to ascertain whether the negative effects on offspring of intrauterine exposure to maternal age-related obstetric complications may explain the reported negative effects of delayed motherhood on offspring. To this end, a literature search was performed to identify relevant publications up to March 2016 on PubMed; references cited in relevant articles …

Interventions to prevent, delay or reverse frailty in older people: a journey towards clinical guidelines

AbstractBackgroundAge-related frailty is a multidimensional dynamic condition associated with adverse patient outcomes and high costs for health systems. Several interventions have been proposed to tackle frailty. This correspondence article describes the journey through the development of evidence- and consensus-based guidelines on interventions aimed at preventing, delaying or reversing frailty in the context of the FOCUS (Frailty Management Optimisation through EIP-AHA Commitments and Utilisation of Stakeholders Input) project (664367-FOCUS-HP-PJ-2014). The rationale, framework, processes and content of the guidelines are described.Main textThe guidelines were framed into four questions …

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Additional file 2. Narrative synthesis of the effect of interventions on secondary outcomes, as offered to the guideline panellists.

Menopause and diabetes: EMAS clinical guide

Abstract Introduction Whether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. Aims To summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. Materials and methods Literature review and consensus of experts’ opinions. Results and conclusion Metabolic changes during the menopausal transition include an increase in and the central redis…