Antonio Cano

• University of Valencia

Bone cell metabolism is strongly regulated by estrogens and therefore the risk of osteoporosis is favored by menopause. Fragility fractures define the outcome to be prevented in osteoporosis. Since age adds to menopause as a risk factor, and menopause occurs at a relatively early age, preventive measures during the early postmenopausal period are d...

The biological basis of menopause stems from the exhaustion of follicular endowment in the ovary and clinically manifests as loss of menses and of fertility. Menopause is preceded by a series of clinical stages, as depicted in the Staging of Reproductive Aging Workshop (STRAW). The updated version STRAW+10 includes the different reproductive stages...

The main indication for the use of hormone therapy is to control symptoms during the years around menopause. 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...

Frailty is a dynamic and multidimensional clinical condition characterized by the depletion of system reserves, resulting in a loss of redundancy and increased vulnerability to any stressful event. This loss of resilience implies not only a poorer and more difficult recovery from baseline homeostasis but a disproportionate increase in harmful healt...

The Stages of Reproductive Aging Workshop (STRAW) + 10 extend from menarche till the end of the lifespan. Much attention has been traditionally given to issues related with the reproductive period, including obstetrical care, contraception, or fertility, while the years around menopause have concentrated attention on the menopausal transition and t...

The widespread distribution of estrogen receptors (ER) conditions that the decline in the circulating levels of estrogens with menopause has a series of effects. Some of them may influence the risk to some noncommunicable diseases (NCD) or, if not attaining sufficient impact to modify the risk for disease, unless some level of organ dysfunctions. T...

This study evaluated the safety and tolerability of fezolinetant in women with vasomotor symptoms (VMS) due to menopause in a pooled analysis of data from three 52-week phase 3 studies (SKYLIGHT 1, 2, and 4). SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies where women (≥ 40 to ≤ 65 years), with moderate to severe VMS (minimum average...

Objectives To assess the efficacy and safety of the non-hormonal, neurokinin 3 receptor antagonist, fezolinetant, to treat moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy. Design Phase 3b randomised controlled trial. Setting 16 countries. Participants 453 individuals aged 40-65 years wit...

Background and objectives: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. Methods: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MO...

Many women seek treatment to improve menopausal vasomotor symptoms (VMS). The selection of women most likely to benefit from menopause hormone therapy (MHT) is crucial in clinical practice. There is general agreement that women younger than 60 years or who initiate MHT within the first 10 years of menopause, with no contraindications, have greater...

The menopausal transition in defined by the presence of clinically evident irregularities in the cycle. Prevalence and type of bleeding disturbances varies among studies. The Study of Women’s Health Across the Nation (SWAN) reveals that bleeding is usually associated with acceptable estrogen levels while amenorrhea is associated with low or undetec...

Objective Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves...

Objective To explore the association between anxiety and frailty in community-dwelling postmenopausal women. Methods This was a cross-sectional study in which 390 postmenopausal women (aged 60–83 years) who were attending a comprehensive care program were surveyed between January 2018 and February 2020. Each participant was administered a validate...

Objective: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERβ genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. Methods: A cross-sectional study was performed i...

Objective To assess the effect of fezolinetant treatment on health‐related quality of life using pooled data from SKYLIGHT 1 and 2 studies. Design Prespecified pooled analysis. Setting USA, Canada, Europe; 2019–2021. Population 1022 women aged ≥40 to ≤65 years with moderate‐to‐severe vasomotor symptoms (VMS; minimum average seven hot flushes/day...

Ovarian decortication may affect ovarian function. We investigated the status of ovarian reserve after ovarian decortication plus chemotherapy at a stage of presumed stabilized recovery in women surviving cancer. We searched our database for cancer survivors subjected to ovarian decortication and chemotherapy at least 3 years previously. Ovarian fu...

Cancer is one of the main noncommunicable diseases in terms of health impact. Factors such as a progressively aging population point to future increases in the incidence of cancer on a global level. The elevated number of affected individuals, together with continuous improvements in cancer prevention and therapy, is creating a growing population o...

Introduction BRCA 1 and 2 genes increase a patient’s risk for developing cancer of breast and ovarian origin. There are two methods of preventative care offered to BRCA-positive patients: prophylactic surgery or high risk screening for cancer accompanied by endocrine therapy. Preventative surgeries for BRCA-positive patients – bilateral salpingo-oo...

Introduction Preventative surgical procedures for patients who are breast cancer (BRCA) positive—namely, bilateral salpingo-oophorectomy and mastectomy—have been linked to changes in sexual function, including surgically induced menopause. A patient’s decision to undergo preventive surgery as opposed to high-risk screening is heavily reliant on adv...

Background: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomot...

Background: Dynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. Aim: To analyze the association between genet...

Chronic pain induced by endometriosis is a maladaptive pain experienced by half of women with this disease. The lack of pharmacological treatments suitable for the long-term relief of endometriosis-associated pain, without an impact on fertility, remains an urgent unmet need. Progress has been slowed by the absence of a reproducible rodent endometr...

Introduction The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly regarding early cancer diagnosis, sparking public health concerns that possible delays could increase the proportion of patients diagnosed at advanced stages. In 2009, a cancer fast-track program (CFP) was implemented at the Clinico-Malvarro...

Background Telehealth has emerged as an alternative to conventional, face-to-face visits, and the COVID pandemic has hastened its introduction. Telephone appointments make use of an easy-to-use and accessible technology. Aim To investigate the usability of telephone-based telehealth in a women's health outpatient clinic and whether this may be aff...

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best ava...

Bone pathologies such as osteoporosis (OTP) and osteoarthritis (OA) are rising in incidence with the worldwide rise in life expectancy. The diagnosis is usually obtained using imaging techniques such as densitometry, but with both being multifactorial diseases, several molecular mechanisms remain to be understood. Metabolomics offers the potential...

Objectives: This study elicited the views of physicians and patients with vasomotor symptoms (VMS) associated with menopause on the impact of VMS and treatment patterns/perceptions. Study design: Data from the Adelphi VMS Disease Specific Programme, a point-in-time survey conducted in 5 European countries and the United States in 2020, were used...

Menopause imposes a dramatic fall in estrogens, which is followed by an increase in the proportion of fat. The rising androgen/estrogen ratio along the menopause transition favors the accumulation of central fat, which contributes to insulin resistance and a series of concatenated effects, leading to a higher incidence of metabolic syndrome. The mo...

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 wa...

Postmortem 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 la...

The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunoh...

Menopause is the permanent cessation of menstrual cycles secondary to follicle depletion in the ovary. Some women may have their menopause at an early age, before age 40. This occurs in around 1% of the population who receive a diagnosis of primary ovarian insufficiency, also known as premature ovarian failure or premature menopause. The staging of...

Much of the genetic variance associated with osteoporosis is still unknown. Bone mineral density (BMD) is the main predictor of osteoporosis risk, although other anthropometric phenotypes have recently gained importance. The aim of this study was to analyze the association of SNPs in genes involved in osteoblast differentiation and function with BM...

Background The role of the menopause in weight gain is an understudied yet important field, given the rising prevalence of obesity and its associated risk of disease. Objective To review the current evidence regarding the impact of the menopausal transition on changes in body composition and fat accrual in women and the hormonal mechanisms underly...

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanis...

To what extent the intake of fruit and vegetables (FV) influences inflammatory status remains elusive, particularly in older populations. The aim of the present study was to determine the effect of increased FV intake for 16 weeks on circulating biomarkers of inflammation in a population of older men and women. Sixty-six participants (65–70 years)...

The rising incidence of bone pathologies such as osteoporosis and osteoarthritis is negatively affecting the functional status of millions of patients worldwide. The genetic component of these multifactorial pathologies is far from being fully understood, but in recent years several epigenetic mechanisms involved in the pathophysiology of these bon...

The receptor activator of nuclear factor-κB (RANK) and its ligand RANKL are members of the tumor necrosis factor (TNF) super-family of cytokines with a role in progestogen-associated malignancies in breast. Basic and clinical data support the participation of the cytokine pathway in metastatic disease and as poor prognosis markers. The value of RAN...

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, performa...

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 previou...

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 t...

Background . 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 against frailty, yet use of ICT among older people, particularly women, is an understudied area. Aim : To analyze...

The objective of this project is to create eligibility criteria for the use of menopausal hormone therapy (MHT) similar to those established for contraceptive methods. A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by patients with medical conditions based on the...

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 w...

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 phenot...

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 clin...

Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS p...

Background: Demographic changes have forced communities and people themselves to reshape ageing concepts and approaches and try to develop actions towards active and healthy ageing. In this context, the European Commission launched different private-public partnerships to develop new solutions and answers on questions related to this topic. The Eu...

Objective 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 has not been explored. We investigated the effect of bazedoxifene on endothelial cell proliferation. Methods Primary cultures from human umbili...

Background In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. Methods...

An amendment to this paper has been published and can be accessed via the original article.

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 V...

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 in...

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...

To identify new candidate genes in osteoporosis, mainly involved in epigenetic mechanisms, we compared whole gene-expression in osteoblasts (OBs) obtained from women undergoing hip replacement surgery due to fragility fracture and severe osteoarthritis. Then, we analyzed the association of several SNPs with BMD in 1028 women. Microarray analysis yi...

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 evidenc...

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...

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theo...

Background: In the last years, the identification of different genetic and phenotypic biomarkers for prevention, early diagnostics and patient stratification have been a main objective in cancer research. Different proposals for multivariable models using biomarkers have been presented for the evaluation of individual risk of women to develop breas...

Background: In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. Methods...

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...

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 CTLA-4 genes that code for key proteins in the T-cell co-stimulation process, in a female...

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the managem...

Objectives To compare progestin ovarian stimulation protocols with gonadotropin-releasing hormone analogue (agonists and antagonists) protocols on newborn outcomes.Methods The PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched for studies comparing progestin prime ovarian stimulation (PPOS) pr...

COVID-19 is associated with a systemic inflammatory response with activation of coagulation in symptomatic patients. The possibility of coagulopathies in peri- and postmenopausal women taking estrogen therapies makes it necessary to consider antithrombotic strategies, such as the use of low molecular weight heparins (LMWH) at specific prophylactic...

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 investig...

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 compr...

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)...

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...

The original article unfortunately contained a mistake. In Table 2, the headers “Development set” and “Validation set” were not aligned to to their sub-headers.

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 (...

Purpose To call attention to the fact that cumulative live birth (LB) proportions exhibit an inverted pattern to that displayed by each individual oocyte retrieval cycle (ORC-specific LB proportions) as well as when grouping together all the ORCs undergone by a woman (TNORC-specific LB proportions). Methods A retrospective study of 1433 infertile...

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 epide...

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 mod...

Background: Age-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...

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 postmenopa...

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, oste...

Peripheral blood biomarkers able to predict disease activity in multiple sclerosis (MS) patients have not been identified yet. Here, we analyzed the immune phenotype of T lymphocyte subpopulations in peripheral blood samples from 66 RRMS patients under DMF ( n=22 ) or fingolimod ( n=44 ) treatment, by flow cytometry. A correlation study between the...

The drastic reduction in the circulating levels of estrogens along the menopausal transition triggers a list of symptoms, where hot flashes (HF) constitute a frequently reported episode. Women describe hot flashes as a sudden feeling of heat affecting the upper body, trunk, head, and neck and spreading upwards or, less frequently, downwards. The wh...

Purpose The present study aims to ascertain whether there is a causal relationship between women’s disease conditions present at the starting time of the first intended oocyte retrieval cycle and IVF/ICSI outcomes, primarily odds of live birth in the first IVF/ICSI treatment. Methods This is a retrospective study of infertile healthy and diseased...

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 p...