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INTRODUCTION There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations

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

The Vaginal Health Index Score (VHIS) and vulvodynia swab tests are used to assess vaginal health and vulvodynia. However, few studies have used these tests in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). IC/BPS is a chronic, debilitating disorder, characterised by urinary frequency, urinary urgency and pelvic pain. It adversely affects organs adjacent to the urinary system, leading to complications of sexual dysfunction. This study was aimed at understanding sexual dysfunction in patients with IC/BPS, as well as deterioration of vaginal health and vulvodynia.This study compared the vaginal health of IC/BPS patients with that of asymptomatic control individuals. The Pain Urgency Frequency (PUF) score, Female Sexual Function Index (FSFI), VHIS, and vulvodynia swab tests, were used as tools. The PUF and FSFI are questionnaire-based surveys of bladder symptoms and sexual function respectively. VHIS evaluation and vulvodynia swab tests are performed by physicians. The PUF was used to assess baseline IC/BPS symptoms to validate the patient population, and FSFI, vulvodynia swab tests and VHIS were used to determine between-group differences.Thirty-seven patients were recruited in each group. The IC/BPS group had a higher PUF score (18.19±3.51 vs 3.56±2.35; p0.05), worse total FSFI (15.72±4.46 vs 26.3±4.93; p0.05), and worse vulvodynia swab test and total VHIS (11.59±2.87 vs 22.05±3.05; p0.05) scores than those of the control group.Asian women with IC/BPS experienced greater sexual dysfunction, worsened vaginal health and increased vulvodynia compared with control individuals. Information on vaginal and vulva health is very useful in evaluating IC/BPS patients.

This prospective pilot study aimed to evaluate the effects of associating a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with a vaginal erbium laser (VEL), as a non-ablative photothermal therapy for superficial dyspareunia in postmenopausal women (PMW) suffering from genitourinary syndrome of menopause (GSM).Two groups of sexually active PMW reporting superficial dyspareunia were selected: one (15 patients, VEL) was treated using an erbium:yttrium-aluminum-garnet laser crystal (XS Fotona SMOOTH; Fotona, Ljubljana, Slovenia) with a wavelength of 2940 nm; in the other group (15 patients, VEL + Nd:YAG) this treatment was followed by Nd:YAG laser (Fotona SP Dynamis, PIANO mode) treatment. Treatment consisted of three laser applications at 30-day intervals. Symptoms were assessed before, after each laser application and after 1 and 3 months from the end of the treatment, using the subjective visual analog scale (VAS) for superficial dyspareunia.Both groups showed a rapid and significant improvement of superficial dyspareunia over time (The addition of Nd:YAG to VEL may induce greater improvement in superficial dyspareunia in PMW with GSM.

INTRODUCTION The menopause, or the cessation of menstruation, is a stage of the life cycle which will occur in all women. Managing perimenopausal and postmenopausal health is a key issue for all areas of healthcare, not just gynecology. AIM To provide recommendations for the curriculum of education programs for healthcare professionals worldwide, so that all can receive high quality training on menopause. MATERIALS AND METHODS Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS Training programs for healthcare professionals worldwide should include menopause and postmenopausal health in their curriculum. It should include assessment, diagnosis and evidence-based management strategies.

Ospemifene is a selective estrogen-receptor modulator approved for treating menopause-related moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy (VVA), in the United States, and for treating menopause-related, symptomatic VVA in women not appropriate for local estrogen therapy in Europe. This review summarizes the effects of ospemifene on bone, including bone biomarker data from a phase 3 vaginal dryness study. Early-phase studies of postmenopausal women showed that ospemifene dose-dependently decreased bone turnover markers versus placebo, similar to raloxifene. A 12-week, phase 3 study of ospemifene 60 mg/day in postmenopausal women showed improvements in all VVA parameters and significantly greater decreases in seven of nine bone biomarkers versus placebo. Lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤5 years or5 years) or baseline bone mineral density (BMD) (normal [

Purpose: The aim of the study was to examine the discontinuation rate of hormonal contraception with estradiol valerate (E2V) and dienogest (DNG). Patients and methods: We collected data at the Family Planning Clinics of the Departments of Obstetrics and Gynecology of Pisa and Cagliari. We included in the analysis 354 consecutive women using oral contraceptive pills containing E2V and DNG. We analyzed the rate and the reason for discontinuation, classifying the reasons in 5 categories: 1) minor side effects, 2) adverse events, 3) other events not directly caused by the drug or conditions for which the pill could represent a risk factor, 4) no compliance with the method and 5) no further need. Results: Of the 354 women examined, 50.8% had discontinued E2V/DNG pill. Excluding women who stopped the pill because of no further need (10.5%), 27.4% discontinued because of minor side effects, 1.7% discontinued for adverse events, 9.9% because of other events not directly caused by the drug or conditions for which the pill could represent a risk factor and 1.4% because of difficulties with compliance. Irregular bleedings were the main reasons reported for discontinuation. The time to discontinuation for irregular bleedings was significantly (p

Nowadays, postmenopausal women are largely undertreated. Analysis of conflicting results among different studies suggests that hormone replacement therapy (HRT) can prevent osteoporosis and cardiovascular disease in symptomatic, early postmenopausal women. In fact, climacteric symptoms are related to an increased risk of chronic conditions, including hypertension and cardiovascular disease. Different scientific societies have pointed out that patient selection, timing of initiation, and the choice of the type and dose of HRT used are the major determinants of the ultimate effect of HRT on women's health and quality of life in selected women. HRT may prevent chronic conditions when started in symptomatic women before the age of 60 years or within 10 years of the onset of the menopause, taking into consideration the characteristics and risk profiles of each given woman. The bulk of scientific evidence from preclinical, clinical, epidemiological, and also randomized studies indicates that wisely selected HRT is generally useful and rarely dangerous. Following simple and well-established rules, HRT benefits outweigh all of the possible risks. Progestogen choice can make the difference in terms of cardiovascular disease benefits.

Objective we aimed to explore the use of an estro-androgenic symptom questionnaire in women (EASQ-W), including items typically associated with menopausal hypoestrogenism and some others possibly related to androgen insufficiency that may be relevant to further characterize women reporting VVA/GSM at midlife. Methods web-based survey involving a representative sample of 1505 Italian women (age range: 40-65 years). The responders completed a structured, online questionnaire, reporting symptoms (yes/no option) and rating them (from 1 to 10), if present during the past 4 weeks. A factor analysis methodology (principal component analysis and K-MEANS clustering algorithm) was used to segment women. Statistically significant differences between groups were determined at the 95% level of confidence. Results more than half of our study sample were aged 50-65 years (n = 901; 59.9%) and 55% were postmenopausal women (PMW). We obtained 8 principal domains of the EASQ-W with PMW reporting significantly more severe symptoms in the majority of domains related to well-being at mid-life. The K-MEANS clustering algorithm identified 4 clusters of women characterized by different symptoms: vasomotor (VMS; n = 341), sexual (SEX; n = 301), poorly symptomatic (LOWSYMPT; n = 766), sexual and anatomic, mainly at genital level (SEX + ANAT; n = 97), independently from the menopausal status. The cluster SEX + ANAT was the one reporting overall more symptoms in each of the other principal domains. Some symptoms (impression of being diminished in height, deterioration in work performance, more memory lapses/confusion than before, more wrinkles/signs of aging in the mirror, put on more tummy than usual) and the entire urological (UROL) cluster were significantly more reported by women in the cluster SEX + ANAT. Even when only severe symptoms were analysed, women in the SEX + ANAT cluster were the ones more symptomatic. The SEX only cluster identified younger women, with significantly less day and night hot flushes and sweats and less vaginal dryness and low lubrication associated with sexual pain as compared to SEX + ANAT. Conclusion our results provide insight into the constellation of symptoms associated with VVA/GSM by identifying women with distinct clusters of complaints that may require a tailored diagnostic and therapeutic approach across age and menopause.

The purpose of this publication is to summarize the results of the vaginal erbium:yttrium-aluminum-garnet (Er:YAG) Smooth® laser (VEL) on the vaginal atrophy component of the genitourinary syndrome of menopause (GSM). GSM has two categories of clinical signs related to estrogen deficiency: symptoms of vulvovaginal atrophy (VVA) and urinary symptoms. This symptomatology is chronic, progressive over the years and affects a majority of women concerned by natural menopause but not exclusively: we must also consider the growing number of survivors of gynecological or non-gynecological cancers (breast, cervix, uterus, vagina, anus, etc.). At a time when hormonal treatment of menopause is contested as is the installation of under urethra prosthesis, the innovation provided by the VEL technology has the merit of offering the women concerned an effective therapeutic alternative with the security of a patent. The VEL technology has an original and unique process: acting only by thermal effect and not by ablation on tissue, VEL is a safe solution in terms of side effects and potential complications. Studies have been increasing since 2012 and all demonstrate a significant improvement in the GSM signs and symptoms, as well as an improved sexual life after VEL treatment. Double-blind, placebo-controlled, randomized studies are expected in order to ultimately confirm the safety and effectiveness of VEL.

A new approach for multivariate modelling and prediction of asset returns is proposed. It is based on a two-component normal mixture, estimated using a fast new variation of the minimum covariance determinant (MCD) method made suitable for time series. It outperforms the (shrinkage-augmented) MLE in terms of out-of-sample density forecasts and portfolio performance. In addition to the usual stylized facts of skewness and leptokurtosis, the model also accommodates leverage and contagion effects, but is i.i.d., and thus does not embody, for example, a GARCH-type structure. Owing to analytic tractability of the moments and the expected shortfall, portfolio optimization is straightforward, and, for daily equity returns data, is shown to substantially outperform the equally weighted and classical long-only Markowitz framework, as well as DCC-GARCH (despite not using any kind of GARCH-type filter).

OBJECTIVE The aim of this study was to evaluate the efficacy and acceptability of a second generation of vaginal laser treatment, the vaginal erbium laser, as a nonablative photothermal therapy for the management of genitourinary syndrome of menopause in postmenopausal breast cancer survivors. METHODS The study was performed using an erbium laser crystal yttrium-aluminum-garnet (XS Fotona Smooth, Fotona, Ljubljana, Slovenia) with a wavelength of 2,940 nm. Forty-three postmenopausal breast cancer survivors were treated with three laser applications every 30 days. Symptoms were assessed before the treatment and after 1, 3, 6, 12, and 18 months, using two methods, subjective Visual Analog Scale (VAS) and objective Vaginal Health Index Score (VHIS). The procedures were performed on an outpatient basis without anesthesia or drug use before or after the intervention. RESULTS From baseline values of 8.5 ± 1.0 cm, vaginal dryness VAS scores were 4.4 ± 1.2 cm after the third treatment and 5.5 ± 1.5 cm 12 months after the treatment (P

Drospirenone (DRSP) is an antialdosterone agent with progestogenic and antiandrogenic effects. This compound, has been recently used in combination with 17β-estradiol (E2) as hormonal therapy in postmenopausal women and has been shown to exert a significant antihypertensive effect in hypertensive post-menopausal women. Aim of the present study was to compare the effect of DRSP/E2 with those of Tibolone (T) on endothelial function, arterial stiffness, and lipid profile of early postmenopausal women naive on post-menopausal hormonal therapy. Twenty-four women met the inclusion criteria and entered the study. Women were randomized to receive either DRSP/E2 or T for 6months. Blood pressure and heart rate were similar in both groups at baseline and at the end of the study. Compared to baseline, endothelial function assessed by Reactive Hyperemia (RH) significantly improved in women receiving E2/DRSP, whereas no significant differences between baseline and follow up were detected in women receiving Tibolone. Women receiving E2/DRSP showed a significant decrease in pulse wave velocity and Augmentation Index compared to baseline while no changes were observed in women receiving Tibolone. The capacity of sera to trigger endothelial cells apoptosis in vitro measured by cell death assay was significantly reduced by E/DRSP but not by T (HFA-E 70±5,6% vs HFD-E 41±4,5%, p

ulvovaginal atrophy (VVA) has an impact on the quality of life (QoL) of women. This post hoc analysis of the EVES study provides an overview of the QoL in postmenopausal Italian women in relation with VVA severity. We included 1066 women attending menopause/gynaecologic centres. A face-to-face survey (including QoL and sexual life questionnaires), joining an objective gynaecological examination to confirm VVA, were performed. The 65.5% of the participants presented severe vaginal, vulvar and/or urinary symptoms; an 86.9% had an objective confirmed VVA. Women with severe symptoms presented with significantly worse QoL scores than the women without. We found there were moderately significant correlations between vaginal and vulvar symptoms' severity and lower overall DIVA QoL scores (p

The aim of this retrospective study was to evaluate the effects of a long-term treatment with α-lipoic acid (ALA) combined with myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Fifty-seven women with PCOS and a history of oligoamenorrhea were treated with MI and ALA (800 mg + 2000 mg per day). Forty-four of them had complete clinical charts and were considered eligible for the study. Information about cycle length and body mass index (BMI) was checked after 6, 12, and 24 months. After 12 months ovarian volume, total testosterone plasma levels and changes in hirsutism were also evaluated. The metabolic parameters were evaluated in 16 women after 6 and 18 months of the treatment. Cycle length was significantly reduced at 6 (p .001), 12, and 24 months of treatment (p .01). BMI showed a reduction only at 6 months (p .05), thereafter returning similar to the basal values. No changes of testosterone and ovarian volume were observed. HOMA-IR and fasting insulin were unchanged, but the insulin response to a 3 h OGTT was improved after 6 (p .01) and 18 months (p .05) of treatment. No individual suffered from any adverse event. In conclusion, the combination of ALA and MI showed to be useful as long-term therapy in PCOS women, providing a normalization of the menstrual cycle and an amelioration of insulin levels with a high tolerability.

Laser therapy has a therapeutic role for different medical conditions and most recently has gained interest as a non-hormonal treatment for vulvovaginal atrophy or genitourinary syndrome of menopause (GSM). Both microablative fractional CO2 laser and the second-generation non-ablative vaginal Er:YAG laser (VEL) can alleviate the symptoms of dryness and dyspareunia. VEL was also reported to improve SUI as well as vaginal prolapse. The currently available data on the effects of laser on GSM in peer-reviewed publications unequivocally demonstrate the clinical effectiveness of laser therapies on GSM-related symptoms, associated with a high tolerability and a negligible rate of short-term complications. Some controversial issues remain to be solved as the preferred energy-based device, namely, CO2 versus VEL, i.e., ablative versus non-ablative technology. Although comparative, randomized trials have not been reported to date, existing evidences suggest that non-ablative VEL can be offered as a safe and efficacious therapy for GSM, due to the high efficacy, the duration, and the intrinsic safety of repeated applications. Studies will still be necessary to evaluate the additive effect of local or systemic treatments in conjunction with laser treatment.

In the last decade, the risk benefits ratio of MHT has been evaluated mainly in terms of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these Recommendations is to provide a simple and updated reference on postmenopausal MHT. The term MHT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential (Seq) when progestogen is added to ERT for 10-14 days a month, or continuous combined (CC) when progestogen is administered continuously every day along with a fixed amount of estrogen. MHT also includes Tibolone and the Tissue Selective Estrogen Complex (TSEC).

Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.

Current evidence shows that cholesterol management either reduces the likelihood of cardiovascular disease (CVD) or slows down its progression. Hence, it is important that all health professionals make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and positive lifestyle changes to the use of functional foods, food supplements, and drugs. This review examines the effect of the most frequently occurring cholesterol-lowering substances in functional foods or in supplements across Europe, namely plant sterols and stanols, monacolin K found in red yeast rice, berberine and beta-glucans. We conclude that currently available supplements and functional foods can effectively reduce plasma LDL cholesterol levels by about 5 to 25%, either alone or in combination. Suitable candidates for these products are mainly individuals at low absolute cardiovascular risk at a young age or according to classic algorithms. Of note, despite being freely available for purchase, these products should be used following shared agreement between the caring physician and the patient ("concordance").

L’ultimo decennio e stato caratterizzato da un attento riesame dei rischi e benefici della terapia ormonale sostitutiva in menopausa. La terapia ormonale non deve essere consigliata in assenza di una chiara indicazione, personalizzandola e escludendo coloro che presentano controindicazioni. Il rapporto rischi/benefici e sicuramente piu favorevole nelle donne sintomatiche che iniziano una terapia ormonale al di sotto dei 60 anni e comunque entro i 10 anni dall’avvento della menopausa. La dose da impiegare e la minima efficace, iniziando con dosi basse per poi eventualmente modificarle in funzione della risposta clinica della paziente.

Aim To evaluate the effects of the vaginal erbium laser (VEL) in the treatment of postmenopausal women suffering from genitourinary syndrome of menopause (GSM). Method GSM was assessed in postmenopausal women before and after VEL (one treatment every 30 days, for 3 months; n = 45); the results were compared with the effects of a standard treatment for GSM (1 g of vaginal gel containing 50 μg of estriol, twice weekly for 3 months; n = 25). GSM was evaluated with subjective (visual analog scale, VAS) and objective (Vaginal Health Index Score, VHIS) measures. In addition, in 19 of these postmenopausal women suffering from stress urinary incontinence (SUI), the degree of incontinence was evaluated with the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) before and after VEL treatments. Results VEL treatment induced a significant decrease of VAS of both vaginal dryness and dyspareunia (p < 0.01), with a significant (p < 0.01) increase of VHIS. In postmenopausal women suffering from mild to moderate SUI, VEL treatment was associated with a significant (p < 0.01) improvement of ICIQ-SF scores. The effects were rapid and long lasting, up to the 24th week of the observation period. VEL was well tolerated with less than 3% of patients discontinuing treatment due to adverse events. Conclusion This pilot study demonstrates that VEL induces a significant improvement of GSM, including vaginal dryness, dyspareunia and mild to moderate SUI. Further studies are needed to explore the role of laser treatments in the management of GSM.

Menopausal disorders may include shorter-term symptoms, such as hot flushes and night sweats (vasomotor symptoms, VMS) and longer-term chronic conditions such as cardiovascular disease (CVD), osteoporosis, and cognitive impairment. Initially, no clear link between the shorter-term symptoms and longer-term chronic conditions was evident and these disorders seemed to occur independently from each other. However, there is a growing body of evidence demonstrating that VMS may be a biomarker for chronic disease. In this review, the association between VMS and a range of chronic postmenopausal conditions including CVD, osteoporosis, and cognitive decline is discussed. Prevention of CVD in women, as for men, should be started early, and effective management of chronic disease in postmenopausal women has to start with the awareness that VMS during menopause are harbingers of things to come and should be treated accordingly.

Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.