The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Postmenopausal women with higher TSH values within the normal range present improved handgrip strength: a pilot study.

OBJECTIVE: To evaluate the possible association between thyroid function within the euthyroid range and musculoskeletal parameters as well as body composition in a sample of postmenopausal women. METHODS: This cross-sectional study included 96 postmenopausal women with serum thyroid-stimulating hormone (TSH) within the normal laboratory reference range. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Bone status and body composition were measured using Dual Energy X-ray absorptiometry (DXA). Physical activity was quantified using the International Physical Activity Questionnaire (IPAQ) index. RESULTS: Serum TSH correlated with handgrip strength (HGS, r-coefficient = 0.233, p = .025), and total body bone mineral density (BMD) T-score values (r-coefficient = 0.321, p = .003). HGS measures were associated with BMD (r-coefficient = 0.415, p < .001), with bone mineral content (BMC, r-coefficient = 0.427, p < .001), and lean mass (r-coefficient = 0.326, p = .003). Women with low muscle strength, defined as HGS < 16 kg, had lower TSH levels than women with normal muscle strength (low vs. normal muscle strength, ANCOVA 1.13 ± 0.49 mU/L vs. 1.60 ± 0.83 mU/L, p = 0.024) independently of age, BMD, percentage of body fat or absolute lean mass. Multivariable linear regression analysis showed that HGS values were associated with TSH measurements (ß-coefficient = 0.246, p = .014) and BMD T-score values (ß-coefficient = 0.306, p = .002). All models were adjusted for age, body mass index (BMI), vitamin D, low-density lipoprotein cholesterol, current smoking, physical activity, and homeostasis model assessment of insulin resistance. CONCLUSIONS: In this sample of postmenopausal women, lower serum TSH values, within normal range, were associated with lower muscle strength compared to higher normal TSH values. Further research is needed to elucidate the significance of our preliminary findings.

Development and external validation of a home-based risk predicTion modEl of natUral onseT of menopAuse -TEUTA.

OBJECTIVE: To develop and externally validate a 10-year risk prediction model of natural onset of menopause using ready-to-use predictors. DESIGN: Population-based prospective cohort study. PARTICIPANTS: Community-dwelling, premenopausal women aged 28 years and older enrolled in the Swiss (CoLaus) and Dutch (PREVEND) study. MAIN OUTCOME MEASURE: Incidence of self-reported natural menopause. MODEL DEVELOPMENT: Based on existing literature, 11 predictors were tested in this study. The CoLaus cohort was used to develop the model by applying the backward-elimination approach and Bayesian Model Averaging. Internal validation was performed by bootstrapping. External validation was performed using data from the PREVEND cohort and recalibrating the baseline survival estimate. C-statistic, calibration slopes, and expected/observed probabilities were calculated as measures of model internal and/or external performances. RESULTS: The final analysis included 750 and 1032 premenopausal women from the CoLaus and the PREVEND cohort, respectively. Among them, 445 (59%) from CoLaus and 387 (38%) from PREVEND experienced menopause over a median follow-up of 10.7 and 9 years, respectively. The final model included age, alcohol consumption, smoking status, education level, and systolic blood pressure. Upon external calibration in the PREVEND cohort, the model exhibited good discrimination, with a C-statistic of 0.888 and an expected/observed probability of 0.82. CONCLUSIONS: We present the first internally and externally validated prediction model of natural menopause onset using readily available predictors. Validation of our model to other populations is needed.

Statin use and incident type 2 diabetes mellitus in women after menopause.

Menopause is associated with adverse cardiometabolic changes which increase the risk of new-onset type 2 diabetes (T2DM) and cardiovascular disease (CVD). Statins are widely used for primary and secondary CVD prevention, given their beneficial effects on the lipid profile and the vessel wall. On the other hand, statins increase the risk of T2DM. This association has been evaluated mainly in mixed-gender studies, without gender-specific evaluation. This narrative review evaluates the use of statins and the related risk of new-onset T2DM among postmenopausal women. Studies that incorporated a gender-specific analysis report a higher risk of new-onset T2DM in women than in men on treatment with statins. Fewer studies evaluated female-only samples; these confirm the observed association between statin use and new-onset T2DM. Factors influencing the association between statin use and T2DM include the type and dose of statin and the baseline metabolic status. Women may benefit from stratification of their metabolic risk before initiating a statin for CVD prevention.

Lower Urinary Tract Symptoms in Greek Women After Menopause: The LADY Study.

INTRODUCTION AND HYPOTHESIS: The genitourinary syndrome of menopause (GSM), apart from symptoms related to vulvovaginal atrophy (VVA), also consists of lower urinary tract symptoms (LUTS). Based on the common embryological origin of the genital and lower urinary system, the presence of estrogen receptors, and the high prevalence of VVA and LUTS in the menopausal population, the two conditions can coexist. This study is aimed at investigating the prevalence and risk factors of LUTS in a sample of Greek peri- and postmenopausal women. METHODS: Four hundred and fifty (450) women, aged 40-70 years, attending three outpatient gynecology clinics for routine examination, completed a structured interview and responded to a validated questionnaire (International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms, ICIQ-FLUTS). RESULTS: Urinary urgency or frequency affected 51.6% and dysuria 43.6% of the participants. Mild urgency or frequency was described by 25.6%, moderate by 14.4%, and severe by 11.6% of the women. Mild dysuria was reported by 26.26%, moderate by 5.8%, and severe by 11.6%. Age, weight, BMI, and number of pregnancies and abortions correlated with a higher ICIQ-FLUTS score. Women with moderate/severe symptoms of VVA, such as irritation, a burning sensation, and pruritus of the vulva or vagina, had a higher ICIQ-FLUTS score than women without such symptoms (beta coefficient 2.42, CI 1.204, 3.635, p < 0.001). CONCLUSIONS: Lower urinary tract symptoms are very common among peri- and postmenopausal women and are linked to symptoms of VVA. Our data support the need for prompt evaluation of women transitioning to menopause, as these symptoms compromise the quality of life.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Efficacy and safety of metformin during pregnancy: an update.

During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.

EMAS position statement: Testosterone replacement therapy in older men.

INTRODUCTION: Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. AIM: To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12 months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

The severity of menopausal symptoms is associated with diabetes, and cardiometabolic risk factors in middle-aged women.

BACKGROUND: Ovarian senescence is associated with increased cardiovascular risk. We aimed to evaluate the association between menopausal symptoms and cardiometabolic risk factors in a cohort of apparently healthy middle-aged women. METHODS: The cohort included 2793 peri- and postmenopausal women not on menopausal hormone therapy. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric Scale (GCS). RESULTS: GCS-Total Score was associated with BMI (b=0.12, 95% CI: 0.04 to 0.20), T2DM (b=2.10, 95% CI: 0.06 to 4.15), and late-postmenopause (b=-1.24, 95% CI: -2.17 to -0.33). GCS-psychological score was associated with BMI (b=0.06, 95% CI: 0.00 to 0.11). GCS-Physical Score was associated with BMI (b=0.06, 95% CI: 0.03 to 0.09), central obesity (b=0.18, 95% CI: 0.02 to 0.34), and postmenopause (early-/late-postmenopause vs. perimenopause, b=-0.36, 95% CI: -0.59 to -0.13 and b=-0.65, 95% CI: -0.97 to -0.34, respectively). All GCS-scores were negatively associated with age. GCS-Sexual Score was associated with early-postmenopause (incidence rate ratio (IRR)=1.53, 95% CI: 1.21 to 1.94), central obesity (IRR=1.18, 95% CI: 1.00 to 1.39), smoking, diastolic blood pressure, age. Cox-regression analysis showed that incident T2DM was positively associated with increasing age, BMI, daily alcohol consumption, moderate-to-severe vasomotor symptoms (VMS, OR=1.045, 95% CI: 1.011 to 1.079), and negatively with moderate-to-strenuous physical activity. These associations persisted in lean but not in obese women. CONCLUSIONS: The severity of menopausal symptoms is associated with T2DM, obesity, and smoking in a cohort of peri-/postmenopausal women. VMS were associated with incident T2DM, especially in lean women. These associations must be considered in implementing primary and secondary prevention strategies.

Early menopause and cardiovascular risk factors: a cross-sectional and longitudinal study.

OBJECTIVE: The aim of the study is to evaluate the cross-sectional and longitudinal association of early natural menopause with changes in cardiovascular risk factors (CVRFs). METHODS: Postmenopausal women from the Swiss CoLaus study, reporting age at natural menopause (ANM) and having CVRFs measurements (blood lipids, blood pressure, glucose, homeostatic model assessment for insulin resistance [HOMA-IR], and inflammatory markers) at baseline (2003-2006) and first follow-up (2009-2012) were eligible for analysis. Age at natural menopause was analyzed as a continuous variable and in categories (ANM <45 and ≥45 y old). Linear regression analysis and linear mixed models were used to assess whether ANM is associated cross-sectionally and longitudinally with changes in CVRFs. Models were adjusted for demographic characteristics, lifestyle-related factors, time since menopause, medication, and clinical conditions. RESULTS: We analyzed 981 postmenopausal women. The cross-sectional analysis showed that women with ANM younger than 45 years had lower diastolic blood pressure (ß = -3.76 mm Hg; 95% confidence interval [CI] = -5.86 to -1.65) compared with women whose ANM was 45 years or older. In the longitudinal analysis, ANM younger than 45 years was associated with changes in log insulin (ß = 0.26; 95% CI = 0.08 to 0.45) and log homeostatic model assessment for insulin resistance levels (ß = 0.28; 95% CI = 0.08 to 0.48). No associations were found between ANM and other CVRFs. CONCLUSIONS: Early menopause may be associated with changes in glucose metabolism, while it may have little to no impact on other CVRFs. Larger longitudinal studies are needed to replicate our findings.

Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis.

INTRODUCTION: Vasomotor symptoms (VMS) are the symptoms most frequently experienced by women transitioning to menopause and are a primary indication for menopausal hormone therapy. A growing body of evidence has associated the presence of VMS with future risk for cardiovascular disease (CVD) events. This study aimed to systematically evaluate, qualitatively and quantitatively, the possible association between VMS and the risk for incident CVD. METHODS: This systematic review and meta-analysis included 11 studies evaluating peri- and postmenopausal women in a prospective design. The association between VMS (hot flashes and/or night sweats) and the incidence of major adverse cardiovascular events, including coronary heart disease (CHD) and stroke, was explored. Associations are expressed as relative risks (RR) with 95 % confidence intervals (CI). RESULTS: The risk for incident CVD events in women with and without VMS differed according to the age of participants. Women with VSM younger than 60 years at baseline had a higher risk of an incident CVD event than women without VSM of the same age (RR 1.12, 95 % CI 1.05-1.19, I2 0%). Conversely, the incidence of CVD events was not different between women with and without VMS in the age group >60 years (RR 0.96, 95 % CI 0.92-1.01, I2 55%). CONCLUSION: The association between VMS and incident CVD events differs with age. VMS increases the incidence of CVD only in women under 60 years of age at baseline. The findings of this study are limited by the high heterogeneity among studies, pertaining mainly to different population characteristics, definitions of menopausal symptoms and recall bias.

Human Leukocyte Antigen Alleles Compatibility and Immunophenotypic Profile Associations in Infertile Couples.

INTRODUCTION: The maternal immune system has a major role in the successful embryo implantation and maintenance of the pregnancy. This study aimed to investigate the maternal immunophenotyping profile (percentage of Natural Killer [NK] cells and the CD4/CD8 [cluster designation] ratio in peripheral blood lymphocytes) and the HLA (Human Leukocyte Antigen)-DQA1 alleles sharing in infertile couples. METHODS: This cross-sectional study included 78 women who had experienced at least two spontaneous miscarriages and 110 women with a history of recurrent implantation failures after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF-ET failures). The NK cell percentage and the CD4/CD8 ratio were determined by flow cytometry. Genotyping of the HLA-DQA1 alleles was carried out for all women and their partners, and couple HLA-DQA1 compatibility was expressed as the percentage of common HLA-DQA1 alleles (totaling 35 alleles) shared between spouses to the sum of the unique alleles observed. RESULTS: In women with recurrent miscarriages, high values (%) of the NK population with a median (interquartile range [IQR]) of 10.3% (7.7% to 12.5%) and CD4/CD8 ratio (1.7) (1.5 to 2.1) were found. In women with IVF-ET failures, the (%) NK population (10.5%) (8.6% to 12.5%) and CD4/CD8 ratio (1.8) (1.5 to 2.1) were similarly increased (p=0.390, and p=0.490, respectively). The proportion of women with >10% NK cells was 53.8% and 58.2% in women with miscarriages and IVF-ET failures, respectively (p=0.554). The prevalence of HLA-DQA1*5 allele carriage was elevated in women with miscarriages as well as those with IVF-ET failures (52.6% and 61.8%, respectively; p=0.206). The proportion of couples with high (>50%) HLA-DQA1 sharing was 65.4% in the group with miscarriages and 73.6% in the group with IVF-ET failures, respectively (p=0.222). The CD4/CD8 ratio was statistically significantly positively correlated with the (%) NK population in women with IVF-ET failures (rho = 0.297, p=0.002) and with the (%) HLA-DQA1 sharing in the group with miscarriages (rho = 0.266, p=0.019). The couples in which both spouses were carriers of the HLA-DQA1*5 allele had an increased probability of high (>50%) HLA-DQA1 compatibility compared with the couples in which neither of the spouses carried the allele in the miscarriage group (OR = 24.3, 95% CI: 3.0 to 198.9, p<0.001), and the IVF-ET failure group (OR = 10.5, 95% CI: 2.2 to 49.8, p<0.001). CONCLUSION: The peripheral NK (%) population and CD4/CD8 ratio, as well as the prevalence of the HLA-DQA1*5 allele, were elevated in women with recurrent miscarriages and IVF-ET failures. Furthermore, these couples with negative reproductive outcomes had a high percentage of HLA-DQA1 allele similarity. The presence of the HLA-DQA1*5 allele in spouses was strongly associated with overall couple HLA-DQA1 compatibility, implying that it could be used as a surrogate marker for assessing overall immunological compatibility in infertile couples.

Implementation of risk enhancers in ASCVD risk estimation and hypolipidemic treatment eligibility: A sex-specific analysis.

OBJECTIVE: Sex-specific data are limited regarding eligibility for hypolipidemic treatment. We aim to explore the sex-specific clinical utility of high-sensitivity C-reactive protein (hsCRP) and carotid ultrasound as risk modifiers for hypolipidemic treatment in primary prevention of atherosclerotic cardiovascular disease (ASCVD). METHODS: We aimed to explore these sex-specific trends in two pooled contemporary independent Greek cohorts (Athens Vascular Registry n = 698, 50.9% women and Menopause Clinic n = 373, 100% women) of individuals without overt ASCVD. Baseline ASCVD risk was estimated using the Systematic COronary Risk Evaluation-2 (SCORE2) tools. The presence of carotid plaque and hsCRP ≥2 mg/L were integrated as risk modifiers. RESULTS: Men had increased odds to achieve target LDL-C levels based on ASCVD risk (23.8% vs. 17.7%, OR: 1.45 95% CI: 1.05-2.00, p = 0.023, for men vs. women). Additionally, considering carotid plaque or high hsCRP levels did not change this association but reduced on-target LDL-C rate in both sexes. Women had decreased odds of being eligible for hypolipidemic treatment by ASCVD risk estimation (11.5% vs. 26.4%, p < 0.001) compared with men. The addition of carotid plaque presence or high hsCRP levels and their combination resulted in a higher relative increase in hypolipidemic treatment eligibility in women (from 11.5% to 70.9% vs. 26.4% to 61.4% for carotid plaque, from 11.5% to 38.5% vs. 26.4% to 50.8% for hsCRP and from 11.5% to 79.1% vs. 26.4% to 75% for their combination, all for women vs. men, pforinteraction < 0.001 for all) than men. CONCLUSIONS: Implementation of carotid plaque and hsCRP levels increases hypolipidemic treatment eligibility more prominently in women than in men. The impact on clinical outcomes in these untreated patients merits further investigation.

Vitamin D, Menopausal Health and COVID-19: Critical Appraisal of Current Data.

Inconsistency exists across studies conducted in postmenopausal women regarding the effect of vitamin D deficiency (VDD) and supplementation on several aspects of menopausal health, such as fractures, vasomotor symptomatology, cardiovascular disease (CVD), cancer and infections, including coronavirus disease 2019 (COVID-19). The aim of this review is to critically summarize the evidence provided by observational studies and randomized controlled trials (RCTs) of vitamin D supplementation in postmenopausal women with VDD. Observational studies have found that VDD is associated with an increased risk of falls and fractures after the menopause. VDD also has a negative effect on menopausal symptomatology. VDD, especially its severe form, is associated with an increased risk of CVD risk factors and CVD events. VDD is associated with increased risk and mortality from several cancer types and risk of infections. The evidence from RCTs regarding the effect of vitamin D supplementation on falls, fractures, menopausal symptoms, cardiovascular disease, cancer and infections is not robust. Thus, skeletal health may benefit only when vitamin D is co-administered with calcium, especially in those ≥70 years old and with severe VDD. There is no evidence of a favorable effect on menopausal symptoms or risk of CVD or cancer, except for a modest reduction in cancer-related mortality. Inconsistency still exists regarding its effect on infection risk, disease severity and mortality due to COVID-19.

Climacteric symptoms, age, and sense of coherence are associated with sexual function scores in women after menopause.

BACKGROUND: Postmenopausal sexual function presupposes the integration of hormonal, neural, and vascular interactions and is subject to optimal crosstalk among psychological, interpersonal, cultural, and environmental factors. Sense of coherence (SOC) reflects a person's ability to cope with stressors and may influence the occurrence of menopausal symptoms and sexual dysfunction. AIM: To investigate the association of severity of climacteric symptoms, cardiometabolic risk factors, and SOC with sexual function in postmenopausal women. METHODS: Overall 281 sexually active postmenopausal women without significant psychopathology or cardiovascular disease attending the Menopause Unit of Aretaieion Hospital were evaluated by the Female Sexual Function Index (FSFI), Greene Climacteric Scale, Beck Depression Scale, and Sense of Coherence Scale. Hormonal and biochemical parameters and cardiometabolic risk factors were evaluated. FSFI scores <26.5 were considered pathologic. OUTCOMES: Total and subdomain scores of sexual response were determined. RESULTS: Pathologic FSFI scores were found in 79.7% of the sample. Linear models of multivariable regression analysis showed that FSFI scores were associated with (1) Beck scores (b = -0.200; 95% CI, -0.472 to -0.073, P = .001), vasomotor symptom severity (b = -0.324; 95% CI, -0.985 to 0.051; P < .001), and age and (2) SOC (b = 0.150, 95% CI, 0.036-0.331; P = .008), vasomotor symptom severity (b = -0.361; 95% CI, -0.743 to 0.245; P < .001), and age. Both models were adjusted for menopausal age, diabetes mellitus, hypertension, type of menopause, and menopausal hormone therapy intake. SOC was associated with Beck depression scores (ß = -0.487, P < .001; Greene Climacteric Scale total scores, ß = -0.199, P < .001). FSFI score <26.5 vs >26.5 was associated with SOC (odds ratio, 0.982; 95% CI, 0.563 to 1.947; P = .006) and moderate to severe vasomotor symptom severity (odds ratio, 2.476; 95% CI, 1.478 to 3.120; P = .009) independent of age, diabetes mellitus, hypertension, menopausal hormone therapy intake, type of menopause, or Beck depression classification. CLINICAL IMPLICATIONS: The results indicate the importance of psychometric assessment of postmenopausal women when presenting with scores of low sexual function. The severity of vasomotor symptoms should also be addressed in any case. STRENGTHS AND LIMITATIONS: This is the first study investigating the relationship between SOC and sexuality in menopause in a carefully selected homogenous population. Limitations included the cross-sectional design and the fact that sexual distress was not assessed. CONCLUSIONS: Pathologic FSFI scores were highly prevalent in this sample of postmenopausal women. FSFI is associated positively with age and severity of vasomotor symptoms and negatively with SOC.

EMAS position statement: Vitamin D and menopausal health.

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 <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.

Screening and management of major endocrinopathies during pregnancy: an update.

Endocrinopathies during pregnancy constitute a challenging issue, being prevalent and requiring appropriate management to avoid maternal and fetal complications. This review aims to summarize and present major endocrine problems during pregnancy, the appropriate screening, maternal monitoring and management, fetal monitoring, and follow-up. Glucose metabolism, thyroid function, as well as calcium and vitamin D metabolism are the main endocrine domains that should be screened and monitored during pregnancy. Gestational diabetes mellitus (GDM) is the most prevalent endocrine disease during pregnancy, followed by thyroid disorders. Specific recommendations are provided for the optimal clinical care of pregnant women and their offspring for GDM, thyroid disorders, and calcium and vitamin D disorders.

The effect of menopause on lipoprotein (a) concentrations: A systematic review and meta-analysis.

OBJECTIVE: Transition to menopause has been associated with an increased risk of cardiovascular disease (CVD), attributed mainly to atherogenic dyslipidemia. Whether lipoprotein (a) [Lp(a)], an independent cardiovascular risk factor, also contributes to menopause-associated CVD has not yet been clarified. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the effect of menopause on Lp(a) concentrations. METHODS: A comprehensive search was conducted in PubMed and Scopus databases up to March 8th, 2022. Data were expressed as weighted mean difference (WMD) with 95 % confidence intervals (CI). The I2 index was employed to assess heterogeneity. RESULTS: Seventeen studies were included in the qualitative and 15 in the quantitative analysis, yielding 4686 premenopausal and 8274 postmenopausal women. Lp(a) concentrations were lower in premenopausal than in postmenopausal women [WMD -3.77 (95 % CI -5.37, -2.18) mg/dl, p < 0.001; I2 99%, p < 0.001]. This difference was maintained when the analysis was restrained to good-quality studies (n = 9). Four studies included pre- and postmenopausal women, matched for age, and these found no difference in Lp(a) concentrations between groups [WMD -1.22 (95 % CI -3.15, 0.72) mg/dl, p < 0.001; I2 99%, p < 0.001]. Three studies provided data for Lp(a) in women before and after bilateral oophorectomy, and these found no difference between them [WMD -3.38 (95 % CI -7.29, 0.54) mg/dl, p = 0.09; I2 0%, p < 0.44]. CONCLUSIONS: Transition to menopause may increase Lp(a) concentrations, although the effect of aging cannot be excluded by current data.

Menopause, androgens, and cardiovascular ageing: a narrative review.

Cardiovascular disease is the leading cause of death worldwide; however, women tend to be less affected than men during their reproductive years. The female cardiovascular risk increases significantly around the time of the menopausal transition. The loss of the protective action of ovarian oestrogens and the circulating androgens has been implicated in possibly inducing subclinical and overt changes in the cardiovascular system after the menopausal transition. In vitro studies performed in human or animal cell lines demonstrate an adverse effect of testosterone on endothelial cell function and nitric oxide bioavailability. Cohort studies evaluating associations between testosterone and/or dehydroepiandrosterone and subclinical vascular disease and clinical cardiovascular events show an increased risk for women with more pronounced androgenicity. However, a mediating effect of insulin resistance is possible. Data on cardiovascular implications following low-dose testosterone treatment in middle-aged women or high-dose testosterone supplementation for gender affirmatory purposes remain primarily inconsistent. It is prudent to consider the possible adverse association between testosterone and endothelial function during the decision-making process of the most appropriate treatment for a postmenopausal woman.