Efficacy and safety of visnadine in the treatment of symptoms of sexual dysfunction in heterosexual women: a systematic review of randomized clinical trials.

OBJECTIVE: To synthesize the primary evidence on the efficacy and safety of visnadine on symptoms of sexual dysfunction (SD) in heterosexual women. METHODS: We conducted a systematic review of randomized clinical trials (RCTs) with a primary search without language restriction in PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, and international clinical trial registries. Trials reporting the use of visnadine by any route in women with SD were eligible. We performed screening, data extraction, and risk of bias assessment in a double-blind approach. The primary outcomes were the Female Sexual Function Index (FSFI) and its domains. Secondary outcomes were safety, arousal, lubrication, pleasure, orgasm, negative sensations, duration, and overall satisfaction. RESULTS: Initially, 242 records were retrieved. We selected nine papers for full-text reading and finally included two RCTs: one with a parallel design and one with a crossover design with a total of 96 patients. One study compared visnadine aerosol with a placebo, while the other compared different frequencies of visnadine aerosol use. Visnadine use showed a statistically significant improvement (p < 0.05) in overall FSFI scores, regardless of the frequency of use. A meta-analysis was not possible due to the high clinical and methodological heterogeneity between available studies. CONCLUSION: RCTs regarding the use of visnadine for the Female SD are scarce and methodologically limited. This preliminary evidence shows visnadine as a potentially effective and safe option to alleviate some of the clinical symptoms of SD in heterosexual women. However, future better-designed randomized studies with larger sample numbers are required.

Neck Circumference in Polycystic Ovary Syndrome: A Systematic Review and Bootstrapped Meta-Analysis with GRADE Approach.

INTRODUCTION: Our aim was to perform a systematic review and meta-analysis for the association of neck circumference (NC) in polycystic ovary syndrome (PCOS) patients as compared to non-PCOS controls. METHODS: Primarily the PubMed/MEDLINE database and others such as SCOPUS, Google Scholar, Cochrane Library, were searched up to November 15, 2023 for observational studies comparing NC in PCOS versus non-PCOS women. The mean and SD values of NC and other covariates in PCOS and control groups were extracted by two independent reviewers, and the quality and risk of bias assessment was done using Newcastle-Ottawa Scale. The meta-analysis employed combined standardized mean differences (SMD) with 95% confidence intervals (CI) to compare NC between PCOS patients and controls. The heterogeneity and validity were addressed by subgroup, meta-regression, and sensitivity analyses. We conducted a Bootstrapped meta-analysis using 1,000 and 10,000 simulations to test the accuracy of the obtained results. The certainty of evidence was assessed by the GRADE approach. RESULTS: Our meta-analysis included 9 observational studies. The PCOS patients showed significantly higher NC values than the non-PCOS controls (SMD: 0.66, 95% CI: 0.41-0.91, p < 0.0001). In the bootstrap meta-analysis, the accuracy of the observed findings was proved (SMD = 0.66, 95% CI = 0.42-0.91) for the NC outcome. No publication bias was detected in the funnel plot analysis using Begg's and Egger's tests. The 95% prediction interval of 0.036-1.28 suggests that the true outcomes of the studies are generally in the same direction as the estimated average outcome. The sensitivity analysis provided the robustness of the outcome, and no single study was overly influential on the pooled estimate. CONCLUSION: This meta-analysis provides accurate evidence for significantly higher NC values in PCOS as compared to non-PCOS controls. There is no sufficient evidence on the diagnostic accuracy measures for NC in PCOS. Hence, further research on its diagnostic utility in PCOS is needed.

Gestational diabetes mellitus management according to ultrasound fetal growth versus strict glycemic treatment in singleton pregnancies: A systematic review and meta-analysis of clinical trials.

AIM: The objective of this meta-analysis was to evaluate obstetric outcomes in gestational diabetes mellitus (GDM) patients treated with flexible management based on intrauterine ultrasound fetal growth (FMIUFG) or strict maternal glycemic adjustment (SMGA). METHODS: We performed a comprehensive systematic review of electronic databases for randomized clinical trials (RCTs) comparing obstetrics outcomes of singleton GDM patients managed according to FMIUFG or SMGA. The review protocol was registered in PROSPERO (CRD497888). Searches were conducted in PubMed, Embase, Cochrane, and LILACS. Primary outcomes were gestational age at delivery and birth weight. Random-effect model meta-analyses were used to minimize the effects of uncertainty associated with inter-study variability. Results are reported as standardized mean differences (SMDs) or as odds ratios (ORs) and their 95% confidence interval (CI). Heterogeneity between studies was estimated using the I2 statistic. The Cochrane Risk of Bias Scale was used to assess the quality of studies. There were five RCTs with low to moderate risk of bias, including 450 patients managed according to the FMIUFSG and 381 according to the SMGA. RESULTS: The macrosomia (birthweight >4000 g) rate was lower in pregnancies managed according to FMIUFG than SMGA adjustments (OR: 0.34; 95%CI: 0.16, 0.71). There were no significant differences in hypertensive disorder, cesarean section, neonatal intensive care unit admission, and large newborn for gestational age rates. CONCLUSIONS: The macrosomia rate was lower in women managed with the FMIUFG. There were no significant differences in other obstetric and neonate outcomes.

Maternal and cord blood betatrophin (angiopoietin-like protein 8) in pregnant women with gestational diabetes and normoglycemic controls: A systematic review, meta-analysis, and meta-regression.

AIMS: This systematic review and meta-analysis examined maternal and cord blood betatrophin levels in pregnant women with gestational diabetes mellitus (GDM) and normoglycemic controls. MATERIAL AND METHODS: PubMed, Cochrane Library, Embase, LILACS, WangFang, and China National Knowledge Infrastructure were searched for literature from inception until May 2022. The primary outcomes were maternal and cord blood betatrophin levels. A random-effect meta-analysis was used to estimate the pooled results. The mean differences (MDs) or standardised MDs (SMD) and their 95% confidence intervals (CIs) were calculated. I2 tests were used to evaluate the heterogeneity. The quality of studies was evaluated using the Newcastle-Ottawa Scale. RESULTS: Betatrophin levels were reported in 22 studies with a total of 3034 pregnant women, and in seven studies including cord blood from 456 infants. Women with GDM display higher betatrophin levels than the normoglycemic controls (SMD = 0.85, 95% CI: 0.38-1.31) during the second half of the pregnancy. The sensitivity analysis indicated that no single study had significantly influenced the betatrophin overall outcomes. There was heterogeneity between the studies as evidenced by high I2 values. Meta-regression analysis indicated a significant regression coefficient for maternal betatrophin and glycosilated haemoglobin. There was no significant difference in cord blood betatrophin in infants from women with and without GDM (SMD = 0.34, 95% CI: -0.15-0.83). Women with GDM also had significantly higher insulin, glucose, glycosylated haemoglobin, HOMA-IR, LDL-cholesterol, HDL-cholesterol, triglycerides, and body mass index compared with the normoglycemic controls. CONCLUSIONS: Maternal betatrophin levels were higher in women with GDM than in the normoglycemic controls. There was no difference in cord blood betatrophin. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022311372.

Association of Early Pregnancy Free and Total Triiodothyronine With the Subsequent Risk of Gestational Diabetes Mellitus.

OBJECTIVE: To estimate the association of free triiodothyronine (FT3) and total triiodothyronine (TT3) in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk and define appropriate TT3 thresholds for GDM screening. METHODS: This investigation is a hospital-based cohort study of pregnant women submitted to a universal thyroid function test before 24 weeks of gestation. GDM was diagnosed according to a 75-g oral glucose tolerance test. The association of maternal high FT3 and TT3 levels in early pregnancy with the risk of GDM was estimated using logistic regression. The potential nonlinear association was probed by the restricted cubic spline curve method. RESULTS: A total of 27 184 pregnant women and 3073 GDM cases were included in the analysis. FT3 and TT3 were associated with an increased subsequent risk of GDM in a nonlinear fashion. The adjusted odds ratios were 1.59 (95% confidence interval, 1.50-1.68) and 2.80 (95% confidence interval, 2.46-3.18) for FT3 and TT3 continuous levels, respectively. Associations were strong in euthyroid women, showed heterogeneity in women with mild thyroid dysfunction, and lacked in patients with overt hypothyroidism and hyperthyroidism. The TT3 thresholds of 1.5 and 2.0 ng/mL between 7 and 12 weeks of gestation and 1.6 and 2.1 ng/mL for 13 to 23 weeks of gestation effectively distinguished the subsequent risk of GDM. CONCLUSION: The increased FT3 and TT3 levels in early pregnancy were associated with a subsequent higher risk of GDM. These findings provide measures for early detection and potential prevention of GDM.

Maternal expectations of fetal gender and risk of postpartum depression.

BACKGROUND: Female offspring was associated with a high risk of postpartum depression (PPD) during the one-child policy period in China. However, little is known about the association between maternal expectations on fetal gender and the risk of PPD in the context of the new two children policy implemented in 2016. METHODS: We conducted a hospital-based cohort study of women with singleton pregnancies between 2017 and 2018 (n = 991) to address this concern. Logistic regression was run to estimate the association between unexpected fetal gender and the risk of PPD. RESULTS: A total of 127 women (12.8%) were diagnosed with PPD. Compared with women who achieved fetal gender expectations, the odds ratio (OR) for PPD among those who had an unexpected fetal gender was 2.44 (95% confidence interval (CI): 1.30-4.58) (in the backward method logistic regression model) and 2.25 (95% CI: 1.21-4.18) (in the forward method model), respectively. The disparity of the association was significant among primiparous and pluriparous women (OR, 2.52, 95% CI: 1.32-4.84, P = 0.005 vs. OR, 0.91, 95% CI: 0.09-8.75, P = 0.932). Fetal gender expectations accounted for about 15% of the risk of PPD in the structural equation models. CONCLUSIONS: These results indicated that unexpected fetal gender was associated with an increased risk of PPD among Chinese primiparous women.

Prevalence of menopausal symptoms and severity related factors among mid-aged Paraguayan women as measured with the 10-item Cervantes Scale.

Objective: To determine the prevalence of menopausal symptoms and factors related to severity in mid-aged women.Methods: Cross-sectional study in which 216 urban-living women from Asunción-Paraguay (40-60 years) were surveyed with the 10 item Cervantes Scale (CS-10) and a general questionnaire (personal and partner data).Results: Median (interquartile range [IQR]) age of the sample was 48 [9] years, 48.1% were postmenopausal, 8.8% used menopausal hormone therapy, 39.4% psychotropic drugs, 43.5% had hypertension, 6.5% diabetes, 51.9% abdominal obesity, and 89.3% had a partner (n = 193). A history of sexual abuse was present in 2.8%. Median total CS-10 score was 8.5 [9.75]. Overall, 93.3% (180/193) of women having a partner were sexually active, with a median coital frequency of 8 times per month. According to the CS-10, the three most prevalent menopausal symptoms were: aching in muscles and/or joints (70.8%), anxiety and nervousness (70.8%) and hot flashes/night sweats (54.2%). Factors associated with higher CS-10 scores were: female age and educational level, marital status, menopausal status, and marital sexual aspects. Partner educational level was inversely correlated (rho Spearman coefficient) with CS-10 total scores. However, multiple linear regression analysis found that higher total CS-10 scores (more severe menopausal symptoms) negatively correlated to coital frequency and positively correlated with peri- and postmenopausal status, parity, sedentary lifestyle and a history of sexual abuse.Conclusion: Menopausal symptoms in this mid-aged urban female Paraguayan sample were related to hormonal, sexual and other female aspects.

Asprosin levels in women with and without the polycystic ovary syndrome: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and without the polycystic ovary syndrome (PCOS).Method: We performed a comprehensive literature search in Pubmed, Web of Science, Scielo, and Chinese National Knowledge Infrastructure for studies published until May 20, 2022, that evaluated circulating asprosin levels in women with and without PCOS, regardless of language. The quality of studies was assessed with the Newcastle-Ottawa Scale. Random-effects models were used to estimate mean differences (MD) or standardized MD (SMD) and their 95% confidence interval (CI).Results: We evaluated eight studies reporting 1,050 PCOS cases and 796 controls of reproductive age. Participants with PCOS were younger (MD = -2.40 years, 95% CI -2.46 to -2.33), with higher values of asprosin (SMD = 2.57, 95% CI 1.64-3.50), insulin (SMD = 2.73, 95% CI 1.18-4.28), homeostatic model assessment of insulin resistance (SMD = 2.70, 95% CI 0.85-4.55), luteinizing hormone (SMD = 2.33, 95% CI 0.60-4.06), total testosterone (SMD = 4.06, 95% CI 1.89-6.22), dehydroepiandrosterone sulfate (SMD = 2.38, 95% CI 0.37-4.40), and triglycerides (SMD = 1.20, 95% CI 0.13 to 2.27). Moreover, PCOS women had lower circulating levels of sex hormone-binding globulin (SMD = -3.36, 95% CI -4.92 to -1.80), and high-density lipoprotein-cholesterol (SMD = -0.85, 95% CI -1.69 to -0.01); with no significant differences observed for glucose, total cholesterol, and low-density lipoprotein-cholesterol levels.Conclusion: Circulating asprosin levels were significantly higher in women with PCOS as compared to those without the syndrome.

Effect of metformin intervention on circulating irisin levels in polycystic ovary syndrome: a systematic review and collaborative meta-analysis.

BACKGROUND: Irisin is an adipo-myokine with potential implications in metabolic disorders such as polycystic ovary syndrome (PCOS). Despite of a strong evidence showing increased irisin level in PCOS, there is no conclusive evidence on the effect of metformin intervention on circulatory irisin in PCOS. AIM: The aim of this meta-analysis was to compare the circulatory (serum/plasma) irisin levels before and after metformin intervention in subjects with PCOS. METHODS: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. A one-study leave-out sensitivity analysis was conducted to validate the overall obtained results. RESULTS: A total of five observations were included in this meta-analysis. The results based on random effects meta-analysis indicated that irisin levels were significantly decreased after metformin intervention as compared to the baseline pretreatment levels in PCOS (SMD: -1.00, 95% CI: -1.60 to -0.41, Z: 3.29, p = .001). The sensitivity analysis leaving-out a particular observation at a time and repeating the meta-analysis validated the robustness of the overall finding suggesting the significant effect of metformin treatment on irisin levels in PCOS. CONCLUSION: Circulating irisin levels were significantly decreased upon metformin intervention in PCOS patients. The higher pretreatment irisin levels in PCOS may recede once the altered metabolic state is restored upon metformin intervention. Well-designed randomized trials with large sample sizes are warranted to further substantiate the reported evidence reported and to establish the possible mechanisms.

Maternal serum irisin levels in normotensive and preeclamptic pregnancies: a systematic review and meta-analysis.

BACKGROUND: Altered irisin levels have been reported in pregnancy-associated disorders, such as preeclampsia. OBJECTIVE: A systematic review and meta-analysis were conducted to evaluate the changes in maternal circulatory irisin levels in preeclampsia as compared to normotensive healthy pregnant controls. METHODS: Relevant studies were identified by searching PubMed and other databases. Random-effects model was used to obtain standardized mean differences (SMDs) and its 95% confidence intervals (CIs). The sub-group meta-regression analyses were conducted to explore heterogeneity. The presence of publication bias and the study robustness was tested using funnel plot and sensitivity analyses, respectively. RESULTS: This meta-analysis finally included 14 observations from eight studies. Compared with controls, preeclampsia patients showed significantly decreased serum irisin levels (SMD: -1.13; 95% CI: -1.63 to -0.62, p < .0001). The sub-group analysis showed that this decrease in irisin is regardless of body mass index (BMI) and gestational age of preeclampsia patients. The meta-regression analysis indicated that blood pressure is significantly associated with the observed results. There was no significant publication bias as indicated by the funnel plot analysis followed by Begg's (p = .35) and Egger's tests (p = .39). The sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. CONCLUSIONS: This meta-analysis showed significantly decreased maternal serum irisin level in preeclampsia patients as compared to normotensive pregnant women. This study highlights the need for future studies evaluating the diagnostic utilities and associations of irisin with the fetal and neonatal outcomes in preeclampsia.

Maternal adropin levels in patients with gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Adropin is a regulatory protein with potential implications in energy homeostasis, glucose regulation, and insulin resistance. AIM: The aim of this meta-analysis was to compare the maternal serum/plasma adropin levels between gestational diabetes mellitus (GDM) patients and non-GDM controls. METHODS: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. A one-study leave-out sensitivity analysis and trimester-wise subgroup analysis were performed. RESULTS: A total of eight observations were included in this meta-analysis. The results based on random-effects meta-analysis indicated that adropin levels were significantly increased in GDM patients as compared to non-GDM controls (SMD = 2.41, 95% CI = 0.52-4.29, p= .01). The sensitivity analysis indicated that no single study had significantly influenced the overall outcome. CONCLUSIONS: The results indicate that maternal serum/plasma adropin concentrations were significantly higher in GDM patients as compared to non-GDM controls suggesting the potential associations of adropin in GDM. Despite this, further studies are needed to investigate the mechanistic, diagnostic and prognostic roles of trimester-wise adropin levels in GDM and associated fetal outcomes.

Leukocyte telomere length in women with and without polycystic ovary syndrome: a systematic review and meta-analysis.

AIM: To study the telomere length and the telomerase activity in women with and without polycystic ovary syndrome (PCOS). METHODS: Relevant studies were searched from PubMed, Embase, and LILACS online databases and manual screening. The mean differences (MDs) or standardized MDs (SMDs) with their 95% confidence intervals (CIs) were calculated. The methodological quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS), and heterogeneity with the I2 and Tau2 statistics. RESULTS: Six studies including 2109 non-pregnant women with (n = 1155) or without (n = 954) PCOS assessed leukocyte telomere length. There was a non-significant leukocyte telomere length difference (SMD = 0.25, 95% CI: -0.01, 0.51, p = .06, I2 = 81%, Tau2 = 0.08) comparing PCOS patients with the control group. Studied PCOS women were younger (MD = -1.39, 95% CI: -2.47, -0.31 years, I2 = 83%), and had higher body mass index (BMI; MD = 3.66, 95% CI: 2.11, 5.20 kg/m2, I2 = 94%). There were significantly higher testosterone (SMD = 0.88, 95% CI: 0.65, 1.10) and luteinizing hormone levels (SMD = 0.60, 95% CI: 0.12, 1.08) in women with PCOS as compared to controls. There was a low risk of bias and there were not sufficient studies to meta-analyze other cell types. CONCLUSIONS: Leukocyte telomere length did not differ between women with and without PCOS. Further studies with large sample sizes and including other outcomes are warranted to further substantiate the reported evidence.

Apelin levels in pregnant women with and without gestational diabetes mellitus: a collaborative systematic review and meta-analysis.

Aims: This systematic review and meta-analysis investigated maternal apelin levels in pregnant women with and without GDM. Secondary outcomes were glucose- and lipid-related results.Methods: Databases including PubMed, Embase, Cochrane Library, LILACS, CNKI, and Wang Fang were searched. The methodological quality of included studies was evaluated with the Newcastle-Ottawa Scale. Mean differences (MDs) or standardized MDs (SMDs) with their 95% confidence intervals (CIs) were evaluated. Random effect model analyses were carried out and heterogeneity with the I2 and Tau2 statistics.Results: Fourteen observational studies (sample size: 1033 women with GDM and 1053 for control women) with a low or moderate risk of bias were included in the analysis. During the second half of pregnancy, maternal apelin estimate was significantly higher in women with GDM (SMD = 0.64; 95% CI: 0.03 to 1.25), as well as insulin (SMD = 1.41% CI: 0.84 to 1.99), glucose (SMD = 1.56; 95% CI 1.20 to 1.91), glycated hemoglobin (SMD = 1.11, 95% CI: 0.69 to 1.54), HOMA-IR (MD = 2.25; 95%CI: 1.51 to 2.98), BMI (MD = 0.80 kg/m2, 95%CI: 0.52 to 1.08), total cholesterol (SMD = 0.42, 0.12 to 0.73), LDL-cholesterol (SMD = 0.63, 95%CI: 0.23 to 1.02), and triglycerides (SMD = 0.40, 95%CI: 0.19 to 0.61) as compared to control women. There was heterogeneity between studies as evidence by high I2 values. Meta-regression analysis indicated statistically significant regression coefficients for age of women, glucose and total cholesterol.Conclusions: GDM was associated with increased circulating apelin, insulin, glucose, glycated hemoglobin, total cholesterol, LDL-cholesterol levels, and HOMA-IR index.

Systematic review and meta-analysis regarding maternal apelin in pregnant women with and without preeclampsia.

Aims: To investigate maternal circulating apelin levels in pregnancies with and without preeclampsia.Design and Method: Systematic review and meta-analysis of observational studies reporting circulating apelin in women who develop preeclampsia. We searched databases for appropriate studies published through December 2021, without language restriction. The quality of studies was evaluated using the Newcastle-Ottawa-Scale. Data were pooled as mean difference (MDs) or standardized MDs (SMDs) and 95% confidence interval (95% CI). A random-effects model enabled reporting of differences between groups, minimizing the effects of uncertainty associated with inter-study variability on the effects of different endpoints.Results: We identified a total of 122 studies, and ten of them reported circulating apelin in women with and without preeclampsia. Maternal apelin did not show a difference in preeclamptic compared to normotensive women (SMD: -0.38, 95%CI -0.91 to 0.15), although there was high heterogeneity between the included studies (I2 = 95%). Participants with preeclampsia had higher body mass index, lower gestational age at delivery, and birth weight. Preeclamptic pregnant women with higher BMI showed significantly lower apelin levels in the subgroup analysis. There was no significant apelin difference in the preeclampsia severity sub-analysis.Conclusion: There was no significant difference in apelin levels in pregnant women with and without preeclampsia.

Female sexual function before and during the severe acute respiratory syndrome coronavirus-2 pandemic: a systematic review and Meta-analysis of longitudinal studies.

PurposeTo compare the female sexual function before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic using the Female Sexual Function Index (FSFI).MethodsRelevant studies were retrieved by online databases and manual searching reporting FSFI scores before and during the SARS-CoV-2 pandemic. The methodological quality of reviewed articles was evaluated using the Newcastle-Ottawa Scale, and heterogeneity with the I2 statistic. The standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were calculated by random-effect meta-analyses.ResultsFour studies met the inclusion criteria reporting 1002 sexually active non-pregnant women comparing results of the 19-item FSFI. The meta-analysis of the overall FSFI score showed an SMD (95% CI) of -1.16 (-1.97 to -0.35), comparing the pandemic with the pre-pandemic scores. In addition, SMD scores for the FSFI domains were also significantly lower during the pandemic for arousal -0.80 (-1.13 to -0.48), orgasm -0.66 (-1.07 to -0.25), satisfaction -0.59 (-0.97 to -0.22), and pain -0.35 (-0.54 to -0.16), whereas there were not significant differences for desire and lubrication domains. There was a low risk of bias and the sensitivity analysis suggests that results are robust.ConclusionThe available studies showed a lower overall FSFI score during the pandemic, suggesting an increased risk of female sexual dysfunction compared to prepandemic results. Also, there were increased risks of sexual arousal, orgasm, satisfaction, and pain disorders. However, there were no alterations in the desire and the lubrication domains. Limitations are related to the heterogeneity populations, and pandemic confounding and aggravating factors.

Vitamin E supplementation improves testosterone, glucose- and lipid-related metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials.

AIM: This systematic review and meta-analysis assessed the effect of vitamin E supplementation on testosterone, glucose, lipid profile, pregnancy rate, hirsutism, and body mass index (BMI) in women with polycystic ovary syndrome (PCOS). METHODS: A multi-database search was performed from inception to January 2022 for randomized controlled trials (RCTs) reporting the effects of vitamin E supplementation with or without another nutritional supplement on women with PCOS. A random-effects model was used to obtain mean differences (MDs) and its 95% confidence intervals (95%CI). Evidence certainty was assessed with GRADE methodology. RESULTS: We meta-analyzed eight RCTs reporting vitamin E supplementation alone or combined with other individual substances like omega-3, vitamin D3, or magnesium oxide in adult women ≤40 years old with PCOS. Vitamin E supplementation reduced fasting glucose (MD: -1.92 mg/dL, 95%CI: -3.80 to -0.05), fasting insulin (MD: -2.24 µIU/mL, 95%CI: -3.34 to -1.14), HOMA-IR (MD: -0.42, 95%CI: -0.65 to -0.19), total cholesterol (MD: -18.12 mg/dL, 95%CI: -34.37 to -1.86), LDL-cholesterol (MD: -15.92 mg/dL, 95%CI: -29.93 to -1.90), triglycerides (MD: -20.95 mg/dL, 95%CI: -37.31 to -4.58), total testosterone (MD: -0.42 ng/mL, 95%CI: -0.55 to -0.29), and increased sex hormone-binding globulin (MD: 7.44 nmol/L, 95%CI: 2.68 to 12.20). However, it had no impact on female sex hormones, HDL-cholesterol, BMI, and hirsutism. Two RCTs assessed pregnancy and implantation rates with inconsistent results. The certainty of the evidence was very low to moderate. CONCLUSION: Vitamin E supplementation improves glucose, lipid, and androgenic-related biomarkers in women with PCOS.

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review.

OBJECTIVE: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP. MATERIALS AND METHODS: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database. RESULTS: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively. CONCLUSIONS: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.

Management of postmenopausal vulvovaginal atrophy: recommendations of the International Society for the Study of Vulvovaginal Disease.

OBJECTIVE: To develop a best practice document for the management of postmenopausal vulvovaginal atrophy (VVA). METHOD: Literature review carried out using clinical terms, treatments or interventions and comorbidity related to VVA. RESULTS: There is a wide variety of interventions that may produce temporal benefits for VVA. However, there are significant limitations in scientific publications concerning VVA and related issues, including variable outcome evaluations, variability in population age range, and small, often underpowered sample sizes. Therapeutic management of VVA should follow a sequential order, considering women's age, symptoms, general health as well as treatment preference. Beneficial options include lubricants, moisturizers, vaginal estrogens (estradiol, estriol, promestriene, conjugated estrogens), androgens, prasterone, and laser application. In women with general menopausal symptoms who are candidates for systemic hormone therapy, the lowest effective dose should be used. Oral ospemifene is an effective selective estrogen receptor modulator to treat VVA. Systemic androgens have a limited role. Although laser procedures are commonly used, at this moment the International Society for the Study of Vulvovaginal Disease does not endorse its use out of the setting of clinical trials. Pelvic floor muscle training improves blood flow and elasticity of the vulvovaginal tissue. In breast cancer survivors, moisturizers and lubricants are first line therapy. However, limited absorption of low/ultra-low doses of estrogens suggests safety, especially in women under treatment with aromatase inhibitors. As clinical practice and available preparations vary between countries this text should be adapted to local circumstances. CONCLUSIONS: There is a wide range of therapeutic options to individualize VVA treatments.

Clinical manifestations and evaluation of postmenopausal vulvovaginal atrophy.

INTRODUCTION: It is estimated that 50% of women will suffer a severe form of vulvovaginal atrophy (VVA) related to menopause. Equally, young women may temporarily present this clinical problem while receiving various pharmacological or endocrine treatments or radiotherapy. AIM: To determine clinical and diagnostic exams required to confirm the presence of VVA (also referred to as atrophic vaginitis, urogenital atrophy, or genitourinary syndrome of menopause) and rule out other genital or pelvic clinical conditions. MATERIALS AND METHODS: Literature review searches were carried out on the main scientific article search engines (PubMed, SciELO, Cochrane) using different clinical terms, treatments or interventions and comorbidity related to VVA. RESULTS: The development and severity of VVA depend mainly on the duration of hypoestrogenism. Hypoestrogenism causes changes in the urogenital tissue, generating signs and symptoms, such as dryness, burning, soreness, itching, and irritation of the genital skin. The diagnosis can be made through anamnesis (patient history), questionnaires, physical exam, and, sometimes, complementary exams. Objective vaginal assessment is essential and can be completed with the Vaginal Health Index, the Vaginal Maturation Index, or vaginal pH in the absence of infection or semen. The exclusion of other vulvovaginal organic pathology is essential to reach an accurate diagnosis and provide adequate treatment. CONCLUSIONS: The specialist should be able to identify VVA, rule out other pathologies that make a differential diagnosis and conduct proper management.

Association of breastfeeding duration with carotid intima-media thickness in later life: a systematic review and meta-analysis.

OBJECTIVE: To assess the relationship of breastfeeding duration with maternal ultrasound carotid intima-media thickness (CIMT) in later life. METHODS: PubMed, Scopus, Web of Science, Embase, and Cochrane Central database searching up to December 15, 2020, for eligible studies that reported on the breastfeeding duration and ultrasound measurement of CIMT in later life. The exposed group corresponded to breastfeeding duration ≥ 6 months whereas the control group was women with breastfeeding of shorter duration or nil breastfeeding. The methodological quality of reviewed articles was appraised using the Newcastle-Ottawa Scale (NOS). Results are reported as the mean difference (MD) or the standardized MD (SMD) and their 95% confidence intervals (CIs). The study was registered in the PROSPERO database. RESULTS: Of 532 unique studies, three studies met inclusion criteria including 1721 women with a mean age ranging between 36.6 ± 6.9 and 55.7 ± 5.3 years, comparing breastfeeding duration ≥ 6 months versus 1-5 months (NOS: 7-8). Common CIMT was lower in women who breastfed for a longer duration (SMD = -0.10, 95% CI -0.20 to -0.00). Circulating HDL-cholesterol was higher in women with longer breastfeeding duration (MD = 3.25, 95% CI 0.88-5.61). There were no significant differences for total cholesterol, LDL-cholesterol, triglycerides, glucose, and blood pressure between breastfeeding 6 or more months and the control group. CONCLUSIONS: The available studies showed lower CIMT and higher HDL-cholesterol levels in women who breastfed for 6 or more months as compared to controls.