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.

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.

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.

Adherence to the Mediterranean diet is associated with handgrip strength in postmenopausal women.

OBJECTIVE: This study aimed to assess the possible association of adherence to the Mediterranean diet (MD) with muscle strength and body composition. METHODS: The cross-sectional study evaluated 112 postmenopausal women (aged 41-71 years). Fasting blood samples were obtained for biochemical/hormonal assessment. The Mediterranean Dietary Score (MedDietScore) was calculated and used to stratify adherence by tertiles (low [T1], moderate [T2] or high [T3]). Handgrip strength (HGS) was measured by dynamometry and body composition with dual-X-ray absorptiometry. RESULTS: Women with low-moderate MedDietScore (T1/T2) had lower HGS values than those with higher scores (19.5 ± 4.9 kg vs. 21.9 ± 3.9 kg, p = 0.023). A linear stepwise increase of HGS values per MedDietScore tertile was found (T1 vs. T2 vs. T3: 18.4 ± 4.4 kg vs. 20.6 ± 5.2 kg vs. 21.9 ± 3.9 kg, ANOVA p-value for linear trend = 0.009, ANCOVA p-value = 0.026). Multivariable models confirmed that HGS values were independently associated with the MedDietScore (ß-coefficient = 0.266, p = 0.010). Lean mass values were associated with the MedDietScore (ß-coefficient = 0.205, p = 0.040). All models were adjusted for age and cardiometabolic risk factors. CONCLUSIONS: The data suggest that the higher the adherence to the MD, the better the muscle strength and lean mass in postmenopausal women. Prospective studies are required to evaluate the significance of these observations in cardiovascular prevention strategies at midlife.

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.

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.

Does reproductive stage impact cardiovascular disease risk factors? Results from a population-based cohort in Lausanne (CoLaus study).

CONTEXT: Menopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories. DESIGN: The CoLaus study is a prospective population-based cohort study in Lausanne, Switzerland. PATIENTS: We used data from women at baseline and follow-up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow-up. MEASUREMENTS: We measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors. RESULTS: We used the data from 1710 women aged 35-75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin-6 and interleukin-1ß decreased with advancing age. CONCLUSION: The current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5-year changes in cardiovascular risk factors may not depend on the reproductive stage.

Daughters of polycystic ovary syndrome pregnancies and androgen levels in puberty: a Meta-analysis.

Purpose: To provide an overview and critical analysis of the literature related to the circulating androgen levels of daughters of PCOS mothers during prepubertal and pubertal stage who have not yet been diagnosed with PCOS or precocious puberty. Methods: We critically considered and meta-analyzed observational studies comparing androgens concentration in daughters of PCOS mothers compared to daughters of mothers without PCOS. A literature search was conducted in MEDLINE, Scopus and other sources from 01/09/2021 until 01/12/2021. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The primary outcome included total testosterone levels whereas the secondary outcomes included 17a-hydroxyprogesterone (17-OHP), androstenedione (Δ4Α) and Sex Hormone Binding Globulin (SHBG) levels respectively. Results: Our search yielded 1073 studies, 9 of which were included in our analysis. The results are presented differently according to pubertal stage. Pubertal daughters of PCOS mothers exhibited significantly higher total testosterone (pooled mean difference 14.95 (95%CI: 6.98 to 22.93), higher 17-OHP (pooled mean difference 0.11 (95%CI: 0.02 to 0.20) and lower SHBG levels (pooled mean difference -10.48 (95%CI: -16.46 to -4.61). Instead, prepubertal daughters of PCOS mothers presented greater SHBG levels (pooled mean difference 7.79 (95%CI: 0.03 to 15.54) compared to controls. No difference was found in Δ4Α levels in both groups. Conclusion: The onset of puberty is a critical point in the development of the disease and an early intervention may be imperative.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.

Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation.

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radiotherapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments.

Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis.

Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

Assessing the efficacy of a structured stress management program in reducing stress and climacteric symptoms in peri- and postmenopausal women.

To evaluate the effectiveness of a structured education program on lifestyle habits, which is also incorporating teaching on deep breathing, progressive muscle relaxation, and guided visualization, in the control of various components of the climacteric symptomatology in peri- and postmenopausal women. Sixty-one women aged 40-65 years with varying climacteric and stress symptoms were included in this study. Women were randomly assigned to the intervention group (31) or the control group (30). The intervention group followed an 8-week stress management program. The following parameters were assessed at baseline and at the end of the 8-week follow-up period in both groups: climacteric symptoms (Green Climacteric Scale (GCS)), sleep quality (Pittsburg Sleep Quality Index (PSQI)), mood status (Depression-Anxiety-Stress Scale), self-esteem (Rosenberg Self-esteem Scale), and health-related control (health locus of control (HLC)). A mixed-model ANOVA showed significant time × group × GCS interaction (within subjects: F = 23.830, p value<0.001; between subjects: F = 39.078, p value<0.001). With regard to HLC, there was a non-significant between subjects but a significant within-subjects effect (HLC × group × time, F = 3.848, p value = 0.024). Regarding DASS scores, there was a significant between-subjects' effect (F = 10.258, p value = 0.003) but a non-significant within-subjects' effect. With regard to PSQI, the analysis showed significant within-subjects' effects (PSQI × group × time: F = 4.691, p value = 0.003) and non-significant between-subjects' effects (F = 0.022, p = 0.883). Finally, regarding RSS, there was a significant within-subjects' (RSS × group × time, F = 4.183, p value = 0.029) but non-significant between-subjects' effect (F = 1.582, p value = 0.213). Stress management may offer an alternative approach to the management of climacteric symptoms.

MTHFR Polymorphisms in Girls with Anorexia Nervosa: Implications on Body Weight.

The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the methyltetrahydrofolate reductase (MTHFR) gene. This cross-sectional pilot study recruited 48 girls with AN and 10 age-matched control girls with normal menstruation. We recorded anthropometric parameters and obtained blood samples for genotyping and hormonal assessment. Classification of AN was performed according to the DSM-V criteria. Girls with AN had 2.66 times higher odds of carrying at least one genetic polymorphism from the MTHFR panel (C677T and A1298C) compared with girls without AN (OR = 2.660, p-value = 0.041; CI 95% 1.057-6.720). The presence of atypical vs typical AN was associated independently with the presence of any of the assessed MTHFR polymorphisms (C677T, OR = 4.929, 95% CI 1.076-22.579, p-value = 0.040; A1298C, OR = 0.097, 95% CI 0.011-0.866, p-value = 0.037) in age and estrogen adjusted models. The atypical presentation of AN is mainly linked with higher prevalence of the MTHFR C677T and lower prevalence of the A1298C polymorphism.

Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis.

There is evidence showing a positive correlation between prenatal androgens and their effect on the development of central nervous system and the autistic spectrum disorder (ASD) phenotype in offspring of mothers with polycystic ovary syndrome (PCOS). We applied a systematic review to investigate whether women with PCOS have increased odds of having a child with ASD, while, secondarily, if these women themselves are at high risk of having the disease. Major databases from inception until 14th October 2018 were searched. The primary outcome measure was the odds of an ASD diagnosis in children of mothers with diagnosed PCOS, while the secondary outcome was the odds of ASD diagnosis in women with PCOS. Scheduled subgroup analyses were according to the time of birth and maternal age. We assessed the odds ratio (OR), using a random-effects model; heterogeneity was assessed by I2 and τ2 statistics. The quality of the evidence was evaluated using the Newcastle-Ottawa Scale. Ten studies were eligible for inclusion, including a total of 33,887 ASD children and 321,661 non-ASD children. Diagnosed PCOS was associated with a 1.66 times increase in the odds of ASD in the offspring [95% CI: 1.51, 1.83, p = 1.99 × 10-25, 7 studies, I2 = 0%, τ2 = 0]. Women with PCOS were 1.78 times more likely to be diagnosed with ASD (95% CI: 1.10, 2.87, p = 0.0179, 5 studies, I2 = 85.4%, τ2 = 0.2432). Additional analyses did not change the initial result. The overall quality of the evidence was high. The pooled effects size displayed low heterogeneity (I2 = 0%) for the primary outcome. While the heterogeneity in the secondary outcome appears to attenuate when only high quality studies are synthesized, still the result exhibits significant heterogeneity. Τhe available data allowed a subgroup analysis only for classification system for PCOS diagnosis and showed a significant increase of ASD diagnosis in the offspring of women with Read Code and ICD diagnosed PCOS. In conclusion, the available evidence suggests that women with PCOS have increased odds of having a child with ASD, an effect size estimate based on a large number of patients from studies of good quality. Regarding the evidence on the prevalence of ASD in PCOS women, results suggest that women with PCOS are more likely to be diagnosed with ASD.

Breastfeeding is associated with lower subclinical atherosclerosis in postmenopausal women.

Objective: To evaluate the association between a personal history of lactation and indices of subclinical atherosclerosis in postmenopausal women.Methods: We evaluated the association between a history of breastfeeding and indices of subclinical atherosclerosis (pulse wave velocity, PWV; intima-media thickness [IMT]; atherosclerotic plaque presence) in 197 parous postmenopausal women with history of breastfeeding.Results: Women who reported breastfeeding ≥6 months when compared with women who reported breastfeeding for 1-5 months exhibited significantly lower values of common carotid artery IMT (Model R2=15.7%, b-coefficient = -0.170, 95% CI: -0.208-0.001, p-value = .019) and lower odds of subclinical atherosclerosis (Model X2=28.127, OR = 0.491, 95% CI 0.318-0.999, p-value = .049), adjusting for traditional cardiovascular risk factors.Conclusions: Postmenopausal women with a history of breastfeeding for at least 6 months have a lower prevalence of subclinical atherosclerosis, independently of traditional cardiovascular risk factors. A longer duration of breastfeeding may have a beneficial effect on subclinical atherosclerosis later in life.

Global Consensus Position Statement on the Use of Testosterone Therapy for Women.

This Statement is being simultaneously published in the journals Climacteric, Maturitas, Journal of Sexual Medicine, and Journal of Clinical Endocrinology and Metabolism on behalf of the International Menopause Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, and The Endocrine Society, respectively. This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women's Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynaecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Predictors of incident hypertension in healthy non-diabetic postmenopausal women with normal renal function.

Introduction: We aimed to investigate the incidence of hypertension and to identify potential risk factors in healthy, non-diabetic recently postmenopausal Greek women with normal renal function.Patients and methods: This retrospective cohort study evaluated 141 recently postmenopausal women at baseline and annually thereafter (follow-up time: 1 to 8 years). Blood samples were obtained, and ultrasound evaluations were performed at baseline. A detailed medical history, anthropometric parameters, blood pressure and cardiovascular risk factors were recorded for every woman at each visit. Incident hypertension was defined as the first occurrence of office systolic or diastolic blood pressure, measured at 2 different visits within 2 months or history of initiation of antihypertensive medication.Results: Incident hypertension was diagnosed in 30 out of 141 women (21.3%). The median time to incident hypertension was 3.5 years. Adiposity, elevated cholesterol and triglyceride levels, insulin resistance and parity were positively associated with incident hypertension. In multivariate analysis, however, obesity and insulin resistance were the only statistically significant variables associated with more than 3-fold and 2-fold respectively increased risk of incident hypertension (HOMA-IR, O.R = 1.988, p-value =.043; obesity, O.R = 3.746, p-value =.019).Conclusion: A significant proportion of women entering the menopause present incident hypertension and this is mostly associated with obesity and insulin resistance.

Association of menopausal symptoms with sociodemographic factors and personality traits.

AIM OF THE STUDY: To investigate the association of personality traits with the severity of vasomotor symptoms (VMS) in a predominantly Greek population. MATERIAL AND METHODS: A questionnaire-based study of women from the Menopause Clinic of a University Hospital in Athens, Greece. Sociodemographic parameters were documented through a structured interview. All women completed the Menopause Rating Scale (MRS) for the assessment of severity of menopausal symptoms, the Hot Flush Beliefs Scale (HFBS) for the assessment of how women were coping with their symptoms and the Big Five Inventory questionnaires for the assessment of personality traits. Associations between baseline parameters and menopausal symptoms were assessed with univariate and multivariate regression analyses. RESULTS: One hundred women were included. Employed women had lower MRS sub-scores (psychological p< 0.001, somatic p< 0.047, urogenital p< 0.008). Married women scored higher in the psychological and somatic domains. Women of university educational level coped significantly better with hot flushes (ß coefficient [SE]: 0.72 [0.25], p< 0.01) and night sweats (0.57 [0.19], p< 0.01) than women of primary education, although the significance of these findings was not replicated when taking into account confounders. Regarding personality traits, women with low openness (-0.33 [0.11], p< 0.01) and empathy (-0.83 [0.37], p = 0.03) and high agreeableness (1.13 [0.21], p< 0.001) had more severe menopausal symptoms. In contrast, women with high agreeableness could better cope with their menopausal symptoms (-0.75 [0.36], p = 0.04). These associations were independent of sociodemographic factors. CONCLUSIONS: Personality traits, especially agreeableness, openness and empathy are associated with menopausal symptoms and functionality in postmenopausal women. These associations might serve as indicators of women at risk of experiencing more severe VMS.

Endogenous sex hormones and memory performance in middle-aged Greek women with subjective memory complaints.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R 2 = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.