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Summary Background and aims We aimed to evaluate the impact of perinatal food manipulation on skeletal characteristics and insulin levels of Wistar rats at the age of 1 year. Methods Sixty-seven first-time pregnant rats were randomized, to either normally fed (Control Diet, CD), food-restricted (FR), or fat-fed (FF), from the 12th gestational day, and gave birth on the 21st day of pregnancy. Pups born to FR-mothers were divided into: fetal growth restricted (FGR) and non-FGR, based on their birth weight. Maternal food manipulation continued through the lactation period. Following delivery, all neonates were cross-fostered until the 25th day postpartum; the offspring of normally-fed mothers were lactated by FR-, FF- or CD-fed mothers. A similar process was followed for the offspring of mothers FF- or FR-during pregnancy. On the 26th day postpartum, all pups were weaned to the diet of their foster mother until one year old. Bone density was assessed by peripheral quantitative computed tomography. Results FF/FF rats had lower values of total bone density and total/subcortical area compared to CD/CD. FF/FR showed lower subcortical density compared to FF/FF group. FGR/CD showed lower values of all assessed skeletal parameters compared to those receiving CD throughout the experiment. Non-FGR/FF rats had higher values of all assessed skeletal parameters compared to those food restricted postnatally. FGR-pups that were fat-fed postnatally had higher insulin vs rats FF/FR. Similar insulin levels were identified in rats fat-fed postnatally, irrespective of prenatal food-restriction or high-fat diet. Conclusions Perinatal food manipulation is associated with distinct skeletal acquisition and insulin levels' profiles in Wistar rats at the first year of life.

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

Objective Recent evidence in postmenopausal women suggested lack of association between serum levels of retinol-binding protein 4 (RBP4) and subclinical atherosclerosis; however, associations with arterial stiffness in this population remain unexplored. We evaluated the association among RBP4 and cardiovascular risk factors, including homocysteine, a marker involved in retinoic acid synthesis, and indices of arterial stiffness, in a sample of apparently healthy postmenopausal women. Methods This cross-sectional study included 123 healthy postmenopausal women, not on hormone therapy, antihypertensive, or hypolipidemic treatment and with a menopausal age 10 years or less. We performed biochemical/hormonal assessment and sonographic evaluation, including carotid-femoral pulse wave velocity (PWV) and carotid artery stiffness index (SI). Results Univariate analysis showed that RBP4 values correlated with age, low-density lipoprotein-cholesterol and estradiol levels. There was a trend of association of SI and PWV with homocysteine and triglycerides. RBP4 differed according to PWV, using the median PWV value as cut-off (RBP4, PWV ≤8.1 vs >8.1 m/s: 10.09 ± 2.05 vs 10.85 ± 1.91 ng/mL, analysis of covariance P value 0.014 adjusted for age, menopausal age, estradiol, pulse pressure). Linear regression analysis showed that PWV was independently associated with RBP4, age, and pulse pressure, whereas SI was independently associated with RBP4. An increase of one standard deviation in RBP4 levels (2.54 ng/mL) was associated with an increase of 0.577 m/s in PWV. Conclusions RBP4 serum levels are associated with arterial stiffness, in a sample of healthy postmenopausal women. If this association is causative, serum RBP4 levels could serve as a marker of arterial stiffness. Prospective studies are required to investigate the significance of our findings. : Video Summary:http://links.lww.com/MENO/A621.

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.Pa...

Menopause is the condition in which the gradual decline in ovarian function finally leads to the permanent cessation of menstruation. Oestrogen deficiency may cause early symptoms during the menopausal transition and late symptoms after menopause. Menopause is a normal period of life. During this period, women need adaptation to new biological, social, and psychological parameters. Vasomotor symptoms are among the most common menopausal symptoms. Menopause per se is not correlated with specific psychiatric disorders, but data suggest that perimenopausal women are more likely to develop depressive disorders even without a previous history. Vasomotor symptoms are correlated with mood and sleep disturbances, neuroticism, anxiety, decreased cognitive function, and stress. Personality traits, social, and other factors are also important mediators of vasomotor symptoms during the menopausal transition phase. This is a review based on the existing evidence concerning the correlation between psychosomatic and vasomotor symptoms of menopause during the menopausal transition period. Healthcare providers should take these correlations into consideration when planning the treatment of vasomotor symptoms. Vasomotor symptoms during menopause are associated with significant social costs. There are numerous traditional hormone therapy, and complementary and alternative therapy including over-the-counter treatments and dietary supplements for managing menopause-related vasomotor symptoms. Additional costs include follow-up physician visits, laboratory testing, management of adverse events, and loss of productivity at work. Social support and planning may help women to deal with menopausal symptoms and may reduce overall social costs during this transitional phase.

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 (β 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.

Background: Ovarian senescence is associated with increased cardiovascular disease 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 2,793 peri- and postmenopausal women (menopausal age≤15 years), not on menopausal hormone therapy. Participants were classified into perimenopausal (-3 to +2 years), early- (EM, 2 to 7 years) or late-menopausal (LM, >7 years) after the last menstrual period. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric scale (GCS). Findings: Fitting mixed-effects models, GCS-total score associated with BMI (b=0.12, 95%CI: 0.04 to 0.20), T2DM (b=2.10, 95%CI: 0.06 to 4.15), LM (b=-1.24, 95%CI: -2.17 to -0.33). GCS-psychological score associated with BMI (b=0.06, 95%CI: 0.00 to 0.11). GCS-Physical score 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), menopausal status (EM and LM 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 previous GCS-scores associated negatively with age. GCS-vasomotor score associated negatively with LM. Fitting poisson mixed models, GCS-sexual score associated positively with EM (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. Interpretation: The severity of menopausal symptoms is associated with T2DM, obesity and smoking, in a cohort of peri- and postmenopausal women. These associations must be considered on the implementations of primary and secondary prevention strategies. Funding Information: This study did not receive any funding. Declaration of Interests: None to declare. Ethics Approval Statement: All participants signed an informed consent; institutional review board approval was obtained by the Ethics Committee of the Aretaieion Hospital.

Background Accumulating evidence suggests that circulating amyloidβ 1–40 (Αβ1–40), a proatherogenic aging peptide, may serve as a novel biomarker in cardiovascular disease (CVD). We aimed to explore the role of plasma Αβ1–40 and its patterns of change over time in atherosclerosis progression in postmenopausal women, a population with substantial unrecognized CVD risk beyond traditional risk factors (TRFs). Methods In this prospective study, Αβ1–40 was measured in plasma by enzyme-linked immunosorbent assay and atherosclerosis was assessed using carotid high-resolution ultrasonography at baseline and after a median follow-up of 28.2 months in 152 postmenopausal women without history or symptoms of CVD. Results At baseline, high Αβ1–40 was independently associated with higher carotid bulb intima-media thickness (cbIMT) and the sum of maximal wall thickness in all carotid sites (sumWT) (p Conclusion In postmenopausal women, a pattern of increasing or persistently high Αβ1–40 was associated with the rate of progression of subclinical atherosclerosis irrespective of its baseline levels. These findings provide novel insights into a link between Αβ1–40 and atherosclerosis progression in menopause and warrant further research to clarify the clinical value of monitoring its circulating levels as an atherosclerosis biomarker in women without clinically overt CVD.

Background Anti-Müllerian hormone (AMH) constitutes a marker of ovarian reserve and appears to have a predictive role regarding the time of menopause. Moreover, AMH is associated with adverse cardiac events. History of premature menopause and early onset of menopause have been associated with increased risk of cardiovascular (CV) disease. In addition, menopausal transition and duration of menopause have been associated with increased burden of subclinical atherosclerosis. However, the association between AMH as a marker of female reproductive age with atherosclerosis in premenopausal women is currently unknown. Purpose To investigate whether AMH concentrations are associated with markers of early atherosclerosis in healthy, normally menstruating women. Methods In a cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima-media thickness (IMT), lipid profile and serum AMH concentrations were assessed. Exclusion criteria were clinically overt CV disease, abnormal ovulatory cycles, polycystic ovarian syndrome, acute infection or chronic inflammatory disease, risk factors for CV disease and any medication Results Seventy premenopausal women, aged 32.7±6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or traditional CV risk factors was found. After multi-variable adjustment for traditional CV risk factors, the association between AMH concentrations combined IMT and carotid bulb IMT, remained significant. Conclusions In healthy, normally ovulating women, low AMH concentrations are associated with an adverse lipid profile and subclinical atherosclerosis, independently of traditional CV risk factors. This finding suggest a role of decreased follicular reserve with atherosclerotic disease. Funding Acknowledgement Type of funding source: None

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

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 his...

Introduction: The impact of gender on the development of cardiovascular disease has long been recognized. The potential effect of sex-specific cardiovascular risk factors on molecular mediators of oxidative stress has received limited attention and the results remain conflicting. Hypothesis: To assess the link between retinol binding protein 4 (RBP4) and menopause-specific cardiovascular risk factors, on indices of early subclinical atherosclerosis, in a sample of apparently healthy young, postmenopausal women. Methods: This cross-sectional study included a total of 123 healthy postmenopausal women, recruited from a University Menopause Clinic. Participating women were, not on hormone therapy, antihypertensive or hypolipidemic treatment and had a menopausal age of up to 10 years. Fasting venous blood samples were obtained for hormonal and biochemical assessment, including levels of RBP4. Sonographical studies were performed on the same day and included carotid-femoral pulse wave velocity (PWV) and calculation of the carotid artery stiffness index (SI). Major results: Univariate analysis showed that RBP4 values correlated positively with age, total cholesterol, triglycerides, LDL-cholesterol, testosterone-to-estrogen ratio; negatively with circulating estrogen and almost significantly with homocysteine levels. Levels of homocysteine were inversely associated with RBP4 (homocysteine: RBP4 Conclusion: RBP4 levels are linked with measures of local carotid and aortic arterial stiffness, in this sample of healthy postmenopausal women. This association seems to be mediated by higher levels of homocysteine, which may interfere with retinoic acid synthesis. Larger studies are required to further elucidate the significance of our findings. References 1. Majerczyk M, Olszanecka-Glinianowicz M, Puzianowska-Kuznicka M, Chudek J: Retinol-binding protein 4 (RBP4) as the causative factor and marker of vascular injury related to insulin resistance. Postepy Hig Med Dosw 2016;70:1267-1275. 2. Smolders RG, van der Mooren MJ, Sipkema P, Kenemans P: Estrogens, homocysteine, vasodilatation and menopause: basic mechanisms, interactions and clinical implications. Gynecol Endocrinol 2003;17:339-354. 3. Limpach A, Dalton M, Miles R, Gadson P: Homocysteine inhibits retinoic acid synthesis: a mechanism for homocysteine-induced congenital defects. Exp Cell Res 2000;260:166-174.

The impact of physical exercise, as preventative measure, to control the progression of cardiovascular disease in midlife remains under investigation. We aimed to investigate the effect of different levels of intensity of physical activity on metabolic and vascular profile in healthy postmenopausal women. A total of 625 healthy postmenopausal women (mean age 57.7 ± 7.6 years) were evaluated using the short IPAQ questionnaire for quantification of physical activity. The energy expenditure was estimated in metabolic equivalent of energy (MET) hours per week. Pulse wave velocity (PWV) was measured as an index of arterial stiffness. Intima-media thickness of both right and left common carotid artery, carotid bulb and internal carotid artery, and combined carotid IMT were also assessed by non-invasive and well-validated methods. Mean values of PWV decreased linearly with increasing intensity of physical activity (classes of physical activity: sedentary vs walking vs moderate vs vigorous activity: 9.07 ± 1.22 m/s vs 9.12 ± 1.72 m/s vs 8.47 ± 1.31m/s vs 7.94 ± 0.40 m/s, ANOVA P for linear trend .003). In non-obese postmenopausal women, PWV values associated with: (a) the total number of METs (b-coefficient = -0.261, P = .002) as well as with SBP; (b) or with the number of moderate METs (b-coefficient = -0.192, P = .025) as well as with age and SBP. No significant associations were observed between the intensity of physical exercise and arterial stiffness in the overweight-obese group. Physical activity is negatively associated with arterial stiffness in postmenopausal women with normal weight. This association was not observed in overweight or obese women.

Anti-Müllerian hormone (AMH), which is secreted by granulosa cells of late preantral and small antral follicles, is a marker of ovarian reserve. The association of ovarian reserve with subclinical atherosclerosis in women of reproductive age is currently unknown. We primary investigated whether AMH levels are associated with markers of subclinical atherosclerosis in healthy, normally menstruating women. In this cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima–media thickness (IMT), flow-mediated dilation, carotid–femoral pulse wave velocity and augmentation index. Lipid profile and serum AMH concentrations were also measured. Seventy premenopausal women, aged 32.7 ± 6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and femoral and carotid IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or established cardiovascular (CV) risk factors was found. After multivariable adjustment, the association between AMH concentrations and combined carotid IMT or carotid bulb IMT remained significant. In conclusion, in healthy, normally ovulating women, AMH concentrations are negatively associated with subclinical atherosclerosis indices and TC levels, independently of established CV risk factors.

Objective Aging and menopause are associated with an adverse cardiometabolic profile, predisposing to cardiovascular disease. Diet may also affect their cardiometabolic risk. The aim of this study is to assess dietary habits and patterns of postmenopausal women and their association with adiposity measures, cardiometabolic parameters and subclinical atherosclerosis. Study protocol The study will include two parts. The first part consists of cross-sectional evaluation of 750 postmenopausal women recruited consecutively from the Menopause Unit of an academic hospital. Dietary intake will be assessed by a food frequency questionnaire. Nutrient and food group intake will be calculated and adherence to the Mediterranean diet and other dietary patterns will be evaluated. A-priori and a-posteriori defined dietary patterns will be tested for associations with major and minor outcome measures. The second part consists of a prospective follow-up of all women recruited at baseline and re-assessment of the same variables after 3 years. Adherence to predefined or a-posteriori defined dietary patterns over these 3 years will be evaluated in association with changes in obesity indices and lipid levels, as well as in the progression of subclinical atherosclerosis. Major outcome measures Body mass index, lipid profile, carotid and femoral artery intima-media thickness and plaques. Minor outcome measures Waist circumference, waist-to-hip ratio, abdominal fat layers, incident hypertension and diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), c-reactive protein and markers of subclinical arterial disease, including flow-mediated dilation, pulse wave velocity, augmentation index and ankle-brachial index. Results The study is expected to complete baseline enrolment by the end of 2018 and follow-up assessment by the end of 2021. The results of the study will address the question of whether dietary patterns and eating habits are associated with cardiometabolic risk as well as with accelerated subclinical arterial disease and arterial aging in postmenopausal women.

Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS) and the NADH/NADPH oxidase system are related with atherosclerosis in the general population, but their significance in women is not sufficiently assessed. We investigated the potential association between the G894T polymorphism of the NOS3 gene and the C242T polymorphism of the CYBA gene with subclinical vascular disease. Seventy (70) healthy, normally ovulating, premenopausal women were recruited for this study. Venous blood samples were obtained for biochemical/hormonal assessment as well as for genotyping, using real-time PCR. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD), carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3% (38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4% (22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After multivariable adjustment, the hC242T polymorphism was a predictor of both internal carotid IMT (b-coefficient - 0.119, p = 0.011) and combined-IMT (b-coefficient - 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T determined values of FMD (b-coefficient - 1.604, p = 0.034). Concerning the NOS3 G894T polymorphism, carriers of the polymorphic variant had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis. In healthy premenopausal women, the CYBA C242T polymorphism is an independent determinant of endothelial function and subclinical atherosclerosis of the carotid arteries. The NOS3 G894T polymorphic variant also correlated with atherosclerosis, an association probably mediated by the traditional risk factors for CVD. The relevance of these findings in the clinical setting remains to be elucidated.

Background There is increasingly recognized undetected residual cardiovascular (CV) risk in postmenopausal women, suggesting the need for new risk biomarkers in this population. We have previously shown that amyloid-beta (1–40) (Aβ1–40), a proinflammatory and pro-atherosclerotic peptide, is associated with concurrent subclinical cardiovascular disease (CVD) in the general population and with major adverse cardiac events in patients with established cardiac disease. However, the clinical value of Aβ1–40 in menopause or whether this peptide is linked with an increased rate of progression of atherosclerotic disease is unknown. Purpose To examine the association of Aβ1–40 levels with the rate of progression of carotid intima-media thickness (IMT) in postmenopausal women. Methods In the settings of a Menopause Clinic, postmenopausal women (n=140) without clinically overt CVD or diabetes were consecutively recruited and re-evaluated after a median follow-up period of 24 months. IMT in the carotid arteries was measured by ultrasonography. The average of maximal IMT (mean cIMT) measured at both left and right common carotid, carotid bulb (cb)and internal carotid (ic) artery were used as the main end-point of the analysis. Aβ1–40 was measured in plasma samples at baseline and follow up. Fasting insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Results Women with increased plasma levels Aβ1–40 in the highest tertile presented the highest probability to have increased mean cIMT (adjusted OR=2.97, 95% CI 1.18–7.52, p=0.021) independently of age, smoke, hypertension, and hyperlipidemia. After adjustment for HOMA-IR, this association remained significant. Similarly, Aβ1–40 levels were associated with increased mean cb and icIMT (adjusted OR=3.34 for highest versus lower tertile, 95% CI 1.27–8.81, p=0.015). Mean cIMT significantly increased across the follow up period (0.73mm (0.065–0.08) to 0.77mm (0.07–0.089), median increase rate per year 0.024mm, p Conclusion Aβ1–40 is an independent predictor of the rate of progression of subclinical carotid atherosclerosis in menopausal women. This finding supports the clinical value of Aβ1–40 in menopause and warrants further investigation for its prognostic role in this population.

Turner syndrome is one of the most common sex chromosomal anomalies, characterized by the complete or partial loss of one X chromosome. Females with Turner syndrome are characterized by skeletal abnormalities, short stature and primary ovarian insufficiency. The aim of this narrative review was to identify the underlying mechanisms of osteoporosis in Turner syndrome, summarize its clinical manifestations and provide suggestions regarding the management of osteoporosis. Girls and women with Turner syndrome have lower bone mineral density and a higher fracture rate than healthy individuals. The most important risk factors for osteoporosis are inadequately treated primary ovarian insufficiency, followed by intrinsic bone abnormalities. Comorbidities that further increase the risk of osteoporosis include vitamin D deficiency, celiac disease and inflammatory bowel disease. In addition, hearing problems can predispose to falls. Early initiation of hormone replacement therapy (HRT) at the age of 11-13 years, prompt titration to the adult dose after 2 years and long-term follow-up to ensure compliance with HRT are the cornerstones of osteoporosis prevention in women with Turner syndrome.

The aim of this article is to analyze and critically appraise the literature regarding optimal bone health care in women with breast cancer and, more specifically, to present (1) the causes of bone loss in breast cancer patients, (2) the appropriate screening for osteoporosis and fracture risk estimation, (3) optimal prevention and therapeutic strategies for osteoporosis and fractures, (4) the role of antiresorptive agents as adjuvant therapy for the prevention of bone metastases and increase of overall survival, and (5) current data on the possible use of menopausal hormone therapy (MHT) in these patients. The objective is to provide a sound pathophysiological background along with evidence-based and practical recommendations for physicians managing such women.