Understanding of and clinical approach to cardiometabolic transition at the menopause.

Cardiovascular disease (CVD) represents the leading cause of death and accounts for almost 50% of all deaths in women worldwide. The menopausal transition is associated with central body fat accumulation, a decrease in energy expenditure, weight gain, insulin resistance and a pro-atherogenic lipid profile. Moreover, menopause is independently associated with an adverse effect on functional and structural indices of subclinical atherosclerosis. Women with premature ovarian insufficiency have heightened CVD risk compared to women of natural age at menopause. Furthermore, women with severe menopausal symptoms may have a more adverse cardiometabolic profile than those without symptoms. We reviewed the latest evidence on the cardiovascular management of perimenopausal or postmenopausal women. Clinicians should aim for cardiovascular risk stratification, followed by dietary and lifestyle advice as required based on individual needs. The medical management of cardiometabolic risk factors at midlife should always be individualized, focusing on hypertension, diabetes and dyslipidemia. Menopausal hormone therapy, when prescribed for the management of bothersome menopausal symptoms or for the prevention of osteoporosis, has also a beneficial effect on cardiometabolic risk factors. This narrative review aims to summarize the cardiometabolic alternations occurring during the menopausal transition and to outline the appropriate prevention strategies to prevent future cardiovascular adverse outcomes.

The LADY study: epidemiological characteristics of prevalent and new genitourinary syndrome of menopause cases in Greece.

OBJECTIVE: The genitourinary syndrome of menopause (GSM) is often underdiagnosed and undertreated despite its significant impact on postmenopausal quality of life. We assessed the prevalence of GSM and associated symptoms in Greek perimenopausal/postmenopausal women attending gynecology clinics. METHODS: Four hundred and fifty women, aged 40-70 years (93.1% postmenopausal), attending three gynecology clinics at university hospitals completed a validated questionnaire and underwent pelvic examination. RESULTS: GSM was diagnosed in 87.6% of the women at the study visit, whereas only 16% of the overall sample had been previously diagnosed with the condition. Vaginal dryness (72.7%), vulvar burning sensation or itching (58.0%) and dyspareunia (52.7%) were the most prevalent symptoms. Pelvic signs consisted of vaginal dryness (89.1%), loss of vaginal rugae (80.6%) and vulvovaginal pallor (86.9%). However, only 31.3% of the participants had discussed genitourinary symptoms with their health-care professionals (HCPs). Regarding management, only 11.1% of women had prior experience with any form of therapy, and currently only 8.7% were receiving treatment. CONCLUSION: GSM is highly prevalent in this Greek perimenopausal/postmenopausal population. Nevertheless, the majority of women remain undiagnosed and untreated. Education for both women and HCPs regarding GSM will lead to improved diagnosis and better management of this syndrome.

Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones.

The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.

Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women.

OBJECTIVES: To clarify potential differences between denosumab (DNS) and bisphosphonates (BIS) in terms of bone density and bone metabolism, in a sample of postmenopausal women. METHODS: A total of 113 postmenopausal women aged 53-66 years were treated with either DNS or BIS for 12 months. Bone densitometry and laboratory tests were compared between baseline and follow-up. RESULTS: Femoral neck BMD increased in both treatment-arms (FN-BMD, DNS: 0.69±0.07 g/cm2 to 0.75±0.09 g/cm2; BIS: 0.69±0.06 g/cm2 to 0.71±0.07 g/cm2; p≤0.001 in both cases). Lumbar spine BMD (LS-BMD) increased significantly only in the DNS-group (0.83±0.14 g/cm2 to 0.89±0.14 g/cm2, p=0.0001). Only women under treatment with DNS had a significant increase in serum parathyroid hormone (PTH: 44.87±17.54 pg/mL to 53.27±15.77 pg/mL, p=0.04), independently of baseline vitamin D levels. DNS-administration resulted in higher increase from baseline in FN-BMD compared to BIS (DNS vs BIS: 8.7%±8.5 vs 3.8%±7.3, p=0.004). Finally, baseline 25OH vitamin D levels did not determine the extent of PTH-increase following administration of DNS- or BIS-treatment. CONCLUSIONS: Both treatments increased BMD, however, the effect of DNS on FN-BMD was superior compared to that of BIS. DNS-treatment increased serum PTH. Baseline 25OH vitamin D levels did not predict the extent of PTH increase at follow-up.

The intensity of menopausal symptoms is associated with episodic memory in postmenopausal women.

OBJECTIVE: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women. METHODS: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene's Climacteric scale. RESULTS: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = -0.568, p = 0.009 and b-coefficient = -0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = -0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = -0.558, p = 0.001 and b-coefficient = -0.474, p = 0.005) and HVLT discrimination index (b-coefficient = -0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = -0.457, p = 0.006) and HVLT total (b-coefficient = -0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = -0.593, p < 0.001), BVMT delayed recall (b-coefficient = -0.492, p = 0.002). CONCLUSION: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory.

Circulating androgens are associated with mood disturbances in young postmenopausal women.

OBJECTIVES: We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. METHODS: Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. RESULTS: The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = -0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = -0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. CONCLUSION: Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women.

OBJECTIVES: To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. METHODS: One hundred and ten postmenopausal women aged 45-55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima-media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. RESULTS: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. CONCLUSIONS: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.

BsmI vitamin D receptor's polymorphism and bone mineral density in men and premenopausal women on long-term antiepileptic therapy.

BACKGROUND: utilization of antiepileptic drugs (AEDs) has long been associated with bone deleterious effects. Furthermore, the BsmI restriction fragment polymorphism of the vitamin D receptor (VDR) has been associated with reduced bone mineral density (BMD), mostly in postmenopausal women. This study evaluates the association between bone metabolism of patients with epilepsy and the BsmI VDR's polymorphism in chronic users of AEDs. METHODS: this study evaluated 73 long-term users of antiepileptic drug monotherapy, in a cross-sectional design. Fasting blood samples were obtained to estimate the circulating serum levels of calcium, magnesium, phosphorus, parathormone, 25 hydroxyvitamin D as well as the VDR's genotype. Bone mineral density at the lumbar spine was measured with Dual Energy X-Ray Absorptiometry. RESULTS: bone mineral density was significantly associated with the genotype of VDR (mean BMD: Bb genotype 1.056 ± 0.126 g/cm(2) ; BB genotype 1.059 ± 0.113 g/cm(2) ; bb genotype 1.179 ± 0.120 g/cm(2) ; P < 0.05). Additionally, the presence of at least one B allele was significantly associated with lower bone mineral density (B allele present: BMD = 1.057 ± 0.12 g/cm(2) , B allele absent: BMD = 1.179 ± 0.119 g/cm(2) ; P < 0.01). Patients with at least one B allele had lower serum levels of 25 hydroxyvitamin D when compared with bb patients (22.61 ng/ml vs. 33.27 ng/ml, P < 0.05), whilst they tended to have higher levels of parathyroid hormone. DISCUSSION: vitamin D receptor polymorphism is associated with lower bone mass in patients with epilepsy. This effect might be mediated through the vitamin D-parathormone pathway.

Dietary patterns and cardiovascular risk in postmenopausal women: Protocol of a cross-sectional and prospective study.

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.

Comparison Between Minimally Invasive and Open Gastrectomy for Gastric Cancer in Europe: A Systematic Review and Meta-analysis.

AIMS: We compared laparoscopic and robotic gastrectomies with open gastrectomies and with each other that were held for gastric cancer in Europe. METHODS: We searched for studies conducted in Europe and published up to 20 February 2015 in the PubMed database that compared laparoscopic or robotic with open gastrectomies for gastric cancer and with each other. RESULTS: We found 18 original studies (laparoscopic vs open: 13; robotic vs open: 3; laparoscopic vs robotic: 2). Of these, 17 were non-randomized trials and only 1 was a randomized controlled trial. Only four studies had more than 50 patients in each arm. No significant differences were detected between minimally invasive and open approaches regarding the number of retrieved lymph nodes, anastomotic leakage, duodenal stump leakage, anastomotic stenosis, postoperative bleeding, reoperation rates, and intraoperative/postoperative mortality. Nevertheless, laparoscopic procedures provided higher overall morbidity rates when compared with open ones, but robotic approaches did not differ from open ones. On the contrary, blood loss was less and hospital stay was shorter in minimally invasive than in open approaches. However, the results were controversial concerning the duration of operations when comparing minimally invasive with open gastrectomies. Additionally, laparoscopic and robotic procedures provided equivalent results regarding resection margins, duodenal stump leakage, postoperative bleeding, intraoperative/postoperative mortality, and length of hospital stay. On the contrary, robotic operations had less blood loss, but lasted longer than laparoscopic ones. Finally, there were relatively low conversion rates in laparoscopic (0%-6.7%) and robotic gastrectomies (0%-5.6%) in most studies. CONCLUSION: Laparoscopic and robotic gastrectomies may be considered alternative approaches to open gastrectomies for treating gastric cancer. Minimally invasive operations are characterized by less blood loss and shorter hospital stay than open ones. In addition, robotic procedures have less blood loss, but last longer than laparoscopic ones.

Prolactin as a predictor of endothelial dysfunction and arterial stiffness progression in menopause.

Postmenopausal women are at increased risk for progression of arteriosclerosis and hypertension. Recent cross-sectional evidence suggests that high normal circulating prolactin levels may accelerate vascular ageing in menopause. Postmenopausal women (n=201) were consecutively recruited from a Menopause Clinic and re-evaluated in at least one follow-up visit within the next 3 years. Baseline circulating prolactin levels were measured while both baseline and follow-up vascular and biochemical measurements were performed. Endothelial function was assessed by flow-mediated dilation (FMD), aortic stiffness by pulse-wave velocity (PWV) and arterial wave reflections by applanation tonometry. Baseline prolactin significantly correlated with lower FMD at follow-up (P=0.005). After multivariable adjustment for age, follow-up time, blood pressure (BP), body mass index, smoking and medication, this correlation remained significant (P=0.003). In addition, baseline circulating prolactin levels were independently associated with changes in mean BP (ß=0.131, P=0.021), peripheral diastolic BP (ß=0.169, P=0.004) and new-onset hypertension (OR=1.235, P=0.001). Owing to significant interaction between baseline prolactin and age for changes in PWV over time (P=0.036), a subgroup analysis based on median age was performed. This analysis revealed that in women younger than 55 years, prolactin was an independent predictor of changes in PWV over time (P=0.008). In conclusion, high normal circulating prolactin levels predict changes in haemodynamic indices and worsening endothelial function in healthy postmenopausal women. Particularly in young postmenopausal women, prolactin predicts accelerated arterial stiffening.

[Hepatocellular carcinoma. Our experience]. / Il carcinoma epatocellulare. Nostra esperienza.

From June 1991 to february 1993, 29 patients with hepatocarcinoma in cirrhosis were admitted to our department. After a careful preoperative assay, 17 patients underwent hepatic resection. These patients were suffering from unifocal or superficial tumours with Child A or Child B hepatic function. In the other 12 patients, with multifocal hepatocarcinoma or with Child C hepatic function, a Port-a-cath was implanted in the hepatic artery for chemotherapy. The hepatic resection, performed after clampage of the hepatic hilum, was always restricted to exeresis of the tumor at 1 cm, of its border, avoiding damage to the poor hepatic function because of cirrhosis. The average time in performing such an important procedure was 20 minutes. There was no postoperative death and all patients still alive. Postoperative complications were ascites, always treated with diuretic therapy and albumin, and moderate pleuritis. Our good results depend on accurate preoperative assay and especially on the restricted hepatic resection that didn't reduce the hepatic functional reserve further. The implantation of a Port-a-cath in the hepatic artery, performed in patients not suitable for surgical procedures, allows us to carry ut the right chemotherapy in the other patients, eliminating the risk of postoperative deaths.

Home breastfeeding support by health professionals: findings of a randomized controlled trial in a population of Italian women.

AIM: We conducted a randomized controlled trial to assess the effectiveness of a support intervention delivered by health professionals to increase the rate and duration of breastfeeding. METHODS: A randomized controlled intervention study was conducted in the period 2000-2001 among 605 mothers who had given birth in a public maternity ward located in the city of Rome, Italy. The intervention consisted of a home visit by a midwife from the maternity ward of the hospital. The outcome of the study was the infant's feeding habits, assessed by a 24-h recall. The effect of the intervention on the duration of breastfeeding was estimated by the Kaplan-Meier method and by the Cox multivariate regression model. RESULTS: According to intention-to-treat analysis, there was no significant difference between the intervention and the control group, after controlling for confounding factors (hazard ratio (HR) 1.04; 95% confidence interval (95% CI): 0.85-1.26). The duration of breastfeeding was shorter (HR 1.61; 95% CI: 1.13-2.31) for women in the intervention group who refused the obstetric visit. CONCLUSION: Our study shows that an early home support programme delivered by health professionals was not effective in increasing breastfeeding initiation and duration.

Videolaparoscopic Vertical Banded Gastroplasty.

BACKGROUND: In June 1993, the authors started performing the Vertical Banded Gastroplasty (VBG) via laparoscopy. METHODS: Since June 1993, 25 patients have undergone laparoscopic VBG. RESULTS: Weight loss did not differ from the traditional open VBG. CONCLUSIONS: The laparoscopic procedure, which can be performed simply, permits minimal trauma compared to the traditional open operation, with a reduction in hospitalization and in short-term as well as long-term complications.