Early menopause and premature ovarian insufficiency are associated with increased risk of dementia: A systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Among other risk factors, the decline in estrogen concentrations during menopause may compromise cognitive function. Whether early menopause (EM) is associated with an increased risk of dementia remains unclear. The purpose of this study was to systematically review and meta-analyze current evidence regarding the association between EM or premature ovarian insufficiency (POI) and the risk of dementia of any type. MATERIALS AND METHODS: A comprehensive literature search was conducted through the PubMed, Scopus and CENTRAL databases up to August 2022. Study quality was assessed using the Newcastle-Ottawa scale. Associations were calculated as odds ratio (OR) with 95 % confidence interval (CI). The I2 index was employed for heterogeneity. RESULTS: Eleven studies (nine assessed as of good and two as of fair quality) were included in the meta-analysis (n = 4,716,862). Women with EM demonstrated a greater risk of dementia of any type than women of normal age at menopause (OR 1.37, 95 % CI 1.22-1.54; I2 93%). However, after excluding a large retrospective cohort study, the results were altered (OR 1.07, 95 % CI 0.78-1.48; I2 94%). Increased risk of dementia was also found in women with POI (OR 1.18, 95 % CI 1.15-1.21; I2 0%). Subgroup analysis showed that this risk was mostly evident in cohort studies, and those which included women with natural menopause. CONCLUSIONS: Women with EM or POI may be at increased risk of dementia compared with women of normal age at menopause, but further research investigating that hypothesis is warranted.

Preoperative Vitamin D Deficiency is a Risk Factor for Postthyroidectomy Hypoparathyroidism: A Systematic Review and Meta-Analysis of Observational Studies.

CONTEXT: Whether preoperative vitamin D deficiency (VDD) contributes to postoperative hypoparathyroidism (hypoPT) risk is unknown. OBJECTIVE: This work aimed to meta-analyze the best available evidence regarding the association between preoperative vitamin D status and hypoPT risk. METHODS: A comprehensive literature search was conducted in PubMed, CENTRAL, and Scopus databases, up to October 31, 2020. Study selection included patients undergoing thyroidectomy with preoperative vitamin D status and postoperative hypoPT data. Two researchers independently extracted data from eligible studies. Data were expressed as risk ratio (RR) with 95% CI. The I2 index was employed for heterogeneity. RESULTS: Thirty-nine studies were included in the quantitative analysis (61 915 cases with transient and 5712 with permanent hypoPT). Patients with VDD demonstrated a higher risk for transient hypoPT compared with those with preoperative vitamin D sufficiency (RR 1.92, 95% CI, 1.50-2.45, I2 = 85%). These results remained significant for patients with preoperative 25-hydroxyvitamin D concentrations less than or equal to 20 ng/mL (mild VDD; RR 1.46, 95% CI, 1.10-1.94, I2 = 88%) and less than or equal to 10 ng/mL (severe VDD; RR 1.98, 95% CI 1.42-2.76, I2 = 85%). The risk of permanent hypoPT was increased only in cases with severe VDD (RR 2.45, 95% CI, 1.30-4.63, I2 = 45%). No difference was evident in subgroup analysis according to study design or quality. CONCLUSION: Patients with preoperative VDD are at increased risk of transient hypoPT following thyroidectomy. The risk for permanent hypoPT is increased only for those with severe VDD.

Estrogen and bones after menopause: a reappraisal of data and future perspectives.

Menopausal hormone therapy (MHT) is effective in preventing menopause-related bone loss and decreasing vertebral, non-vertebral and hip fracture risk. MHT contains estrogens that exert both antiosteoclastic and osteoanabolic effects. These effects are dose-dependent, as even ultra-low doses preserve or increase bone mineral density. The transdermal route of administration is effective on cancellous and cortical bone, although fracture data are still lacking. Hormone replacement therapy is the treatment of choice to preserve skeletal health in women with premature ovarian insufficiency and early menopause. MHT can be considered in women aged < 60 years or within 10 years since menopause as, in this population, benefits outweigh possible risks, such as breast cancer and cardiovascular events. Despite the ensuing bone loss after MHT discontinuation, a residual antifracture effect persists. However, in women at risk of fracture, subsequent antiosteoporotic therapy may be needed, either with an antiosteoclastic or osteoanabolic agent. In any case, longitudinal data from randomized controlled trials comparing different estrogen doses and routes of administration, as well as designating the optimal treatment strategy after MHT discontinuation, are needed to elucidate these issues further.

Esophageal perforation in case of thyroid lymphoma.

Esophageal perforation is a rare and serious complication of thyroid lymphoma and should be taken under consideration in cases with rapid deterioration in their course. Clinical suspicion and prompt diagnosis are key factors for reducing mortality risks in these cases.

Efficacy and safety of statin use in children and adolescents with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized-controlled trials.

PURPOSE: Statins are the mainstay of treatment for patients with familial hypercholesterolaemia (FH). However, their efficacy and safety in children and adolescents with FH has not been well-documented. The purpose of this study was to systematically investigate and meta-analyze the best available evidence from randomized-controlled trials (RCTs) regarding the efficacy and safety of statins in this population. METHODS: A comprehensive search was conducted in PubMed, Scopus and Cochrane, up to 10 January 2020. Data were expressed as mean differences with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Ten RCTs were included in the qualitative and quantitative analysis (1191 patients, aged 13.3 ± 2.5 years). Compared with placebo, statins led to a mean relative reduction in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride and apolipoprotein B (apo-B) concentrations by -25.5% (95% CI -30.4%, -20.5%; I2 91%), -33.8% (95% CI -40.1%, -27.4%; I2 90%), -8.4% (95% CI -14.8%, -2.03%; I2 26%) and -28.8% (95% CI -33.9%, -23.6%; I2 83%), respectively. High-density lipoprotein cholesterol (HDL-C) was increased by 3.1% (95% CI 1.1%-5.2%; I2 0%). Statins were well-tolerated, with no significant differences in transaminase and creatine kinase levels or other adverse effects compared with placebo. Statins exerted no effect on growth or sexual development. CONCLUSION: Statins are quite effective in reducing TC, LDL-C, TG and apo-B and increasing HDL-C concentrations in children and adolescents with FH. No safety issues were seen with statin use.

Non-coronary atherosclerotic cardiovascular disease in patients with familial hypercholesterolaemia.

Objective: Familial hypercholesterolaemia (FH) is a common autosomal dominant inherited disease, affecting 1 in 200-500 individuals worldwide. FH is characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) concentrations. Its association with increased risk of coronary heart disease (CHD) (>10-fold, compared with patients without FH) is well documented. However, the association between FH and non-CHD atherosclerotic cardiovascular disease (ASCVD) risk has been poorly documented.Methods: PubMed was searched for English language publications regarding the association between FH and carotid artery stenosis, stroke, peripheral artery disease (PAD; lower limbs and other arterial beds), aortic valve calcification (AoVC), aortic and renal artery disease, chronic kidney disease, atrial fibrillation and heart failure, from conception until 22 December 2019.Results: Despite the small number of available studies, as well as their characteristics (sample size, diagnostic criteria used, retrospective or cross-sectional design), there is evidence for a positive association between FH and stroke, PAD or AoVC. More data are needed for definitive conclusions regarding aortic and renal artery disease, chronic kidney disease, atrial fibrillation and heart failure. There is paucity of data with respect to homozygous FH. Increased lipoprotein (a) concentrations, often seen in FH patients, may also contribute to this non-CHD atherosclerotic process. A key question is whether statins or other LDL-C-lowering therapies, provide an additional reduction in the risk of these less-recognized vascular and non-vascular complications in FH patients.Conclusions: Heterozygous FH is associated with increased risk for stroke, PAD and AoVC. Clinicians should take these non-CHD ASCVD aspects into consideration for optimal management of FH patients.

Management of dyslipidaemias in the elderly population-A narrative review.

The impact of dyslipidaemias on the risk of cardiovascular disease (CVD) is well documented. However, it is often under-estimated and, sometimes, suboptimally managed in the elderly population. The prevalence of dyslipidaemias seems to decline from the 7th decade of life in both genders. The association of dyslipidaemias with CVD weakens after the 7th decade, perhaps due to other age-related comorbidities. Low-density lipoprotein cholesterol remains the main target in the management of CVD risk. Although the evidence is not robust for the elderly, statins are the cornerstone of the management of CVD. Statins do have a potentially beneficial role in elderly individuals with established CVD and/or a history of type 2 diabetes mellitus. Data on their use in other elderly populations are inconsistent. There is no clear evidence for a beneficial effect of other hypolipidaemic drug categories in the elderly, such as ezetimibe, fibrates, niacin, omega-3 fatty acids and the new proprotein convertase subtilisin/kexin type 9 inhibitors. Their use should be balanced against possible adverse effects, such as the increased risk of myopathy with fibrates. Potential drug-drug interactions should be also taken into account. In conclusion, there is a need to establish the most effective lipid-lowering strategy in the elderly population with respect to CVD risk reduction, in future well-designed trials.