Association between age at menopause and fracture risk: a systematic review and meta-analysis.

PURPOSE: Early menopause (EM, age at menopause < 45 years) and premature ovarian insufficiency (POI, age at menopause < 40 years) are associated with an increased risk of osteoporosis. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The primary aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and fracture risk. The secondary aim was to evaluate this effect concerning the site of fractures. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 January 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for quantifying heterogeneity. RESULTS: Eighteen studies were included in the qualitative and quantitative analysis (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36, 95% CI 1.11-1.66, p < 0.002, I² 81.5%). Women with POI did not display any difference in fracture risk compared either with women with age at menopause > 40 (OR 1.23, 95% CI 0.72-2.09, p = 0.436, I² 62.5%) or >45 years (OR 0.54, 95% CI 0.22-1.29, p = 0.17, I2 0%). No difference was evident when a separate analysis was performed for vertebral, non-vertebral and hip fractures. CONCLUSIONS: This is the first meta-analysis showing that EM is associated with increased fracture risk compared with normal age at menopause, without any distinct effect on the site of the fracture.

Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis.

Objective/Design Menopausal transition has been associated with a derangement of glucose metabolism. However, it is not known if early menopause (EM, defined as age at menopause <45 years) or premature ovarian insufficiency (POI, defined as age at menopause <40 years) are associated with increased risk of type 2 diabetes mellitus (T2DM). To systematically investigate and meta-analyze the best evidence regarding the association of age at menopause with the risk of T2DM. Methods A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to January 31, 2018. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I 2 index was employed for heterogeneity. Results Thirteen studies were included in the qualitative and quantitative analysis (191 762 postmenopausal women, 21 664 cases with T2DM). Both women with EM and POI were at higher risk of T2DM compared with those of age at menopause of 45-55 years (OR: 1.15, 95% CI: 1.04-1.26, P = 0.003; I 2: 61%, P < 0.002 and OR: 1.50, 95% CI: 1.03-2.19, P = 0.033; I 2: 75.2%, P < 0.003), respectively). Similar associations emerged when women with EM and POI were compared with those of age at menopause >45 years (OR: 1.12, 95% CI: 1.01-1.20, P < 0.02; I 2: 78%, P < 0.001 and OR: 1.53, 95% CI: 1.03-2.27, P = 0.035; I 2: 78%, P < 0.001), respectively). Conclusions Both EM and POI are associated with increased risk of T2DM.

The effect of antidiabetic medications on the cardiovascular system: a critical appraisal of current data.

Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results. Briefly, metformin is still considered safe and confers a beneficial effect on CVD risk. Conflicting data exist as concerns sulfonylureas, although the second and third generation representatives are regarded as relatively safe. Pioglitazone use seems to be associated with a reduction in CVD risk, whereas the dipeptidyl-dipeptidase-4 inhibitors (DPP-4i), lixisenatide and exenatide-LAR [from the category of glucagon-like-peptide-1 receptor (GLP-1R) agonists], confer a neutral effect. Two other GLP-1R agonists, liraglutide and semaglutide, as well as the sodium-glucose transporter-2 (SGLT2)-inhibitors, empagliflozin and cangliflozin, have shown an additional effect on CVD risk reduction, although their safety is in doubt. Insulin analogues and newer long-acting compounds are also safe for the cadiovascular system. The aim of this narrative review is to present and critically analyse the current data for each antidiabetic drug category with regard to their effect on CVD risk.