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  • Steroidal contraceptives: effect on bone fractures in women

    Cochrane Database Syst Rev. 2014 Jun 24;6:CD006033. [Epub ahead of print].

    Lopez LM1, Grimes DA, Schulz KF, Curtis KM, Chen M.

    Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear.OBJECTIVES:Our aim was to evaluate the effect of using hormonal contraceptives beforemenopause on the risk of fracture in women.SEARCH METHODS:Through April 2014, we searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. Eligible interventions included comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive that differed in terms of drug, dosage, or regimen. MAIN RESULTS:We found 19 RCTs that met our eligibility criteria. Eleven trials compared different combined oral contraceptives (COCs) or regimens of COCs; five examined an injectable versus another injectable, implant, or IUD; two studied implants, and one compared the transdermal patch versus the vaginal ring...... 

  • Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III.

    Eur J Clin Nutr. 2014 Jun 25. doi: 10.1038/ejcn.2014.117. [Epub ahead of print]

    Batsis JA1, Mackenzie TA2, Barre LK3, Lopez-Jimenez F4, Bartels SJ3.

    Background:Sarcopenia is defined as the loss of skeletal muscle mass and quality, which accelerates with aging and is associated with functional decline. Rising obesity prevalence has led to a high-risk group with both disorders. We assessed mortality risk associated with sarcopenia and sarcopenic obesity in elders.Methods:A subsample of 4652 subjects ⩾60 years of age was identified from the National Health and Nutrition Examination Survey III (1988-1994), a cross-sectional survey of non-institutionalized adults. National Death Index data were linked to this data set. Sarcopenia was defined using a bioelectrical impedance formula validated using magnetic resonance imaging-measured skeletal mass by Janssen et al. Cutoffs for total skeletal muscle mass adjusted ......

  • Hysterectomy and urinary incontinence in postmenopausal women.

    Int Urogynecol J. 2014 Jun 26. [Epub ahead of print]

    Kudish BI1, Shveiky D, Gutman RE, Jacoby V, Sokol AI, Rodabough R, Howard BV, Blanchette P, Iglesia CB.

    INTRODUCTION AND HYPOTHESIS:To evaluate an association between hysterectomy and urinary incontinence (UI) in postmenopausal women.METHODS:Women (aged 50-79) with uteri (N = 53,569) and without uteri (N = 38,524) who enrolled in the Women's Health Initiative (WHI) Observational Study between 1993 and 1996 were included in this secondary analysis. Baseline (BL) and 3-year demographic, health/physical forms and personal habit questionnaires were used. Statistical analyses included univariate and logistic regression methods.RESULTS:The baseline UI rate was 66.5 %, with 27.3 % of participants having stress urinary incontinence (SUI), 23 % having urge UI (UUI), and 12.4 % having mixed UI (MUI). 41.8 % of women had undergone hysterectomy, with 88.1 % having had the procedure before age 54. Controlling for health/physical variables, hysterectomy was associated with UI at BL (OR 1.25, 95 % CI 1.19, 1.32) and over the 3-year study period (OR 1.23, 95 % CI 1.11, 1.36)......

  • Distinct role of estrogen receptor-alpha and beta on postmenopausaldiabetes-induced vascular dysfunction.

    Gen Comp Endocrinol. 2014 Jun 23. pii: S0016-6480(14)00246-9. [Epub ahead of print]

    Bansal S1, Chopra K2.

    Estrogen is known to influence vascular functions and insulin sensitivity, but the relative contribution of estrogen receptor (ER) isoforms in postmenopausal diabetes-induced vascular dysfunction is unclear. The aim of the present study was to delineate the distinct role of estrogen receptor-α and beta β on the vascular function in ovariectomized diabetic rats. Age matched 60 female sprague dawley rats (200-250g) were divided in nine groups. Bilateral ovariectomy was performed and streptozotocin was used to induce experimental diabetes. Rats were administered with 10μg/kg/s.c. of a nonselective estrogen receptor agonist, 17-β estradiol (E2), selective ER-α agonist (4,4',4″-(4-propyl-[1H] pyrazole-1,3,5-triyl) tris phenol (PPT) and selective ER-β agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) for 4weeks after STZ injection. Treatment with selective ER-α agonist and E2 improved the impaired glycemic and lipid profile in ovariectomized diabetic rats, however selective ER-β agonist did not show any effect. Vascular endothelial dysfunction was assessed by acetylcholine and sodium nitroprusside-induced endothelium dependent and independent relaxation in isolated rat aortic ring preparation as well as by electron microscopy 

  • Bazedoxifene versus Oral Bisphosphonates for the Prevention of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis at Higher Risk of Fracture: A Network Meta-Analysis.

    Value Health. 2014 Jun;17(4):424-32. doi: 10.1016/j.jval.2014.01.008. Epub 2014 May 5.

    Ellis AG1, Reginster JY2, Luo X3, Cappelleri JC3, Chines A4, Sutradhar S5, Jansen JP6.

    OBJECTIVE:To compare the efficacy of bazedoxifene and oral bisphosphonates for the prevention of nonvertebral fractures (NVFs) in women with higher risk of postmenopausal osteoporosis (i.e., the Fracture Risk Assessment Tool [FRAX] score ≥ 20%), based on currently available evidence from randomized controlled trials.METHODS:Randomized controlled trials evaluating the NVF relative risk reduction (RRR) with oral bisphosphonates or bazedoxifene were identified by a systematic literature review and combined by means of a network meta-analysis. A subgroup of patients with a FRAX score of 20% or more in the bazedoxifene phase III osteoporosis study was selected as the population of interest on the basis of the bazedoxifene label. In one analysis (analysis 1), the placebo response of the subgroup with a FRAX score of 20% or more was the benchmark to select comparable bisphosphonate trials. Additional analyses incorporated the aggregate data from the bisphosphonate trials with all the FRAX subgroups (analysis 2) or with the individual.....

  • Prevention of diseases after menopause

    Climacteric. 2014 Jun 27:1-17. [Epub ahead of print]

    Lobo RA1, Davis SR, De Villiers TJ, Gompel A, Henderson VW, Hodis HN, Lumsden MA, Mack WJ,et al.

    Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopausehave to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management....

  • Consumption of sweet foods and mammographic breast density: a cross-sectional study.

    BMC Public Health. 2014 Jun 26;14:554. doi: 10.1186/1471-2458-14-554.

    Duchaine CS, Dumas I, Diorio C1.

    BACKGROUND:The increasing consumption of sugar worldwide seems to lead to several health problems, including some types of cancer. While some studies reported a positive association between sweet foods intake and breast cancer risk, little is known about their relation to mammographic density (MD), a strong breast cancer risk factor. This study examined the association of sweet foods and drinks intake with MD among 776 premenopausal and 779postmenopausal women recruited at mammography.METHODS:A food-frequency questionnaire was used to assess intake of sweet foods, sugar-sweetened beverages and spoonsful of sugar added. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate generalized linear models were used to evaluate associations. All models were adjusted for potential confounders, including age and body mass index....

  • Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.

    Lancet Diabetes Endocrinol. 2014 Jun 25. pii: S2213-8587(14)70113-5.

    Vimaleswaran KS1, Cavadino A2, Berry DJ2; LifeLines, et al. Cohort Study investigators.

    BACKGROUND:Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.METHODS:In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood.....

  • Novel, potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors as potential therapeutics for osteoporosis with dual human and mouse activities.

    Eur J Med Chem. 2014 Jun 17;83C:317-337. doi: 10.1016/j.ejmech.2014.06.036. [Epub ahead of print]

    Perspicace E1, Cozzoli L2, Gargano EM1, Hanke N3, Carotti A4, Hartmann RW5, Marchais-Oberwinkler S6.

    17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) is responsible for the oxidation of the highly active estradiol (E2) and testosterone (T) into the less potent estrone (E1) and Δ4-androstene-3,17-dione (Δ4-AD), respectively. As 17β-HSD2 is present in bones and as estradiol and testosterone are able to induce bone formation and repress bone resorption, inhibition of this enzyme could be a new promising approach for the treatment of osteoporosis. Herein, we describe the design, the synthesis and the biological evaluation of 24 new 17β-HSD2 inhibitors in the 5-substituted thiophene-2-carboxamide class. Structure-activity and structure-selectivity relationships have been explored by variation of the sulfur atom position in the central core, exchange of the thiophene by a thiazole...

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