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There is evidence suggesting that infection with SARS-CoV-2 can lead to several long-term sequelae including diabetes. This mini-review examines the rapidly evolving and conflicting literature on new-onset diabetes after COVID-19, which we term NODAC. We searched PubMed, MEDLINE, and medRxiv from inception until December 1, 2022 using both MeSH terms and free text words including “COVID-19,” “SARS-CoV-2,” “diabetes,” “hyperglycemia,” “insulin resistance,” and “pancreatic β-cell.” We also supplemented searches by examining reference lists from retrieved articles. Current evidence suggests that COVID-19 increases the risk of developing diabetes, but the attributable risk is uncertain due to limitations of study designs and the evolving nature of the pandemic, including new variants, widespread population exposure to the virus, diagnostic options for COVID-19 and vaccination status. The etiology of diabetes after COVID-19 is likely multifactorial and includes factors associated with host characteristics (e.g., age), social determinants of health (e.g., deprivation index), and pandemic-related effects both at the personal (e.g., psychosocial stress) and the societal-community level (e.g., containment measures). COVID-19 may have direct and indirect effects on pancreatic β-cell function and insulin sensitivity related to: the acute infection and its treatment (e.g., glucocorticoids); autoimmunity; persistent viral residency in multiple organs including adipose tissue; endothelial dysfunction; and hyperinflammatory state. While our understanding of NODAC continues to evolve, consideration should be given for diabetes to be classified as a post-COVID syndrome, in addition to traditional classifications of diabetes (e.g., type 1 or type 2), so that the pathophysiology, natural history and optimal management can be studied.

OBJECTIVE Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS We included 108,681 postmenopausal women without T2D at baseline from the Women’s Health Initiative (WHI) (primary cohort) and 34,616 adults without T2D from the U.K. Biobank (UKB) (replication cohort). Cox proportional hazard models were used for estimation of protein-T2D associations. Mediation analysis was performed to assess the mediating roles of biomarkers in case-control studies nested in the WHI. RESULTS In the WHI, 15,842 incident T2D cases were identified during a median follow-up of 15.8 years. Intake of animal protein was associated with increased T2D risk (hazard ratio in comparing the highest to the lowest quintile = 1.31 [95% CI 1.24–1.37]) and plant protein with decreased risk (0.82 [0.78–0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk and whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for BMI. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (0.79 [0.74–0.84]), which was mediated by levels of hs-CRP, interleukin-6, leptin, and SHBG. CONCLUSIONS Findings from these two large prospective cohorts support the notion that substituting plant protein for animal protein may decrease T2D risk mainly by reducing obesity-related inflammation.

Purpose: Short and long sleep duration and poor sleep quality are risk factors for weight gain and cancer mortality. The purpose of this study is to investigate the relationship between sleep and weight change among postmenopausal breast cancer survivors. Methods: Women participating in the Women’s Health Initiative who were diagnosed with incident breast cancer between year 1 and year 3 were included. Self-reported sleep duration was categorized as ≤5 hours (short), 6 hours, 7-8 hours (optimal), and ≥9 hours (long). Self-reported sleep quality was categorized as poor, average, and above average. Post-diagnosis weight change was the difference of weight closest to, but preceding diagnosis, and year 3 weight. We used linear regression to evaluate sleep duration and sleep quality associations with post-diagnosis weight change adjusted for potential confounders. Results: Among 1,156 participants, 63% were weight stable after diagnosis; average weight gain post cancer diagnosis was 3.2 kg. Six percent of women reported sleeping ≤5 hours, 26% reported 6 hours, 64% reported 7-8 hours, and 4% reported ≥9 hours. There were no differences in adjusted estimates of weight change among participants with short duration (0.37kg; 95%CI -0.88, 1.63), or long duration (-0.56kg; 95% CI -2.03, 0.90) compared to optimal duration, nor was there a difference among poor quality (-0.51kg; 95% CI -1.42, 0.41) compared to above average quality. Conclusion: Among postmenopausal breast cancer survivors, sleep duration and quality were not associated with weight change after breast cancer diagnosis. Future studies should consider capturing change in adiposity and to expand beyond self-reported sleep.

Purpose To determine the prevalence and morphologic features of reticular pseudodrusen (RPD) and their association with participant demographics and age-related macular degeneration (AMD) status in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) sample, an ancillary study of the Women’s Health Initiative Observational Study. Design Cross-sectional, multicenter, natural history study. Participants Nine hundred and twenty-seven eyes from 466 postmenopausal women 69 to 101 years of age. Methods Multimodal imaging, including spectral-domain (SD) OCT and infrared reflectance (IR), were used to identify RPD characteristics, including location (within or outside the 6-mm diameter circle centered at the macula), presence of peripapillary RPD, pattern of RPD, and RPD area. Age-related macular degeneration features from SD OCT, IR, and color photographs also were assessed and AMD severity was categorized. Main Outcome Measures Reticular pseudodrusen prevalence using SD OCT and IR imaging and AMD status. Results Reticular pseudodrusen were present in 130 eyes (14% of eyes, 16% of participants), with increasing prevalence with age: 7% in those younger than 78 years, 14% in those 78 to 83 years of age, and 30% in those older than 83 years. Using clinical classification of AMD with color photography, RPD were seen in 2.4% of eyes with no AMD or aging changes, 11.5% in early AMD, 25.1% in intermediate AMD, and 51.1% in late AMD. Mean RPD area was 17.4 mm2 (standard deviation, 14.7 mm2). Ribbon morphologic RPD (53%) was more common than dot morphologic RPD (36%). Reticular pseudodrusen mostly were located both within and outside the 6-mm circle with primarily superior retinal distribution. Reticular pseudodrusen were visualized with corresponding color fundus photography in only 38 eyes (4% of total eyes). Participants with and without RPD had a visual acuity±standard error of 77.9 ± 1.4 letters and 81.3 ± 0.4 letters, respectively (P = 0.02). Conclusions The prevalence of RPD in CAREDS2 increased with age and was associated with AMD severity. Reticular pseudodrusen were detected in eyes without other features of AMD and could represent an earlier disease state. Multimodal imaging with SD OCT and IR has significantly greater sensitivity for visualizing RPD than color fundus photography.

Objective: Describe baseline characteristics of the NIH/ADA-supported D2d study, the first diabetes prevention trial in the U.S. to apply current ADA diagnostic glycemia criteria. Research Design and Methods: Multicenter (22 sites), randomized, double-blind, placebo-controlled, primary prevention trial testing efficacy of oral daily 4000 IU cholecalciferol (D3) compared to placebo on incident diabetes in adults at high risk. Eligible participants met at least 2-of-3 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100-125 mg/dL, 2-hour glucose post-75g oral glucose load (2hPG) 140-199 mg/dL, and/or hemoglobin A1c (HbA1c) 5.7-6.4%. Results: 2423 participants (45% women, 33% non-white) were randomized. Mean (±SD) age was 59 (±9.9) years, and BMI was 32 (±4.5) kg/m2. Thirty-five percent met 3 prediabetes criteria, 49% met FPG/HbA1c criteria only, 9.5% met 2hPG/FPG criteria only, and 6.3% met 2hPG/HbA1c criteria only. Black participants had higher HbA1c and lower FPG concentration than white, Asian, and other races (P Conclusions: D2d will establish the efficacy and safety of vitamin D supplementation for diabetes prevention and inform on the natural history of prediabetes per contemporary ADA criteria. Disclosure E. LeBlanc: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc.. B. Dawson-Hughes: None. M.A. Staten: None. P.R. Sheehan: None. M.R. Lewis: None. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC.. S.H. Kim: None. R. Chatterjee: None. V. Aroda: Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc., AstraZeneca, Calibra Medical, Eisai Inc., Sanofi. Consultant; Self; Sanofi. Research Support; Self; Theracos, Inc.. Employee; Spouse/Partner; Merck & Co., Inc.. Other Relationship; Self; American Diabetes Association. Consultant; Self; ADOCIA. C. Chadha: None. A. Pittas: None.

BACKGROUND: Vitamin D deficiency has been associated with adverse health outcomes. PURPOSE: To systematically review benefits and harms of vitamin D screening in asymptomatic adults. DATA SOURCES: Ovid MEDLINE (through the third week of August 2014), Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. STUDY SELECTION: Randomized trials of screening for and treatment of vitamin D deficiency and case-control studies nested within the Women's Health Initiative. DATA EXTRACTION: One investigator abstracted data, a second reviewed data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. DATA SYNTHESIS: No study examined the effects of vitamin D screening versus no screening on clinical outcomes. Vitamin D treatment was associated with decreased mortality versus placebo or no treatment (11 studies; risk ratio [RR], 0.83 [95% CI, 0.70 to 0.99]), although benefits were no longer seen after trials of institutionalized persons were excluded (8 studies; RR, 0.93 [CI, 0.73 to 1.18]). Vitamin D treatment was associated with possible decreased risk for having at least 1 fall (5 studies; RR, 0.84 [CI, 0.69 to 1.02]) and falls per person (5 studies; incidence rate ratio, 0.66 [CI, 0.50 to 0.88]) but not fractures (5 studies; RR, 0.98 [CI, 0.82 to 1.16]). Vitamin D treatment was not associated with a statistically significant increased risk for serious adverse events (RR, 1.17 [CI, 0.74 to 1.84]). LIMITATION: Variability across studies in 25-hydroxyvitamin D assays and baseline levels, treatment doses, use of calcium, and duration of follow-up. CONCLUSION: Treatment of vitamin D deficiency in asymptomatic persons might reduce mortality risk in institutionalized elderly persons and risk for falls but not fractures. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Language: en

ObjectiveVasomotor symptoms (VMS, ie, hot flashes or night sweats) are reported by many, but not all, women. The extent to which VMS are genetically determined is unknown. We evaluated the relationship of genetic variation and VMS.MethodsIn this observational study, we accessed data from three genome-wide association studies (GWAS) (SNP Health Association Resource cohort [SHARe], WHI Memory Study cohort [WHIMS+], and Genome-Wide Association Studies of Treatment Response in Randomized Clinical Trials [GARNET] studies, total n = 17,695) of European American, African American, and Hispanic American postmenopausal women aged 50 to 79 years at baseline in the Women's Health Initiative Study. We examined genetic variation in relation to VMS (yes/no) in each study and using trans-ethnic inverse variance fixed-effects meta-analysis. A total of 11,078,977 single-nucleotide polymorphisms (SNPs) met the quality criteria.ResultsAfter adjustment for covariates and population structure, three SNPs (on chromosomes 3 and 11) were associated with VMS at the genome-wide threshold of 5 × 10 in the African American SHARe GWAS, but were not associated in the other cohorts. In the meta-analysis, 14 SNPs, all located on chromosome 4 in the tachykinin receptor 3 (TACR3) locus, however, had P < 5 × 10. These SNPs' effect sizes were similar across studies/participants' ancestry (odds ratio ∼1.5).ConclusionsGenetic variation in TACR3 may contribute to the risk of VMS. To our knowledge, this is the first GWAS to examine SNPs associated with VMS. These results support the biological hypothesis of a role for TACR3 in VMS, which was previously hypothesized from animal and human studies. Further study of these variants may lead to new insights into the biological pathways involved in VMS, which are poorly understood.

OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D(3)) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100–125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140–199 mg/dL, and/or a hemoglobin A(1c) (HbA(1c)) 5.7–6.4% (39–46 mmol/mol). RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m(2). Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA(1c) criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA(1c) criteria only. Black participants had the highest mean HbA(1c) and lowest FPG concentration compared with white, Asian, and other races (P < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA(1c) and FPG concentrations. CONCLUSIONS: D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.

The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk.Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes.In age-adjusted models, women with the shortest (30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment.Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

Objectives: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. Design: Post hoc analysis of a randomized double-blind placebo-controlled trial. Setting: Forty Women's Health Initiative (WHI) clinical centers across the United States. Participants: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. Intervention: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D3 (treatment) and 2,109 to placebo. Measurements: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. Results: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71�1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72�1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. Conclusion: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.

OBJECTIVES: To examine the association between metabolic syndrome (MetS) and objective measures of physical performance. DESIGN: Cross-sectional analysis of the cohort study, the Osteoporotic Fractures in Men Study. SETTING: Six clinical sites in the United States. PARTICIPANTS: Five thousand four hundred fifty-seven ambulatory men (mean age 73.6 ± 5.9). MEASUREMENTS: Physical performance assessed according to grip strength, narrow walk speed, walking speed, and time to complete five repeated chair stands. Individual scores were converted to quintiles (worst=1 to best=5; unable to complete=0) and summed for an overall score (mean 11.6 ± 4.3, range, 1�20). MetS was defined according to World Health Organization criteria that include evidence of glucose dysregulation (insulin resistance, diabetes mellitus, or hyperinsulinemia) and at least two additional characteristics: high blood pressure, low high-density lipoprotein cholesterol, high triglycerides, obesity. RESULTS: More than one-quarter (26.3%) of participants met criteria for MetS. In separate linear regression models, four of five MetS components were related to performance (P

Context: The relationship between sex steroids and fracture is poorly understood. Objective: The objective of the study was to examine associations between nonvertebral fracture risk and bioavailable estradiol (bioE2), bioavailable testosterone (bioT), and SHBG. Design: This was a case-cohort study. Setting: The Osteoporotic Fractures in Men Study (MrOS) was conducted in a prospective U.S. cohort in 5995 community-dwelling men 65 yr old or older. Participants: Participants included a subcohort of 1436 randomly chosen white men plus all 446 minorities and all those with incident hip and other nonvertebral fractures. Main Outcome Measures: Baseline testosterone and estradiol were measured by mass spectrometry (MS) and SHBG by RIA. Results: Men with the lowest bioE2 ( 59.1 nm) had greater risk of all nonvertebral fractures [adjusted hazard ratio (HR) [95% confidence interval]: 1.5 (1.2–1.9) and 1.4 (1.1–21.8), respectively]. Men with the lowest bioT (

OBJECTIVE This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events. METHODS CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events. RESULTS Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P

Summary Question What is the effect of hormone therapy with oestrogen, or oestrogen plus progesterone on cognitive function in postmenopausal women aged 65 years or older? Study design Randomised controlled trail. Main results Hormone therapy significantly decreased cognitive function compared with placebo, after 5 to 7 years (see Results table). This decrease in cognitive function was greater in women who had a lower base-line cognitive function score (pooled p value: Authors’ conclusions Oestrogen, or oestrogen plus progesterone, has no protective affect on cognitive function in postmenopausal women aged 65 years or older.

This study aims to determine whether vitamin D levels are associated with menopause-related symptoms in older women.A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were included in these analyses.Borderline significant associations between 25(OH)D levels and total number of menopausal symptoms were observed (with P values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. No associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue were observed (P's0.10 for fully adjusted models).There is no evidence for a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or

The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women.We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women's Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations.In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05-1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21-2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (≥ 10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS.Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women.

To examine the association between metabolic syndrome (MetS) and objective measures of physical performance.Cross-sectional analysis of the cohort study, the Osteoporotic Fractures in Men Study.Six clinical sites in the United States.Five thousand four hundred fifty-seven ambulatory men (mean age 73.6 ± 5.9).Physical performance assessed according to grip strength, narrow walk speed, walking speed, and time to complete five repeated chair stands. Individual scores were converted to quintiles (worst=1 to best=5; unable to complete=0) and summed for an overall score (mean 11.6 ± 4.3, range, 1-20). MetS was defined according to World Health Organization criteria that include evidence of glucose dysregulation (insulin resistance, diabetes mellitus, or hyperinsulinemia) and at least two additional characteristics: high blood pressure, low high-density lipoprotein cholesterol, high triglycerides, obesity.More than one-quarter (26.3%) of participants met criteria for MetS. In separate linear regression models, four of five MetS components were related to performance (P.001); only high blood pressure was unrelated. Men with MetS had a 1.1-point lower performance score (mean 10.8, 95% confidence interval (CI)=10.6-11.0) than men without MetS (mean 11.9, 95% CI=11.8-12.0) (P.001), adjusting for age, race, education, and site. With further covariate adjustment, this difference was reduced but remained significant (β=-0.78, P.001). A graded association was observed between number of MetS components (0, 1, 2, or ≥3) and performance (P for trend.001). Findings were similar excluding men with diabetes mellitus or obese men.Metabolic dysregulation is related to objectively assessed poorer physical performance in relatively healthy older men.

Purpose In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial. Methods Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication. Results Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; Pinteraction = .038), which was not observed in women without history of NMSC. Conclusion Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.

The prevalence of 25 hydroxyvitamin D [25(OH)D] deficiency, defined as 25(OH)D level less than 20 ng/mL, is high, especially among the elderly, with 25% to 65% affected.1–6 While much research has focused on the adverse effect of 25(OH)D deficiency on bone health,5,7 associations between 25(OH)D deficiency and non–bone health outcomes, including hypertension,8 cardiovascular morbidity,9 diabetes,10,11 and cancer,12,13 have also been reported. In addition, there is a growing body of literature to support the role of vitamin D in brain function and development.14–25 Despite the experimental and animal evidence supporting an important role for vitamin D in mood and cognition, epidemiologic studies testing this hypothesis are scarce. Cross-sectional studies that examined the association between 25(OH)D levels and cognition were limited by small sample size,26–28 did not control for potential confounding factors,28 had suboptimal analytic methods to measure 25(OH)D levels,6,26–31 or reported conflicting results.30 To our knowledge, there are no prospective cohort studies examining the association between 25(OH)D level and cognitive decline. To test the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline, we measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 community-dwelling men aged 65 years or older who were enrolled in the Osteoporotic Fractures in Men (MrOS) Study and followed them prospectively for an average of 4.6 years for changes in cognitive function.

Summary Objective To examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men. Design Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men of 65 years or older. Patients One thousand six hundred and two men were chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and twenty-three MrOS participants with sex steroids measured using RIA were also examined. Measurements Baseline and follow-up (4·5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and oestradiol were measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analysed using linear regression. Results Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (P = 0·03) and 3MS performance (P = 0·02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance. Conclusions Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or oestradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.

Objective: To examine how menopausal symptoms and estrogen therapy (ET)Yinduced symptom relief affect cognition in early menopause. Design: There were two components. Part 1 was a cross-sectional study of 37 healthy, recently postmenopausal women with diverse menopausal symptoms. Women were categorized as having low (n = 20) or high symptoms (n = 17) based on a validated symptom questionnaire. Women completed mood and sleep questionnaires and underwent cognitive testing, which included verbal memory, visual memory, emotional memory, and verbal fluency. Thirty-two of these women went on to part 2 of the study. Fourteen were randomly assigned to receive ET and 18 to receive placebo for 8 weeks. Before treatment and at 4 and 8 weeks, women completed the same measures as in part 1 of the study. Results: High symptom women had more negative mood (P = 0.01) and lower quality sleep (P G 0.001) than low symptom women. Despite suffering from more menopausal symptoms, worse mood, and poorer sleep, women in the high symptom group performed the same on cognitive testing as women in the low symptom group. Women receiving ET had greater improvements in menopausal symptoms and sleep compared with those receiving the placebo (P e 0.05). ET did not improve mood compared with placebo. Women receiving ET did not have any improvement in cognitive performance compared with those receiving the placebo. Conclusions: Menopausal symptoms do not impair cognition. ET does not improve cognition despite alleviating symptoms and improving sleep in recently naturally menopausal women with diverse menopausal symptoms.

ContextSome observational data suggest that hormone replacement therapy (HRT) may reduce the risk of cognitive decline and dementia but results have been conflicting.ObjectiveTo review and evaluate studies of HRT for preventing cognitive decline and dementia in healthy postmenopausal women.Data SourcesStudies with English-language abstracts identified in MEDLINE (1966-August 2000), HealthSTAR (1975-August 2000, PsychINFO (1984-August 2000); Cochrane Library databases; and articles listed in reference lists of key articles.Study SelectionRandomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline; cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were identified.Data ExtractionTwenty-nine studies met inclusion criteria and were rated. Two reviewers rated study quality independently and 100% agreement was reached on Jadad scores and 80% agreement was reached on US Preventive Services Task Force quality scores. A final score was reached through consensus if reviewers disagreed.Data SynthesisStudies of cognition were not combined quantitatively because of heterogeneous study design. Women symptomatic from menopause had improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions. Generally, no benefits were observed in asymptomatic women. A meta-analysis of observational studies suggested that HRT was associated with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence interval, 0.53-0.82). However, possible biases and lack of control for potential confounders limit interpretation of these studies. Studies did not contain enough information to assess adequately the effects of progestin use, various estrogen preparations or doses, or duration of therapy.ConclusionsIn women with menopausal symptoms, HRT may have specific cognitive effects, and future studies should target these effects. The meta-analysis found a decreased risk of dementia in HRT users but most studies had important methodological limitations.