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Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

ABSTRACT: Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer.

SUBMITTER: Gong Z

PROVIDER: S-EPMC4830266 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

Gong Zhihong Z Aragaki Aaron K AK Chlebowski Rowan T RT Manson JoAnn E JE Rohan Thomas E TE Chen Chu C Vitolins Mara Z MZ Tinker Lesley F LF LeBlanc Erin S ES Kuller Lewis H LH Hou Lifang L LaMonte Michael J MJ Luo Juhua J Wactawski-Wende Jean J

International journal of cancer 20151215 8

Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associa ...[more]

PMID: 26616262

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Project description:IMPORTANCE:Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. OBJECTIVE:To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS:Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women's Health Initiative (WHI) observational study. Participants in the prospective cohort included 93?676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. MAIN OUTCOMES AND MEASURES:Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. RESULTS:Of the 93?676 participants, 90?014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28?718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. CONCLUSIONS AND RELEVANCE:Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women.

Project description:BACKGROUND:There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women. The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year 3 in postmenopausal Hispanic women. METHODS:For the analyses in this paper, we included a total of 4,680 Hispanic women who participated in the Women's Health Initiative (WHI), a randomized clinical trial and observational study, at baseline (1994-1998) and at third-year follow-up and for whom blood pressure was measured at year 3 (n = 3,848). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of hypertension status, defined as systolic blood pressure ?140 mm Hg and/or diastolic blood pressure ?90 mm Hg, to assess the odds of incident hypertension at year 3 of follow-up in association with the factors included in the baseline models. RESULTS:At year 3 of follow-up, 27.3% of Hispanic women who were normotensive at baseline had progressed to prehypertension, and 9.0% had become hypertensive. Among the prehypertensive participants at baseline, 30.4% had progressed to hypertension. Compared with normotensive Hispanic women, hypertensive participants had a higher number of cardiovascular risk factors: body mass index ?30 kg/m(2) (OR = 3.76; 95% CI = 3.01-4.71), a family history of diabetes, stroke, and/or myocardial infarction (OR = 1.12; 95% CI 1.03-1.23), treated hypercholesterolemia (OR = 1.57; 95% CI = 1.23-1.99), treated diabetes (OR = 2.04; 95% CI = 1.40-2.97), and a history of cardiovascular disease (OR = 2.04; 95% CI = 1.58-2.64). CONCLUSIONS:Hispanic women seem to experience an increased risk of incident hypertension in later adulthood. On a practical level, recommendations for preventive care and population-wide adoption of health behaviors, such as community-focused campaigns to engage in physical activity, may contribute to reductions in hypertension risk factors. CLINICAL TRIALS REGISTRATION:Trial Number NCT00000611.

Project description:ImportanceCarpal tunnel syndrome (CTS) is a common and debilitating condition that commonly affects postmenopausal women.ObjectiveTo determine the effect of menopausal hormone therapy (HT) in healthy postmenopausal women on CTS risk.DesignWe conducted a secondary analysis of the Women's Health Initiative's (WHI) HT trials linked to Medicare claims data. Separate intention-to-treat analyses were performed for the two trials; the conjugated equine estrogens alone (CEE alone) and the trial of CEE plus medroxyprogesterone acetate (MPA) trial. (ClinicalTrials.gov, NCT number): NCT00000611.SettingTwo randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers.ParticipantsThe sample size included in the analysis was 16,053 community-dwelling women aged ≥65 years at study entry or those who later aged into Medicare eligibility, and who were enrolled in Medicare (including Part A and/or Part B coverage).InterventionWomen with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E+P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14203).Main outcome(s)The primary outcome was incident CTS and the secondary outcome was therapeutic CTS procedure occurring during the intervention phases of the trials.ResultsA total of 16,053 women were randomized in both trials. During mean follow up of 4.5 ± 2.8 years in the CEE trial (n = 6,833), there were 203 incident CTS cases in the intervention and 262 incident CTS cases in the placebo group (HR, 0.78; 95% CI, 0.65-0.94; P = 0.009). The CEE+MPA trial (n = 9,220) followed participants for a mean of 3.7 ± 2.3 years. There were 173 incident CTS cases in the intervention compared to 203 cases in the placebo group (HR, 0.80, 95% CI, 0.65-0.97; P = 0.027).ConclusionsThese findings suggest a protective effect of menopausal HT on the incidence of CTS among postmenopausal women. A potential therapeutic role for other forms of estrogen therapy in the management of CTS warrants future research.

Dataset Information

Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

Publications

Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

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