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Metformin use is associated with a lower risk of uterine leiomyoma in female type 2 diabetes patients.

ABSTRACT: Background:Whether metformin may reduce the risk of uterine leiomyoma in type 2 diabetes patients has not been investigated. This retrospective cohort study compared the risk of uterine leiomyoma in ever versus never users of metformin. Methods:Female patients with new-onset type 2 diabetes during 1999-2005 were enrolled from the reimbursement database of Taiwan's National Health Insurance and followed up from 1 January 2006 until 31 December 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort of 10,998 ever users and 10,998 never users of metformin. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS. Results:A total of 321 never users and 162 ever users developed uterine leiomyoma during follow up, with respective incidence of 704.65 and 329.82 per 100,000?person-years. The overall hazard ratio was 0.467 (95% confidence interval: 0.387-0.564). The hazard ratios for the first (<23.3?months), second (23.3-53.1?months), and third (>53.1?months) tertiles of cumulative duration were 0.881 (0.685-1.132), 0.485 (0.367-0.642), and 0.198 (0.134-0.291), respectively; and were 0.751 (0.576-0.980), 0.477 (0.360-0.632), and 0.277 (0.198-0.386), respectively, for the first (<655,000?mg), second 655,000-1,725,500?mg), and third (>1,725,500) tertiles of cumulative dose. Sensitivity analyses after excluding users of sulfonylurea, users of estrogen, users of insulin, users of incretin-based therapies during follow up, patients with irregular drug refills, patients who discontinued the use of metformin, patients who received metformin prescription less than four times, or redefining uterine leiomyoma by using 'diagnostic code' plus 'procedure codes' consistently supported a lower risk of uterine leiomyoma in ever users of metformin. Conclusion:Metformin use is associated with a lower risk of uterine leiomyoma.

SUBMITTER: Tseng CH

PROVIDER: S-EPMC6920594 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Metformin use is associated with a lower risk of uterine leiomyoma in female type 2 diabetes patients.

Tseng Chin-Hsiao CH

Therapeutic advances in endocrinology and metabolism 20191218

<h4>Background</h4>Whether metformin may reduce the risk of uterine leiomyoma in type 2 diabetes patients has not been investigated. This retrospective cohort study compared the risk of uterine leiomyoma in ever <i>versus</i> never users of metformin.<h4>Methods</h4>Female patients with new-onset type 2 diabetes during 1999-2005 were enrolled from the reimbursement database of Taiwan's National Health Insurance and followed up from 1 January 2006 until 31 December 2011. Analyses were conducted i ...[more]

PMID: 31897287

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Project description:BackgroundType 2 diabetes (T2D) has been associated with increased breast cancer risk, but commonly prescribed antidiabetic medications such as metformin may reduce risk. Few studies have investigated T2D and medications together in relation to breast cancer.Patients and methodsData came from 44 541 Sister Study participants aged 35 to 74 years at enrollment (2003-2009) who satisfied eligibility criteria, followed through 15 September 2017. Information on time-varying, self-reported, physician-diagnosed, prevalent and incident T2D, use of antidiabetic medications, and covariates was obtained from baseline and follow-up questionnaires. Incident breast cancers were confirmed with medical records. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated.ResultsDuring follow-up (median, 8.6 years), 2678 breast cancers were diagnosed at least 1 year after enrollment. There were 3227 women (7.2%) with prevalent and 2389 (5.3%) with incident T2D, among whom 61% (n = 3386) were ever treated with metformin. There was no overall association between T2D and breast cancer risk (HR 0.99; 95% CI, 0.87-1.13). However, T2D was associated with increased risk of triple-negative breast cancer (HR 1.40; 95% CI, 0.90-2.16). Compared with not having T2D, T2D with metformin use was not associated with overall breast cancer risk (HR 0.98; 95% CI, 0.83-1.15), but it was associated with decreased risk of estrogen receptor (ER)-positive breast cancer (HR 0.86; 95% CI 0.70-1.05) and increased risk of ER-negative (HR 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive cancer was stronger for longer duration (≥10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend = 0.09). Results were supported by sensitivity analyses.ConclusionOur findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.

Project description:ObjectiveInvestigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.MethodsWe conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.ResultsOf participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).ConclusionRecent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.

Dataset Information

Metformin use is associated with a lower risk of uterine leiomyoma in female type 2 diabetes patients.

Publications

Metformin use is associated with a lower risk of uterine leiomyoma in female type 2 diabetes patients.

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