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Title: The benefits of adding metformin to tamoxifen to protect the endometrium- a randomized placebo-controlled trial.
Austin Authors: Davis, Susan R;Robinson, Penelope J;Jane, Fiona;White, Shane ;Brown, Kristy A;Piessens, Sofie;Edwards, Andrew;McNeilage, Jane;Woinarski, Jillian;Chipman, Mitchell;Bell, Robin J
Affiliation: Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Weill Cornell Medicine, NY, NY, USA
Camberwell Ultrasound for Women, Melbourne, Malvern, Vic, Australia
Epworth Healthcare, East Melbourne, Vic, Australia
Victorian Breast & Oncology Care, East Melbourne, Vic, Australia
Women's Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia
Issue Date: Nov-2018
Date: 2018-08-14
Publication information: Clinical Endocrinology 2018; 89(5): 605-612
Abstract: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. This was a single centre, randomized, double-blind, placebo-controlled, parallel group trial. Postmenopausal women with hormone receptor-positive breast cancer taking tamoxifen were randomly allocated to metformin 850mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA-IR). 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43-72) years, 5(0.5-28) years post menopause and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9mm (1.4-21.9) for the placebo group (n=52) and 2.5mm (1.3-14.8) for the metformin group (n=50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n=36) than the placebo group (n=45), (2.3 mm (1.4-7.8) vs 3.0 (1.2-11.3); p=0.05). 13.3% allocated to placebo had an ET greater than 4mm vs 5.7% for metformin (p=0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline adjusted reductions in weight (p<0.001), waist circumference (0.03) and HOMA-IR (p<0.001). Metformin appears to inhibit tamoxifen-induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent, EH and cancer is warranted. This article is protected by copyright. All rights reserved.
DOI: 10.1111/cen.13830
Journal: Clinical Endocrinology
PubMed URL: 30107043
Type: Journal Article
Appears in Collections:Journal articles

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