The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo-controlled trial

Susan R. Davis, Penelope J. Robinson, Fiona Jane, Shane White, Kristy A. Brown, Sofie Piessens, Andrew Edwards, Jane McNeilage, Jillian Woinarski, Mitchell Chipman, Robin J. Bell

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3 Citations (Scopus)

Abstract

Background: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: 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 850 mg 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). Results: A total of 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, with 5(0.5-28) years postmenopause, and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4-21.9) for the placebo group (n = 52) and 2.5 mm (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 for 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 4 mm 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). Conclusions: 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.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalClinical Endocrinology
Volume89
Issue number5
DOIs
Publication statusPublished - 1 Nov 2018

Cite this

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. / The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo-controlled trial. In: Clinical Endocrinology. 2018 ; Vol. 89, No. 5. pp. 605-612.
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title = "The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo-controlled trial",
abstract = "Background: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: 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 850 mg 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). Results: A total of 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, with 5(0.5-28) years postmenopause, and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4-21.9) for the placebo group (n = 52) and 2.5 mm (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 for 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 4 mm 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). Conclusions: 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.",
author = "Davis, {Susan R.} and Robinson, {Penelope J.} and Fiona Jane and Shane White and Brown, {Kristy A.} and Sofie Piessens and Andrew Edwards and Jane McNeilage and Jillian Woinarski and Mitchell Chipman and Bell, {Robin J.}",
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The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo-controlled trial. / 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.

In: Clinical Endocrinology, Vol. 89, No. 5, 01.11.2018, p. 605-612.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo-controlled trial

AU - Davis, Susan R.

AU - Robinson, Penelope J.

AU - Jane, Fiona

AU - White, Shane

AU - Brown, Kristy A.

AU - Piessens, Sofie

AU - Edwards, Andrew

AU - McNeilage, Jane

AU - Woinarski, Jillian

AU - Chipman, Mitchell

AU - Bell, Robin J.

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N2 - Background: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: 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 850 mg 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). Results: A total of 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, with 5(0.5-28) years postmenopause, and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4-21.9) for the placebo group (n = 52) and 2.5 mm (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 for 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 4 mm 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). Conclusions: 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.

AB - Background: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: 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 850 mg 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). Results: A total of 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, with 5(0.5-28) years postmenopause, and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4-21.9) for the placebo group (n = 52) and 2.5 mm (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 for 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 4 mm 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). Conclusions: 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.

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