The effect of metformin vs placebo on sex hormones in Canadian cancer trials group MA.32

Research output: Contribution to journalArticlepeer-review


  • Isabel Pimentel
  • Bingshu E. Chen
  • Ana Elisa Lohmann
  • Marguerite Ennis
  • Jennifer Ligibel
  • Lois Shepherd
  • Dawn L. Hershman
  • Timothy Whelan
  • Vuk Stambolic
  • Ingrid Mayer
  • Timothy Hobday
  • Julie Lemieux
  • Alastair Thompson
  • Priya Rastogi
  • Karen Gelmon
  • Manuela Rabaglio
  • Susan Ellard
  • Mihaela Mates
  • Philippe Bedard
  • Lacey Pitre
  • Theodore Vandenberg
  • Ryan J.O. Dowling
  • Wendy Parulekar
  • Pamela J. Goodwin

Colleges, School and Institutes

External organisations

  • Vall d`Hebron Institute of Oncology (VHIO)
  • Queen's University
  • University of Western Ontario
  • Applied Statistician
  • Dana-Farber Cancer Institute
  • Columbia University
  • Juravinski Cancer Centre at Hamilton Health Sciences
  • University Health Network
  • Vanderbilt-Ingram Cancer Center
  • Mayo Clinic
  • Hopital Enfant Jesus Site
  • Baylor College of Medicine
  • National Surgical Adjuvant Breast and Bowel Project
  • BCCA-Vancouver Cancer Centre
  • IBCSG Coordinating Centre
  • BCCA-Cancer Centre for the Southern Interior
  • Cancer Centre of Southeastern Ontario
  • Health Sciences North
  • London Regional Cancer Program
  • University of Toronto


BACKGROUND: Metformin has been associated with lower breast cancer (BC) risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones. We evaluated the effect of metformin on sex hormones in MA.32, a phase III trial of nondiabetic BC subjects who were randomly assigned to metformin or placebo.

METHODS: We studied the subgroup of postmenopausal hormone receptor-negative BC subjects not receiving endocrine treatment who provided fasting blood at baseline and at 6 months after being randomly assigned. Sex hormone-binding globulin, bioavailable testosterone, and estradiol levels were assayed using electrochemiluminescence immunoassay. Change from baseline to 6 months between study arms was compared using Wilcoxon sum rank tests and regression models.

RESULTS: 312 women were eligible (141 metformin vs 171 placebo); the majority of subjects in each arm had T1/2, N0, HER2-negative BC and had received (neo)adjuvant chemotherapy. Mean age was 58.1 (SD=6.9) vs 57.5 (SD=7.9) years, mean body mass index (BMI) was 27.3 (SD=5.5) vs 28.9 (SD=6.4) kg/m2 for metformin vs placebo, respectively. Median estradiol decreased between baseline and 6 months on metformin vs placebo (-5.7 vs 0 pmol/L; P < .001) in univariable analysis and after controlling for baseline BMI and BMI change (P < .001). There was no change in sex hormone-binding globulin or bioavailable testosterone.

CONCLUSION: Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers.

Bibliographic note

Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email:


Original languageEnglish
Pages (from-to)192-198
Number of pages7
JournalJournal of the National Cancer Institute
Issue number2
Early online date4 Jun 2020
Publication statusPublished - Feb 2021

ASJC Scopus subject areas

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