Citations 1
The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32
Pimentel, Isabel , Chen, Bingshu E. , Lohmann, Ana Elisa , Ennis, Marguerite , Ligibel, Jennifer A. , Shepherd, Lois E. , Hershman, Dawn L. , Whelan, Timothy J. , Stambolic, Vuk , Hobday, Timothy J. , Lemieux, Julie , Thompson, Alastair, Rastogi, Priya , Rea, Daniel , Mates, Mihaela , Bédard, Philippe L. , Pitre, Lacey D. , Vandenberg, Theodore A. , Parulekar, Wendy R. , Goodwin, Pamela J. , Hobday, Timothy, Ennis, Marguerite , Chen, Bingshu E , Hershman, Dawn L , Stambolic, Vuk , Rea, Daniel W , Mayer, Ingrid A. , Gelmon, Karen A. , Rabaglio, Manuela , Ellard, Susan L. , Dowling, Ryan J.O.
JNCI: Journal of the National Cancer Institute | June 1, 2020 | Volume: 113 | Issue: 2 | Pages: 192-198
Abstract 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.