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Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia
  1. Koji Matsuo1,2,
  2. Rachel S Mandelbaum1,
  3. Marcia Ciccone1,2,
  4. Mahdi Khoshchehreh1,
  5. Heena Pursuwani1,
  6. Elise B Morocco1,
  7. Shinya Matsuzaki1,
  8. Christina E Dancz1,
  9. Begum Ozel1,
  10. Richard J Paulson1 and
  11. Lynda Roman1,2
  1. 1Obstetrics and Gynecology, University of Southern California, Los Angeles, California, USA
  2. 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California, USA
  1. Correspondence to Dr Koji Matsuo, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA; koji.matsuo{at}gmail.com

Abstract

Introduction Previous studies have suggested that metformin use may enhance the therapeutic effect of progestin therapy for endometrial hyperplasia or malignancy. However, it is not known how the impact of concurrent metformin may be altered by route of progestin therapy, either locally via an intrauterine device or systemically. This study examined the effectiveness of concurrent metformin use and progestin therapy for women with complex atypical hyperplasia stratified by progestin route (systemic vs local).

Methods This single-institution retrospective study examined consecutive women with complex atypical hyperplasia who received progestin therapy from 2003 to 2018. Time-dependent analyses for complete response rate were performed comparing concurrent metformin users versus non-users in the oral progestin group and in the levonorgestrel-releasing intrauterine device group.

Results Across the study cohort (n=245), there were 137 (55.9%) women who responded to progestin therapy. In the oral progestin group (n=176), the median age and body mass index were 36 years and 37.7 kg/m2, respectively. 36 (20.5%) of women on oral progestins also took metformin. After controlling for diabetes status, women taking both oral progestins and metformin had a complete response rate similar to those not taking metformin (6 month cumulative rates, 23.1% vs 27.8%, adjusted hazard ratio (aHR) 0.71, 95% confidence interval (95% CI) 0.36 to 1.41). In the levonorgestrel-releasing intrauterine device group (n=69), the median age and body mass index were 35 years and 39.9 kg/m2, respectively. There were 15 (21.7%) women who took metformin in addition to the levonorgestrel-releasing intrauterine device. After controlling for diabetes status, women who had the levonorgestrel-releasing intrauterine device and took metformin had a significantly higher complete response rate compared with those not taking metformin (6 month cumulative rates, 86.7% vs 58.9%, aHR 2.31, 95% CI 1.09 to 4.89).

Conclusion In a predominantly obese population, concurrent metformin may possibly offer treatment benefit when used with the levonorgestrel-releasing intrauterine device.

  • endometrial hyperplasia
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Footnotes

  • KM and RSM contributed equally.

  • Contributors Conceptualization: KM; Data curation: RSM, MAC, MK, HP, EBM; Formal analysis: KM; Funding acquisition: KM, LDR; Investigation: all authors; Methodology: KM; Project administration: MAC, CED; Resources: all; Software: KM; Supervision: KM; Validation: KM; Visualization: KM, SM; Writing - original draft: KM; Writing - review & editing: all authors.

  • Funding This study was funded by Ensign Endowment for Gynecologic Cancer Research (KM).

  • Competing interests Consultant, Quantgene (LDR); honorarium, Chugai, textbook editorial expense, Springer, and investigator meeting attendance expense, VBL therapeutics (KM); Research funding, MSD (SM).

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available.

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