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Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis
  1. Jennifer Chae-Kim1,2,
  2. Gunjal Garg3,
  3. Larisa Gavrilova-Jordan4,
  4. Lindsay E Blake5,
  5. Tongil "TI" Kim6,
  6. Qiang Wu7 and
  7. Clifford C Hayslip8
  1. 1Department of Obstetrics and Gynecology, East Carolina University Brody School of Medicine, Greenville, North Carolina, USA
  2. 2Department of Obstetrics and Gynecology, Baylor Scott & White Medical Center Temple, Temple, Texas, USA
  3. 3Division of Gynecologic Oncology, East Carolina University Brody School of Medicine, Greenville, North Carolina, USA
  4. 4Division of Reproductive Endocrinology, Infertility and Genetics, Augusta University Medical College of Georgia, Augusta, Georgia, USA
  5. 5University of Arkansas for Medical Sciences Library, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
  6. 6Department of Marketing, Naveen Jindal School of Management, The University of Texas at Dallas, Richardson, Texas, USA
  7. 7Department of Biostatistics, East Carolina University, Greenville, North Carolina, USA
  8. 8Division of Reproductive Endocrinology and Infertility, East Carolina University Brody School of Medicine, Greenville, North Carolina, USA
  1. Correspondence to Dr Jennifer Chae-Kim, Department of Obstetrics and Gynecology, Baylor Scott & White Medical Center Temple, Temple, Texas, USA; jennifer.chaekim{at}bswhealth.org

Abstract

Objective Progestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.

Methods A systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.

Results In total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).

Conclusion For reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.

PROSPERO registration number CRD42020179069.

disease remission,

  • endometrial hyperplasia
  • endometrial neoplasms

Data availability statement

Data are available upon reasonable request.

Statistics from Altmetric.com

Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Contributors JC-K: conceptualization, methodology, validation, investigation, writing – original draft, writing – review & editing, visualization, project administration, guarantor. GG: methodology, verification, writing – review & editing, visualization, supervision. LG-J: writing – review & editing, visualization, supervision. LEB: methodology, investigation, resources, data curation. TK: methodology, software, formal analysis. QW: methodology, software, formal analysis. CCH: writing – review & editing, visualization, supervision.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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