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#Grand Rounds

Complex Atypical Hyperplasia: LNG-IUD vs Systemic Progestin Therapy

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BACKGROUND AND PURPOSE:

  • For patients who desire fertility or are poor surgical candidates, treatment for complex atypical hyperplasia is an option  
  • Mandelbaum et al. (AJOG, 2020) examined differences in complex atypical hyperplasia treatment effectiveness between
    • Levonorgestrel-releasing IUD
    • Systemic progestin therapy

METHODS:

  • Retrospective study (2003 to 2018)
  • Participants
    • Women with complex atypical hyperplasia who received progestin therapy 
  • Exposures
    • Levonorgestrel-releasing IUD
    • Systemic progestin therapy
  • Study design
    • Treatment response was assessed by histopathology on subsequent biopsies
    • Time-dependent analyses of complete response and progression to cancer were performed comparing exposures
    • Propensity score used to create a weighted cohort to account for treatment type
    • Impact of body habitus on treatment response was assessed

RESULTS:

  • 245 women included
    • IUD: 69 women
    • Systemic: 176 women
    • Mean age 36.9 years | Mean BMI 40.0 kg/m2
  • Systemic therapy
    • Oral megestrol acetate: 79.5%
    • Oral medroxyprogesterone acetate: 15.9%
    • Other oral or injectable progestins: 4.5%
  • Levonorgestrel-releasing IUD group had
    • Higher rates of complete response
      • IUD: 78.7%
      • Systemic: 46.7%
      • Adjusted hazard ratio 3.32 (95% CI, 2.39 to 4.62)
    • Lower likelihood of progression to cancer
      • IUD: 4.5%
      • Systemic: 15.7%
      • aHR 0.28 (95% CI, 0.11 to 0.73)
  • Class 3 obesity was associated with a higher relative benefit from IUD therapy in achieving complete response
    • Class 3 obesity: aHR 4.72 (95% CI, 2.83 to 7.89)
    • Class 1 and 2 obesity: aHR 1.83 (95% CI, 1.09 to 3.09)
    • Nonobese: aHR 1.26 (95% CI, 0.40 to 3.95)
  • After 2007
    • LNG-IUD increased: 6.3% to 82.7%; 13.2-fold increase
    • Obesity rate increased: 77.8% to 88.2%; 13.4% relative increase
    • Improved rates of complete response increased: 32.9% to 81.4%; 2.5-fold increase (P = .005)

CONCLUSION:

  • The patient population analyzed in this study was mostly comprised of women with obesity
  • Localized progestin therapy with the levonorgestrel-releasing IUD may be a more effective treatment option for complex atypical hyperplasia, compared with systemic treatment
  • The authors state that these improved outcomes, including complete response rates, were 

…most pronounced in morbidly obese women, who had a more than 4 times greater likelihood of complete response with the LNG-IUD

Moreover, treatment paradigm shifts toward increasing LNG-IUD use in an increasingly obese population led to improved complete response rates overall

Learn More – Primary Sources:

Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy

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Atypical Hyperplasia Confined to Polyps: What is the Incidence of Endometrial Carcinoma?
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