Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial

Gynecol Oncol. 2021 Apr;161(1):143-151. doi: 10.1016/j.ygyno.2021.01.029.


Purpose: Intrauterine levonorgestrel (LNG-IUD) is used to treat patients with endometrial adenocarcinoma (EAC) and endometrial hyperplasia with atypia (EHA) but limited evidence is available on its effectiveness. The study determined the extent to which LNG-IUD with or without metformin (M) or weight loss (WL) achieves a pathological complete response (pCR) in patients with EAC or EHA.

Patients and methods: This phase II randomized controlled clinical trial enrolled patients with histologically confirmed, clinically stage 1 FIGO grade 1 EAC or EHA; a body mass index > 30 kg/m2; a depth of myometrial invasion of less than 50% on MRI; a serum CA125 ≤ 30 U/mL. All patients received LNG-IUD and were randomized to observation (OBS), M (500 mg orally twice daily), or WL (pooled analysis). The primary outcome measure was the proportion of patients developing a pCR (defined as absence of any evidence of EAC or EHA) after 6 months.

Results: From December 2012 to October 2019, 165 patients were enrolled and 154 completed the 6-months follow up. Women had a mean age of 53 years, and a mean BMI of 48 kg/m2. Ninety-six patients were diagnosed with EAC (58%) and 69 patients with EHA (42%). Thirty-five participants were randomized to OBS, 36 to WL and 47 to M (10 patients were withdrawn). After 6 months the rate of pCR was 61% (95% CI 42% to 77%) for OBS, 67% (95% CI 48% to 82%) for WL and 57% (95% CI 41% to 72%) for M. Across the three treatment groups, the pCR was 82% and 43% for EHA and EAC, respectively.

Conclusion: Complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups.

Trial registration: U.S. National Library of Medicine, NCT01686126.

Keywords: Endometrial cancer; Fertility preservation; Levonorgestrel intrauterine device; Metformin; Physical activity; Progestin/progesterone; Weight loss.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / therapy
  • Female
  • Humans
  • Intrauterine Devices, Medicated*
  • Levonorgestrel / administration & dosage*
  • Metformin / administration & dosage
  • Middle Aged
  • Neoplasm Staging
  • Weight Loss
  • Weight Reduction Programs / methods


  • Levonorgestrel
  • Metformin

Associated data