Differences in response to dienogest therapy among different phenotypes of endometriosis: A single-center retrospective cohort analysis

Medicine (Baltimore). 2026 Feb 13;105(7):e47624. doi: 10.1097/MD.0000000000047624.

Abstract

This study aims to investigate the differences in response to dienogest (DNG) therapy among patients with 3 different phenotypes of endometriosis: ovarian endometrioma (OMA), superficial peritoneal endometriosis (SUP), and deep infiltrating endometriosis (DIE). This study was a single-center retrospective cohort analysis. A total of 501 consecutive patients with endometriosis diagnosed and treated in our hospital from January 2023 to January 2024 were enrolled and divided into the OMA group (n = 276), SUP group (n = 125), and DIE group (n = 100) based on imaging/surgical phenotypes. All patients received monotherapy with DNG (2 mg/day) for at least 6 months. Differences in pain visual analog scale (VAS) scores, lesion size, serum CA125 levels, quality of life (36-Item Short Form Health Survey), and adverse reactions before and after treatment were compared among the 3 groups. Multivariate logistic regression analysis was used to identify independent influencing factors for significant pain relief (defined as ≥50% reduction in VAS score). At baseline, disease duration, revised American Society for Reproductive Medicine stage and score, CA125 levels, and pain intensity in the DIE group were significantly higher than those in the OMA and SUP groups (P < .001). After 6 months of treatment, pain VAS scores, lesion size, and CA125 levels significantly decreased from baseline in all 3 groups (P < .001). Intergroup comparisons showed statistically significant differences in the reduction of VAS scores (ΔVAS) for dysmenorrhea and chronic pelvic pain (P < .01), with the SUP group showing the smallest improvement. Meanwhile, the lesion reduction rate in the OMA group was significantly higher than that in the SUP and DIE groups (47.5% vs 39.4% vs 37.9%, P < .001). Multivariate regression analysis showed that, compared with the OMA phenotype, the DIE phenotype was an independent negative predictor for significant pain relief (odds ratio = 0.67, 95% confidence interval: 0.43-0.99, P = .046). DNG is significantly effective for all 3 endometriosis phenotypes, effectively relieving pain, reducing lesion size, and improving quality of life. However, patients with the DIE phenotype, due to the inherently more severe nature of their disease, have a relatively lower likelihood of achieving significant pain relief and a higher incidence of adverse reactions, necessitating special attention in clinical management.

Keywords: dienogest; endometriosis; pain; phenotype; retrospective studies; treatment outcome.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • CA-125 Antigen / blood
  • Endometriosis* / drug therapy
  • Endometriosis* / pathology
  • Female
  • Hormone Antagonists* / therapeutic use
  • Humans
  • Nandrolone* / administration & dosage
  • Nandrolone* / analogs & derivatives
  • Nandrolone* / therapeutic use
  • Pain Measurement
  • Pelvic Pain / drug therapy
  • Pelvic Pain / etiology
  • Phenotype
  • Quality of Life
  • Retrospective Studies
  • Treatment Outcome

Substances

  • dienogest
  • Nandrolone
  • CA-125 Antigen
  • Hormone Antagonists