Continuous estetrol/drospirenone regimen for the treatment of endometriosis-related pain: preliminary results

Gynecol Endocrinol. 2026 Dec 31;42(1):2662694. doi: 10.1080/09513590.2026.2662694. Epub 2026 Apr 22.

Abstract

Purpose: Endometriosis is a chronic inflammatory condition that causes significant physical and psychological distress. This study aimed to evaluate the therapeutic efficacy and safety of a combined oral contraceptive containing estetrol (E4, 14 mg) and drospirenone (DRSP, 3 mg) in managing endometriosis-related pain.

Materials and methods: A retrospective cohort study was carried out at the Endometriosis Center, Federico II University Hospital, Naples, from January 2024 to November 2024. Forty patients with diagnosis of endometriosis and significant pain symptoms (VAS > 6) were included and received E4/DRSP under a continuous regimen for 6 months. Chronic pelvic pain, dyspareunia, dysmenorrhea, and patient quality of life were assessed at baseline, after 3 and 6 months. In the group of patients with endometrioma, reduction in size was evaluated.

Results: E4/DRSP significantly reduced chronic pelvic pain and dyspareunia. Dysmenorrhea was resolved entirely due to amenorrhea induction. Endometriomas decreased in size by 30% on average after 6 months. Adverse effects were mild and occurred in 13/40 of patients (32.5%).

Conclusion: E4/DRSP demonstrated efficacy and tolerability for managing endometriosis-related pain, offering a promising option for long-term treatment. Further research is needed to confirm its impact on lesion regression and disease progression.

Keywords: Endometriosis-related pain; combined hormonal contraceptives; dysmenorrhea; endometrioma; estetrol/drospirenone.

MeSH terms

  • Adult
  • Androstenes* / administration & dosage
  • Androstenes* / therapeutic use
  • Chronic Pain / drug therapy
  • Chronic Pain / etiology
  • Contraceptives, Oral, Combined* / administration & dosage
  • Contraceptives, Oral, Combined* / therapeutic use
  • Drug Combinations
  • Dysmenorrhea / drug therapy
  • Dysmenorrhea / etiology
  • Dyspareunia / drug therapy
  • Dyspareunia / etiology
  • Endometriosis* / complications
  • Endometriosis* / drug therapy
  • Ethinyl Estradiol* / administration & dosage
  • Female
  • Humans
  • Pelvic Pain* / drug therapy
  • Pelvic Pain* / etiology
  • Quality of Life
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Androstenes
  • drospirenone
  • Contraceptives, Oral, Combined
  • Ethinyl Estradiol
  • Drug Combinations
  • drospirenone and ethinyl estradiol combination