Assessment of biomarkers in women with endometriosis-associated pain using the ENG contraceptive implant or the 52 mg LNG-IUS: a non-inferiority randomised clinical trial

Eur J Contracept Reprod Health Care. 2018 Oct;23(5):344-350. doi: 10.1080/13625187.2018.1531117. Epub 2018 Oct 29.


Objective: The aim of the study was to assess the serum levels of the following biomarkers in women with endometriosis-associated pelvic pain before and after six months of using the etonogestrel (ENG) contraceptive implant or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS): cancer antigen (CA)-125, cluster of differentiation (CD) 23 and endometrial nerve fibre density.

Methods: The study was conducted at the Department of Obstetrics and Gynaecology, University of Campinas Medical School, Brazil. A total of 103 women with endometriosis-associated pain diagnosed by surgery, transvaginal ultrasound and/or magnetic resonance imaging were included. Endometrial nerve fibre density and serum levels of CA-125 and soluble CD23 were assessed before and after six months of using the allocated method and were correlated to 10 cm visual analogue scale (VAS) scores for non-cyclical pelvic pain and dysmenorrhoea.

Results: Both contraceptive methods significantly reduced concentrations of serum soluble CD23 and endometrial nerve fibre density (p < .001); however, CA-125 was significantly reduced only among users of the ENG implant (p < .05). No correlation was observed between reduction of biomarkers and improvement of VAS pain and dysmenorrhoea scores. No differences were observed between the ENG implant and the LNG-IUS.

Conclusion: Both progestin-only contraceptives significantly reduced two out of the three biomarkers evaluated. These two biomarkers could, therefore, be used as surrogate markers to follow up medical treatment of endometriosis-associated pain.

Keywords: Biomarkers; CA-125; CD23; endometrial nerve fibres; endometriosis; etonogestrel implant; levonorgestrel-releasing intrauterine system.

Publication types

  • Equivalence Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / blood
  • Brazil
  • CA-125 Antigen / blood
  • Contraceptive Agents, Female / administration & dosage*
  • Desogestrel / administration & dosage*
  • Drug Implants / administration & dosage
  • Endometriosis / blood*
  • Endometriosis / complications
  • Endometriosis / drug therapy
  • Endometrium / innervation
  • Female
  • Humans
  • Intrauterine Devices, Medicated
  • Levonorgestrel / administration & dosage*
  • Nerve Fibers / pathology
  • Pelvic Pain / blood*
  • Pelvic Pain / etiology
  • Receptors, IgE / blood
  • Treatment Outcome


  • Biomarkers
  • CA-125 Antigen
  • Contraceptive Agents, Female
  • Drug Implants
  • Receptors, IgE
  • etonogestrel
  • Levonorgestrel
  • Desogestrel