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

Abstract

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.

摘要

目的：这项研究的目的是评估在子宫内膜异位症相关的女性盆腔疼痛患者中用依托孕烯 （ENG）避孕植入装置或52毫克左炔诺孕酮宫内节育器（LNG-IUS）之前和之后六个月的血清生物标志物水平：肿瘤抗原（CA）-125年, 分化抗原簇（CD）-23和子宫内膜神经纤维密度。

方法：这项研究是在巴西坎皮纳斯大学医学院妇产科进行的。纳入103例经手术、经阴道超声和/或磁共振成像诊断为子宫内膜异位相关疼痛的妇女。采用分配法测定干预前后6个月的子宫内膜神经纤维密度、血清CA-125和可溶性-CD23水平, 并用10cm视觉模拟评分（VAS）与非周期性盆腔疼痛和痛经患者进行相关性分析。

结果：两种避孕方法均显著降低血清可溶性CD23浓度和子宫内膜神经纤维密度（p< .001）；然而, 只有在用ENG避孕植入装置的患者中, CA-125水平显著降低（p< 0.05）。生物标志物的降低与VAS疼痛和痛经评分的改善之间没有相关性。ENG避孕植入装置与LNG-IUS无明显差异。

结论：两种仅用孕激素的避孕药物都显著降低了所评估的三种生物标志物中的两种。因此, 这两种生物标记物可以作为子宫内膜异位相关疼痛的替代标记物来追踪治疗。

Keywords:

• Biomarkers
• CA-125
• CD23
• endometrial nerve fibres
• endometriosis
• etonogestrel implant
• levonorgestrel-releasing intrauterine system

Acknowledgment

The LNG-IUS were donated by the ICA Foundation, Turku, Finland, under an unrestricted grant. The donors did not participate in the study protocol design, study conduct, analysis of data or writing of the manuscript.

Disclosure statement

LB receives an honorarium as an advisory board member and has been an invited speaker at scientific meetings for Bayer Healthcare Pharmaceuticals and Merck. He is also a non-remunerated member of the International Contraceptive Access (ICA) Foundation. No potential conflict of interest was reported by the authors.

Additional information

Funding

This study received partial financial support from the Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP), awards 2015/20504-9 and 2015/10021 and from the National Research Council (CNPq), [grant 573747/2008-3]. Funds for the study were also provided by Merck, in addition to the ENG implants.