Endometriosis-associated pain scores and biomarkers in users of the etonogestrel-releasing subdermal implant or the 52-mg levonorgestrel-releasing intrauterine system for up to 24 months

Abstract

Objectives: The aims of the study were to correlate endometriosis-associated pain, evaluated by visual analogue scale (VAS) scores, with serum levels of etonogestrel (ENG), levonorgestrel (LNG), CA-125 and soluble CD23 in users of the ENG implant or the 52-mg LNG-releasing intrauterine system (52 mg LNG-IUS) for up to 2 years after device placement.

Methods: A randomised trial was conducted at the University of Campinas Medical School, Brazil. All participants (n = 103) had had endometriosis-associated chronic pelvic pain or dysmenorrhoea, or both, for more than 6 months. Participants were randomly assigned to use an ENG implant (experimental treatment) or a 52-mg LNG-IUS (active comparator). Follow-up was conducted 6 monthly for up to 24 months after device placement. Dysmenorrhoea and chronic pelvic pain were evaluated using a VAS and the scores were correlated with serum levels of ENG, LNG, CA-125 and soluble CD23.

Results: Both progestin-only contraceptives significantly reduced VAS scores for dysmenorrhoea and chronic pelvic pain and reduced serum levels of soluble CD23 (p < 0.001). Serum levels of CA-125 decreased only in the ENG implant group after 24 months’ use of the device (p < 0.001). No correlation was found between pain scores and ENG or LNG serum levels over time (p > 0.005).

Conclusion: Both contraceptives improved dysmenorrhoea and chronic pelvic pain scores in women with endometriosis-associated pain and they reduced serum levels of soluble CD23; however, serum levels of CA-125 were reduced only in ENG implant users over the 24-month study period.

摘要

目的：本研究的目的是通过视觉模拟量表（VAS）评分评估的子宫内膜异位症相关疼痛与长达2年的ENG植入或释放52 mg释放LNG的子宫内系统（52mg LNG-IUS）的使用者血清依托孕烯（ENG）, 左炔诺孕酮（LNG）, CA-125和可溶性CD23血清水平的相关性。

方法：在巴西坎皮纳斯大学医学院进行了一项随机试验, 所有参与者（n = 103）均患有子宫内膜异位症相关的慢性骨盆痛或痛经, 或两者兼有, 并超过6个月。参与者被随机分配使用ENG植入物（实验治疗）或52 mg LNG-IUS（活性比较剂）, 在放置设备后的24个月内, 每6个月进行随访。使用VAS对痛经和慢性盆腔痛进行评估, 并将其比较与血清ENG, LNG, CA-125和可溶性CD23的血清水平的相关性。

结果：两种仅使用孕激素的避孕药均可明显降低痛经和慢性盆腔痛的VAS评分, 并降低血清可溶性CD23的水平（p<0.001）；使用ENG植入装置24个月后, 血清CA-125水平下降（p <0.001）；随着时间的推移, 疼痛评分与ENG或LNG血清水平之间未发现相关性（p> 0.005）。

结论：两种避孕药均能改善子宫内膜异位症相关疼痛妇女的痛经和慢性盆腔疼痛评分, 并降低血清可溶性CD23水平。 但是, 在只有24个月的研究期内, 仅ENG植入使用者中的CA-125血清水平会降低。

Keywords:

• Biomarkers
• CA-125
• chronic pelvic pain
• endometriosis
• etonogestrel implant
• 52-mg levonorgestrel-releasing intrauterine system
• soluble CD23

Acknowledgements

The LNG-IUS devices were donated by the International Contraceptive Access Foundation, Turku, Finland, under an unrestricted grant.

Disclosure statement

LB receives honoraria as an advisory board member and has been an invited speaker at scientific meetings for Bayer HealthCare Pharmaceuticals and MSD. He is a non-remunerated member of the International Contraceptive Access Foundation. The other authors report no conflict of interest.

Funding

The study received partial financial support from the Fundação de Apoio à Pesquisa do Estado de São Paulo [awards 2015/20504-9 and 2015/10021] and from CNPq, the Brazilian National Council for Scientific and Technological Development [grant 573747/2008-3]. ENG implants and financial assistance for the study were provided by MSD. The donors did not participate in the protocol design, conduct of the study, analysis of the data or drafting of the manuscript.

Box B

Lost to follow-up at 24 months (n = 21)

Discontinued intervention up to 24 months (n = 11)

• Surgery and device removal (n = 1)

  • No reason given

• Surgery without device removal (n = 1)

• Device removal and change to progestin-only pill (n = 2)

• Device removal and change to ENG implant (n = 2)

• Device expelled (n = 5)