Comparison of the hemostatic effects of a levonorgestrel-releasing intrauterine system and leuprolide acetate in women with endometriosis: a randomized clinical trial

Abstract

Introduction: The hemostatic and inflammatory systems may activate each other. Endometriosis is a chronic inflammatory disease affecting 10% of women. The objective of this study was to compare the hemostatic effects of two treatments widely prescribed to women with endometriosis: the levonorgestrel intrauterine system (LNG-IUS) and the gonadotropin-releasing hormone analog (GnRHa) leuprolide acetate.

Materials and methods: In this randomized open-label controlled trial, 44 women with endometriosis were randomly allocated to one of two groups: 22 women were assigned to use LNG-IUS and 22 to use GnRHa. The assessed variables were D-dimers, fibrinogen, prothrombin time, activated partial thromboplastin time, coagulation factors (F) II, V, VII, VIII, IX, X, and XI, antithrombin (AT), protein C, free protein S, tissue plasminogen activator (t-PA), α2-antiplasmin, thrombin-antithrombin complex, and prothrombin fragment 1+2. All variables were assessed before treatment and six months after treatment onset.

Results: In the LNG-IUS group, FVIII decreased 10% after six months of use. In the GnRHa group, there was a 6% increase in AT, 29% reduction in D-dimers, and 19% increase in t-PA. The LNG-IUS users exhibited a significantly greater reduction of FVIII than the GnRHa users (LNG-IUS: -6.4 ± 14.3% vs. GnRHa: 4.2 ± 12.3%, p=0.02). The women in the GnRHa group exhibited a greater increase of AT than the LNG-IUS users (LNG-IUS: -0.7 ± 9.5% vs. GnRHa: 6.5 ± 10.1%, p=0.02).

Conclusion: Both hormonal treatments for endometriosis exhibited no association with a procoagulant profile.

Keywords: Blood coagulation; Endometriosis; GnRH agonist; Levonorgestrel; Progesterone-releasing intrauterine device.