Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue

Abstract 

Background

The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-IUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment.

Study Design

This was a randomized, prospective, open clinical study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion, and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index; systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment.

Results

After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean±SD) of VCAM (92.8±4.2 to 91.2±2.7 ng/mL, p=.04), CRP (0.38±0.30 to 0.28±0.21 mg/dL, p=.03), total cholesterol (247.0±85.0 to 180.0±31.0 mg/dL, p=.0002), triglycerides (118.0± 76.0 to 86.5±41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5±66.0 to 114.5±25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0±20.5 to 48.5±10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5±2.9 to 13.0±2.7 μmol/L, p=.04) and a reduction in IL-6 levels (4.3±3.9 to 2.3±0.8 pg/mL, p=.005), VCAM (94.0±3.8 to 92.0±1.6 ng/mL, p=.03) and total leukocytes (7330±2554 to 6350±1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference.

Conclusions

This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment.

Keywords: Endometriosis, Levonorgestrel, Cardiovascular diseases, Leuprolide, Risk factors