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


METHODS
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 mumol/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.
Ferreira
Rodrigo Alves
RA
Department of Obstetrics and Gynecology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil. rodrigoalf@ufscar.br
Vieira
Carolina Sales
CS
Rosa-E-Silva
Júlio César
JC
Rosa-e-Silva
Ana Carolina J Sá
AC
Nogueira
Antonio A
AA
Ferriani
Rui A
RA
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002319:Cardiovascular System / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000008:administration & dosage; D004715:Endometriosis / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007436:Intrauterine Devices, Medicated; D016729:Leuprolide / Q000008:administration & dosage*; D016912:Levonorgestrel / Q000008:administration & dosage*; D010146:Pain / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D010147:Pain Measurement; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D003271:Contraceptive Agents, Female; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D016912:Levonorgestrel; D016729:Leuprolide