Original ArticleCardiovascular risk markers among obese women using the levonorgestrel-releasing intrauterine system: A randomised controlled trial☆
Introduction
The prevalence of obesity has increased in recent years, varying according to ethnicity and geographical location. In Brazil, 25% of women present obesity [1], [2]. Many of these women with obesity are of reproductive age, and addressing their contraceptive needs by providing them with safe and effective contraceptive methods is essential [3].
According to the World Health Organization’s (WHO) medical eligibility criteria (MEC) for contraceptive use, any hormonal contraceptive can be safely used by women with obesity who have no other comorbidities [4]. However, these women are at increased risk for hypertension and metabolic syndrome, which are Category 3 (a condition for which the risks usually outweigh the advantages of using the method) or 4 (a condition that represents an unacceptable health risk if the contraceptive method is used) for combined hormonal contraceptives (CHCs) use. Progestogen-only contraceptives (POCs), especially long-acting reversible contraceptives (LARCs) [implants and levonorgestrel-releasing intrauterine system (LNG-IUS)], and non-hormonal contraceptives can therefore be a safer option for these women [4].
Obesity itself may increase the risk for venous thrombosis two to three folds, even in the absence of associated comorbidities [5]. According to the Royal College of Obstetricians and Gynecologists (from the United Kingdom), the use of CHCs is category 3 for women with obesity with a body mass index (BMI) ≥ 35 kg/m2 [6] and only POCs and non-hormonal methods are eligible for these women [7].
Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species causes cardiovascular diseases, atherosclerosis, and diabetes [8]. Carotid intima-media thickness (c-IMT), arterial stiffness and vascular calcification are considered important markers of atherosclerosis and have been associated with an increased in cardiovascular events [9], [10]. Accurate, reproducible and easy detection of these parameters could increase the prognostic value of traditional cardiovascular risk factors in many subjects at low and intermediate risk [10]. Therefore, these markers are useful for evaluating cardiovascular risk before over clinical disease develops, particularly in adolescents or women of reproductive age [11], [12], [13].
Since obesity is an exclusion criterion in most contraceptive clinical studies, no randomised studies have previously evaluated the impact of POCs on cardiovascular risk markers in women with obesity. The objective of this study was to evaluate the effects of a LNG-IUS on subclinical markers of cardiovascular risk in women with obesity over a follow-up period of 12 months.
Section snippets
Study design
This was an open, randomised clinical trial study. Screening was carried out consecutively between April 2009 and October 2010 through radio announcements and print media available at the Hospital of Ribeirão Preto Medical School, University of São Paulo (HCFMRP-USP), and at primary care units in Ribeirão Preto, Brazil. The study was registered at ClinicalTrials.gov (www.clinicaltrials.gov — NCT01320917).
Participants
Inclusion criteria were 18–40 years-old women with a BMI ≥ 30 kg/m2 and <40 kg/m2 and who
Results
A total of 407 women were screened for eligibility. Of these, 251 were not eligible (25 due to BMI ≥ 40 kg/m2, 32 had BMI < 30 kg/m2, 9 were >40 years-old, 12 had no need for contraception, 18 were breastfeeding, 7 were pregnant, 16 met exclusion criteria due to medication use, 26 had hypertension, 19 had type 2 diabetes mellitus, 39 were using CHCs with no willingness to change it, 26 were smokers, 7 had hyperprolactinemia, 10 had hypothyroidism, and 5 had liver diseases). A total of 156 women met
Discussion
The main finding of this study is that LNG-IUS use is not associated with worsening subclinical cardiovascular risk variables compared to non-hormonal contraceptive use at 12 months of follow-up. LNG-IUS users had lower BMI, WC, and glycemia compared to non-hormonal contraceptive users at 12 months of follow-up. In addition, both groups had reduced insulin levels at the end of the study.
To our knowledge, the only study evaluating FMD in LNG-IUS users was a prospective observational study
Funding
CNPq (National Council of Technological and Scientific Development), through the National Institute of Science and Technology — Hormones and Women’s Health. The intrauterine system releasing levonorgestrel was kindly donated by the International Contraceptive Access (ICA) Foundation and the TCu380A intrauterine devices were donated by FMRP-USP.
References (28)
- et al.
Progestin-only contraception and thromboembolism: a systematic review
Contraception
(2016) - et al.
Combined assessment of flow-mediated dilation of the brachial artery and brachial-ankle pulse wave velocity improves the prediction of future coronary events in patients with chronic coronary artery disease
J Cardiol
(2014) - et al.
The relationship between endothelial function in the brachial artery and intima plus media thickening of the coronary arteries in patients with chest pain syndrome
Atherosclerosis
(2007) - et al.
Endothelial function in women using levonorgestrel-releasing intrauterine system (LNG-IUS)
Contraception
(2013) - et al.
Adolescent obesity is associated with high ambulatory blood pressure and increased carotid intimal-medial thickness
J Pediatr
(2005) - et al.
Effects of progestin-only long-acting contraception on metabolic markers in obese women
Contraception
(2013) - et al.
Effects of Mirena (levonorgestrel-releasing intrauterine system) and Ortho Gynae T380 intrauterine copper device on lipid metabolism: a randomized comparative study
Contraception
(2009) - et al.
Cardiovascular health in brazil: trends and perspectives
Circulation
(2016) - et al.
Cohort profile: longitudinal study of adult health (ELSA-Brasil)
Int J Epidemiol
(2015) - et al.
Risk of pregnancy complications in relation to maternal prepregnancy body mass index: population-based study from Finland 2006–10
Paediatr Perinat Epidemiol
(2015)
Medical eligibility criteria for contraceptive use
Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations
Br J Haematol
UK medical eligibility criteria for contraceptive use
Therapeutic strategies for oxidative stress-related cardiovascular diseases: removal of excess reactive oxygen species in adult stem cells
Oxid Med Cell Longev
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Metabolomics profile of 5649 users and nonusers of hormonal intrauterine devices in Finland
2022, American Journal of Obstetrics and GynecologyCitation Excerpt :Similarly, a population-based study reported similar levels of insulin, glucose, LDL cholesterol, triglycerides, and C-reactive protein in Finnish participants aged 31 years irrespective of 52-mg LNG IUD use or nonuse of any HCs.29 Moreover, several studies of at-risk populations, such as patients with thrombophilia, cardiovascular disease, obesity, endometriosis, PCOS, or at risk for venous thromboembolism, supported the safety of 52-mg LNG IUD in terms of systemic effects, with minimal or beneficial metabolic changes, such as moderate, often nonsignificant weight gain, increase of fat mass, and changes in the lipid metabolism.8,9,30–33 Most of the associations for the lipid panel were related to the absolute concentrations of lipids and lipids in lipoproteins, whereas associations with proportions of lipids in lipoproteins were less consistently significant (Figure 1).
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Clinical trial registration number: NCT01320917 (www.clinicaltrials.gov).