Metabolic safety of the etonogestrel contraceptive implant in healthy women over a 3-year period

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Abstract

Objective

To ascertain whether placement of the etonogestrel contraceptive implant induces significant changes in carbohydrate and lipid metabolism, as reflected by metabolic parameters, in healthy women.

Study design

Prospective cohort study of 213 healthy patients who received etonogestrel implants. Weight, BMI, blood pressure and a comprehensive metabolic profile were assessed at baseline, 1, 2 and 3 years. In 21 of the 213 participants, AUC for glucose levels, fasting insulin levels at baseline and year 3 (immediately before implant removal), HOMA-IR score, and the QUICK index were assessed. Parameters were expressed as median and interquartile range. The Wilcoxon test and ANOVA were used for comparison of measurements after implant placement (significance level p < 0.05).

Results

Median age was 26 years (range, 22–31.5). Results showed a trend toward increase of the variables weight (63.3–66.1) and BMI (24.7–25.7) and a decrease in TC (172–161.5), TG (75–69.5), and LDL (100.5–98.5) (p > 0.05). Of the metabolic variables, FBG (85–88) and HDL (53–46) had significant differences (p < 0.002). In the subgroup of 21 patients, there were reductions in insulin levels (9.65 vs. 8.4 mU/dL, p = 0.03), HOMA scores (2.06 vs. 1.75, p = 0.02), QUICK index (0.34 vs. 0.35, p = 0.03), TC (178 vs. 160 mg/dL, p = 0.001), HDL (51 vs. 46 mg/dL, p = 0.009), and LDL (110 vs. 100 mg/dL, p = 0.035).

Conclusion

These results provide evidence of the metabolic safety of the ENG implant in healthy women over a 3-year period. Indeed, implant placement induces changes consistent with a lower risk of insulin resistance and dyslipidemia.

Introduction

The long-lasting etonogestrel (ENG) contraceptive implant contains 68 mg of ENG, is placed subdermally in the non-dominant arm and exerts a contraceptive effect for 3 years [1], [2]. The effective contraception provided by long-lasting subdermal implants constitutes a major advance in women's independence. However, it has been speculated that these implants may lead to adverse metabolic effects, including changes in weight, body mass index (BMI), and carbohydrate and lipid metabolism [3].

Few studies have conducted prospective assessments of the safety of this implant in clinically healthy women. The present study evaluated the effects of the etonogestrel (ENG) implant on weight, BMI, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), fasting blood glucose (FBG), insulin, area under the blood glucose curve (AUC), homeostatic model assessment of insulin resistance (HOMA-IR) score, quantitative insulin sensitivity check (QUICK) index, and fasting glucose-to-insulin ratio (FGIR), over a 3-year period, with pairwise comparisons at baseline and year 3 (immediately prior to implant removal), in recipients of this mode of contraception.

Section snippets

Research design and methods

A prospective cohort study was conducted between 2007 and 2011 in a sample of 213 ENG implant recipients with a mean age of 26 years (range, 22–31.5). Weight, BMI, blood pressure, FBG, TC, HDL, LDL, and TG levels were measured at baseline (pre-implant), 1 year, 2 years, and 3 years. Of these 213 women, 21 agreed to take part in paired data collection, including area under the blood glucose curve (0, 30, 60, 90 and 120 min) and insulin measurements, at baseline and year 3 (immediately prior to

Results

Table 1 shows the results of all 213 women included in the study. The median age was 26 years (IQR 22–32), and the most prevalent ethnicities were white (74.6%), black (18.8%), and brown (6.6%). Overall, 23.3% of women were smokers; of these, 6.7% smoked >20 cigarettes/day. Subjects were assessed at four points in time: before implant placement (baseline, T0) and at 1 (T1), 2 (T2), and 3 (T3) years. Blood pressure rates remained constant throughout. On average, weight increased 3 kg and BMI

Discussion

In the present study, subjects exhibited an average weight gain of 3 kg over the 3-year study period. This finding is similar to that of other authors who reported a mean 2.6% increase in body weight over a 2-year period in the ENG implant group of the study. Despite this tendency to increase, the findings reported herein suggest that the weight gain observed after ENG implant placement is no worse than that identified after use of other contraceptive methods or in women unexposed to exogenous

Author contributions

J.V.B. researched data, contributed to the discussion, wrote, reviewed and edited the manuscript; L.C.V. researched data and reviewed the manuscript; H.M. researched data and reviewed the manuscript; M.P.S. contributed to the discussion and edited the manuscript; M.F.J. contributed to the discussion and edited the manuscript; P.E.B. contributed to the discussion, wrote, reviewed and edited the manuscript.

Conflict of interest statement

All authors declare they have no other relationships/conditions/circumstances that present a potential conflict of interest.

Acknowledgements

Dr. P. El Beitune is recipient of a Brazilian National Council for Scientific and Technological Development (CNPq) research fellowship (no. 302183/2012-4).

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