Relationship between patient characteristics and serum etonogestrel concentrations in contraceptive implant users

Abstract

Objective: To determine whether serum etonogestrel concentrations in contraceptive implant users are associated with certain individual patient characteristics.

Study design: We enrolled reproductive-age women using etonogestrel contraceptive implants between 12-36 months duration and measured a single serum etonogestrel concentration. Participants also completed a questionnaire about demographics.

Results: We enrolled 350 participants; median age was 22.5 years (range 18.0-39.1), median months of implant use was 26.0 (range 12.0-36.0), and median body mass index was 25.7 kg/m2 (range 18.5-52.0). Our study population was primarily white/Caucasian (46.6% [163/350]) and Hispanic/Latina ethnicity (51.4% [180/350]). The median serum etonogestrel concentration was 137.4 pg/ml and etonogestrel concentrations varied 12.4 fold in the population (range 55.8-695.1 pg/ml). Using forward stepwise linear regression, months of implant use (β=-1.74, p<.001) and body mass index (β=-3.10, p<.001) were both significantly associated with decreased serum etonogestrel concentration with Black/African American race as a positive effect modifier (β=18.24, p=.099); R-squared for the model=0.13.

Conclusions: Individuals demonstrated a wide variability in serum etonogestrel concentrations, which can potentially affect side-effect profiles and efficacy. Increasing body mass index and longer duration of implant use were associated with small decreases in serum etonogestrel concentrations, while self-reported Black/African American race was associated with a non-significant increase. Despite these findings, most of etonogestrel variability was unaccounted for, suggesting that other clinical, pharmacologic, and genetic factors contributing to variability in etonogestrel concentrations remain to be determined.

Implications: Although increases in body mass index are associated with lower etonogestrel levels in contraceptive implant users, the majority of women will maintain serum concentrations that consistently suppress ovulation. Furthermore, certain patient characteristics can only explain a small portion (13%) of the variability in serum etonogestrel levels among contraceptive implant users.

Trial registration: ClinicalTrials.gov NCT03092037.

Keywords: Body mass index; Contraceptive implant; Etonogestrel; Pharmacokinetics.

Conflict of interest statement

Conflicts of Interest: Dr. Teal has served on scientific advisory boards of Allergan and Bayer Healthcare, and serves on a Data Monitoring Board for a study funded by Merck and Co. Dr. Teal and Dr. Lazorwitz receive research funding from Merck and Co. for an Investigator Initiated Study on drug-drug interactions with the etonogestrel contraceptive implant. The University of Colorado Department of Obstetrics and Gynecology has received research funding from Bayer, Agile Therapeutics, Merck and Co, and Medicines360. Dr. Guiahi’s time was supported by the Society of Family Planning Junior Investigator Career Grant SFPRF10-JI1. The authors have no other conflicts of interest to disclose.

Declaration of interests

☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1:

Box-plot of serum etonogestrel (ENG) concentrations for all 350 participants. The box represents the first and third quartiles (interquartile range = 63.5pg/mL) with the band inside the box representing the median (137.4pg/mL). Whiskers represent the data within 1.5 interquartile range of the upper and lower quartile.

Figure 2:

Scatterplot of etonogestrel (ENG) serum concentrations based on months of contraceptive implant use. Line of best fit denoted by solid black line. The dotted line marks serum ENG concentration of 90pg/mL.

Figure 3:

Scatterplot of etonogestrel (ENG) serum concentrations based on body mass index (BMI) (kg/m2). Line of best fit denoted by solid black line. The dotted line marks serum ENG concentration of 90pg/mL.