An exploratory study on the possible association of serum etonogestrel concentrations with mood concerns and symptoms among contraceptive implant users

Objective: To evaluate if inter-individual variability in serum etonogestrel (ENG) concentrations accounts for variability in mood-related side effects among ENG implant users. Study Design: Participants underwent a single-time blood draw for measurement of serum ENG con-centrations using a liquid-chromatography mass-spectrometry assay, and completed a questionnaire at enrollment that retrospectively assessed mood-related side effects during the period of implant use. For a subset of participants, Patient Health Questionnaire-9 (PHQ-9) scores, obtained for other clinical purposes, were also compared. We used independent medians tests and linear regression to evaluate associations between mood symptoms and serum ENG concentrations as our primary outcome. Results: Among 900 enrolled participants, 34% (306/900) reported mood changes on the baseline ques-tionnaire. Of these, 31 (3.4%) participants also had documented PHQ-9 scores. Serum ENG concentrations (median 126.9 pg/mL [range 39.4-695.1]) were not associated with reported mood changes on the ques-tionnaire (p = 0.19) or on the PHQ-9 (beta = 0.00, 95% CI -0.03, 0.03). Conclusion: Pharmacokinetic variability does not explain the inter-individual variability in mood-related side effects among ENG implant users. Implications: Mood-related side effects and altered mental health metrics are commonly reported by eto-nogestrel contraceptive implant users but demonstrate wide inter-individual variability. Individual differ-ences in serum drug levels do not appear to account for this variability in mood-related side effects, and so future research should focus on novel personal factors. (c) 2023 Elsevier Inc. All rights reserved.