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Background <p>Women are disproportionately affected by major depressive disorder (MDD). Widely used hormonal contraceptives are linked to depression and altered brain function, yet their unstudied impact on EEG-biomarkers of antidepressant response may confound efforts to develop biomarkers for women.</p> Methods <p>In 60 unmedicated premenopausal women with MDD: non-users (n = 25), combined oral contraceptive users (COC, n = 19), and progestin-only contraceptive users (POC, n = 16), we assess five EEG-biomarkers before eight weeks of 10–20 mg escitalopram: Alpha peak frequency (APF), Vigilance level, Loudness-Dependence of Auditory Evoked Potentials (LDAEP), frontal alpha asymmetry (FAA), and theta activity at the anterior cingulate cortex (tACC). Analyses include age-adjusted ANCOVAs, hierarchical logistic regression, and repeated LASSO-regressions to evaluate the effects of hormonal contraceptives on EEG-biomarkers and treatment response.</p> Results <p>No differences between contraceptive groups are found in EEG-biomarkers (ω²&lt;0.03, p &gt; 0.15). Adding contraceptive groups improves EEG-based predictions for all biomarkers (p &lt; 0.044). While hierarchical regressions show no significant EEG-biomarker contraceptive-group interactions, LASSO-regressions select contraceptive status in interaction with APF and tACC in models that best predict treatment outcome. Disregarding EEG, hormonal contraceptive use is associated with treatment response (p = 0.01). COC-users exhibit lower response rates than non-users (24% vs 71%, OR = 0.14 [0.03, 0.65], p = 0.012). POC-users have a 44% response rate (p = 0.140).</p> Conclusions <p>Although hormonal contraceptive use is not associated with EEG-biomarkers in unmedicated depressed women, they may modulate links between specific EEG-biomarkers and antidepressant response. However, contraceptive use, specifically COC, is associated with worse treatment outcomes and may be critical to developing biomarkers, including EEG-based, to guide treatment in women with MDD.</p>

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Hormonal contraceptives and EEG biomarkers for antidepressant treatment response in women

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月24日

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  • K. H. R. Jensen,
  • A. K. Juvik,
  • S. V. Larsen,
  • M. T. Andersen,
  • V. G. Frokjaer,
  • M. B. Jørgensen,
  • C. T. Ip

摘要

Background

Women are disproportionately affected by major depressive disorder (MDD). Widely used hormonal contraceptives are linked to depression and altered brain function, yet their unstudied impact on EEG-biomarkers of antidepressant response may confound efforts to develop biomarkers for women.

Methods

In 60 unmedicated premenopausal women with MDD: non-users (n = 25), combined oral contraceptive users (COC, n = 19), and progestin-only contraceptive users (POC, n = 16), we assess five EEG-biomarkers before eight weeks of 10–20 mg escitalopram: Alpha peak frequency (APF), Vigilance level, Loudness-Dependence of Auditory Evoked Potentials (LDAEP), frontal alpha asymmetry (FAA), and theta activity at the anterior cingulate cortex (tACC). Analyses include age-adjusted ANCOVAs, hierarchical logistic regression, and repeated LASSO-regressions to evaluate the effects of hormonal contraceptives on EEG-biomarkers and treatment response.

Results

No differences between contraceptive groups are found in EEG-biomarkers (ω²<0.03, p > 0.15). Adding contraceptive groups improves EEG-based predictions for all biomarkers (p < 0.044). While hierarchical regressions show no significant EEG-biomarker contraceptive-group interactions, LASSO-regressions select contraceptive status in interaction with APF and tACC in models that best predict treatment outcome. Disregarding EEG, hormonal contraceptive use is associated with treatment response (p = 0.01). COC-users exhibit lower response rates than non-users (24% vs 71%, OR = 0.14 [0.03, 0.65], p = 0.012). POC-users have a 44% response rate (p = 0.140).

Conclusions

Although hormonal contraceptive use is not associated with EEG-biomarkers in unmedicated depressed women, they may modulate links between specific EEG-biomarkers and antidepressant response. However, contraceptive use, specifically COC, is associated with worse treatment outcomes and may be critical to developing biomarkers, including EEG-based, to guide treatment in women with MDD.