Study Examines the Role of Hormonal Contraceptives in EEG-Based Prediction of Antidepressant Response in Women

An international collaborative study involving Prof. Cheng‑Teng Ip, assistant professor at the Centre for Cognitive and Brain Sciences (CCBS), University of Macau (UM), systematically examined whether hormonal contraceptive use influences EEG biomarkers and antidepressant treatment response in women with major depressive disorder (MDD). The findings have been accepted for publication in Communications Medicine (5y IF: 6.4).

MDD affects women at significantly higher rates than men, and hormonal contraceptives are widely used among women of reproductive age. Epidemiological studies have linked the initiation of hormonal contraceptive use with increased risk of depressive episodes. Hormonal contraceptives may also influence brain structure and function, particularly in regions involved in mood regulation. However, the impact of hormonal contraceptives on EEG biomarkers and responses to antidepressant treatment in women with depression have not been investigated, which may pose a potential confounding factor for the development of research on biomarkers of depression in women.

The study enrolled 60 unmedicated premenopausal women with MDD, divided into three groups: non-users (n=25), combined oral contraceptive users (COC, n=19), and progestin-only contraceptive users (POC, n=16). Participants underwent EEG recording before eight weeks of 10–20 mg escitalopram treatment. Five EEG biomarkers were assessed: 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). Statistical analyses included age-adjusted ANCOVAs, hierarchical logistic regression, and repeated LASSO-regressions to evaluate the effects of hormonal contraceptives on EEG biomarkers and treatment response.

The results showed no significant differences in EEG biomarkers among the three groups. However, adding contraceptive status to EEG-based prediction models significantly improved all models. LASSO analyses consistently selected interaction terms between contraceptive status and specific biomarkers, particularly APF and tACC, indicating that contraceptive use may modulate the association between EEG markers and treatment response. Regarding treatment response, non-users had a response rate of 71%, compared to 24% among COC users and 44% among POC users. Women using combined oral contraceptives had significantly lower treatment response rates compared to non-users.

The findings indicate that hormonal contraceptive use does not directly alter EEG biomarkers in unmedicated depressed women but may influence how specific EEG markers relate to antidepressant treatment response. Combined oral contraceptive use is associated with significantly worse treatment outcomes. These results highlight that accounting for hormonal contraceptive use may be crucial for developing reliable biomarkers for treatment response, which may guide the future development of personalized depression treatment in women.

The study was supported by the University of Macau (SRG2023-00040-ICI; MYRG-GRG2024-00022-ICI), the Research Fund of the Mental Health Services – Capital Region of Denmark (R377-2021-340), the Independent Research Fund Denmark (0134-00278B; 7025-00111B), the Lundbeck Foundation (R450-2023-1488) and its BrainDrugs Alliance (R279-2018-1145), and the Innovation Fund Denmark (4108-00004B).

The full version of the article can be viewed at: https://doi.org/10.1038/s43856-026-01438-4

Source: Centre for Cognitive and Brain Sciences, University of Macau