Psychoneuroendocrine profiles of unmedicated men with major depressive disorder and associations to treatment effects and sexual side-effects

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Sex hormones are potentially involved in major depressive disorder (MDD) as there are sex differences in risk for depression, symptomatology and treatment efficacy. Such hormonal contributions to MDD have mainly been studied in women and scarcely in men. We, therefore, investigate whether testosterone and estradiol levels in unmedicated men with MDD are associated with depressive symptom profiles, SSRI treatment response, and sexual side-effects. Pretreatment plasma testosterone and estradiol were available from 26 unmedicated men (age 18–49). The patients were treated with 10–20 mg escitalopram for 12 weeks. Depression severity was measured by Hamilton Depression Rating Scale 17 (HAMD17), and treatment response was the change in HAMD6 from baseline. Sexual side-effects were assessed with a standardized clinician-rated scale. Pretreatment testosterone was positively associated with depression severity (p = 0.016), the association was primarily driven by vegetative symptoms: weight loss, gastrointestinal symptoms, and insomnia (p ≤ 0.027). Pretreatment sex hormone levels were not associated with antidepressant treatment outcome. However, pretreatment sex hormones were lower in patients who experienced sexual side-effects after 8–12 weeks of escitalopram treatment; low estradiol was associated with erectile and ejaculatory dysfunction (p = 0.039) and low testosterone and low estradiol were both associated with decreased libido (p ≤ 0.004). In conclusion, we find low testosterone in men with MDD coupled with depression severity, particularly vegetative symptoms. However, pretreatment sex hormone levels were not associated with treatment efficacy but with sexual side-effects. Taken together, our findings highlight sex hormone profiles as potential prognostic biomarkers of SSRI-induced sexual dysfunction. Clinical study (NCT02869035).