Plasma androgens and the presence and course of depression in a large cohort of men

Anouk E De Wit,Erik J Giltay,Marrit K De Boer,Willem A Nolen,Fokko J Bosker,Brenda W.J.H Penninx,Robert A Schoevers

doi:10.1016/j.psyneuen.2021.105278

Abstract

BackgroundHypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms. MethodsIn 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography–tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years. ResultsNone of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms. ConclusionsThese results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.

Highlights

The idea that adequate testosterone levels serve a protective function for depression in men, was originally rooted in the observation that hypogonadism is associated with more depressive symptoms (Hore, 1969)
We examined whether androgens levels 1) differ be tween men with and without major depressive disorder (MDD) cross-sectionally; 2) are associated with an elevated risk for onset of MDD prospectively; and 3) are asso ciated with all individual MDD symptoms or only with subset of symp toms
In this study on the relationship between androgens and depression in men, we showed that none of the levels of different androgens, including those of free testosterone, were associated with current or new onset MDD, which was in line with our first and second hypothesis

Summary

Introduction

The idea that adequate testosterone levels serve a protective function for depression in men, was originally rooted in the observation that hypogonadism is associated with more depressive symptoms (Hore, 1969) Such a relationship may be a consequence of sex steroid receptor bindings of testosterone that result in serotonin neurotransmitter func tion alterations or other genomic and non-genomic changes in the limbic system (Heberden, 2017; Hofer et al, 2013). The majority of cross-sectional studies that used structured diag nostic assessment procedures to identify MDD symptomatology and di agnoses reported no association between total or free testosterone and MDD (Markianos et al, 2007; Matsuzaka et al, 2013; Seidman et al, 2002) or severity of MDD symptoms (Barrett-Connor et al, 1999a; Monteagudo et al, 2016; T’Sjoen et al, 2005). Conclusions: These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms

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Discussion

Conclusion