Association between testosterone levels and mood disorders: A minireview

Zito, Silvana; Nosari, Guido; Pigoni, Alessandro; Moltrasio, Chiara; Delvecchio, Giuseppe

doi:10.1016/j.jad.2023.02.108

Cited by 8 publications

(2 citation statements)

References 75 publications

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“…Testosterone is an indispensable steroid hormone in men, mainly produced and secreted by Leydig cells in the testes. The numerous sexual and non-sexual physiological processes of males are regulated by the normal circulatory testosterone, including erectile function, sexual libido, reproduction, cardiovascular health, poor cognition, and psychological health [ 1 – 4 ]. However, approximate 30% of adult men aged 40–79 years are affected by decreased testosterone level [ 5 ], diagnosed as testosterone deficiency with a cut-off value (300 ng/dl) of at least 2 measurements [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Visceral Adiposity on Testosterone Levels in American Adult Men: A Cross-Sectional Analysis

Wei

Chen

et al. 2023

Med Sci Monit

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Background Testosterone decline and deficiency importantly affect men’s health, and may be associated with excessive deposition of visceral adipose tissue. This study was conducted to explore the association between visceral adiposity index (VAI) and testosterone level. Material/Methods A total of 1551 participants from the NHANES 2013–2013 cycle and 2015–2016 cycle were selected for our analyses. The VAI index was calculated based on waist circumference (WC), body mass index (BMI), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-c), and serum testosterone was measured by isotope dilution liquid chromatography tandem mass spectrometry. Multivariable adjusted linear and logistic regression were utilized to investigate the associations between VAI index and testosterone level and testosterone deficiency, respectively. Additionally, subgroup analyses were performed to identify sensitive populations. Results A total of 1551 participants with mean VAI index of 1.95±0.08 were eligible for our analysis. After adjusting for all potential cofounders, men with higher VAI index displayed a lower level of total testosterone level (β: −11.74, 95% CI: −17.33, −6.15, P<0.0001), and higher risk of testosterone deficiency (OR: 1.24, 95% CI: 1.09, 1.40, P=0.0022). Comparing to VAI quartile 1, quartile 4 showed the most decreased testosterone level (β: −94.59, 95% CI: −130.04, −59.14, P<0.0001), and highest risk of testosterone deficiency (OR: 5.07, 95% CI: 2.41,10.63, P<0.0001). Subgroup analysis demonstrated that VAI index was strongly related to testosterone level and testosterone deficiency in aged and obese men. Conclusions Men with higher VAI index displayed lower testosterone levels and higher risk of testosterone deficiency, especially in aged men and obese men.

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Section: Introductionmentioning

confidence: 99%

The Impact of Visceral Adiposity on Testosterone Levels in American Adult Men: A Cross-Sectional Analysis

Wei

Chen

et al. 2023

Med Sci Monit

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“…Both positive and negative correlations were observed, reflecting the complex relation between sex hormones and SMI, as seen in non-genetic studies. 49 Notably, depressive disorder showed only negative correlations with sex hormones, while schizophrenia showed only positive correlations, indicating distinct hormonal patterns. It should be noted that genetic correlations are merely a correlation between two GWASs, and apart from shared genetic aetiology, there are multiple mechanisms that could underly this observed correlation.…”

Section: Discussionmentioning

confidence: 97%

The role of sex hormones in severe mental illness: a genetic exploration

Veeneman,

Verweij,

Sommer

et al. 2024

Preprint

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IntroductionDespite advances in psychotherapies and pharmacological treatments, the burden of severe mental illness (SMI) remains high. Prominent sex differences exist in SMI, with increasing evidence pointing towards a pivotal role for sex hormones. Elucidation of these hormonal influences is crucial to tailor sex-specific prevention and treatment.MethodsTo investigate potential shared genetics and bi-directional causal effects between sex hormone traits and SMI, we computed genetic correlations using linkage disequilibrium score regression and bi-directional summary-level Mendelian Randomization (MR). A range of sensitivity methods was applied and potential mediators were investigated using multivariable MR. Sex-stratified data from genome-wide association studies (GWAS)s were used, further stratified on menopausal status when available. The main analysis focused on depressive disorder (N women=23,618 and N men=17,336), bipolar disorder (N women=26,573 and N men=22,381), schizophrenia (N women=54,513 and N men=68,287) as SMIs, and oestrogen (N women=229,966 and N men=206,927) and testosterone (N women=230,454 and N men=194,453) as the primary sex hormone traits. Exploratory analyses included other sex hormone traits (progesterone, sex hormone-binding globulin, prolactin, age of menarche, age of menopause). Potential mediators examined included levels of cortisol and CRP, smoking initiation, alcohol dependence, alcohol intake, BMI and body fat distribution. Only individuals of European ancestry were included.ResultsWe found a widespread pattern of significant genetic correlations between oestrogen/testosterone levels and depressive disorder/schizophrenia, in both positive and negative directions in both sexes (ranging between -0.22 and 0.13). There was no significant genetic correlation for bipolar disorder. In the MR analyses, evidence for causal effects was largely lacking; however, there was consistent evidence for a causal, increasing effect of testosterone levels on schizophrenia risk in men, completely mediated by CRP. Conversely, there was evidence for a causal, increasing effect of liability to schizophrenia on testosterone levels in both sexes.ConclusionThis study offers new insights into the complex aetiology of SMI by comprehensively mapping genetic associations with sex hormone traits, emphasizing the need to further investigate sex hormones’ impact on SMI using larger and more precisely phenotyped samples to identify individuals particularly vulnerable to hormonal disturbances.

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