Testosterone imbalance may link depression and increased body weight in premenopausal women

Abstract

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m 2 ), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance.

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

“…However, total estrogen was lower in premenopausal but higher in postmenopausal obese females compared to respective age-matched healthy counterparts [90] with no difference in free estrogen regardless of the menopausal state [91]. Both free and total testosterone levels increased in obese females regardless of the menopause state compared to the healthy counterparts, with an overall higher testosterone level in premenopausal females [91]. In contrast, there was more free estrogen in obese than healthy males [89].…”

“…Consistent with this, lower LH and follicle-stimulating hormone (FSH) levels and lower sex hormone binding globulin (SHBG) were observed in both premenopausal [87] and postmenopausal [88] obese females, and lower total testosterone, FSH, and SHBG were observed in obese males compared to their respective healthy counterparts [89]. However, total estrogen was lower in premenopausal but higher in postmenopausal obese females compared to respective age-matched healthy counterparts [90] with no difference in free estrogen regardless of the menopausal state [91]. Both free and total testosterone levels increased in obese females regardless of the menopause state compared to the healthy counterparts, with an overall higher testosterone level in premenopausal females [91].…”

Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort

“…Sex differences in anxiety-like behavior partially were affected by aged-related testosterone decline in male rats [ 17 ]. Stanikova et al [ 18 ] suggested that higher free testosterone imbalance may mediate depression in overweight premenopausal women. However, limited efforts have been paid to explore the interactions effects between genetic factors and sex hormone traits for mental traits from sex-specific genetic perspective.…”

Evaluating the genetic effects of sex hormone on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in the UK Biobank cohort

“…Sex differences in anxiety-like behavior partially were affected by aged-related testosterone decline in male rats [17]. Stanikov et al [18] suggested that higher free testosterone imbalance may mediate depression in overweight premenopausal women. However, limited efforts have been paid to explore the interactions effects between genetic factors and sex hormone levels for mental traits from sex-speci c genetic perspective.…”