# The influence of sex steroids on cognition in elderly men

**Authors:** Carolina C.B. Caetano, Sami Liberman, Jéssica M.L. Ie, Valmari C.A. Toscano, Wilson Jacob, Tânia A.S.S. Bachega

PMC · DOI: 10.1016/j.clinsp.2026.100892 · 2026-02-28

## TL;DR

This study found that education years, not testosterone levels, were the main factor influencing cognitive performance in elderly men.

## Contribution

The study provides new insights into the limited role of testosterone in global cognitive function among elderly men.

## Key findings

- Education years were independently associated with higher MMSE scores.
- Testosterone levels were inversely correlated with depression scores.
- Higher BMI was linked to lower MMSE scores and lower testosterone levels.

## Abstract

•Education years predicted global cognitive performance in older men.•Serum testosterone levels inversely correlated with depression scores.•Higher BMI was associated with lower MMSE scores in bivariate analysis.•BMI was negatively correlated with serum testosterone levels.

Education years predicted global cognitive performance in older men.

Serum testosterone levels inversely correlated with depression scores.

Higher BMI was associated with lower MMSE scores in bivariate analysis.

BMI was negatively correlated with serum testosterone levels.

Testosterone plays a crucial role in cognitive development and behavioral differences between sexes. However, it remains unclear whether age-related testosterone decline affects cognitive function in elderly men.

To determine whether serum steroid levels influence cognitive function in elderly males.

Sixty men with a mean age of 73.5 ± 5.9 years were evaluated. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE), administered by a single trained examiner. To rule out the influence of depression on MMSE, the Geriatric Depression Scale (GDS) was applied. Age, BMI, education level, serum Total Testosterone (TT), Free Testosterone (FT), Estradiol (E2), and sex hormone-binding globulin levels were measured and correlated with total and subdomain MMSE scores and GDS scores. Nonparametric tests and multivariable regression analyses were performed.

Age was negatively correlated with TT (r = -0.36; p = 0.003), and TT was inversely associated with BMI (r = -0.45; p < 0.001). BMI was negatively correlated with total MMSE scores (r = -0.30; p = 0.010). TT and E2 levels showed no significant associations with overall MMSE, except for a positive correlation between TT and the Spatial Orientation subdomain (r = 0.26; p = 0.040). TT and FT were both negatively correlated with GDS scores (r = -0.32; p = 0.010; and r = -0.27; p = 0.030, respectively). After adjustment, only education years remained independently associated with MMSE (β = 0.374, p = 0.013).

Although lower serum testosterone levels were associated with depressive symptoms, no significant correlation was found with global cognitive performance; an interesting finding was the impact of years of education on MMSE score.

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** inflammation (MESH:D007249), dyslipidemia (MESH:D050171), neural compromise (MESH:D015441), endothelial dysfunction (MESH:D014652), Diabetes Mellitus (MESH:D003920), cardiac insufficiency (MESH:D000309), Cardiac Chronic Insufficiency (MESH:D051436), DM (MESH:D009223), neuroinflammation (MESH:D000090862), Obesity (MESH:D009765), cardiomyopathy (MESH:D009202), fatigue (MESH:D005221), overweight (MESH:D050177), hypogonadism (MESH:D007006), hallucinations (MESH:D006212), Hypertension (MESH:D006973), delusions (MESH:D063726), hypothyroidism (MESH:D007037), SAH (MESH:D013345), reduced sexual function and desire (MESH:D020018), psychosis (MESH:D011618), cerebrovascular damage (MESH:D002561), insulin resistance (MESH:D007333), heart failure (MESH:D006333), Depression (MESH:D003866), excess adiposity (MESH:D018205), Persistent Depressive Disorder (MESH:D019263), muscle loss (MESH:D009135), dementia (MESH:D003704), LG-PDD (MESH:D008228), cardiac conditions (MESH:D006331), Deficits in cognition (MESH:D003072), communication impairments (MESH:D003147), chronic diseases (MESH:D002908), memory impairment (MESH:D008569)
- **Chemicals:** E2 (MESH:D004958), metformin (MESH:D008687), TT (MESH:D013739), sulfonylureas (MESH:D013453), blood glucose (MESH:D001786), levothyroxine (MESH:D013974), FT (-), steroid (MESH:D013256)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12966642/full.md

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Source: https://tomesphere.com/paper/PMC12966642