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Summary: Objective: Testosterone and sex hormone‐binding globulin (SHBG) concentrations are reported to decline during male ageing, but whether these changes reflect physiological ageing or age‐related comorbidities remains uncertain. We examined longitudinal changes in serum testosterone and SHBG concentrations in middle‐aged to older men, concordance between baseline and follow‐up values and relationships with concomitant changes in lifestyle and medical factors. Design: Population‐based longitudinal cohort study. Participants: Community‐dwelling men aged 40–69 years. Measurements: Immunoassay serum total testosterone (n = 7812) and SHBG (n = 6491) at baseline (2006–2010) and follow‐up (2012–2013). Free testosterone (cFT) was calculated. Bland–Altman analyses and concordance correlation of repeated measurements were conducted. Associations of changes in hormone concentrations with lifestyle and medical factors were explored using Spearman's rank correlation. Results: Over 4.3 years follow‐up, there was a negligible mean change (±SE) in serum total testosterone concentration (+0.06 ± 0.03 nmol/L), whereas mean SHBG concentration increased (+3.69 ± 0.12 nmol/L) and cFT decreased (−10.7 ± 0.7 pmol/L). Concordance estimates were 0.67 (95% confidence interval [CI]: 0.66–0.69) for total testosterone, 0.83 (CI = 0.82–0.84) for SHBG and 0.56 (CI = 0.54–0.58) for cFT. Changes in serum total testosterone correlated with changes in SHBG (Spearman's rank ρ = 0.33, CI = 0.30–0.35), and inversely with changes in body mass index (BMI) (ρ = −0.18, CI = −0.20 to −0.16) and waist circumference (ρ = −0.13, CI = −0.15 to −0.11) and in SHBG with changes in BMI (ρ = −0.34, CI = −0.36 to −0.32) and waist circumference (ρ = −0.21, CI = −0.24 to −0.19). Conclusion: In relatively healthy middle‐aged to older men, mean serum total testosterone concentration is stable with ageing, while mean SHBG concentration increases. Both total testosterone and SHBG concentrations were highly concordant over time. [ABSTRACT FROM AUTHOR]

Background: The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria.Objective: To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.Design: Cohort study.Setting: UK Biobank prospective cohort.Participants: Community-dwelling men aged 40 to 69 years.Measurements: Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors.Results: Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]).Limitation: Observational study; single baseline measurement of testosterone and SHBG.Conclusion: Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined.Primary Funding Source: Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Objective: Serum testosterone concentrations are affected by factors unrelated to hypothalamo‐pituitary‐testicular axis pathology. We evaluated the impact of sociodemographic, lifestyle and medical factors, on serum testosterone and sex hormone–binding globulin (SHBG) in men aged 40‐69 years. Design: Cross‐sectional analysis of 208,677 community‐dwelling men from the UK Biobank. Measurements: We analysed associations of different factors with serum testosterone and SHBG (immunoassays) and calculated free testosterone (cFT), using smoothed centile plots, linear mixed models and effect size estimates. Results: Median (interquartile range) for serum testosterone was 11.6 (9.4‐14.1) nmol/L, SHBG 36.9 (27.9‐48.1) nmol/L and cFT 213 (178‐255) pmol/L. Age and BMI were inversely associated with testosterone and cFT, while SHBG was associated with age and inversely with BMI (all P <.001). Living with a partner, (South) Asian ethnicity, never or previous smoker and some medical conditions were associated with lower testosterone. Poultry or fish eater, and higher physical activity were associated with higher testosterone (all P <.001). Testosterone was lowered by ~0.5 nmol/L across ages, ~1.5 nmol/L for BMI 30 vs 25 kg/m2, ~2 nmol/L for (South) Asian ethnicity, living with partner, college/university qualifications, low red meat eater, insufficient physical activity and 0.3‐1.0 nmol/L with cardiovascular disease or diabetes. Different combinations of these factors varied serum testosterone by ~4 nmol/L, SHBG by ~30 nmol/L and cFT by ~60 pmol/L. Conclusions: The identified modifiable risk factors support lifestyle‐based interventions in men with low testosterone concentrations. Considering sociodemographic, lifestyle and medical factors facilitates more personalized interpretation of testosterone testing results with respect to existing reference ranges. [ABSTRACT FROM AUTHOR]