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1.
  • Marriott, Ross J., et al. (författare)
  • Factors Associated With Circulating Sex Hormones in Men
  • 2023
  • Ingår i: Annals of Internal Medicine. - 0003-4819. ; 176:9, s. 1221-1234
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. Purpose: To clarify factors associated with variations in sex hormone concentrations. Data Sources: Systematic literature searches (to July 2019). Study Selection: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. Data Extraction: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone–binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. Data Synthesis: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone–binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. Limitation: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. Conclusion: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer.
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2.
  • Marriott, Ross J, et al. (författare)
  • Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.
  • 2023
  • Ingår i: Annals of internal medicine. - 1539-3704. ; 176:9, s. 1221-1234
  • Forskningsöversikt (refereegranskat)abstract
    • Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements.To clarify factors associated with variations in sex hormone concentrations.Systematic literature searches (to July 2019).Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry.Individual participant data (IPD) (9 studies; n= 21074) and aggregate data (2 studies; n= 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted.Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years.Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data.Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer.Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).
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3.
  • Yeap, Bu B, et al. (författare)
  • Associations of Serum Testosterone and Sex Hormone-Binding Globulin With Incident Cardiovascular Events in Middle-Aged to Older Men.
  • 2022
  • Ingår i: Annals of internal medicine. - 1539-3704. ; 175:2, s. 159-170
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.Cohort study.UK Biobank prospective cohort.Community-dwelling men aged 40 to 69 years.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.Of 210700 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]).Observational study; single baseline measurement of testosterone and SHBG.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.Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals.
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4.
  • Yeap, Bu B, et al. (författare)
  • Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men.
  • 2021
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.To analyse associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men.The UK Biobank prospective cohort study of community-dwelling men 40-69 years-old, followed for 11 years.All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions and other covariates. Models for testosterone included SHBG, and vice versa.In complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR]=1.14, 95% confidence interval [CI]=1.06-1.22, overall trend P<0.001), and cancer (HR=1.20, CI=1.09-1.33, P<0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had lower mortality from any cause (Q1 vs Q5, HR=0.68, CI=0.63-0.73, P<0.001), CVD (HR=0.70, CI=0.59-0.83, P<0.001), and cancer (HR=0.80, CI=0.72-0.89, P<0.001). A multiply-imputed dataset (N=208,425, 15,914 deaths, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 events) yielded similar results.Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.
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5.
  • Yeap, Bu B, et al. (författare)
  • Sociodemographic, lifestyle and medical influences on serum testosterone and sex hormone-binding globulin in men from UK Biobank.
  • 2021
  • Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 94:2, s. 290-302
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 40-69years.Cross-sectional analysis of 208,677 community-dwelling men from the UK Biobank.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.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 ~0.5nmol/L across ages, ~1.5nmol/L for BMI 30 vs 25kg/m2 , ~2nmol/L for (South) Asian ethnicity, living with partner, college/university qualifications, low red meat eater, insufficient physical activity and 0.3-1.0nmol/L with cardiovascular disease or diabetes. Different combinations of these factors varied serum testosterone by ~4nmol/L, SHBG by ~30nmol/L and cFT by ~60pmol/L.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.
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6.
  • Cawthon, Peggy M, et al. (författare)
  • What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
  • 2021
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 76:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Cut-points to define slow walking speed have largely been derived from expert opinion.Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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