Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study

ObjectiveInsulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease. This relationship may be modulated to some extent by age-related changes in sex hormone status. We examined whether lower testosterone or sex hormone-binding globulin (SHBG) levels in older men are associated with insulin resistance independently of measures of central obesity.DesignCross-sectional analysis of 2470 community-dwelling non-diabetic men aged ≥70 years.MethodsAge, body mass index (BMI) and waist circumference were measured. Early morning sera were assayed for total testosterone, SHBG, LH and insulin levels. Free testosterone was calculated using mass action equations, and insulin resistance was assessed using a homeostatic model (HOMA2-IR).ResultsTotal testosterone, free testosterone and SHBG declined progressively across increasing quintiles of HOMA2-IR (all P<0.001) and correlated inversely with log HOMA2-IR (r=−0.27, −0.14 and −0.24 respectively, all P<0.001). After adjusting for age, BMI, waist circumference, high-density lipoprotein and triglyceride levels, total testosterone was independently associated with log HOMA2-IR (β=0.05, P<0.001), while SHBG was not. Serum total testosterone <8 nmol/l was associated with HOMA2-IR in the highest quintile (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.02–2.73) as was total testosterone ≥8 and <15 nmol/l (OR 1.29, 95% CI 1.03–1.63).ConclusionsIn older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range. Further studies are needed to evaluate interventions that raise testosterone levels in men with reduced insulin sensitivity.

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Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study

Acta Endocrinologica ◽

10.1530/eje-07-0893 ◽

2008 ◽

Vol 158 (6) ◽

pp. 785-792 ◽

Cited By ~ 66

Author(s):

S A Paul Chubb ◽

Zoë Hyde ◽

Osvaldo P Almeida ◽

Leon Flicker ◽

Paul E Norman ◽

...

Keyword(s):

Metabolic Syndrome ◽

Free Testosterone ◽

Older Men ◽

Community Dwelling ◽

Sex Hormone ◽

Mass Action ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Hormone Binding ◽

Cross Sectional

BackgroundReduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men.MethodsWe conducted a cross-sectional study of 2502 community-dwelling men aged ≥70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations.ResultsThere were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone <20 nmol/l, SHBG <50 nmol/l and free testosterone <300 pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18–1.52) and 1.77 (95% CI: 1.53–2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone <8 nmol/l, LH ≤12 IU/l) had the highest prevalence of metabolic syndrome (53%,P<0.001).ConclusionsLower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.

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Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

Acta Endocrinologica ◽

10.1530/eje-10-1063 ◽

2011 ◽

Vol 164 (4) ◽

pp. 569-577 ◽

Cited By ~ 23

Author(s):

Zoë Hyde ◽

Paul E Norman ◽

Leon Flicker ◽

Graeme J Hankey ◽

Kieran A McCaul ◽

...

Keyword(s):

Risk Factors ◽

Heart Disease ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Ischaemic Heart Disease ◽

Free Testosterone ◽

Older Men ◽

Community Dwelling ◽

Mass Action ◽

Age Related

ContextHypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events.ObjectiveTo determine whether testosterone and its associated hormones, sex hormone-binding globulin (SHBG) and LH, predict IHD events in older men.DesignProspective cohort study.MethodsBetween 2001 and 2004, 3637 community-dwelling men aged 70–88 years underwent a clinical assessment of cardiovascular risk factors and biochemical assessment of testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Participants were followed until December 2008 using electronic record linkage to capture IHD events (hospital admission or death).ResultsMean follow-up was 5.1 years. During this period, 618 men (17.0%; 95% confidence interval (CI) 15.8, 18.3%) experienced an event, of which 160 were fatal. Men with higher baseline total or free testosterone levels experienced fewer IHD events (hazard ratio (HR)=0.89; 95% CI 0.82, 0.97 and HR=0.86; 95% CI 0.79, 0.94 for each one s.d. increase in total and free testosterone respectively). These associations were maintained after adjustment for age and waist:hip ratio but did not persist after adjustment for prevalent IHD or other cardiovascular risk factors. SHBG was not associated with IHD events. In contrast, higher LH levels were associated with reduced event-free survival in both univariate (HR=1.15; 95% CI 1.08, 1.22) and adjusted analyses (HR=1.08; 95% CI 1.01, 1.15).ConclusionsDysregulation of the hypothalamic–pituitary–gonadal axis may be a risk factor for IHD. Further studies of men with either elevated LH or low testosterone are warranted.

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Testosterone profile in older men with Alzheimer's disease

Dementia & Neuropsychologia ◽

10.1590/s1980-57642009dn20400010 ◽

2008 ◽

Vol 2 (4) ◽

pp. 289-293

Author(s):

Cristiana Roscito Arenella Dusi ◽

Lílian Schafirovits Morillo ◽

Regina Miksian Magaldi ◽

Adriana Nunes Machado ◽

Sami Liberman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Free Testosterone ◽

Older Men ◽

Sex Hormone Binding Globulin ◽

Control Group ◽

Total Testosterone ◽

Chi Square ◽

Testosterone Levels ◽

Significant Difference

Abstract Evidence suggests low testosterone levels in Alzheimer's disease. Objectives: To compare testosterone levels between older men with and without Alzheimer's disease. Methods: Fourteen men with Alzheimer's disease were compared with twenty eight men without dementia. Demographic variables and clinical profiles were analyzed. Within fifteen days before or after the described evaluation, measures of total testosterone and Sex Hormone Binding Globulin (SHBG) were performed. Free testosterone level was calculated based on total testosterone and SHBG. Quantitative variables were analyzed using Student's t test or Kruskal-Wallis test, while qualitative variables were analyzed using chi-square or Fisher test. Results: Mean age in the Control and Alzheimer's disease groups were 72.0 (SD±4.8) years and 79.3(SD±5.9) years, respectively (p=0.001). Mean schooling between these two groups were 8.78 and (±5.86) years, respectively (p=0.022). There were no statistically significant differences between the two groups for testosterone levels, although a trend was observed for the Alzheimer's disease group to present lower levels than the control group (p=0.066). There was no direct correlation between free testosterone and age, although a trend was evident (p=0.068). Conclusions: There was no significant difference in testosterone between men with AD and those without dementia.

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Effects of SHBG rs1799941 Polymorphism on Free Testosterone Levels and Hypogonadism Risk in Young Non-Diabetic Obese Males

Journal of Clinical Medicine ◽

10.3390/jcm8081136 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1136

Author(s):

Daniel Castellano-Castillo ◽

José Luis Royo ◽

Ana Martínez-Escribano ◽

Lidia Sánchez-Alcoholado ◽

María Molina-Vega ◽

...

Keyword(s):

Regression Models ◽

Biological Function ◽

Free Testosterone ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Hormone Binding ◽

Testosterone Levels ◽

Increased Risk ◽

Lineal Regression

Introduction: Obesity has been associated with increased risk of presenting hypogonadism. Free testosterone (FT) is the fraction of testosterone that carries out the biological function of testosterone, and is determined from total testosterone (TT) and sex-hormone binding globulin (SHBG) levels. We aimed to study the SHBG polymorphism rs1799941 in a cohort of young non-diabetic obese males to unravel the possible implication of this polymorphism in obesity-related hypogonadism. Methodology: 212 young (<45 years) non-diabetic obese (BMI ≥ 30 kg/m2) males participated in this study. Subjects were classified according to TT and FT levels in: Eugonadal (n = 55, TT > 3.5 ng/mL and FT ≥ 70 pg/mL; EuG), normal FT hypogonadism (n = 40, TT < 3.5 and FT ≥ 70 pg/mL; normal FT HG) and hypogonadism (n = 117, TT < 3.5 ng/mL and TL < 70 pg/mL; HG). The SHBG rs1799941 polymorphism (GG/GA/AA) was analyzed using the Taqman Open Array (Applied biosystem). Results: The rs1799941 frequencies were different among the groups. Higher proportion of the allele (A) was found in HG, compared to EuG and normal FT HG. Among the genotypes, the rare homozygous (AA) were found in the normal FT HG group and higher levels of serum SHBG and lower of FT were observed. The presence of the allele A was related (according to lineal regression models) to an increased of SHBG levels ((GA) β = 3.28; (AA) β = 12.45) and a decreased of FT levels ((GA) β = −9.19; (AA) β = −18.52). The presence of the allele (A) increased the risk of presenting HG compared to normal FT HG (OR = 2.54). Conclusions: The rs1799941 of the SHBG gene can partially determine the presence of obesity-related hypogonadism in young non-diabetic males and whether these subjects have normal FT HG.

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Low Testosterone Levels Are Common and Associated with Insulin Resistance in Men with Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2177 ◽

2008 ◽

Vol 93 (5) ◽

pp. 1834-1840 ◽

Cited By ~ 232

Author(s):

Mathis Grossmann ◽

Merlin C. Thomas ◽

Sianna Panagiotopoulos ◽

Ken Sharpe ◽

Richard J. MacIsaac ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Free Testosterone ◽

Total Testosterone ◽

Testosterone Deficiency ◽

Testosterone Levels ◽

Low Testosterone

Abstract Context: Low testosterone levels are common in men with type 2 diabetes and may be associated with insulin resistance. Objective: We investigated prevalence of testosterone deficiency and the relationship between testosterone and insulin resistance in a large cohort of men with type 2 and type 1 diabetes. Design: The study was a cross-sectional survey of 580 men with type 2 diabetes and 69 men with type 1 diabetes. A subgroup of 262 men with type 2 diabetes was then reassessed after a median of 6 months. Results: Forty-three percent of men with type 2 diabetes had a reduced total testosterone, and 57% had a reduced calculated free testosterone. Only 7% of men with type 1 diabetes had low total testosterone. By contrast, 20.3% of men with type 1 diabetes had low calculated free testosterone, similar to that observed in type 2 diabetes (age-body mass index adjusted odds ratio = 1.4; 95% confidence interval = 0.7–2.9). Low testosterone levels were independently associated with insulin resistance in men with type 1 diabetes as well as type 2 diabetes. Serial measurements also revealed an inverse relationship between changes in testosterone levels and insulin resistance. Conclusions: Testosterone deficiency is common in men with diabetes, regardless of the type. Testosterone levels are partly influenced by insulin resistance, which may represent an important avenue for intervention, whereas the utility of testosterone replacement remains to be established in prospective trials.

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Relationship of chronic endurance exercise to the somatotropic and sex hormone status of older men

Acta Endocrinologica ◽

10.1530/eje.0.1380517 ◽

1998 ◽

pp. 517-523 ◽

Cited By ~ 26

Author(s):

CS Cooper ◽

DR Taaffe ◽

D Guido ◽

E Packer ◽

L Holloway ◽

...

Keyword(s):

Body Composition ◽

Muscle Strength ◽

Endurance Exercise ◽

Free Testosterone ◽

Older Men ◽

Sex Hormone ◽

Group Differences ◽

Total Testosterone ◽

Free Androgen Index ◽

Igf I

To investigate putative abrogating effects of habitual endurance exercise on age-related changes in endocrine function and body composition, we compared insulin-like growth factor-I (IGF-I), sex hormonal status and body composition in 15 Masters runners and 15 minimally exercising men (MEM) aged 60-70 years. A higher maximal oxygen uptake (VO2 max.) in the runners (41.4+/-1.6 compared with 27.3+/-1.4 ml/kg/min, P=0.0001; mean+/-S.E.M.) reflected our group allocations. Analysis of body composition and bone mineral density (BMD) by dual energy X-ray absorptiometry showed no group differences in lean tissue mass or in regional or whole body BMD, but MEM were heavier, reflecting greater adiposity. Of nine muscle groups tested, only quadriceps strength differed significantly, being greater in runners (60.3+/-2.8 compared with 51.1+/-2.3 kg, P=0.02). Total IGF-I (129+/-10 compared with 124+/-11 ng/ml, P=0.72) and IGF-binding protein-3 (2854+/-94 compared with 2623+/-128ng/ml, P=0.16), were similarly depressed compared with young adult norms in both groups. There was no relationship between total or bioavailable IGF-I and any body composition, BMD or muscle strength variable. In the runners, concentrations of total testosterone (19.1+/-0.8 compared with 15.0+/-0.9 nmol/l, P=0.002) and sex hormone binding globulin (SHBG) (124.4+/-21.6 compared with 67.7+/-11.6 nmol/l, P=0.03) were significantly greater, but the free androgen index was significantly lower (20.7+/-2.7 compared with 31.4+/-4.1, P=0.04). Directly measured free testosterone, however, was similar between the runners and MEM (47.9+/-1.8 compared with 47.1+/-2.0 nmol/l P=0.80). Therefore the group differences in total testosterone and free androgen index were due to their different SHBG concentrations. Although estrone concentration was higher in MEM (85.1+/-5.2 compared with 108+/-6.7 pmol/l, P=0.03), estradiol concentration was similar between groups (73.0+/-6.3 compared with 81.8+/-8.0 pmol/l, P=0.18), indicating that estrogens were not responsible for the increased SHBG in runners. These results indicate that even high levels of regular endurance exercise do not prevent the decline in the somatotropic axis that occurs with aging. Furthermore, the somatic effects of exercise in older men (reduced adiposity and increased regional muscle strength) occurred independently of somatotropic or androgen status. Although habitual exercise does not influence free testosterone concentrations in older men, it appears to enhance the age-associated increase in SHBG synthesis.

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Association of Serum Testosterone and Luteinizing Hormone With Blood Pressure and Risk of Cardiovascular Disease in Middle‐Aged and Elderly Men

Journal of the American Heart Association ◽

10.1161/jaha.120.019559 ◽

2021 ◽

Author(s):

Mengyuan Qu ◽

Chenzhao Feng ◽

Xiaotong Wang ◽

Yiqun Gu ◽

Xuejun Shang ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Diseases ◽

Luteinizing Hormone ◽

Free Testosterone ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Risk Marker ◽

Hormone Binding ◽

Testosterone Levels

Background The age‐related decline in testosterone levels is thought to be of great importance for male aging and cardiovascular diseases. However, data are controversial on whether abnormal sex hormones are linked to the presence of cardiovascular diseases and it is also uncertain how blood pressure modifies the association between testosterone levels and major cardiovascular diseases. Methods and Results This is a multicenter, population‐based, cross‐sectional study of 6296 men conducted between 2013 and 2016. Basic information and clinical symptoms were obtained by questionnaires. Blood pressure and plasma levels of total testosterone, sex hormone–binding globulin, luteinizing hormone, and free testosterone were determined in men in a multistage random, cluster sampling in 6 provinces of China. There were 5786 Chinese men (mean [SD] age 55.0 [10.1] years) included after exclusion criteria were applied; 37.2% (2150) of them were diagnosed with hypertension. Total testosterone, free testosterone, and sex hormone–binding globulin were inversely associated with the prevalence of hypertension. Age >65 years or body mass index ≥24 negatively impacted the inverse correlation between testosterone levels and hypertension, whereas smoking and family history of hypertension strengthened the correlation. In participants with grade 2 hypertension, total testosterone was positively associated with the presence of stroke, and luteinizing hormone was also positively correlated with cardiovascular and cerebrovascular diseases. Conclusions Lower total testosterone could be a promising risk marker for prevalent hypertension. Both low and high levels of testosterone are associated with greater cardiovascular risk. Primary hypogonadism may be a risk marker for major cardiovascular diseases in men with severe hypertension.

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