Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.

Stellato, Rebecca K.; Feldman, Henry A.; Hamdy, Osama; Horton, Edward S.; McKinlay, John B.

doi:10.2337/diacare.23.4.490

Cited by 554 publications

(421 citation statements)

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“…Prolactin has been found to inhibit production of sex hormone–binding globulin in vitro 34. Low sex hormone–binding globulin has been prospectively associated with increased odds of incident diabetes 33, 35, 36. Although the mechanism and causality of this association has not been fully characterized, it is possible that elevated prolactin may influence diabetes risk by inhibiting production of sex hormone–binding globulin.…”

Section: Discussionmentioning

confidence: 99%

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Therkelsen

Abraham

Pedley

et al. 2016

JAHA

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BackgroundProlactin is an anterior pituitary hormone that may modulate the adverse effects of obesity. Prolactin has been associated with cardiovascular disease mortality, but less is known about whether prolactin predicts incidence of cardiovascular disease risk factors.Methods and ResultsOur sample (n=3232, mean age 40.4 years, 52.1% women) was drawn from Framingham Heart Study participants who attended 2 examinations an average of 6.1 years apart. After excluding those with elevated prolactin (>30 mg/dL for women, >20 mg/dL for men), multivariable‐adjusted regressions modeled the associations between baseline prolactin and changes in cardiovascular disease risk factors. Models were adjusted for age, sex, baseline value of the risk factor, smoking status, hormone replacement therapy, and menopausal status and additionally for body mass index. Mean prolactin levels were 11.9 mg/dL (SD 5.2) in women and 8.0 mg/dL (SD 2.9) in men. No associations were observed for change in weight, body composition, total cholesterol, triglycerides, or fasting glucose. In women, for example, for each 5‐mg/dL increment in prolactin, odds of incident hypercholesterolemia were 1.06, which was not significant (95% CI 0.91–1.23, P=0.46). Some exceptions were of note. In women, for each 5‐mg/dL increment in prolactin, we observed increased odds of low high‐density lipoprotein cholesterol at follow‐up (odds ratio 1.50, 95% CI 1.18–1.91, P=0.001) that persisted after adjustment for body mass index (P=0.001). In men, a 5‐mg/dL increment in prolactin was associated with increased odds of incident hypertension (odds ratio 1.61, 95% CI 1.18–2.20 P=0.002) and incident diabetes (odds ratio 1.70, 95% CI 1.04–2.78, P=0.03).ConclusionsProlactin is not associated with a comprehensive panel of incident cardiovascular disease risk factors. Measurement of circulating prolactin levels in the community likely does not provide substantial insight into cardiometabolic risk.

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Section: Discussionmentioning

confidence: 99%

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Therkelsen

Abraham

Pedley

et al. 2016

JAHA

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“…A high level of obesity is associated with high serum insulin concentration. 22 In vivo insulin is inversely associated with circulating SHBG concentration 12,23 and in vitro insulin inhibits SHBG production in hepatoma cells. 24 As a result, there might be a compensatory reduction in testosterone secretion, with no resultant effect on the bioavailable fraction.…”

Section: Discussionmentioning

confidence: 99%

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study

et al. 2006

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Objectives: To compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e., BMI stable (70.69 kg/m 2 ), decreased (À0.7 kg/m 2 ), increased minimally (0.7-1.74 kg/m 2 ), increased moderately (1.75-3.19 kg/m 2 ) and increased most (X3.20 kg/m 2 )). Design: Eight-year longitudinal cohort study. Subjects: Four hundred and seventy-four black and 695 white men, aged 24-31 years at the time of the first hormone measurement. Measurements: Aging-related changes in serum SHBG, total testosterone and bioavailable testosterone. Results: SHBG significantly increased with age for men whose BMI decreased, and there were progressively smaller increases for men whose BMI was stable, or whose BMI increased minimally or moderately (range 1.1-0.3 nM per year, Pp0.03, respectively). There was no age relationship with SHBG among men whose BMI increased most. Total testosterone did not change with age for men whose BMI decreased, was stable or increased minimally, but for men whose BMI increased moderately and most there was a graded decrease in total testosterone with age (b ¼ À0.2 and À0.4 nM per year, respectively, Pp0.005). However, bioavailable testosterone decreased with age to a similar extent across all groups. Conclusions: These results suggest that changes in BMI during young adulthood modulate age-related changes in SHBG and total testosterone, but not bioavailable testosterone.

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“…quently found to have inverse correlations with body mass index (BMI), waist circumference, waist-hip-ratio (WHR), amount of visceral fat as well as with serum levels of leptin, insulin and free fatty acids [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. These markers of obesity and insulin resistance also show correlations with the cardiovascular risk factors of the metabolic syndrome [1,12].…”

mentioning

confidence: 99%

“…These fluctuations of SHBG concentrations modulate the amount of unbound, bioactive testosterone [26]. Endogenous testosterone concentrations are most likely positively associated with glucose utilization and insulin sensitivity [8,9,13]. This applies to the effects of external testosterone in hypogonadal men, as well [14,15].…”

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confidence: 99%

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

Zitzmann¹,

Gromoll²,

et al. 2003

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Aims/hypothesis. The relationship of androgens to the metabolic syndrome has not been resolved. The polymorphic number of CAG repeats within the androgen receptor gene is inversely associated with the transcriptional activity of target genes.This polymorphism might thus influence testosterone effects on body fat content and serum concentrations of leptin and insulin. The direct and indirect role of androgens within the metabolic syndrome should become clearer if this genetically determined effector is taken into account. Methods. The hypothesis was investigated in a crosssectional study involving 106 healthy 20-50 year old males. Results. Multiple regression models showed a positive independent correlation of the CAG repeat number with body fat content, leptin and insulin (partial r=0.39, 0.36 and 0.28, p<0.001, p<0.001 and p=0.006, respectively). Factor analysis yielded a five-dimensional model: two dimensions were influenced by the androgen receptor polymorphism, namely "body composition" which consisted of leptin, body fat mass, insulin, the number of CAG repeats (positive loadings) and physical activity (negative loading), and "lipid profile" which comprised low density lipoprotein cholesterol, cigarette smoking, triglycerides (positive loadings) as well as high density lipoprotein cholesterol and number of CAG repeats (negative loadings). Conclusions/interpretation. A low number of CAG repeats were independently associated with protective parameters (low body fat mass and plasma insulin) as well as with adverse parameters (low high density lipoprotein cholesterol concentrations). This suggests that the pivotal role of this polymorphism in modulating androgen effects on cardiovascular risk factors is of a complex nature and implies that its clinical impact, similar to that of androgens, is dependent on exogenous cofactors. [Diabetologia (2003) 46:31-39] Keywords Testosterone, body fat, leptin, insulin, androgen receptor, CAG repeat polymorphism. Corresponding author: E. Nieschlag, Institute of Reproductive Medicine of the University, Domagkstr. 11, 48129 Münster, Germany, E-mail: nieschl@uni-muenster.de Abbreviations: Ar, Adrogen Receptor; BFM, body fat mass; CAG, cytosin-adenin-guanin; CAGr, CAG repeats; FFM, fat free mass; HDL, high density lipoprotein; SHBG, sex hormone binding globuline; TBW, total body water; WHR, waist-to-hip ratio. Diabetologia (2003) 46:31-39 DOI 10.1007 The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men The term "metabolic syndrome" describes a pre-diabetic and pro-atherogenic state which is characterized by overweight, impaired glucose tolerance, hyperinsulinaemia, arterial hypertension, low concentrations of high density lipoprotein (HDL) cholesterol, hypertriglyceridaemia and disturbed haemostasis [1,2,3,4,5,6]. Several cross-sectional population studies found correlations between serum concentrations of testosterone and these cardiovascular risk factors, which, however, were opposi...

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Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.

Cited by 554 publications

References 0 publications

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

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