Association between serum testosterone concentration and collagen degradation fragments in men with type 2 diabetes mellitus

The aim of the present study was to evaluate relationships between serum endogenous androgens and urinary concentration of cross-linked N-telopeptides of type I collagen (NTx), a bone resorption marker, in men with type 2 diabetes mellitus because low androgen concentrations are associated with both osteoporosis and cardiovascular disease. Relationships between serum free testosterone and urinary NTx concentrations were investigated in 246 consecutive men with type 2 diabetes mellitus. In addition, relationships between urinary NTx concentration and other variables including age, duration of diabetes, blood pressure, serum lipid concentration, hemoglobin A(1c), and body mass index were evaluated. Urinary NTx concentrations were 27.8 (26.4-29.3) nmol of bone collagen equivalent per millimole of creatinine, correlating inversely with serum free testosterone (r = -0.263, P < .0001). Multiple regression analysis identified serum free testosterone (beta = -.292, P < .0001), hemoglobin A(1c) (beta = .144, P = .0404), and smoking status (beta = .143, P = .0402) as independent determinants of urinary NTx. In conclusion, serum free testosterone concentration correlated inversely with urinary NTx concentration, which may partly account for an observed link between osteoporosis and cardiovascular disease in men with type 2 diabetes mellitus.     

Metabolic syndrome is not associated with markers of subclinical atherosclerosis, serum adiponectin and endogenous androgen concentrations in Japanese men with Type 2 diabetes.

AIMS: Metabolic syndrome is characterized by its association with certain cardiovascular disease risk factors. The aim of this study was to investigate the relationships between metabolic syndrome and markers of subclinical atherosclerosis, serum adiponectin and endogenous androgen concentrations in Japanese men with Type 2 diabetes. METHODS: Using the 2005 International Diabetes Federation (IDF) definition, we assessed the prevalence of the metabolic syndrome in 424 consecutive men with Type 2 diabetes aged 40-75 years in a cross-sectional study. We compared characteristics including ultrasonographic carotid atherosclerosis markers, pulse-wave velocity (PWV), and serum adiponectin, free testosterone, and dehydroepiandrosterone sulphate (DHEA-S) concentrations in diabetic patients with and without the metabolic syndrome. RESULTS: The prevalence of the metabolic syndrome in Japanese men with Type 2 diabetes was 46.9%. Men with the metabolic syndrome had higher urinary albumin excretion rate than those without. Carotid intima-media thickness (0.97 +/- 0.26 vs. 0.91 +/- 0.18 mm), plaque score [3.3 (1.5-8.1) vs. 3.8 (1.3-6.2)], PWV (1818 +/- 331 vs. 1749 +/- 331 cm/s) and ankle-brachial index (1.10 +/- 0.14 vs. 1.08 +/- 0.16) did not differ significantly between patients with and without the metabolic syndrome. Similarly, serum adiponectin [3.70 (2.06-6.09) vs. 4.65 (3.09-7.02) microg/ml], free testosterone (36.4 +/- 10.7 vs. 34.7 +/- 11.1 pmol/l), and DHEA-S concentrations (3.29 +/- 1.83 vs. 3.17 +/- 1.63 micromol/l) did not differ significantly between groups, CONCLUSIONS: The metabolic syndrome, as defined by the IDF, is not significantly associated with subclinical atherosclerosis markers, serum adiponectin, or endogenous androgen concentrations in Japanese men with Type 2 diabetes.     

Low serum testosterone concentration in middle-aged men with type 2 diabetes

Low concentrations of endogenous androgens have been linked with insulin resistance and atherosclerosis. Men with diabetes have been reported to have lower serum testosterone concentration than non-diabetic men; however, there has never been a large study. The aim of this study was to investigate if endogenous androgen concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men, and to identify what factors may be associated with low serum testosterone concentrations in men with type 2 diabetes. Serum free testosterone concentrations were measured in 524 healthy men and in 331 consecutive Japanese men with type 2 diabetes between 40 and 69 years old. In addition, we investigated the relationships between serum free testosterone concentration and luteinizing hormone (LH) concentration as well as major cardiovascular risk factors including age, blood pressure, plasma lipid concentration, glycemic control (HbA(1c)), and BMI. Serum free testosterone concentrations were lower in men with type 2 diabetes than in healthy men in the 40-49 years group (10.9 +/- 3.3 vs. 14.0 +/- 3.6 pg/ml, P<0.0001), in the 50-59 years group (10.4 +/- 3.2 vs. 12.1 +/- 2.9 pg/ml, P<0.0001), and in the 60-69 years group (9.5 +/- 2.6 vs. 10.5 +/- 2.9 pg/ml, P = 0.0104). A negative correlation was found between serum free testosterone and LH concentrations (r = -0.326, P<0.0001). In conclusion, serum free testosterone concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men with each decade of life between 40 and 69 years old.     

In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study

OBJECTIVE: An age-related decline in serum total and free testosterone concentration may contribute to ill health in men, but limited data are available for men > 70 years of age. We sought to determine the distribution and associations of reduced testosterone concentrations in older men. DESIGN: The Health in Men Study is a community-representative prospective cohort investigation of 4263 men aged > or = 70 years. Cross-sectional hormone data from 3645 men were analysed. METHODS: Early morning sera were assayed for total testosterone, sex hormone binding globulin (SHBG) and LH. Free testosterone was calculated using the Vermeulen method. RESULTS: Mean (+/- s.d.) serum total testosterone was 15.4 +/- 5.6 nmol/l (444 +/- 162 ng/dl), SHBG 42.4 +/- 16.7 nmol/l and free testosterone 278 +/- 96 pmol/l (8.01 +/- 2.78 ng/dl). Total testosterone correlated with SHBG (Spearman's r = 0.6, P < 0.0001). LH and SHBG increased with age (r = 0.2, P < 0.0001 for both). Instead of declining, total testosterone increased marginally (r = 0.04, P = 0.007) whilst free testosterone declined with age (r = -0.1, P < 0.0001). Free testosterone was inversely correlated with LH (r = -0.1, P < 0.0001). In multivariate analyses, increasing age, body mass index (BMI) and LH were associated with lower free testosterone. CONCLUSIONS: In men aged 70-89 years, modulation of androgen action may occur via an age-related increase in SHBG and reduction in free testosterone without a decline in total testosterone concentration. Increasing age, BMI and LH are independently associated with lower free testosterone. Further investigation would be required to assess the clinical consequences of low serum free testosterone, particularly in older men in whom total testosterone may be preserved.     

Age-related changes in plasma androgen levels and their association with cardiovascular risk factors in male Japanese office workers

Aim:   To assess the age-related change in plasma androgen levels in healthy middle-aged men and whether any clinical parameters are associated with the hormonal change.
Methods:   The study was comprised of male Japanese office-workers aged 40–64 years, who had undergone an annual health check-up in 2002 and 2007 (96 and 76 men, respectively). Body mass index and blood pressure were measured, and serum concentration of lipids, glucose and uric acid in addition to plasma total testosterone, free testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in the morning after an overnight fast. The 5-year hormonal changes and their associations with clinical parameters were analyzed in 33 men who repeated the examination at both check-ups. The cross-sectional associations of hormonal levels with clinical parameters were also investigated.
Results:   Age was negatively associated with free testosterone ( r  = −0.399, P  < 0.001 in 2002; r  = −0.458, P  < 0.001 in 2007) and DHEA-S ( r  = −0.233, P  = 0.02 in 2002; r  = −0.336, P  < 0.01 in 2007) but not with total testosterone, while the 5-year changes of free testosterone and DHEA-S levels were not significant and showed no associations with major cardiovascular risk factors. Cross-sectionally, after adjustment for age, linear regression analysis showed a positive association between free testosterone and blood hemoglobin and a negative association between total testosterone and serum uric acid.
Conclusion:   In Japanese middle-aged men, 5-year androgen decline is too subtle to detect, and endogenous androgen levels seem to have relatively weak association with cardiovascular risk profiles.     

The relationship between androgens and arterial stiffness in older men

OBJECTIVES: To assess the relationship between endogenous androgen levels and arterial stiffness in older men. DESIGN: A retrospective, cross-sectional study. SETTING: A London hospital-based, clinical research unit for the elderly. PARTICIPANTS: Fifty-five men (mean age+/-standard deviation=71.1+/-8.0). INTERVENTION: Sex hormone-binding globulin (SHBG), testosterone, and dehydroepiandrosterone sulfate (DHEAS) were measured in all subjects who had a stored serum sample drawn the same day as arterial stiffness measures were performed. Free testosterone index (FTI) was calculated ((total testosterone/SHBG) x 100 (%)). The measures of arterial stiffness used were pulse wave velocity (PWV) using the Complior system and systemic arterial compliance (SAC) using the area method. MEASUREMENTS: Relationship between arterial stiffness and serum androgens. RESULTS: : FTI showed a strong positive relationship with SAC (r=0.507, P<.001) and, correspondingly, an inverse relationship with carotid-femoral (C-F) and carotid-radial (C-R) PWV (r=-0.427 and -0.402, respectively, P相似文献   

Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control

Aging in the male is associated with both a higher incidence of type 2 diabetes and hypogonadism. However, little information is available about the complex of symptoms and hormonal changes related to partial androgen deficiency in aging (called andropause) in type 2 diabetic men. Here, for the first time, we used a combination of clinical and hormonal criteria to define andropause and to analyze the relationships between the androgen environment and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/- SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of the diabetic men. The fraction of diabetic men with subnormal levels of total testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69 years) and 36% (> 70 years). The corresponding figures for subnormal values of free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group of type 2 diabetic men, no significant linear correlations between total or free testosterone with fasting plasma glucose, insulin, C-peptide, or fructosamine values could be established. Total testosterone was positively correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01). Although fasting plasma glucose was marginally higher in aging type 2 diabetic patients with andropause than in those without andropause (162 +/- 6.9 v 139 +/- 8.9, mean +/- SEM, P =.05), there were no differences between both subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c) levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men with clinical features of andropause associated with subnormal concentrations of serum testosterone. The treatment induced significant increases in total plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL, mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6 months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall glycemic control. These data show a high prevalence of andropause in aging type 2 diabetic men and suggest that the endogenous androgen environment, as well as correction of the partial androgen deficiency, do not have a meaningful effect on glycemic control.     

Low testosterone level is an independent determinant of endothelial dysfunction in men.

We investigated whether a low plasma testosterone level is related to endothelial dysfunction in men with coronary risk factors. One hundred and eighty-seven consecutive male outpatients (mean age+/-SD: 47+/-15 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. The relationship between plasma hormones and FMD was analyzed. Total and free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were significantly correlated with %FMD (r=0.261, 0.354 and 0.295, respectively; p<0.001), while estradiol and cortisol were not. %FMD in the highest quartile of free testosterone was 1.7-fold higher than that in the lowest quartile. Multiple regression analysis revealed that total and free testosterone were related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (beta=0.198 and 0.247, respectively; p<0.01), and were independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, smoking and nitroglycerin-induced dilation (beta=0.196 and 0.227, respectively; p<0.01). DHEA-S was not significantly related to %FMD in multivariate analysis. In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium.     

Androgenicity and obesity are independently associated with insulin sensitivity in postmenopausal women

An increase in androgenicity may contribute to the development of insulin resistance in postmenopausal women. Increased androgenicity in women has been found to be associated with the development of type 2 diabetes. In addition, obesity and central obesity are associated with greater androgenicity. Insulin sensitivity, androgenicity, and body composition were characterized in 34 nondiabetic postmenopausal women age 72 +/- 1 years (mean +/- SEM) to test the hypothesis that androgenicity is a predictor of insulin sensitivity independent of measures of obesity. Androgenicity was measured using levels of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and free androgen index (FAI). Insulin sensitivity (S(I)) was determined from a frequently sampled intravenous glucose tolerance test. Body composition measures included body mass index (BMI) and dual energy x-ray absorptiometry measurements of total and central fat mass. S(I) was found to be associated with total fat mass (r = -.51, P =.002), central fat mass (r = -.62, P =.0001), BMI (r = -.55, P =.0008), SHBG levels (r =.65, P =.0001), and FAI (r = -.41, P =.01). SHBG levels were inversely correlated with central fat mass (r = -.59, P =.0002). Using multiple regression, SHBG and central fat mass were the only significant independent predictors of S(I), accounting for 50% of its variance (r =.71, P =.0001); total fat mass, BMI, total and free testosterone, DHEA-S, androstenedione, and FAI did not enter the model. We conclude that there is a significant association between insulin sensitivity and androgenicity in postmenopausal women that is independent of obesity. Interventions to decrease androgenicity may therefore be useful in improving insulin sensitivity in postmenopausal women.     

Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To compare plasma androgen levels in diabetic and nondiabetic men and to determine their relation to diabetic dyslipidemia. DESIGN: A population-based, case-control study. SETTING: Community. PARTICIPANTS: Men 53 to 88 years of age from the Rancho Bernardo, California, cohort who were screened for diabetes using an oral glucose tolerance test. MEASUREMENTS: Plasma androgen levels were compared in 44 men with untreated non-insulin-dependent diabetes mellitus and 88 age-matched men who had a normal glucose tolerance test. The relation of lipid and lipoprotein levels to androgen level and diabetic status was assessed before and after adjusting for covariates. RESULTS: Men with diabetes had significantly lower plasma levels of free (4.96 nmol/L compared with 5.58 nmol/L) and total testosterone (14.7 nmol/L compared with 17.4 nmol/L), dihydrotestosterone (428 pg/mL compared with 533 pg/mL), and dehydroepiandrosterone sulfate (DHEA-S) (1.92 mumol/L compared with 2.42 mumol/L) than nondiabetic men. They also had significantly lower high-density lipoprotein (HDL) cholesterol and significantly higher triglyceride levels. Differences were not explained by obesity, alcohol use, or cigarette habit. Overall, the total testosterone level, but not the free testosterone level, was positively correlated with the HDL cholesterol level (P = 0.009) and negatively correlated with the triglyceride level (P = 0.0001). Similar associations were seen in analyses restricted to the men without diabetes. CONCLUSIONS: Lower levels of endogenous androgens are seen in older diabetic men, and low androgen levels are associated with diabetic dyslipidemia.     

Association between alcohol consumption and serum dehydroepiandrosterone sulphate concentration in men with Type 2 diabetes: a link to decreased cardiovascular risk.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with Type 2 diabetes. Both light-to-moderate alcohol consumption and higher serum concentrations of dehydroepiandrosterone (DHEA) are associated with reduced CVD mortality, raising the possibility of DHEA as a causal intermediate in CVD and alcohol consumption. METHODS: Relationships between alcohol consumption and serum DHEA sulphate (DHEA-S) concentration, carotid atherosclerosis as evaluated by carotid ultrasonography and major cardiovascular risk factors were investigated in 404 consecutive men with Type 2 diabetes. Patients were divided into three groups according to mean ethanol consumption per week: non-drinkers, light-to-moderate drinkers (< 210 g per week) or heavy drinkers (> or = 210 g per week). RESULTS: Plasma HDL-cholesterol was positively associated with the degree of alcohol consumption. Intima-media thickness (0.92 +/- 0.21 vs. 1.09 +/- 0.35 mm, P < 0.0001) and plaque score (3.0 +/- 3.3 vs. 5.2 +/- 4.9, P = 0.008) were lower in light-to-moderate drinkers than in non-drinkers. Serum DHEA-S concentrations were higher in light-to-moderate drinkers (1264.2 +/- 592.2 ng/ml, P < 0.0001) and heavy drinkers (1176.2 +/- 607.6 ng/ml, P = 0.0100) than in non-drinkers (956.8 +/- 538.6 ng/ml). In a subgroup aged 60-75-year-old patients (n = 277), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1126.8 +/- 502.5 ng/ml, P = 0.0121) than in non-drinkers (937.9 +/- 505.1 ng/ml). Also, in a subgroup without CVD (n = 339), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1328.5 +/- 593.7 ng/ml, P < 0.0001) than in non-drinkers (970.1 +/- 540.7 ng/ml). CONCLUSIONS: Higher serum DHEA-S concentrations in light-to-moderate drinkers may represent part of the link between light-to-moderate alcohol consumption and lower CVD mortality.     

High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes

Accumulation of advanced glycation end products in vessel walls may increase arterial stiffness and/or thickness, contributing to a high incidence of cardiovascular disease (CVD) in patients with diabetes. We investigated whether serum concentrations of pentosidine, a well-defined advanced glycation end product, are associated with arterial stiffness or thickness in patients with type 2 diabetes. Pentosidine was measured in sera from 98 patients with type 2 diabetes and 61 age-matched control subjects by a competitive enzyme-linked immunosorbent assay. Arterial stiffness was evaluated by heart-brachial and brachial-ankle pulse wave velocities (PWVs) measured using an automatic device. Arterial thickness was determined ultrasonographically as carotid intima-media wall thickness (IMT). Serum concentrations of pentosidine were significantly higher in patients with diabetes than in control subjects (64.4 +/- 21.0 vs 22.8 +/- 7.0 microg/L; P < .0001). In patients with diabetes, serum pentosidine correlated positively with heart-brachial PWV (r = 0.304; P < .01) but not with brachial-ankle PWV. Serum pentosidine also correlated positively with carotid IMT in patients with diabetes (r = 0.300; P < .01). Serum pentosidine concentrations were significantly higher in patients with diabetes with CVD than in those without (72.3 +/- 23.7 vs 62.3 +/- 19.8 microg/L; P = .0453). By multivariate analysis, only age (partial coefficient = 0.308; P < .05) and serum creatinine (partial coefficient = 0.328; P < .01) retained significant influence on serum pentosidine. After adjustment for renal function, carotid IMT still correlated positively with serum pentosidine (partial coefficient = 0.2736; P = .021). In conclusion, serum pentosidine was positively associated with both arterial stiffness and thickness and CVD in patients with type 2 diabetes.     

Bone mass and bone resorption in postmenopausal women with type 2 diabetes mellitus

The aim of the present study was to examine the relationships between bone mass or bone resorption evaluated by urinary cross-linked N-telopeptides of type I collagen (NTx) concentration and known and potential contributors to bone mass or bone resorption such as sex hormones, age, duration of diabetes, glycemic control (hemoglobin A(1c) [HbA(1c)]), body mass index (BMI), severity of diabetic complications, smoking status, and current treatment of diabetes in postmenopausal women with type 2 diabetes mellitus (n = 196). In addition, the relationship of bone mass to pulse wave velocity, which is an earlier indicator of cardiovascular disease, was investigated in a subgroup of patients (n = 120). Bone mass was evaluated by the quantitative ultrasound method. A higher stiffness index indicates higher bone mass. Inverse correlations were found between the stiffness index and age (r = -0.374, P < .0001) and between the stiffness index and log (urinary albumin excretion) (r = -0.170, P = .0398), and a positive correlation was found between the stiffness index and serum dehydroepiandrosterone sulfate (DHEA-S) concentration (r = 0.201, P = .0136). No significant correlations were found between the stiffness index and duration of diabetes, HbA(1c), BMI, or serum estradiol concentration. No significant correlations were found between urinary NTx concentration and age, duration of diabetes, HbA(1c), BMI, serum estradiol concentration, or serum DHEA-S concentration. The stiffness index correlated inversely with urinary NTx concentration (r = -0.262, P = .0002). No significant correlation was found between the stiffness index and pulse wave velocity (r = -0.165, P = .0714). Multiple regression analysis demonstrated that serum DHEA-S concentration was an independent determinant of the stiffness index (beta = .207, P = .0428). In conclusion, serum DHEA-S concentration correlated positively with bone mass, whereas glycemic control, BMI, or duration of diabetes did not correlate with bone mass or urinary NTx concentration in postmenopausal women with type 2 diabetes mellitus.     

Serum uric acid is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus

Hyperuricemia has been reported to be associated with increased risk of renal insufficiency as well as cardiovascular events. The aim of this study was to evaluate the relationships between serum uric acid concentration and degree of urinary albumin excretion as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Serum uric acid concentrations were measured in 343 men with type 2 diabetes mellitus. We then evaluated relationships of serum uric acid concentrations to degree of urinary albumin excretion as well as to major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, and glycemic control (hemoglobin A1c). The relationships between serum uric acid concentration and pulse wave velocity or ankle-brachial index (n=236) and between serum uric acid concentration and carotid intima-media thickness or plaque score (n=125) were investigated additionally in a subgroup of patients. Serum uric acid concentration correlated positively with logarithm of urinary albumin excretion (r=0.302, P<.0001). Positive correlation was found between serum uric acid concentration and intima-media thickness (r=0.233, P=.0087), whereas inverse correlation was found between serum uric acid concentration and ankle-brachial index (r=-0.150, P=.0207). Multiple regression analysis demonstrated that serum uric acid concentration (beta=.281, P<.0001), duration of diabetes (beta=.253, P<.0001), hemoglobin A1c (beta=.166, P=.0034), serum triglyceride concentration (beta=.125, P=.0472), and systolic blood pressure (beta=.275, P=.0013) were independent determinants of logarithm of urinary albumin excretion. In conclusion, serum uric acid concentration is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus.     

Plasma adrenal, gonadal, and conjugated steroids following long-term exercise-induced negative energy balance in identical twins.

There are few reports of the change in sex hormone levels accompanying a weight change in men, although an excessive decline in testosterone (TESTO) has been described as an associate of stress-induced weight loss. Plasma levels of cortisol, TESTO, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), androsterone glucuronide (ADT-G), and androstane-3alpha, 17beta-diol glucuronide (3alphaDIOL-G) were measured in seven pairs of sedentary male monozygotic twins (age, 21.0 +/- 0.8 years; body mass index [BMI], 26.2 +/- 5.5 kg/m2) before and after 93 days of standardized submaximal (50% to 55% maximum oxygen consumption) cycle-ergometer exercise. A total energy deficit of 244 +/- 9.7 MJ induced significant changes (P < .0001) in body weight ([BW] -5.0 +/- 2.2 kg) and body fatness measures. Plasma TESTO and DHEA-S increased and 3alphaDIOL-G decreased. The increase in TESTO was a significant inverse correlate of loss in all measures of body fat, particularly central adiposity (r = -.58 to -.86, P < .001, fat loss-adjusted). Lower postexercise levels of 3alphaDIOL-G correlated positively with decreased body composition measures (r = .65 to .68, P < .01). The increase in plasma TESTO accompanying the loss of abdominal visceral fat (AVF) was greater in men with lower fasting insulin levels (P < .0001). The baseline within-twin-pair resemblance in TESTO and 3alphaDIOL-G (intraclass correlation coefficients [ICC] = .83 and .78, respectively, P < .01) was lost with intervention. Cortisol, DHEA-S, and ADT-G developed within-twin-pair similarity (ICC adjusted for fat loss: cortisol, .72; ADT-G, .62, P < .05; DHEA-S, .85, P < .002). We conclude that a steroid profile characterized by high TESTO and low androgen metabolite levels accompanied the changes in body composition and body fat distribution generated by the exercise-induced negative energy balance. Furthermore, these changes were characterized by a significant resemblance within identical-twin pairs.     

Low serum dehydroepiandrosterone sulfate concentration is a predictor for deterioration of urinary albumin excretion in male patients with type 2 diabetes

We recently found that serum dehydroepiandrosterone sulfate (DHEA-S) concentration correlated inversely with the degree of urinary albumin excretion in a cross-sectional study. We therefore performed an observational study to investigate the relationship between serum DHEA-S concentrations and changes in urinary albumin excretion in male patients with type 2 diabetes to answer the question as to whether DHEA is a causal rather than simply coincidental intermediate linking urinary albumin excretion to cardiovascular disease (CVD). The relationship between serum DHEA-S concentration and changes in urinary albumin excretion was investigated in 207 consecutive male patients with type 2 diabetes. Baseline serum DHEA-S concentration and urinary albumin excretion were measured in 2003. After 12 months, urinary albumin excretion was measured and any changes in urinary albumin excretion were calculated. Patients were divided into tertiles according to DHEA-S concentration. Greater changes in urinary albumin excretion were seen in patients with low DHEA-S concentration (29.6+/-7.6mg/g creatinine) than in patients with high DHEA-S concentration (5.1+/-3.6mg/g creatinine, P=0.0091). An inverse correlation was observed between serum DHEA-S concentration and changes in urinary albumin excretion (r=-0.193, P=0.0052). Multiple regression analysis demonstrated that HbA1c (beta=0.241, P=0.0009), and serum DHEA-S concentration (beta=-0.195, P=0.0054) were independent determinants of changes in urinary albumin excretion. In conclusion, serum DHEA-S concentration was inversely correlated with changes in urinary albumin excretion, which may indicate causality in the increased CVD mortality in male patients with type 2 diabetes and low DHEA-S concentration.     

Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenism of healthy aging in men.

To evaluate the impact of healthy aging on specific features of endogeneous LH secretion and clearance, we applied deconvolution analysis to 24-h serum immunoradiometric LH concentration series obtained in normal men whose ages ranged from 21-73 yr. Deconvolution analysis was employed to quantitate the number, amplitude, duration, and mass of individual LH secretory bursts underlying the serum LH concentration profiles, and simultaneously estimate the half-life of LH in individual men. Plasma total and free testosterone and estradiol concentrations and body mass index (a measure of relative adiposity) were studied as possible significant covariates of age and LH secretion. We found that age was a negative determinant of LH secretory burst amplitude (r = -0.519, P = 0.013), and a positive predictor of LH secretory burst frequency (r = +0.435, P = 0.043) and basal LH secretory rates (r = +0.486, P = 0.029). Increasing age also correlated positively with LH secretory burst half-duration (duration of the secretory event at half-maximal amplitude, r = +0.656, P less than 0.001). In contrast, age did not relate to daily pulsatile LH production rate, the mass of LH secreted per burst, or the mean (24-h) serum concentration of immunoradiometric LH. Age correlated negatively with serum free testosterone (r = -0.622, P = 0.0034) but not estradiol concentrations. The serum free testosterone concentration also declined significantly with increasing body mass index (r = -0.519, P = 0.023). Although there were strong combined effects of age, body mass index, and LH secretory burst amplitude on serum free testosterone concentrations (P = 0.0006, multi-r value 0.820), LH secretory burst amplitude was the most prominent single determinant of blood androgen concentrations.     

Serum androgen levels in adolescents with type 1 diabetes: relationship to pubertal stage and metabolic control

Delayed sexual maturation is still frequently seen in adolescents with type 1 diabetes. A close relationship between insulin and androgen metabolism has been found in a number of studies. Our study was designed to investigate whether or not abnormalities in androgen secretion could play a role in the onset of sexual maturation in adolescents with type 1 diabetes. We have asked whether or not there was a correlation between daily insulin dosage, duration of diabetes, metabolic control, age, pubertal stage, and body mass index (BMI) versus serum androgen concentrations. Basal total and free testosterone, dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha diol-G) plasma concentrations were measured in 36 pubertal boys and 31 pubertal girls with type 1 diabetes and in 59 sex- and pubertal stage-matched control subjects without diabetes. Significantly higher serum total testosterone (p<0.01) and free testosterone (p<0.05) levels were found in females and males with type 1 diabetes than in controls at pubertal stage 5. DHEA-S, SHBG, DHT and 3alpha diol G concentrations in patients with diabetes were not significantly different from those in controls. There was no correlation between daily insulin requirements and serum androgen levels. These data suggest that adolescents with diabetes have similar serum levels of DHEA-S, SHBG, DHT and 3alpha diol G as healthy subjects at all stages of puberty. However, there are significant differences in serum testosterone and free testosterone levels in adolescents with diabetes when compared to healthy, sex- and pubertal stage-matched controls in late puberty. We hypothesize that the increased testosterone levels in patients with diabetes could relate to reduced fertility in females, disorders of sexual maturation and an increased risk for cardiovascular complications later in life.     

Endogenous androgens and carotid intimal-medial thickness in women.

The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P < 0.03-0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P < 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P < 0.02), while A was negatively associated with body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.     

Blood testosterone threshold for androgen deficiency symptoms

There are few systematic studies of the relationship between blood testosterone concentrations and the symptoms of overt androgen deficiency. Because most testosterone preparations are relatively short-term, the rapid changes in blood testosterone concentrations they cause make it difficult to define any testosterone threshold. By contrast, subdermal testosterone implants provide stable blood testosterone concentrations over days to weeks, while gradually declining to baseline over 5-7 months. Hence, this provides an opportunity to define a blood testosterone threshold for androgen deficiency symptoms by observing androgen-deficient men as their familiar androgen deficiency symptoms return as testosterone pellets slowly dissolve. Among 52 androgen-deficient men who underwent 260 implantations over 5 yr, at the time of return of androgen deficiency symptoms the blood total and free testosterone concentrations were highly reproducible within individuals (F = 0.8, P = 0.49 and F = 1.4, 0.24, respectively) but varied markedly between men (F = 167 and F = 138, both P < 0.001), indicating that each person had a consistent testosterone threshold for androgen deficiency symptoms that differed markedly between individuals. The most reported symptoms of androgen deficiency were lack of energy, lack of motivation, and reduced libido. The symptomatic threshold was significantly lower in men with secondary hypogonadism compared with men with primary or mixed hypogonadism (total, 9.7 +/- 0.5 nmol/liter vs. 11.7 +/- 0.4 nmol/liter and 10.2 +/- 0.3 nmol/liter, P = 0.006; free, 146 +/- 10 pmol/liter vs. 165 +/- 6 pmol/liter and 211 +/- 18 pmol/liter, P = 0.002) but was not affected by the underlying cause of hypogonadism or by specific symptoms of any severity. Despite a wide range in individual thresholds for androgen deficiency symptoms, the mean blood testosterone threshold corresponded to the lower end of the eugonadal reference range for young men. The implications of these observations for the development of more specific quality-of-life measures, as well as for other potential androgen deficiency states such as chronic diseases and aging, remain to be determined.