The within-pair resemblance in serum levels of androgens, sex-hormone binding globulin and cortisol in female obese identical twins - effect of negative energy balance induced by very low-calorie diet.

The first aim of the present study was to evaluate the changes in serum levels of cortisol, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SHBG) in response to weight loss induced by one month of treatment with a very low-calorie diet (VLCD) in twelve pairs of female obese monozygotic twins. The second aim of the study was to investigate any within-pair resemblance in serum levels of steroids and SHBG before and after a negative balance protocol, as well as the resemblance in changes in response to therapeutic weight loss. VLCD-induced weight loss of 8.7+2.9 kg was associated with significant increases in serum testosterone (p<0.05) and SHBG (p<0.001) levels, whereas no significant changes in serum levels of cortisol, DHEA and DHEA-S were observed. Significant within-pair resemblances for both pre-treatment and post-treatment concentrations were revealed for DHEA-S (pre-treatment ICC = 0.795, p < 0.01, post-treatment ICC = 0.712, p < 0.01) and for testosterone (pre-treatment ICC = 0.594, p <0.05, post-treatment ICC = 0.735, p < 0.01). The baseline within-twin-pair resemblance in serum cortisol level at 7 a.m. (ICC=0.747, p < 0.05) was lost with VLCD treatment, while its concentration at 9 p.m. developed a within-pair similarity with weight loss (ICC = 0.824, p < 0.001). Similarly, VLCD treatment led to a significant within-pair resemblance in post-treatment level of DHEA (ICC = 0.755, p < 0.01), while no within-twin-pair resemblance was shown for either pre-treatment or post-treatment SHBG levels. None of the hormones measured exhibited any within-pair resemblance in response to VLCD-induced energy deficit, except for serum cortisol levels. A significant within-twin-pair resemblance in the changes in serum cortisol levels at 7 a. m. (ICC = 0.789, F = 8.5, p < 0.001), at 1 p.m. (ICC = 0.660, F = 4.9, p <0.01) and at 9 p.m. (ICC = 0.795, F = 8.8, p <0.001) were demonstrated even after adjustment for fat mass loss. An absence of any within-pair similarity was observed in both pretreatment and post-treatment levels of SHBG, while a significant within-pair resemblance in SHBG response to VLCD treatment (ICC = 0.658, p < 0.05) was recorded. We conclude that the significant within-twin-pair resemblance demonstrated for androgens and cortisol might suggest an important role for genetic factors in the regulation of their serum levels. Our results also suggest that the mechanisms controlling baseline levels of cortisol and SHBG differ from those influencing their responses to energy deficit induced by VLCD.     

Serum Adiponectin Confers Little Protection Against Diabetes and Hypertension in Turkish Men

We determined serum adiponectin's role as a biomarker of metabolic syndrome (MetS), type 2 diabetes (DM) and hypertension among Turkish adults who have a high prevalence of MetS. Individuals with measured serum adiponectin concentrations, constituting a random sample of Turkish adults, were studied cross‐sectionally. MetS was identified by criteria of the Adult Treatment Panel‐III modified for male abdominal obesity. Median age of 547 men and 652 women was 54 years. MetS was identified in 46%. Linear regression analysis among nine variables revealed homeostatic model assessment (HOMA) index in both sexes and C‐reactive protein (CRP) only in men as inversely associated covariates of adiponectin, and sex hormone‐binding globulin (SHBG) as positive covariate in women. Age‐adjusted sex‐specifically dichotomized high vs. low adiponectin levels were significantly associated with DM (odds ratio (OR) 0.55, P = 0.01) and hypertension (OR 0.64, P = 0.012) in women, but not in men. Further adjustment for smoking status and presence of high/low BMI did not alter this sex‐based relationship. As regards association with MetS, low adiponectin and high BMI interacted significantly in each sex. Yet adiponectin was associated only in men additively to the simultaneously adjusted five MetS components. We conclude that adiponectin concentrations, clearly linked to metabolic disorders, may diverge among sexes regarding protection against cardiometabolic risk through anti‐inflammatory or antioxidative function, Turkish men alone revealing significant dysfunction independent of obesity. This dysfunction may underlie also the association of adiponectin levels with MetS in men to be independent of the MetS components.     

Interrelations and associations of serum levels of steroids and pituitary hormones with markers of insulin resistance,inflammatory activity,and renal function in men and women aged >70 years in an 8-year longitudinal study of opposite-sex twins

Background: The physiological serum levels of steroids and pituitary hormones in older men and women have been sparsely reported in the literature.Objectives: The aims of this study were to investigate the normal variation and sex differences in steroids and pituitary hormones in those aged >70 years, and to study the interrelation between these hormones and indicators of the metabolic syndrome, inflammatory activity, and renal function.Methods: The investigation comprised a population-based sample of pairs of white opposite-sex twins from the Swedish Twin Registry. At baseline in 1996 and at the 8-year follow-uup in 2004, serum levels of progesterone, cortisol, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, creatinine, C-reactive protein (CRP), and urea were analyzed. Serum levels of insulin and cystatin were analyzed only at the follow-up.Results: The study sample included 219 men and 183 women aged 71 to 80 years (mean [SD], 74.5 [2.5] years) at baseline in 1996, and 127 men and 135 women at follow-uup in 2004. At baseline, in both men and women, the variation of progesterone in serum was positively correlated with that of estradiol (men: r = 0.226, P < 0.01; women: r = 0.115, P = NS), testosterone (men: r = 0.178, P < 0.01; women: r = 0.315, P < 0.001), and cortisol (men: r = 0.314, P < 0.001; women: r = 0.296, P < 0.001). The values of progesterone and other steroid hormones were associated with markers of insulin resistance (iie, insulin, waist circumference), inflammatory activity (ie, CRP) for progesterone (men: r = 0.267, P < 0.001; women: r = 0.150, P < 0.05), and renal function (ie, creatinine) for progesterone (men: r = 0.424, P < 0.001; women: r = 0.212, P < 0.01). Estradiol and prolactin were associated with insulin resistance, inflammation, and renal function. Furthermore, progesterone was associated with prolactin (men: r = 0.275, P < 0.001; women: r = 0.172, P < 0.05).. Among both men and women, there was a strong correlation between testosterone and estradiol (men: r = 0.753, P < 0.001; women: r = 0.526, P < 0.001); in women, there was also a link between testosterone and cortisol at follow-up (r = 0.340, P < 0.01). For progesterone, there was a significant correlation between the values of the co-twins (in 1996: r = 0.16, P < 0.05; in 2004: r = 0.45, P < 0.001). Higher serum levels of progesterone (2.0 [0.7] nmol/L in men and 1.7 [0.8] nmol/L in women) and prolactin (6 [5] μg/L in men and 8 [10] μg/L in women) were found among those who were deceased at follow-up compared with survivors (progesterone: 1.8 [0.5] nmol/L in men and 1.4 [0.6] nmol/L in women, P < 0.01; prolactin: 4 [3] μg/L in men and 5 [2] μg/L in women, P < 0.001).Conclusions: In this study of opposite-sex Swedish twins aged >70 years, there was a sex difference in the serum levels of steroids and pituitary hormones between men and women. Progesterone and other steroid hormones were associated with markers of insulin resistance, inflammatory activity, and renal function. Progesterone and prolactin levels were associated with increased risk of mortality in this sample.     

The relationship between testosterone and dehydroepiandrosterone sulfate concentrations, insulin resistance and visceral obesity in elderly men

INTRODUCTION: Sex hormones deficiency--hypotestosteronemia (20-30% of men) and dehydroepian-drosterone sulfate deficiency (60-70% of men) are often observed in elderly men. In these men also changes of body composition (visceral obesity, increasing of fat mass), and metabolic disturbances (hypercholesterolemia, hyperinsulinism and insulin resistance) are common disorders. Visceral obesity and insulin resistance may be either reasons or effects of testosterone deficiency. Probably also DHEA-S deficiency is the risk factor of visceral obesity and insulin resistance, but it is not clear, whether this possible influence is independent from testosterone deficiency. OBJECTIVES: The aim of this study was to analyze the association between testosterone and DHEA deficiency and waist/hip ratio (WHR), levels of glucose and insulin resistance (HOMA and FG/FI) in elderly men as well as analysis, whether these sex hormones influent on measured parameters separately. MATERIAL AND METHODS: Together 85 men with age from 60 to 70 years men (mean 66.3+/-1.5 years; mean+/-SEM) was analyzed. Testosterone levels<4 ng/ml or DHEA levels<2000 ng/ml and BMI<30 kg/m2 were including criteria. Patients were divided into three groups: 52 with testosterone deficiency (L-T), 32 with DHEA deficiency (L-DHEA-S) and 67 with deficiency of both sex hormones (L-T/DHEA-S). Statistical analysis was made using Student-t, Kruskal-Wallis, and Mann-Whitney tests. RESULTS: Testosterone levels in L-T, L-DHEA and L-T/DHEA groups were respectively 3.19+/-0.23 ng/ml, 4.89+/-0.45 ng/ml and 3.25+/-0.34 g/ml (p<0.002). While DHEA-S levels were respectively 2498+/-98 ng/ml, 1435+/-1010 ng/ml and 1501+/-89 ng/ml). BMI values do not differ between groups. WHR ratio values were the highest in L-T/DHEA-S group (p<0.05 vs. L-T) group, significant lower in L-T group (p<0.005 vs. L-DHEA-S) and the lowest in L-DHEA-S group. Insulin fasting levels were lowest in L-DHEA-S group, higher in L-T group (p<0.01) and the highest in L-T/DHEA-S group (p<0.001 vs, L-T group). FG/FI values were the highest in L-DHEA-S group, lower in L-T group (NS) and lowest in L-T/DHEA group (p<0.002 vs. L-T group). HOMA ratio values similarly did not change significantly between L-T (6.6+/-3.21) and L-DHEA-S group (5.5+/-2.92), although tendency to higher values in L-T group was noticed, while WHR ratio values were significantly higher in L-T/DHEA group (7.3+/-2.45; p<0.002 vs. L-T group). CONCLUSIONS: DHEA-S and testosterone deficiency were independently associated with higher insulin resistance and obesity. WHR ratio seems to be more sensitive then BMI ratio to reflect the androgen deficiency on obesity and body composition in elderly men.     

Selective muscle hypertrophy, changes in EMG and force, and serum hormones during strength training in older women.

Effects of strength training (ST) for 21 wk were examined in 10 older women (64 +/- 3 yr). Electromyogram, maximal isometric force, one-repetition maximum strength, and rate of force development of the leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF) and of vastus lateralis (VL), medialis (VM), intermedius (VI) and rectus femoris (RF) throughout the lengths of 3/12--12/15 (Lf) of the femur, muscle fiber proportion and areas of types I, IIa, and IIb of the VL were evaluated. Serum hormone concentrations of testosterone, growth hormone (GH), cortisol, and IGF-I were analyzed for the resting, preexercise, and postexercise conditions. After the 21-wk ST, maximal force increased by 37% (P < 0.001) and 1-RM by 29% (P < 0.001), accompanied by an increase (P < 0.01) in rate of force development. The integrated electromyograms of the vastus muscles increased (P < 0.05). The CSA of the total QF increased (P < 0.05) throughout the length of the femur by 5--9%. The increases were significant (P < 0.05) at 7/15--12/15 Lf for VL and at 3/15--8/15 Lf for VM, at 5/15--9/15 for VI and at 9/15 (P < 0.05) for RF. The fiber areas of type I (P < 0.05), IIa (P < 0.001), and IIb (P < 0.001) increased by 22--36%. No changes occurred during ST in serum basal concentrations of the hormones examined, but the level of testosterone correlated with the changes in the CSA of the QF (r = 0.64, P < 0.05). An acute increase of GH (P < 0.05), remaining elevated up to 30 min (P < 0.05) postloading, was observed only at posttraining. Both neural adaptations and the capacity of skeletal muscle to undergo training-induced hypertrophy even in older women explain the strength gains. The increases in the CSA of the QF occurred throughout its length but differed selectively between the individual muscles. The serum concentrations of hormones remained unaltered, but a low level of testosterone may be a limiting factor in training-induced muscle hypertrophy. The magnitude and time duration of the acute GH response may be important physiological indicators of anabolic adaptations during strength training even in older women.     

Serum leptin, insulin-like growth factor-I components and sex-hormone binding globulin. Relationship with sex, age and body composition in healthy population

Leptin plays an important role in the regulation of food intake and thermogenesis, regulates long term energy balance and reproductive function and its concentrations are closely linked to body mass index. Leptin secretion is influenced by many factors and the age-related changes in different hormones might modify circulating leptin concentrations. Sex dimorphism in leptin concentrations has been clearly shown in previous studies and its concentrations were lower in men than in women in all decades of life. Insulin growth factor-I (IGF-I) is a peptide growth factor that is present in all types of physiologic fluids and is also produced by connective tissue cell types and its autocrine/paracrine secretion is nearly always present within tissues. There is a physiological decline of the growth hormone (GH)/IGF-I axis with ageing and in addition, insulin, thyroid hormones and the supply of dietary energy may directly regulate the circulating levels of the IGFs and growth hormone binding protein (GHBP). Furthermore, there is no doubt that GH participates in the regulation of body composition, and with advanced age there is a decrease in muscle and an increase in adiposity associated with a decline in GH and total IGF-I. The biological activities of the IGF ligands are modulated by the family of high affinity GHBP. Sex hormone binding globulin (SHBG) concentrations are thought to be regulated primarily through opposing actions of sex steroids on hepatic SHBG production, with oestrogen stimulating and androgen inhibiting SHBG production, and thyroid hormones are also a potent stimulator of SHBG production concentrations. Some studies support an independent IGFBP3 contribution to SHBG variability and these findings are compatible with the hypothesis that some of the anabolic effects ascribed to the GH/IGF axis may be caused by SHBG-mediated changes in testosterone activity or SHBG/total testosterone index.     

Insulin resistance (HOMA) in relation to plasma cortisol,IGF-I and IGFBP-3. A study in normal short-statured and GH-deficient children

OBJECTIVE: To investigate the possible contribution of plasma cortisol and growth hormone (GH) as reflected by insulin-like growth factor-I (IGF-I)/insulin-like growth factor-binding protein-3 (IGFBP-3) on insulin action in short-statured children. METHODS: In this study, insulin resistance (HOMA) was determined in 34 normal short-statured (age 9.4 +/- 3.5 years) and in 19 GH-deficient children (age 10.4 +/- 2.2 years). HOMA was examined in relation to fasting plasma cortisol, IGF-I, IGFBP-3 and in addition to birthweight and body mass index (BMI). RESULTS: Birthweight was not correlated to insulin resistance. In GH-deficient children, BMI was significantly augmented and was associated with HOMA (p < 0.02). In both groups of patients, fasting plasma cortisol was related to HOMA (normal: r = 0.295, p < 0.05, GH-deficient: r = 0.495, p < 0.02). Only in normal short-statured children IGF-I (r = 0.338, p < 0.03) and IGFBP-3 (r = 0.493, p < 0.002) were associated with insulin resistance. CONCLUSION: The results indicated that at a young age cortisol contributed to insulin resistance in short-statured children. In normal short-statured children HOMA was associated with IGF-I and IGFBP-3. Possibly GH, a known cause of insulin resistance, contributed to HOMA as IGF-I and IGFBP-3 do not mediate insulin resistance but reflect growth hormone secretion. The results in GH-deficient children supported this conclusion as in the absence of GH insulin resistance was not associated with IGF-I/IGFBP-3.     

Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men

We have investigated the role of steroid hormones as coronary risk factors in Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/1; P<0.005, of DHEAS 8.0 vs 5.8 μmol/1; P<0.001, of 3AdiolG 18.3 vs 8.4 nmol/1; P<0.001, of androstenedione 5.7 vs 5.1 nmol/1; P<0.02, and of cortisol 426 vs 358 nmol/1; P<0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/1; P=0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/1; P=0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P=0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r=0.267; P<0.01) and DHEA (r=0.282; P<0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3-AdiolG (r=−0.400; P<0.001) and cortisol (r=−0.281; P<0.01) levels in the gemfibozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocorticol function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.     

Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men

Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1-5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline (DPD) cross-links in 53 women and 71 men aged 65-88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 (P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 (P = 0.0001). In women, IGFBP-1 was inversely related to insulin (P < 0.0005) and glucose (P < 0.005) and IGFBP-4 to osteocalcin (P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men (P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration (P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men (P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH (P < 0.05) and 56% after GH + testosterone (P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additionally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined.     

Dehydroepiandrosterone sulfate linked to physiologic response against hot spring immersion

The steroid dehydroepiandrosterone sulfate (DHEA-S) is associated with longevity and adaptation against external stress in humans. The aim of the study was to investigate the acute effect of a 30-min hot spring immersion at 41 °C on insulin resistance measures of 16 male subjects, in relation to DHEA-S level. To elucidate the role of DHEA-S in the coping against the heat stress, all subjects were evenly divided into lower and upper halves according to their baseline DHEA-S concentrations. The levels of glucose, insulin, blood pressure, and stress hormones (growth hormone, testosterone, and cortisol) in both groups were compared before and after hot spring immersion. The result shows that hot spring immersion significantly increased heart rate and reduced diastolic blood pressure, both of which were paralleled with a drop of DHEA-S concentration. Homeostasis model assessment for insulin resistance (HOMA-IR) and area under curve of glucose (GAUC) of oral glucose tolerance test were significantly increased by the hot spring immersion only in the Low DHEA-S group. Likewise, hot spring immersion caused an opposing effect on cortisol changes for the Low and High DHEA-S groups (+95% vs. −33%, p < 0.05), respectively. In conclusion, hot spring bathing induced insulin resistance confined only to those Low DHEA-S individuals. This response may be associated with a stress response such as increased cortisol levels.     

Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women

Objective:

Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB‐R) in healthy midlife women.

Design and Methods:

Cross‐sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow‐up visit of the multiethnic Study of Women's Health Across the Nation.

Results:

T was weakly negatively associated with both HMW adiponectin and sOB‐R (r = ?0.12 and r = ?0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB‐R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = ?0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB‐R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB‐R, independent of fat mass.

Conclusions:

These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

     

Postmenopausal sex hormones in relation to body fat distribution

Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone-binding globulin (SHBG). The purpose of this study was to investigate whether a woman's body fat distribution shows a BMI-independent association with these breast cancer-related biomarkers. Performing cross-sectional analyses among 1,180 postmenopausal women, we assessed whether associations of surrogates for an abdominal (waist circumference; waist-to-hip ratio, WHR) and gluteofemoral (hip circumference) fat distribution with estrone, total and free estradiol, androstenedione, total and free testosterone, and SHBG changed after adjustment for, or stratification by, BMI. All anthropometric measures were positively associated with estrogens and free testosterone, and negatively with SHBG. After adjustment for BMI, associations of free estradiol, free testosterone, and SHBG with both waist circumference and WHR remained significant, but all initially significant associations with hip circumference were abolished. In stratified analyses, waist circumference and WHR correlated with free estradiol, free testosterone, and SHBG in women with a BMI < 30 kg/m(2) but not in women with a BMI ≥ 30 kg/m(2). The latter suggests that in obese women, a possibly unique effect of abdominal fat on these biomarkers may be masked by the already large amount of overall body fat. On the whole, our results indicate that waist circumference and WHR, but not hip circumference, are associated with SHBG and SHBG-related sex hormones (free estradiol and free testosterone) independently of BMI.     

Testosterone,Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men: An Individual Participant Data Meta-Analysis of Observational Studies

Background

Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.

Objectives

We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.

Data sources

Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.

Study Eligibility Criteria

Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.

Methods

We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.

Results

Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.

Conclusions

Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.     

SHBG,plasma, and urinary androgens in weight lifters after a strength training

Previous studies with different results have suggested that total and bioavailable testosterone levels are modified by physical exercise. Such changes may be related to modifications in cortisol levels and could be reflected in some urine androgens. To determine how weight lifting training may affect serum and urinary androgens, we measured total serum testosterone (T), cortisol, sex hormone binding globulin (SHBG) and urinary testosterone, epitestosterone, androsterone, and etiocholanolone, in a group of 19 elite weight lifters after 20 weeks of training. SHBG increased (from 27.5 ± 9.5 to 34.7 ± 8.1 nM, p < 0.05) whereas T/SHBG decreased significantly (from 1.10 ± 0.4 to 0.85 ± 0.3, p < 0.05). Serum total testosterone and cortisol did not change significantly. In urine, androsterone and etiocholanolone decreased significantly, whereas testosterone and epitestosterone remained unchanged. Changes in T/SHBG were related positively with changes in urinary androgens (r = 0.680, p < 0.01), and changes in SHBG were negatively related with changes in urinary androgens (r = −0.578, p < 0.01). These results suggest that intense physical activity may have an influence on the elimination of androgenic hormones due mainly to changes in their transporting protein SHBG.     

Clinical association of metabolic syndrome,C‐reactive protein and testosterone levels with clinically significant prostate cancer

Recently, the influence that metabolic syndrome (MetS), hormonal alterations and inflammation might have on prostate cancer (PCa) risk has been a subject of controversial debate. Herein, we aimed to investigate the association between MetS‐components, C‐reactive protein (CRP) and testosterone levels, and the risk of clinically significant PCa (Sig‐PCa) at the time of prostate biopsy. For that, men scheduled for transrectal ultrasound guided biopsy of the prostate were studied. Clinical, laboratory parameters and criteria for MetS characterization just before the biopsy were collected. A total of 524 patients were analysed, being 195 (37.2%) subsequently diagnosed with PCa and 240 (45.8%) meet the diagnostic criteria for MetS. Among patients with PCa, MetS‐diagnosis was present in 94 (48.2%). Remarkably, a higher risk of Sig‐PCa was associated to MetS, greater number of MetS‐components and higher CRP levels (odds‐ratio: 1.83, 1.30 and 2.00, respectively; P < 0.05). Moreover, higher circulating CRP levels were also associated with a more aggressive Gleason score in PCa patients. Altogether, our data reveal a clear association between the presence of MetS, a greater number of MetS‐components or CRP levels >2.5 mg/L with an increased Sig‐PCa diagnosis and/or with aggressive features, suggesting that MetS and/or CRP levels might influence PCa pathophysiology.     

SHBG Gene Polymorphism (rs1799941) Associates with Metabolic Syndrome in Children and Adolescents

BackgroundMetabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.MethodsGenetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls).ResultsLogistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963).ConclusionsThe significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.     

Relation of BMI and physical activity to sex hormones in postmenopausal women

Objective: Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones. Research Methods and Procedures: Associations among adiposity, physical activity, and diet and concentrations of estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone‐binding globulin (SHBG), androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin were evaluated in 267 postmenopausal women randomly selected from the Women's Health Initiative Dietary Modification Trial. Results: In multiple regression analyses on log‐transformed hormones, BMI was positively associated with estrone (β = 0.031, p < 0.001), estradiol (β = 0.048, p < 0.001), free estradiol (β = 0.062, p < 0.001), free testosterone (β = 0.017, p = 0.02), and prolactin (β = 0.012, p = 0.02) and negatively associated with SHBG (β = ?0.02, p = 0.001). Total physical activity (metabolic equivalent tasks per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione (β = ?0.006, ?0.007, and ?0.005, respectively, all p ≤ 0.05). Using a composite variable of BMI and physical activity dichotomized by median values, women with high BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL, compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical activity, low BMI/low physical activity, and low BMI/high physical activity, respectively (p trend < 0.001). Similar trends were observed for estradiol and free estradiol and, in inverse, for SHBG. Discussion: These associations may, in part, explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk.     

The relationship between androgens concentrations (testosterone and dehydroepiandrosterone sulfate) and metabolic syndrome in non-obese elderly men

INTRODUCTION: The metabolic syndrome characterized by central obesity, insulin and lipid dysregulation, and hypertension, is a precursor state for atherosclerotic process and, in consequence, cardiovascular disease. Decline of both testicular and adrenal function with aging causes a decrease in androgen concentration in men. It has been postulated that low levels of total testosterone and dehydroepiandrosterone sulfate (DHEA-S) are associated with unfavorable levels of several strong cardiovascular disease risk factors, such as lipids and blood pleasure, which are components of the metabolic syndrome, and insulin levels. Both testosterone and DHEA-S deficiency are risk factors of obesity and insulin resistance, but it is not clear, whether this possible influence is independent. The aim of this study was to determined whether lower androgens (testosterone and DHEA-S) levels are associated with the development of metabolic syndrome in non-obese elderly men as well as analysis, whether these sex hormones influents on measured parameters separately. MATERIAL AND METHODS: Together 85 men age from 60 to 70 years (mean 66.3 +/- 1.5 years; mean +/- SEM) were analyzed. Testosterone levels < 4 ng/ml or DHEA levels < 2000 ng/ml and BMI < 30 kg/m(2) were including criteria. Patients were divided into three groups: 52 with testosterone deficiency (L-T), 32 with DHEA deficiency (L-DHEA-S) and 67 with deficiency of both sex hormones (L-T/DHEA-S). The influence of sex hormones deficiency in these groups on blood pressure, lipids, visceral obesity and fasting glucose were measured (according to metabolic syndrome definition NCEP III/IDF). RESULTS: Testosterone levels in L-T, L-DHEA and L-T/DHEA-S groups were respectively 3.19 +/- 0.23 ng/ml, 4.89 +/- 0.45 ng/ml and 3.25 +/- 0.34 g/ml (p < 0.002). While DHEA-S levels were respectively 2498 +/- 98 ng/ml, 1435 +/- 1010 ng/ml and 1501 +/- +/- 89 ng/ml). BMI values do not differ between groups. Waist circumference was significantly higher in L-T/DHEA-S group than in L-T i L-DHEA-S groups (respectively: 99.9 +/- 6,1 cm, 97.1 +/- 7.1 cm i 96.2 +/- 6.4 cm; mean +/- SD, p < 0.05 vs. L-T and L-DHEA-S groups). Mean triglycerides concentration in L-T/DHEA-S group was significantly higher than in L-T and L-DHEA-S groups (respectively: 188.2 +/- 13.3 mg/dl, 161.7 +/- 14.7 mg/dl and 152.2 +/- 12.8 mg/dl (mean +/- SD; p < 0.02 vs. L-T and L-DHEA-S groups). Analysis of prevalence of risk factors showed, that in L-T/DHEA-S group they were more frequent than in other groups. The most significant percentage difference was observed for triglycerides: concentration > or = 150 mg/dl was measured in 31% men in L-T group, 28% men in L-DHEA-S group and 42% men in L-T/DHEA-S group. According metabolic syndrome definition NCEP III/IDF prevalence of this syndrome was: 71% patients in L-T/DHEA-S group, 67% patients in L-T group and 64% patients in L-DHEA-S group. CONCLUSIONS: The DHEA-S and testosterone deficiency was a significant and independent risk factor of the metabolic syndrome in non-obese elderly men. It seems, that triglycerides concentration and waist circumference are more sensitive then others parameters to reflect the influence of sex hormones deficiency on risk of the metabolic syndrome in elderly men.     

Serum levels of 5-androstene-3 beta,17 beta-diol sulphate, 5 alpha-androstane-3 alpha, 17beta-diol sulphate and glucuronide, in late onset 21-hydroxylase deficiency

Serum sulphates of 5-androstene-3 beta,17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G) and unconjugated androstenedione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI) and 17 alpha-hydroxyprogester-one (17OHP) were measured by specific radioimmunoassays (RIA) in 14 women with late-onset 21-hydroxylase deficiency (LOCAH), and in normal women (n = 73). The diagnosis of LOCAH was made on the finding of a (17OHP) response level greater than 30 nmol/l following ACTH stimulation, and/or an elevation of urinary metabolites of 17OHP. Mean values for serum concentrations of all steroids measured and the free androgen index (100 X T nmol/l divided by SHBG nmol/l) were significantly elevated, and SHBG levels depressed in patients with LOCAH. These studies show that in LOCAH, in addition to the unconjugated steroids AD and T, the sulphoconjugated steroids DHEA-S, 5-ADIOL-S and 3 alpha-DIOL-S are increased, as is the glucuronide conjugate 3 alpha-DIOL-G and the index of bioavailable testosterone (FAI), and that mean SHBG levels are depressed. These data suggest that as well as AD, 5-ADIOL-S and DHEA-S may act as pro-hormones for more potent steroids (T and 5 alpha-dihydrotestosterone) in peripheral tissues, while 3 alpha-DIOL-S and 3 alpha-DIOL-G may both reflect peripheral androgen metabolism in patients with LOCAH.