Low Sex Hormone-binding Globulin Levels Research Articles

Endocrine function in obesity

Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels.

P1-446 Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

IntroductionPrevious studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone...

Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes

Men with obesity, the metabolic syndrome, and type 2 diabetes have low total and free testosterone and low sex hormone–binding globulin (SHBG). Conversely, the presence of low testosterone and/or SHBG predicts the development of metabolic syndrome and type 2 diabetes. Visceral adiposity present in men with low testosterone, the metabolic syndrome, and/or type 2 diabetes acts through proinflammatory factors. These inflammatory markers contribute to vascular endothelial dysfunction with adverse sequelae such as increased cardiovascular disease (CVD) risk and erectile dysfunction. This review focuses on the multidirectional impact of low testosterone associated with obesity and the metabolic syndrome and its effects on erectile dysfunction and CVD risk in men with type 2 diabetes. Whenever possible in this review, we will cite recent reports (after 2005) and meta-analyses. ### Epidemiological studies of low testosterone, obesity, metabolic status, and erectile dysfunction Epidemiological studies support a bidirectional relationship between serum testosterone and obesity as well as between testosterone and the metabolic syndrome. Low serum total testosterone predicts the development of central obesity and accumulation of intra-abdominal fat (1–3). Also, low total and free testosterone and SHBG levels are associated with an increased risk of developing the metabolic syndrome, independent of age and obesity (1–3). Lowering serum T levels in older men with prostate cancer treated with androgen deprivation therapy increases body fat mass (4). Conversely, high BMI, central adiposity, and the metabolic syndrome are associated with and predict low serum total and to a lesser extent free testosterone and SHBG levels (1–3,5). Because obesity suppresses SHBG and as a result total testosterone concentrations, alterations in SHBG confound the relationship between testosterone and obesity. Low total testosterone or SHBG levels are associated with type 2 diabetes, independent of age, race, obesity, and criteria for diagnosis of diabetes (6,7). In longitudinal studies, low serum total and free testosterone …

Testosterone, SHBG and risk of type 2 diabetes in the second evaluation of the Pizarra cohort study

To evaluate the association between serum levels of testosterone, sex hormone-binding globulin (SHBG) and calculated bioavailable testosterone (bioT), and the risk of type 2 diabetes mellitus (T2D) in a prospective cohort from southern Spain (Pizarra study). The study was performed in the Pizarra Cohort Study, a prospective study started in 1995 with a follow-up of 11 years. Anthropometric and metabolic variables were measured at baseline and at 6 and 11 years of follow-up. Total testosterone (TT), SHBG and calculated bioT were determined at the 6-year follow-up. The levels of TT and bioT in men were negatively associated with the risk of obesity, T2D and the metabolic syndrome. In women, the levels of TT and bioT were associated positively with the risk of insulin resistance. The levels of SHBG were associated negatively with the risk of T2D, obesity and insulin resistance in both men and women. For all groups, the association was higher at the 11-year follow-up. Low levels of testosterone and SHBG increase the risk of T2D in men, and high levels of testosterone increase the risk of insulin resistance in women. The association between TT levels and the risk of T2D is not completely independent of other variables, such as exposure time, adiposity, insulin resistance or SHBG levels. This study also shows that the different responses between men and women are probably because of the protective effect of SHBG, levels of which are higher in women than in men.

Correlation of sex hormone and androgen receptor with diabetes mellitus in elderly men

Aim. To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men.Methods. The cross-sectional study included 492 elderly men comprising 104 healthy subjects (mean age 71.4 ± 5.2 years), 259 subjects without DM (71.5 ± 5.0 years) and 129 DM patients (73.0 ± 6.3 years). Plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG), estradiol (E2), luteinising hormone) and follicle-stimulating hormone (FSH) were determined. AR-positive cells were measured by flow cytometry.Results. TT concentrations were significantly lower in the DM group (13.8 ± 4.7 nmol/l) than in the healthy (17.1 ± 6.1 nmol/l) and non-diabetes groups (15.8 ± 6.0 nmol/l; all P < 0.01). FT, SHBG, AR-positive proportion (AR%) and AR fluorescence intensity showed a decreasing trend among the healthy, non-DM and DM groups, but the differences were not significant. TT, E2, E2/testosterone and SHBG were negatively correlated with blood glucose. SHBG was positively correlated and TT and AR% were negatively correlated with the course of DM. Logistic multiple regression analysis revealed that age, waist/hip ratio, FSH, SHBG and AR% are potential risk factors for DM.Conclusions. Low levels of TT, SHBG and AR may be potential risk factors for DM in elderly men.

Sex hormone–binding globulin and risk of hyperglycemia in patients with androgenetic alopecia

Low circulating levels of sex hormone-binding globulin (SHBG) are a strong predictor of the risk of type 2 diabetes. Androgenetic alopecia (AGA) has been related to an increase in cardiovascular risk, but the mechanism of this association has not been elucidated. AGA can be associated with low levels of SHBG and insulin resistance, which could be related to hyperglycemia and type 2 diabetes. The objective of this study was to evaluate SHBG and blood glucose levels in men and women with early-onset AGA and control subjects to determine whether low levels of SHBG are associated with hyperglycemia. This case-control study included 240 patients consecutively admitted to the outpatient clinic (Dermatology Department of San Cecilio University Hospital, Granada, Spain), 120 with early-onset AGA (60 men and 60 women) and 120 control subjects (60 men and 60 women) with skin diseases other than alopecia. Of patients with AGA, 39.1% presented with hyperglycemia (>110 mg/dL) versus 12.5% of controls (P < 0.0001). AGA patients with hyperglycemia or diabetes presented lower significant levels of SHBG than alopecic patients without hyperglycemia or type 2 diabetes, respectively. Patients with AGA and hyperglycemia presented significantly lower levels of SHBG than controls with hyperglycemia (22.3 vs 39.4 nmol/L for AGA patients and controls, respectively, P = .004). No significant differences in SHBG levels were noticed between patients and controls without hyperglycemia. Binary logistic regression showed a strong association between lower SHBG levels and glucose levels greater than 110 mg/dL in patients with AGA even after additional adjustment for sex, abdominal obesity, and free testosterone (odds ratio = 3.35; 95% confidence interval = 1.9-5.7; P < .001). The study of a wider sample of AGA patients would confirm these findings and would permit analysis of the pathogenic mechanisms underlying the increase in cardiovascular risk in patients with AGA. An association between early-onset AGA, hyperglycemia/diabetes, and low levels of SHBG was observed in the current study. Low levels of SHBG could be a marker of insulin resistance and hyperglycemia/diabetes in patients with AGA.

Associations of endogenous testosterone and SHBG with glycated haemoglobin in middle-aged and older men

Low circulating levels of testosterone and sex-hormone-binding globulin (SHBG) are associated with increased cardiovascular risk in men. This association may be partially mediated through changes in glucose metabolism, but relatively few data are available on the relationship between sex hormones and markers of long-term glycaemia. We assessed the associations of endogenous testosterone and SHBG with glycated haemoglobin (HbA(1c) ) in men. Cross-sectional study of 1292 men from the Norfolk population of European Prospective Investigation into Cancer (EPIC-Norfolk). Glycated haemoglobin, total testosterone (TT) and SHBG levels were measured, and free testosterone (FT) levels were calculated. Multiple linear regression models were used to assess the associations of TT, SHBG and FT with HbA(1c). Men with diabetes had lower testosterone and SHBG levels. In non-diabetic men, HbA(1c) levels were inversely associated with TT and calculated FT independently of age, body mass index, smoking, alcohol consumption and physical activity. The adjusted change in HbA(1c) was 0·055 (95% CI 0·025; 0·085) per standard deviation (SD) decrease in TT and 0·041 (95% CI 0·010; 0·073) per SD decrease in calculated FT, respectively. SHBG levels were inversely associated with HbA(1c) after multivariable adjustment (β = 0·038 per SD decrease (95% CI 0·004; 0·071)). In middle-aged and older men, low endogenous testosterone and SHBG levels are associated with glycaemia, even below the threshold for diabetes. Further studies are needed to determine the effects of interventions that raise testosterone levels in men having increased HbA(1c) and subnormal testosterone levels.

461 FREE AND BIOAVAILABLE SERUM TESTOSTERONE WERE ELEVATED BY DECREASING SEX HORMONE BINDING GLOBULIN IN PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: We aimed to identify the relationship between the serum testosterone (TS) axis and the prostate cancer and its association with clinicopathological features. METHODS: Between May 2006 and October 2009, 741 patients (mean age, 64.6 6.7 years) with prostate cancer undergoing RP without hormonal therapy or chemotherapy and age-matched 741 men (mean age, 64.6 7.2 years) who had visited health promotion center for routine health exam were enrolled prospectively. Total serum TS, sex hormone binding globulin (SHBG) and albumin were measured at 8 AM after midnight fasting. In the cancer group, we followed the hormone levels after RP. Between the two groups, we compared total serum TS, TS-derivatives and SHBG. In the cancer group, further subgroup analysis was done between the preoperative hormone levels and the perioperative changes in relationship with various clinicopathological characteristics. RESULTS: Lower levels of SHBG (53.8 21.5 vs. 59.0 23.9 nmol/L, p 0.001), total TS (4.09 1.54 vs. 4.31 1.64 ng/ml, p 0.001), higher levels of free TS (70.2 24.7 vs. 63.4 28.6 pg/ml, p 0.012), bioavailable TS (1.54 0.55 vs. 1.39 0.59 ng/ml, p 0.016), and free TS index (FTI) (8.98 3.46 vs. 7.97 3.45, p 0.001) were observed in the cancer group compared to the control group. Preoperative SHBG was an independent predictor for high pathologic Gleason score ( 7) (p 0.013, HR 1.540). After RP, both SHBG and total TS significantly increased from 53.8 21.5 to 59.0 22.9 nmol/L and from 4.09 1.54 to 4.30 1.22 ng/ml, respectively (both, p 0.001). Subsequently free TS was reduced from 70.2 24.7 to 64.26 18.01 pg/ml, bioavailable TS reduced from 1.54 0.55 to 1.42 0.40 ng/ml, and FTI from 8.98 3.46 to 7.89 3.15 (all, p 0.001). CONCLUSIONS: We have demonstrated that patients with prostate cancer have increased TS bioactivity compared to agematched controls. SHBG was an independent predictor of cancer differentiation. Following RP, enhanced TS bioactivity normalized and consequently preoperative low TS rebounded to the level comparable to the control group, which was mainly attributable to the postoperatively elevating SHBG, mechanism of which remains to be elucidated.

Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

BackgroundDifferences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo.MethodsA cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians.ResultsJapanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors.ConclusionsWe found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.

Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies

Accumulating evidence suggests a sex-dependent role of circulating testosterone in the metabolic syndrome (MetS). We conducted a meta-analysis of observational studies (PubMed and EMBASE-1 May 2010) relating MetS to determinants of testosterone status [total testosterone (TT), free testosterone (FT) and sex hormone-binding globulin (SHBG)]. A total of 52 studies were identified, comprising 22 043 men and 7839 women and presenting relative risk (RR) estimates or hormone levels for subjects with and without MetS. Endogenous TT and FT levels were lower in men with MetS [TT mean difference = -2.64 nmol/l, 95% confidence interval (CI) -2.95 to -2.32; FT standardized mean difference = -0.26 pmol/l, 95% CI -0.39 to -0.13] and higher in women with MetS (TT mean difference = 0.14 nmol/l, 95% CI 0.07-0.20; FT standardized mean difference = 0.52 pmol/l, 95% CI 0.33-0.71) compared with those without. Similarly, men with higher TT levels had a lower MetS risk (RR estimate = 0.38, 95% CI 0.28-0.50) whereas higher TT levels increased the risk of MetS in women (RR estimate = 1.68, 95% CI 1.15-2.45). In both sexes, higher SHBG levels were associated with a reduced risk (men: RR estimate = 0.29, 95% CI 0.21-0.41; women: RR estimate = 0.30, 95% CI 0.21-0.42). This meta-analysis supports the presence of a sex-dependent association between testosterone and MetS: TT and FT levels are lower in men with MetS, whereas they are higher in women with MetS. There are no indications for a sex-specific association between SHBG and MetS. In both men and women, MetS is associated with lower SHBG levels.

Avaliação antropométrica e metabólica de parentes de primeiro grau do sexo masculino de mulheres com síndrome do ovário policístico

To evaluate clinical and laboratory characteristics of first-degree male relatives of patients with a confirmed diagnosis of polycystic ovary syndrome (PCOS) and to compare the findings with a control group with no family history of PCOS. We randomly selected 28 male individuals aged 18 to 65 years who were first-degree relatives of women diagnosed with PCOS and 28 controls matched for age, waist and body mass index (BMI). Men with 1st degree kinship with women with PCOS had higher levels of triglycerides (189.6±103.1 versus 99.4±37.1, p<0.0001), Homeostasis Model Assessment (HOMA-IR) (3.5±9.1 versus 1.0±1.0, p=0.0077) and glucose (130.1±81.7 versus 89.5±7.8, p=0.005), and lower levels of sex hormone binding globulin (SHBG) (23.8±13.8 versus 31.1±9.1, p=0.003). SHBG levels correlated independently with triglyceride levels. These individuals also had more clinical signs of hyperandrogenism. Male individuals who are first-degree relatives of patients with PCOS have a higher degree of dyslipidemia and insulin resistance, lower levels of SHBG, and more evident clinical signs of hyperandrogenism. These findings suggest that insulin resistance may be of hereditary origin in individuals with a family history of PCOS regardless of anthropometric parameters.

Sex Hormones and Androgen Receptor: Risk Factors of Coronary Heart Disease in Elderly Men

To investigate the variation of sex hormone and its receptor level in elderly male patients with coronary heart disease (CHD) and to evaluate the correlations between CHD and sex hormone as well as sex hormone receptor. Altogether 139 male CHD patients (CHD group) aged 60-92 years and 400 healthy men (control group) aged 60-90 years were included in this cross sectional study. The plasma concentrations of dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT), free testosterone (FT), estradiol (E2), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) was tested by flow cytometry. Correlations between CHD and levels of sex hormones and AR were analyzed. Compared with the control group, the levels of DHEAS, TT, FT, SHBG, and the fluorescence intensity of AR in the CHD group significantly reduced (P < 0.05), while the levels of FSH and E2 significantly increased (P < 0.01). Age was negatively correlated with TT (r = -0.28, P = 0.00) and FT (r = -0.17, P = 0.01), while it was positively correlated with SHBG (r = 0.14, P = 0.04) and E2 (r = 0.33, P = 0.00). AR fluorescence intensity was negatively correlated with systolic blood pressure (r = -0.12, P = 0.01). Binary logistic regression analysis showed that TT, SHBG, and AR were all negatively correlated with CHD (P < 0.05). Elderly male patients with CHD are found to have low levels of DHEAS, TT, FT, SHBG, and AR, while high concentrations of E2 and FSH. Low levels of TT and SHBG may be the potential risk factors of CHD in elderly men.

Testosterone, SHBG and cardiovascular health in postmenopausal women

Cardiovascular disease (CVD) affects men and women differently with women having a lower incidence and later onset of disease. Research has recently refocused interest on the cardiovascular role of androgens. The purpose of this review is to summarize the evidence available on the association between testosterone and cardiovascular health in postmenopausal women. Published studies relating testosterone and sex hormone-binding globulin (SHBG) to CVD and its risk factors were reviewed. Studies included in this review suggest that increased androgenicity, characterized by high testosterone and low SHBG levels, is associated with an adverse CVD risk factor profile in postmenopausal women. However, evidence for an association with cardiovascular events is lacking and it is uncertain whether the observed associations with endogenous testosterone have clinical implications regarding the use of postmenopausal testosterone therapy. Large-scale, longitudinal studies relating testosterone and SHBG levels to cardiovascular risk factors and endpoints are needed to determine the temporal relationship between androgenicity and cardiovascular risk and to ascertain the long-term efficacy and safety of testosterone therapy in postmenopausal women.

Childhood Abuse Is Associated With Adiposity in Midlife Women: Possible Pathways Through Trait Anger and Reproductive Hormones

To examine the association between childhood abuse/neglect and central adiposity and obesity in a sample of 311 women (n = 106 black, 205 white) from the Pittsburgh site of the Study of Women's Health Across the Nation (SWAN). SWAN included a baseline measurement of women in midlife (mean age = 45.7 years) and eight follow-up visits during which waist circumference (WC) and body mass index (BMI) were measured. The Childhood Trauma Questionnaire retrospectively assessed emotional, physical, and sexual abuse, and emotional and physical neglect in childhood. Analyses of covariance showed that women with a history of any abuse/neglect, and specifically physical and sexual abuse, had significantly higher WC and BMI at baseline than women with no abuse history. A significant interaction between abuse and BMI showed that among women with BMI of <30, any abuse/neglect and certain subtypes of abuse predicted greater increases in WC over time. Additional analyses showed that Trait Anger scores and sex hormone-binding globulin (SHBG) attenuated cross-sectional relationships between abuse/neglect and WC and BMI. This study suggests that abused/neglected women seem to have greater anger and lower levels of SHBG, which are associated with adiposity in midlife.

Sex hormone-binding globulin in congenital adrenal hyperplasia.

Sex hormone-binding globulin biosynthesis is influenced by three hormonal systems: gonadal, insular and thyroid. Congenital adrenal hyperplasia is characterized by overproduction of adrenal androgens associated with impaired insulin sensitivity, hyperinsulinemia and often also with hypothyroidism. Only scarce data are available concerning congenital adrenal hyperplasia. The objective of this study was to determine the distribution of sex hormone-binding globulin and free testosterone levels in these patients and to what extent these values correlate with actual 17-hydroxyprogesterone and androstenedione levels, which are commonly used for monitoring of treatment effectiveness. A total of 300 retrospective laboratory records of 78 males and boys and 456 records of 162 girls and premenopausal women with diagnosis of congenital adrenal hyperplasia under common substitution treatment were evaluated statistically. The data were divided artificially into groups of low, normal and high levels, with respect to physiological concentrations for each sex and age. The percentages of the total in each group were calculated. Whereas an almost Gaussian distribution occurred for males, the data for females displayed a considerable shift to low sex hormone-binding globulin and accordingly high free testosterone levels. Sex hormone-binding globulin levels did not correlate with 17-hydroxyprogesterone. Low sex hormone-binding globulin levels in congenital adrenal hyperplasia, at least in females, reflect their involvement in insular and eventually thyroid axes, rather than the effectiveness of substitution.

Evaluation of the Effects of Cigarette Smoking on Testosterone Levels in Adult Men

Cigarette smoking is highly prevalent among men. Many studies have evaluated the effect of cigarette smoking on levels of male reproductive hormones; however, the findings still remain controversial. To evaluate the influence of cigarette smoking on serum levels of total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A total of 255 men (90 smokers and 165 nonsmokers), aged 30 to 70 years, were investigated. Weight and height were obtained and body mass index (BMI) was calculated. Also, waist circumference and hip circumference were measured and waist-to-hip ratio was obtained. Fasting blood samples were drawn for determination of plasmatic glucose levels and serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides, albumin, prolactin, TT, SHBG, LH, and FSH. The values of low-density lipoprotein cholesterol (LDL-c) were determined by Friedwald equation and the values of FT and BT were calculated from TT, SHBG, and albumin. Statistical significance was set at P < or = 0.05. The influence of smoking on levels of TT, FT, and BT. No significant difference was observed in the mean values of TT (P = 0.580), FT (P = 0.869), BT (P = 0.933), SHBG (P = 0.279), LH (P = 0.573), and FSH (P = 0.693) in the different levels of pack-years when compared to nonsmokers. Moreover, after multivariate logistic regression, no association between increased pack-years of smoking and increased odds ratio for occurrence of low hormones and SHBG levels was observed. In this study, smokers and nonsmokers had similar mean values of androgens, gonadotropins and SHBG. However, it is necessary to standardize pack-years of smoking in order to elucidate the influence of cigarette smoking on sex hormone levels, as well as to minimize differences among studies and to confirm our results.

Sex hormone-binding globulin predicts the incidence of hyperglycemia in women: interactions with adiponectin levels

Previous evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG and adiponectin levels in the development of dysglycemia. We used a nested case-control design in the large prospective study, Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). We studied 227 men and women who were normoglycemic at baseline but hyperglycemic at 3 years (glycemia > or = 6.1 mmol/l or type 2 diabetes). They were matched for sex, age, and body mass index with 227 subjects who remained normoglycemic at 3 years. At baseline, the concentration of SHBG was significantly lower in women who subsequently developed hyperglycemia than in those who remained normoglycemic, with no difference for men. In multiple regression, SHBG at baseline was as an independent determinant of plasma adiponectin levels, in both women (P<0.0001) and men (P=0.002). In multivariate conditional logistic regression taking into account physical activity and changes in waist circumference over the follow-up, plasma SHBG remained significantly associated with the development of hyperglycemia in women but not in men. These associations persisted after adjustment for fasting insulinemia, high fasting glucose, and adiponectin levels. These findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes.

Aggression is related to frontal serotonin‐1A receptor distribution as revealed by PET in healthy subjects

Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5-HT(1A) receptor, and sex hormones. Thirty-three healthy volunteers (16 women, aged 26.24 +/- 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl-(11)C]WAY-100635 to quantify 5-HT(1A) binding potentials (BP(ND)s) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17beta-estradiol and sex hormone-binding globulin (SHBG) were measured. Relations between aggression scores, regional 5-HT(1A) BP(ND)s, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions. Statistical analyses revealed higher 5-HT(1A) receptor BP(ND)s in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5-HT(1A) BP(ND)s in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03). The present study provides first-time evidence for a specific interrelation between the 5-HT(1A) receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down-stream control due to higher amounts or activities of frontal 5-HT(1A) receptors in more aggressive subjects, which is presumably modulated by sex hormones.

Obesity, low testosterone levels and erectile dysfunction

Obesity is an important risk factor for many common diseases including cardiovascular disease (CVD), type 2 diabetes, cancer and erectile dysfunction (ED). Adipose tissues produce a number of adipokines and cytokines, which affect endothelial and metabolic function resulting in insulin resistance and the metabolic syndrome (risks factors for CVD). Both ED and metabolic syndrome improve with a reduction in body mass index (BMI). The relationships among obesity, metabolic syndrome, ED, sex hormone-binding globulin (SHBG) and serum total and free testosterone levels are complex and often confusing to the physician. It is known that BMI is inversely proportional to serum total testosterone concentrations; low serum SHBG levels in obesity contribute to the low serum total testosterone. Recent studies show that BMI is also inversely proportional to free testosterone concentration. The characteristic low serum testosterone concentrations observed in obese men are also present in men with the metabolic syndrome and type 2 diabetes mellitus. A small proportion of men with ED have hypogonadism; however, the proportion increases if these men are obese with manifestations of the metabolic syndrome or type 2 diabetes mellitus. ED is a common symptom in patients with type 2 diabetes who also have low testosterone levels. This review describes the relationships between low serum testosterone concentrations and ED in obese patients and those with metabolic syndrome and type 2 diabetes mellitus.

Body Shape and Size and Insulin Resistance as Early Clinical Predictors of Hyperandrogenic Anovulation in Ethnic Minority Adolescent Girls

Purpose To determine whether key associated features of hyperandrogenic anovulation (HA) in predominately Caribbean Hispanic (CH) adolescent girls can be combined to improve the early diagnosis of HA. Methods Unselected observational sample of females aged 12 to 21 years (mean 17.5 ± 2.4 years), (64% CH, 28% African American). One hundred twenty subjects provided a menstrual history, had a physical examination, and a follicular phase fasting blood drawn for LH, FSH, testosterone, sex hormone binding globulin (SHBG), 17-OH progesterone (17-OHP), androstenedione (Δ 4A), glucose, and insulin. We prospectively categorized subjects into four groups: G I (n = 42) had normal menses and normal physical exam; G II (n = 41) had normal menses and abnormal physical exam, that is, signs indicating possible hyperandrogenism and/or insulin resistance, including at least one of obesity, hirsutism, acne, or acanthosis nigricans; G III (n = 15) had abnormal menses and normal physical exam, and G IV (n = 22) had HA with BOTH abnormal menses and abnormal physical exam, that is, girls most likely to develop polycystic ovary syndrome. Hormonal levels and additional clinical and physical characteristics of interest were compared among the four groups. Results Group IV subjects had significantly higher waist circumference measurements, independent of overweight status, than all other groups. As hypothesized, Group IV subjects had significantly higher androgen levels and significantly lower SHBG levels than all other groups. FAI, SHBG, and waist circumference had the highest diagnostic accuracy for predicting Group IV status (i.e., HA phenotype). Conclusions Markers of insulin resistance and hyperandrogenemia, including waist circumference, FAI, and SHBG, best associate with irregular menstrual cycles and the HA phenotype in ethnic minority adolescent girls.