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Query: UMLS:C0028754 (obesity)
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Although many studies indicate that increased androgenicity is associated with insulin resistance and hyperinsulinemia in both premenopausal and postmenopausal women, relatively few data are available on this relationship in men. We examined the association of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol to glucose and insulin concentrations before and during an oral glucose tolerance test in 178 men from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Total and free testosterone and DHEA-SO4 were significantly inversely associated with insulin concentrations. Free testosterone and DHEA-SO4 were also significantly inversely correlated with glucose concentrations. SHBG was weakly positively associated with glucose concentrations. Estradiol was not related to glucose or insulin concentrations. After adjustment for age, obesity, and body fat distribution, insulin concentrations remained significantly inversely correlated with free testosterone (r = -.23), total testosterone (r = -.21), and DHEA-SO4 (r = -.21; all P < .01). In conclusion, we observed that increased testosterone and DHEA-SO4 are associated with lower insulin concentrations in men. This is in striking contrast to women, where increased androgenicity is associated with insulin resistance and hyperinsulinemia.
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PMID:Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentrations in nondiabetic men. 817 48

The prevalence of obesity is increasing in the developed as well as underdeveloped countries. Obesity in women is associated with reproductive disorders. The levels of estrone and androgens are higher in obese women along with a reduction in the levels of sex hormone binding globulin ( SHBG ). The pituitary secretion of hormones is altered either due to a deficient peripheral feedback regulation or a concomitant central defect in the obese. Luteinizing hormone ( LH ) level may increase in some of the obese subjects. The secretion of LH in response to luteinizing hormone releasing hormone ( LHRH or GnRH ), clonidine and naloxone may be altered in obese women. The levels of circulating prolactin may fall along with a delay in the nocturnal surge of the hormone. The secretion of prolactin in response to thyrotropin releasing hormone ( TRH ), insulin-induced hypoglycemia, arginine and chlorpromazine is altered. Similarly growth hormone secretion in response to growth hormone releasing hormone ( GHRH ), clonidine, naloxone and arginine is also altered in obesity. The literature suggests an alteration in the autonomic nervous system activity and the metabolism of carbohydrates and fats in the obese. Steroid hormones could affect the distribution of fat in the various regions of the body, and the distribution of body fat is linked with the severity of hyperandrogenism and metabolic disorders in obese subjects. However, it is heartening to note that many of the endocrinological and reproductive disorders are reversible with weight reduction in the obese subjects.
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PMID:Reproductive functions in obese women. 837 28

The level of sex hormone-binding globulin (SHBG) is associated with glucose metabolism in nondiabetic women and men, and the finding of low SHBG levels is suggested to be a predictor of the development of type 2 (noninsulin-dependent) diabetes mellitus. To further assess the relationship between SHBG levels and glucose metabolism, we measured serum concentrations of sex hormones and SHBG in 23 well characterized diabetic men, and studied the relationship between these variables and parameters of glucose and lipid metabolism. Insulin sensitivity was estimated using the hyperinsulinemic euglycemic glucose clamp technique. There was a strong positive correlation between the level of SHBG and the sensitivity to insulin in these individuals (r = 0.74; P < 0.001), which was independent of obesity and abdominal fat accumulation. Controlling for the effect of fasting C-peptide and insulin levels did not change the correlation coefficient significantly. SHBG levels did not correlate with levels of free testosterone (F-T), free estradiol (F-E2), or F-T/F-E2 ratio. F-E2 was positively correlated with levels of diastolic blood pressure and triglycerides (r = 0.44; P < 0.05 and r = 0.62; P < 0.001, respectively). These findings support earlier observations that associate insulin resistance with levels of SHBG, and for the first time demonstrate a direct correlation between sensitivity to insulin and SHBG levels in men with type 2 diabetes.
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PMID:Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes. 843 67

Insulin has emerged as a regulator of sex hormone-binding globulin (SHBG) production in vitro and in vivo. A role for insulin in regulating SHBG exists in insulin resistant states such as obesity and polycystic ovary syndrome. The relationship of in vivo insulin secretion rates to SHBG levels in healthy normal men is less well documented. Hepatic synthesis of SHBG may be influenced by quantitative insulin exposure as well as qualitative characteristics such as frequency and amplitude of insulin secretory pulses. The present study was undertaken to assess these relationships in 10 normal men. Adiposity was determined by the body mass index and fat distribution by the waist hip ratio. Peripheral insulin sensitivity was determined by the euglycemic clamp technique at an insulin infusion rate of 287 pmol/min.m2. SHBG levels were determined in the fasting state by RIA. Arterialized venous samples for C-peptide were obtained every 2 min for 90 min in the basal state. Individual C-peptide kinetics were derived after a bolus injection of biosynthetic human C-peptide and a previously validated two compartmental model. Insulin secretion rates at each time point were calculated using the plasma C-peptide values and the C-peptide kinetics. Insulin secretion rates were unrelated to SHBG concentrations (r = -0.29, P > 0.05). The insulin secretory pulse interval had a significant positive association with SHBG levels (r = 0.86, P < 0.05). Insulin secretory pulse amplitude, body mass index, waist hip ratio, and peripheral insulin sensitivity were not associated with SHBG concentrations in a regression analysis. We postulate that insulin secretory pulse frequency may be an important determinant of SHBG synthesis in normal man.
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PMID:Relationship of insulin secretory pulses to sex hormone-binding globulin in normal men. 843 67

Between September 1990 and February 1992, we studied 70 women of post-menopausal age, of whom 33 were affected by hormone-dependent gynecologic tumors and 37 by other pathologies, measuring estrogens, androgens, SHBG and also measuring excess fat and its distribution. The aim of our research was to ascertain what relation there was between adipose tissue, taking account central or peripheric localization, the levels of sex steroids and the onset of endometrial and breast cancer. In the group of tumor patients, we found a quantity of fat mass greater than in the control group (p < 0.05); there was, beside, in the first group, an inverse proportional correlation between the SHBG levels and BMI, and between SHBG and the fat mass (P < 0.05). We also observed an inverse relation between the levels of testosterone and SHBG (P < 0.05). These findings confirm the role that the adipose tissue and androgens would have on the globulin production, which in turn would reflect on the percentage of potentially active steroids in endometrial and mammary tissues. We also wished to ascertain if the distribution of fatty tissue (prevalently abdominal or prevalently gluteo-femoral) could have different endocrine-metabolic consequences. We found a directly proportional relation between an index of central obesity, the T/L Ratio, and the levels of DHA-S (P < 0.05), but the significance of this relation is not clear, inasmuch as DHA-S is one of the least active of the androgens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of the endocrine factors and obesity in hormone-dependent gynecological neoplasias. 850 Apr 93

The aim of this study was to investigate the role of body fat distribution on steroid hormone serum concentrations in obese adolescent girls before and after weight reduction. Ninety-two girls (age, 15.1 +/- 0.7 yr) with a mean body mass index of 31.2 +/- 4.6 kg/m2 participated in this 6-week intervention study. Initially, girls with abdominal obesity (waist to hip ratio, > 0.86; n = 30) had higher levels of total and free testosterone and lower levels of sex hormone-binding globulin as well as lower morning levels of total and free cortisol than girls with gluteal-femoral obesity (waist to hip ratio, < 0.80; n = 31) independent of their body mass index. After a mean weight loss of 8.3 +/- 2.6 kg by a standardized weight loss program, significant reductions were observed in estradiol, total and free testosterone, dehydroepiandrosterone sulfate, and the ratio of LH to FSH, whereas sex hormone-binding globulin and free cortisol levels increased significantly. Decreases in total and free testosterone and increases in total and free cortisol were significantly greater in the girls with abdominal obesity than in the girls with gluteal-femoral obesity. Our results suggest that obese girls with an abdominal pattern of fat distribution exhibit more pronounced steroid hormone aberrations, in particular a high androgenic activity, than girls with a gluteal-femoral pattern of fat distribution. The reduction of excess body weight by a conventional treatment regimen is associated with a remarkable improvement of steroid hormone abnormalities in this particular subtype of obese adolescent girls.
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PMID:Body fat distribution and steroid hormone concentrations in obese adolescent girls before and after weight reduction. 853 May 85

The influence of obesity on sex hormone-binding globulin (SHBG) and androgen concentrations in hirsute and nonhirsute women has been evaluated. The study was performed in 226 hirsute women (88 obese and 138 non-obese) classified as being affected by polycystic ovarian syndrome (PCOS) or by idiopathic hirsutism (IH) and in 100 nonhirsute control women ([C] 60 lean and 40 obese). SHBG, free testosterone (fT), androstenedione (A), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and gonadotropin levels were measured during the first week of the menstrual cycle by radioimmunoassay (RIA). A significant negative correlation between SHBG and body mass index (BMI) was observed in PCOS, IH, and C women. In obese women--whether PCOS, IH, or C-fT levels were significantly higher and, conversely, SHBG levels were lower than in non-obese women. A negative correlation between SHBG and fT was evidenced in each group. Upper-body obesity was associated with lower SHBG and higher fT levels than lower-body obesity. In conclusion, obesity, particularly upper-body obesity, is associated with a reduction in SHBG and an increase in fT in both nonhirsute and hirsute women.
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PMID:The impact of obesity on hormonal parameters in hirsute and nonhirsute women. 854 80

This study was designed to investigate the growth hormone (GH) secretory response to the growth hormone-releasing hormone (GHRH) test in women with polycystic ovary syndrome (PCOS). A total of 25 patients with PCOS (13 obese and 12 non-obese) and 15 normal ovulatory women (seven obese and eight non-obese) were included in this study. In the follicular phase patients were subjected to an oral glucose tolerance test (OGTT); 2 days later they underwent a GHRH test. Basal plasma concentrations of gonadotrophins, steroids and sex hormone-binding globulin were measured. Insulin and GH were assayed under the OGTT and GHRH test respectively. Based on the insulin response to OGTT in the PCOS group, nine patients were classified as normoinsulinaemic and 16 as hyperinsulinaemic; none of the patients of the control group had a hyperinsulinaemic response to OGTT. Obese patients showed a trend towards a lower GH response to GHRH. Moreover, hyperinsulinaemic patients showed a significantly (P < 0.05) lower area under the curve for secretion of GH (AUC-GH) as compared to normo-insulinaemic patients. All PCOS patients exhibited a markedly decreased response of GH to GHRH compared with the control population. Obese and hyperinsulinaemic PCOS patients were both found to have a lower response of GH to GHRH than all other groups. Despite the fact that obesity and hyperinsulinaemia have an additive influence on the impairment of GH secretion, our results suggest that other factors may also negatively affect GH secretion in PCOS.
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PMID:The growth hormone response to growth hormone-releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia. 858 56

Few prospective data are available regarding the association of sex hormone-binding globulin (SHBG), testosterone, and the risk of developing diabetes. Stored fasting serum samples from participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) at 22 centers throughout the United States from December 1973 through February 1976 were used to perform a nested case- control study. For 176 initially nondiabetic men who had developed diabetes during 5 years of follow-up, two controls were selected, one matched only for randomization date, treatment group, and clinic ("loose controls") and the other matched additionally for fasting glucose and body mass index ("tight controls"). When cases were compared with lose controls, higher levels of fasting insulin and lower levels of total and free testosterone and SHBG were significantly associated with increased development of diabetes. However, when cases were compared with tightly matched controls, these associations weakened considerably. Low SHBG and testosterone may constitute part of the prediabetic state in men along with previously reported variables, such as higher glucose and insulin levels and obesity.
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PMID:Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial. 861 Jul 2

In order to determine which factors influence the large variations in sensitivity to gonadotrophins witnessed in women with polycystic ovary syndrome (PCOS), a prospective study was conducted of the correlation between basal clinical and endocrinological features and gonadotrophin requirements of 20 women with clomiphene-resistant PCOS undergoing ovulation induction. Baseline evaluation of serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, fasting insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) were performed before administering gonadotrophin-releasing hormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin (HMG) was given in a standard individualized protocol according to ovarian response, until human chorionic gonadotrophin (HCG) was given. Serum concentrations of insulin, IGF-1, and IGFBP-1 were unaffected by GnRHa. The BMI correlated positively with insulin and inversely with IGFBP-1 serum concentrations and insulin and IGFBP-1 were inversely correlated. The amount of HMG required correlated positively with BMI and insulin concentrations and inversely with IGFBP-1 in the whole group and these correlations were maintained in the sub-group of lean women. No correlation was observed between HMG requirements and IGF-1 or other hormones. Women with hyperinsulinaemia and low IGFBP-1 concentrations required significantly more HMG. Multiple regression analysis revealed that insulin concentration is the most significant determinant of HMG requirement even when dissociated from BMI. We concluded that requirements of HMG in PCOS is not merely determined by obesity but by a cardinal role of insulin concentrations which, when high, induce, hypothetically, a hyperandrogenic intrafollicular milieu.
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PMID:Serum levels of insulin-like growth factor-1, IGF binding protein-1 and insulin and the response to human menopausal gonadotrophins in women with polycystic ovary syndrome. 867 13


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