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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the role of biologically active estradiol in the development of endometrial cancer, 25 patients with endometrial tumors and a similar number of control subjects matched for age and body size were studied. No differences between the 2 groups were found for levels of total estradiol, sex hormone-binding globulin (SHBG), non-SHBG-bound estradiol, and absolute free estradiol. Body size correlated positively with levels of total, non-SHBG-bound, and absolute estradiol and negatively with SHBG levels. The obese postmenopausal women had higher total circulating levels and proportionally greater concentrations of free estradiol than nonobese subjects, suggesting a dual risk for the cellular action of circulating estradiol. These factors could contribute to the association of obesity and the occurrence of this tumor in susceptible women.
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PMID:Free estradiol in postmenopausal women with and without endometrial cancer. 719 18

It has been shown that in vitro calcium channel blockers may regulate insulin secretion, and in vivo studies have demonstrated that they can reduce the degree of hyperinsulinemia and ameliorate the insulin-resistant state in subjects (particularly men) with obesity and hypertension. It is also commonly accepted that hyperinsulinemia may be an important factor responsible for the development of hyperandrogenism in obese women with polycystic ovarian syndrome (PCOS). We, therefore, investigated whether the administration of nitrendipine, a widely used calcium channel blocker, may improve both insulin levels and hyperandrogenism in a group of seven insulin-resistant hyperinsulinemic women with obesity and PCOS. They were treated for 7-8 days with oral nitrendipine (10 mg, twice daily) or placebo using a double blind, cross-over design. Before and after treatment, blood samples were obtained for androgen and sex hormone-binding globulin determinations, and an oral glucose tolerance test was performed, measuring glucose and insulin. Both nitrendipine and placebo failed to decrease basal and stimulated insulin levels. Moreover, no significant variations in testosterone, dehydroepiandrosterone sulfate, or sex hormone-binding globulin concentrations were observed after either treatment. Therefore, these data fail to support previous suggestions that calcium channel blockers may play a role in the treatment of hyperandrogenism and hyperinsulinemia in obese women with PCOS.
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PMID:Nitrendipine treatment in women with polycystic ovarian syndrome: evidence for a lack of effects of calcium channel blockers on insulin, androgens, and sex hormone-binding globulin. 759 49

The objective of this study was to examine the relation of endogenous sex hormones to subsequent height loss in postmenopausal women, in whom height loss is usually a surrogate for osteoporotic vertebral fractures. This was a prospective, community-based study. The site chosen was Rancho Bernardo, an upper middle class community in Southern California. A total of 170 postmenopausal women participated, aged 55-80 years. None of them were taking exogenous estrogen between 1972 and 1974. Plasma was obtained for sex hormone and sex hormone-binding globulin (SHBG) assays. Estradiol/SHBG and testosterone/SHBG ratios were used to estimate biologically available hormone levels; bioavailable (non-SHBG-bound) testosterone was measured directly in 60 women. Height loss was based on height measurements taken 16 years apart. Height loss was strongly correlated with age (p = 0.001). These women lost an average 0.22 cm/year in height. Neither estrone nor estradiol levels were significantly and independently related to height loss. Both estimated bioavailable testosterone (testosterone/SHBG ratio) and measured bioavailable testosterone levels predicted future height loss (p = 0.02 and 0.08, respectively) independent of age, obesity, cigarette smoking, alcohol intake, and use of thiazides and estrogen. We conclude that bioavailable testosterone is an independent predictor of height loss in elderly postmenopausal women. The reduced height loss is compatible with a direct effect of testosterone on bone mineral density or bone remodeling.
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PMID:Low bioavailable testosterone levels predict future height loss in postmenopausal women. 761 Sep 37

Although sex steroids have long been known to influence serum concentrations of SHBG, it is now recognized that nutritional factors may be more important in the regulation of SHBG in women. Thus, SHBG concentrations are negatively correlated with body mass index (BMI) and, more particularly, to indices of central adiposity. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is associated with truncal obesity, hyperandrogenism and hyperinsulinaemia. There is evidence that insulin may be the humoral mediator of the weight-dependent changes in SHBG. Serum SHBG concentrations are inversely correlated with both fasting and glucose-stimulated insulin levels, and insulin has been shown to have a direct inhibitory effect on SHBG synthesis and secretion by hepatocytes in culture. However, the interrelationship of BMI, insulin and SHBG appears to be different in women with PCOS from that in normal subjects. The clinical importance of the weight-related suppression of SHBG is illustrated by the finding of a greater prevalence of hirsutism in obese women PCOS compared with their lean counterparts. Obese subjects with PCOS have similar total testosterone concentrations to lean PCO women but have lower SHBG and reciprocally higher free testosterone levels. Calorie restriction results in reduction of serum insulin followed by an increase in SHBG and a fall in free testosterone but an isocaloric, low-fat diet has no significant effect on SHBG concentrations. Weight reduction in obese, hyperandrogenaemic women with PCO is an important approach to the management of both anovulation and hirsutism.
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PMID:Sex hormone-binding globulin and female reproductive function. 762 5

The metabolic complications associated with obesity are dependent upon the degree of obesity and the distribution of adipose tissue. In order to evaluate the associations between sex hormone status, metabolic risk parameters, obesity and distribution of adipose tissue, 25 premenopausal women with a wide range of body mass index (19.3-48.1 kg/m2 were studied. Body composition was determined by dual-energy x-ray absorptiometry scan and anthropometric measurements; in addition, lipid and sex hormone status were determined and an oral glucose tolerance test was performed. We found that sex hormone-binding globulin was correlated negatively with total fat mass (r = -0.77, p < 0.001) and especially with abdominal localization of adipose tissue (r = -0.85, p < 0.001). Free testosterone was correlated positively with total fat mass (r = 0.40, p < 0.05) and with abdominal fat accumulation (r = 0.64, p < 0.001). Free estrogen was correlated negatively with total amount of adipose tissue (r = -0.40, p < 0.05) but not with the distribution of adipose tissue. Finally, total fatness, abdominal localization of adipose tissue and free testosterone were all associated with elevated metabolic risk factors. However, multiple regression analysis revealed that only abdominal localization of adipose tissue was independently associated with a higher risk profile, whereas the effects of sex hormones or total fatness disappeared when abdominal localization of adipose tissue was included in the analysis. In conclusion, these findings in premenopausal women indicate that the connection between sex hormones and metabolic risk factors might be indirect, probably operating through alterations in the amount of adipose tissue in the abdominal region.
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PMID:Relationship between sex hormones, body composition and metabolic risk parameters in premenopausal women. 765 44

Type IIB muscle fibres are among the most insulin-insensitive muscle fibres and are not adapted to oxidation of fat during muscle work. The first characteristic of this type of muscle fibre most probably reflects or contributes to further development of insulin resistance contribute to further perpetuation of obesity and to the channeling of excess free fatty acids to the liver followed by secondary deterioration of its function. The impaired functioning of the liver is epitomized, among other changes, by impairment of insulin extraction. The increasing hyperinsulinaemia is followed by inhibition of synthesis of specific proteins such as carrier proteins for transporting testosterone (sex hormone binding globulin, SHBG). This results in an increased free testosterone concentration which induces androgenization in women and may further increase insulin insensitivity in abdominal obesity in women. The poor capillarization and changed muscle morphology in spite of great interindividual variety is observed in several pathological conditions characterised by insulin sensitivity (stroke, PCO, hypertension, diabetes, obesity). It is suggested that, in addition to the previous concept of the main role of intraabdominal adipose tissue, even muscles and liver are also important organs contributing to the pathogenesis and development of the metabolic syndrome.
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PMID:Role of muscle morphology in the development of insulin resistance and metabolic syndrome. 783 Dec 32

The aim of this work was to examine the effect of an insulin infusion on SHBG levels as well as the relationship between SHBG levels and insulin sensitivity. Acute insulin infusion was used with the insulin-glucose clamp technique. The subjects were 14 consecutive well-characterized hyperandrogenic non-diabetic obese women without biological and echographic symptoms of polycystic ovary syndrome. Adiposity and fat distribution were assessed respectively by the body mass index (BMI: 38.7 +/- 1.6 kg/m2) and by the waist hip ratio (WHR: 0.91 +/- 0.01). Hyperandrogenism was evidenced by hirsutism and serum testosterone greater than 2.8 nM. Circulating SHBG levels were determined in the fasting state by RIA. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic glucose clamp technique with three incremental doses of insulin. Seven non-obese non-hyperandrogenic subjects (BMI: 21.0 +/- 0.6 kg/m2) served as controls for the study of the insulin resistance state. Because of supraphysiological insulin infusion rates (40, 100, and 350 mU/min.m2, each dose for 2 h), insulin sensitivity was mainly studied at peripheral level. We calculated the Km, i.e. the ED50 of the dose-response curve, the glucose disposal rate, and the maximal glucose disposal rate per U insulin (M/I). The hyperandrogenic obese subjects exhibited marked insulin resistance. SHBG levels, although already in the lower half of normal in the basal state, decreased from 34.8 +/- 3.4 nmol/l to 29.7 +/- 3.3 nmol/l (P = 0.001; normal values are 18-83 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between insulin sensitivity and circulating sex hormone-binding globulin levels in hyperandrogenic obese women. 786 76

It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported. It is not known whether changes in the one cause changes in the other, or whether they change in opposite directions in response to some third factor. Because obesity raises insulin levels and lowers SHBG levels in both sexes, we proposed to study the cause-effect question by determining whether the relationship between changes in SHBG and insulin levels during active weight loss. We studied 70 healthy weight-stable men with body mass index (BMI) from 20.7-94 (normal, 22.5 +/- 2.5) and restudied 17 of them during diet-induced weight loss. Fasting serum insulin levels in the weight-stable men showed a positive linear correlation with BMI, increasing 1 microU/mL per unit increase in BMI (P < 0.0001). SHBG levels in the weight-stable men showed a negative linear correlation with BMI, decreasing 0.2 nmol/L per unit increase in BMI (P < 0.0002). In the weight-stable men, there was an inverse hyperbolic correlation between SHBG and insulin levels; SHBG (nmol/L) = 13.1 + [30.1 divided by insulin (microU/mL)] (P < 0.002). During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo.
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PMID:The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss. 796 91

In obese men, sex hormone-binding globulin levels (SHBG) as well as total plasma testosterone (T) levels are decreased. Data concerning the levels of nonprotein-bound testosterone (FT) are discordant, with some researchers reporting normal levels, and other reporting decreased levels. The latter imply an impairment of the feedback regulation mechanism of FT levels. We investigated whether an eventual decrease in FT levels and, hence, functional impairment of the gonadostat might occur only at a more severe degree of obesity than that required for a decrease in SHBG and total T levels. We, therefore, determined androgen and precursor levels in three groups of male subjects: nonobese controls [body mass index (BMI), G (kg)/L2 (m) < 26; n = 70]; moderately (BMI, 30-35; n = 18), and severely (BMI, > 40; n = 22) obese men, respectively. In a subgroup of these controls, moderately and severely obese subjects, respectively, we studied LH levels as well as LH pulsatility. Moreover, as a decrease in FT levels might affect the metabolic pattern of the androgens and, more specifically, 5 alpha-reductase activity, we determined the plasma levels of the major 5 alpha-reduced metabolites, androstanediol glucuronide and androsterone glucuronide (AG), as well as the urinary excretion of the major 5 alpha (androsterone glucuronide) and the major 5 beta (etiocholanolone glucuronide) metabolite of the androgens. In moderately obese men, T levels were decreased, which was the consequence of the decreased SHBG-binding capacity. FT levels, however, were normal as were LH levels and both pulse amplitude and frequency of LH pulses, suggesting a normal hypothalamic control of LH secretion. In severely obese men (BMI, > 40), total T, FT, and LH levels as well as LH pulse amplitude were decreased, indicating a functional impairment of the gonadostat. Even in massively obese subjects with decreased FT levels, androgen metabolism and 5 alpha-reductase activity appeared to be normal, as suggested by similar androstanediol glucuronide and AG levels, determined by RIA or calculated from the conversion rates of precursors obtained in nonobese subjects. This was confirmed by the similar AG/eticholanolone glucuronide ratios in obese and nonobese men.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of the decreased androgen levels in obese men. 796 11

The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively associated with albumin-bound testosterone, DHEA, and DHEAS. An association was found between alcohol intake and DHEA (r = 0.15; P = 0.0001), cortisol (r = 0.10; P = 0.0007), and 3-alpha-androstanediol-glucuronide (r = 0.08; P = 0.0004). Cortisol was the only hormone that was associated with carbohydrate intake (r = -0.09; P = 0.002). The only hormones associated with dietary lipids were DHT (for vegetable fat, r = 0.07; P = 0.02), cortisol (for total fat, r = 0.08; P = 0.007), and SHBG (for animal fat, r = -0.06; P = 0.05). In addition, SHBG was positively associated with dietary (r = 0.07; P = 0.008) and crude (r = 0.08; P = 0.007) fiber. These data suggest that serum adrenal steroid and sex hormone concentrations in middle-aged men are more influenced by cigarette smoking, age, and obesity than by dietary intake; however, serum adrenal steroids were influenced by alcohol intake.
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PMID:The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men. 796 22


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