UMLS:C0028754 - FACTA Search

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

Conflicting information concerning the acute effect of hyperinsulinemia on circulating adrenal androgens, specifically DHEAS, is available. The effect of PCOD or obesity on this response is unclear. We prospectively examined the acute response of circulating DHEAS to the physiological rise in serum insulin after an OGTT in 10 women with PCOD (5 obese and 5 normal weight) and 10 ovulatory euandrogenic women (5 obese and 5 normal-weight). All underwent a standard 75-g 2-hour OGTT. Insulin and DHEAS were measured before and after OGTT. To control for the potential dilutional effects induced by hyperinsulinemia or hyperglycemia on intravascular tonicity, DHEAS levels were correlated to serum protein. As expected, the 2-hour insulin levels were significantly greater than baseline. No significant changes in circulating DHEAS or in the DHEAS to protein ratio was observed in any patient group 2 hours after glucose-induced hyperinsulinemia. The power of this study was greater than 89% for an alpha error of 0.05 and an expected change in DHEAS of 25%. In summary, it appears unlikely that acute increases in insulin within the physiological range are important in the regulation of circulating DHEAS in either PCOD or euandrogenic women, independent of obesity.
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PMID:No acute effect of physiological insulin increase on dehydroepiandrosterone sulfate in women with obesity and/or polycystic ovarian disease. 183 37

Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism.
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PMID:Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist. 210 86

Physiological and many pathological changes in plasma sex-hormone-binding globulin (SHBG) levels have been attributed to the opposing effects of androgens which lower, and oestrogens which elevate, levels. We examined four clinical situations in which changes in SHBG levels may not be explained by sex steroid alterations. (1) Dexamethasone caused an increase in SHBG levels in hyperandrogenaemic hirsute women whether or not androgens were suppressed. (2) In male patients with untreated isolated gonadotrophin deficiency there was a highly significant correlation between SHBG levels and age, but there was no relationship between the levels of SHBG and those of plasma testosterone, androstenedione or DHEAS. (3) Two 46-XY siblings, phenotypic female subjects with complete androgen insensitivity, demonstrated a marked decline in SHBG levels between the ages of 9-13 and 12-16 years. (4) SHBG was suppressed in obese oligomenorrhoeic women while plasma concentrations of testosterone, androstenedione and oestradiol were normal and that of oestrone was elevated; however, the testosterone:SHBG ratio, an index of free testosterone, was elevated. These observations indicate that the decline in SHBG levels which normally occurs in men during the second decade of life is independent of androgen activity and is under the influence of as yet unidentified factors. Glucocorticoids in small doses under the influence of as yet unidentified factors. Glucocorticoids in small doses increase SHBG levels independently of sex steroid alterations while elevated free testosterone concentration may contribute to suppression of SHBG in obesity.
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PMID:The relationship between sex steroids and sex-hormone-binding globulin in plasma in physiological and pathological conditions. 406 18

To explore the relationship between serum DHEAS levels and blood pressure, obesity, smoking habits and drinking habits associated with onset of cardiovascular disease, we examined serum DHEAS levels in 90 males and 183 females, aged 35 to 62 years, who participated in a mass health examination conducted in a town of Aichi prefecture in 1992. The results were as follows. 1. Serum DHEAS levels were significantly higher in males than in females and decreased with age both sexes. 2. Age-adjusted serum DHEAS levels for both sexes decreased with blood pressure and BMI. 3. There were no apparent significance between age-adjusted serum DHEAS levels and smoking habits, whereas age-adjusted serum DHEAS levels were higher in groups of intake of ethanol volume 1-29 g/day than in the groups of intake of more than and less than ethanol volume 1-29 g/day. 4. Age-adjusted serum DHEAS levels were significantly decreased with the rise of sum of factors chosen as risk factor of cardiovascular disease disease in this study. It was suggested that serum DHEAS levels might be useful as an index of accumulation of risk factors of cardiovascular disease. Further studies should be performed to establish the possibilities as an index of genesis and prevention of cardiovascular disease.
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PMID:[The relationship between serum dehydroepiandrosterone sulfate levels and factors associated with cardiovascular diseases: a cross-sectional study in Japan]. 771 11

Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been demonstrated experimentally: binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.
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PMID:Abnormal production of androgens in women with breast cancer. 784 May 9

The diabetes (db) gene is a recessive obesity mutation in the mouse capable of producing diabetes only through interaction with heretofore undefined modifiers in the genetic background of certain inbred strains. Here we identify the genetic map locations of androgen and estrogen sulfotransferase genes important in maintaining the balance of active sex steroids in the liver. The Std locus encoding dehydroepiandrosterone sulfotransferase was mapped to proximal Chromosome 7, and the Ste locus encoding estrogen sulfotransferase was mapped to Chromosome 5. The db mutation in the diabetes-susceptible C57BL/KsJ strain aberrantly regulated mRNA transcript levels from these two loci. Hepatic Ste mRNA transcripts were increased from undetectable levels in normal males and females to high levels in db/db mice of both sexes. An anomalous suppression of Std transcription was observed in db/db females, but not in normal females. These reciprocal changes in mRNA concentrations in mutant females were reflected by an induction of a high affinity estrogen sulfotransferase activity and a concomitant loss of dehydroepiandrosterone sulfotransferase activity. These db gene-elicited effects were specific for the sex steroid sulfotransferases since other potential sex steroid metabolizing enzymes (phenol sulfotransferase, sex steroid sulfohydrolase, and UDP-glucuronyltransferase) were unaffected. These aberrant changes would virilize hepatic metabolism in females by increasing the ratio of active androgens to estrogens. In human females, non-insulin-dependent diabetes mellitus often develops when visceral obesity and hyperinsulinemia are associated with hyperandrogenization. This study demonstrates that background modifier genes interacting deleteriously with an obesity mutation are not necessarily defective alleles. Rather, some are functional genes whose regulation has been altered by pleiotropic effects of the obesity gene.
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PMID:Obesity-induced diabetes (diabesity) in C57BL/KsJ mice produces aberrant trans-regulation of sex steroid sulfotransferase genes. 818 32

Hyperandrogenism must be considered in any girl with premature pubarche, unusual acne, hirsutism, or androgenetic alopecia. An association with menstrual irregularity or obesity should raise the index of suspicion. The most common causes of hyperandrogenism presenting in a teenage girl are functional ovarian hyperandrogenism, one manifestation of which is polycystic ovary syndrome, and functional adrenal hyperandrogenism, which usually seems to be due to an exaggeration of adrenarche. The plasma-free testosterone is a more sensitive indicator of hyperandrogenism than is the total testosterone concentration. The pattern of response of plasma free testosterone, DHEAS, and cortisol to dex-suppression testing can be diagnostic of the source of androgen excess. Treatment, including oral contraceptives, low-dose glucocorticoids, and antiandrogens, should be chosen according to the patient's symptoms and source of androgens and should be combined with traditional therapy for the specific dermatologic disorder.
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PMID:Acne, hirsutism, and alopecia in adolescent girls. Clinical expressions of androgen excess. 824 45

Insulin secretion in response to an oral glucose tolerance test (OGTT) and sex hormone levels (free testosterone, androstenedione, dehydroepiandrosterone sulfate [DHEAS], estradiol, and sex hormone-binding globulin [SHBG]) were evaluated in 49 healthy obese premenopausal women (body mass index [BMI], 30 to 50.6 kg/m2) and 21 control subjects (BMI, 17.8 to 24.0 kg/m2) with normal glucose tolerance and without signs of hyperandrogenism. Obese women were divided into two groups according to waist to hip ratio (WHR): 27 subjects with upper-body obesity (WHR > 0.85) and 22 subjects with lower-body obesity (WHR < 0.8). Both fasting and glucose-induced insulin levels were higher in women with upper-body obesity than in controls (P < .001) and those with lower-body obesity (P < .001). Hyperandrogenism was observed in women with upper-body obesity, as evident by significantly elevated free testosterone (P < .05 v controls and subjects with lower-body obesity) and decreased SHBG (P < .001 v controls). The most important independent determinants of fasting insulin levels were BMI (P < .01) and the ratio of DHEAS to free testosterone (P < .01). The most important determinants of cumulative insulin response were WHR (P < .0005), duration of obesity (P < .01), and androstenedione levels (P < .01). In conclusion, in healthy obese premenopausal women without clinical signs of hyperandrogenism, a high BMI and more pronounced upper-body fat localization resulted in hyperinsulinemia and hyperandrogenism. The duration of obesity exaggerated the glucose-induced insulin level and cumulative insulin response independently of the degree of obesity and obesity type. The ratio of DHEAS to free testosterone was an independent determinant of fasting insulin concentration. Furthermore, the ratio of DHEAS to free testosterone rather than either of these androgens alone may be important in the regulation of insulin action in women.
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PMID:Hyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity. 944 Apr 71

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as "protective" against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.
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PMID:Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. 1115 50

During the process of aging in males a trend toward an unfavourable body fat accumulation, especially within the visceral depots, is observed. This fact is presumed to be associated with the age-related decline in androgen levels among aging men. The aim of this study was to determine the relationships between sex steroid levels (DHEAS, estradiol, free and total testosterone) and BMI, percent fat mass, WHR values in 190 healthy and professionally active men, aged 22-67, inhabitants of the city of Wroclaw, Poland. Hormonal levels were measured using standard immunoassays. BMI was used as a measurement of obesity. Obesity was also assessed using percent fat mass equations according to the Crook formula. WHR was used as an index of fat distribution. All the correlations between sex steroids, BMI, WHR, percent fat mass and age were evaluated using statistical non-parametric analyses (Spearman coefficient) in the entire group of examined subjects, and in two age-specific groups: a) younger males (aged 22-39) and b) older males (aged 40-67). The aging of Polish males is accompanied by both a significant increase of BMI, percent fat mass and WHR values, and by a decline in estradiol, gonadal and adrenal androgen levels. In the younger group only total testosterone levels were significantly negatively related to BMI, percent fat mass and WHR. Within the group of older men both estradiol and DHEAS levels are significantly positively related to WHR. The sex steroids seem to be associated with indices of overall obesity and distribution of fat in men, but these relationships differ considerably when they are evaluated in younger and older age categories. Worthy of notice is the fact that free testosterone levels are not related to any anthropometric parameters in any age category, although free testosterone (not total testosterone) is commonly recognised as a reliable and sensitive endocrinological indicator of the general psycho-physical status of an aging man.
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PMID:Relationships between age-related changes of sex steroids, obesity and body fat distribution among healthy Polish males. 1120 73

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