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

Virilization in women is associated with increased production of testosterone as well as a variety of androgenic prehormones, including androstenedione, androstenediol, DHEA, DHEA-sulfate, dihydrotestosterone and androstanediol. Of these hormones, it is likely that testosterone is the androgen which initiates a series of androgen-receptor mediated events resulting in stimulation of 5 alpha reductase in the skin and hair follicles, producing dihydrotestosterone locally. The metabolism of testosterone to dihydrotestosterone within the hair follicle results in increased clearance of testosterone, however at the expense of hair follicle stimulation. Increased 5 alpha reductase of the skin and hair allows other prehormones to be metabolized to dihydrotestosterone and androstanediol, further stimulating the hair follicle (multiplier effect). In obese women, androgen production rates are elevated and SHBG levels are depressed, in many cases to the same magnitude as that observed in hirsute women. Increased androgen production rates in obesity, however, are associated with major increases in clearance rates of these androgens. Resultant androgen blood levels are even lower than observed in the non-obese population. It appears likely that adipose tissue is the site of the increased clearance rates and metabolism of prehormones to dihydrotestosterone and androstanediol. A delicate balance likely exists between production and clearance of these biologically active hormones. Minor aberrations in this balance may result in the increased incidence of hirsutism seen in the obese female population.
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PMID:A comparison of androgen production and clearance in hirsute and obese women. 688 88

The relationship of sex-hormone-binding globulin (SHBG) with actual body weight (ABW), ideal body weight (IBW), ABW as percentage of the IBW (% IBW), Quetelet index (weight/height2) and plasma concentrations of various androgens and 17 beta-estradiol (E2) were studied in 9 normal and 57 hirsute patients (group 1). In hirsute patients, plasma levels (ng/dl, mean +/- standard error of the mean [SEM]) of testosterone (T; 77 +/- 4), dihydrotestosterone (DHT; 26 +/- 2), androstenedione (delta 4A; 184 +/- 16), and SHBG (0.91 +/- 0.05 micrograms DHT/dl) but not of dehydroepiandrosterone (DHA; 608 +/- 55) and E2 (6.1 +/- 0.1) were significantly different from those in controls. A negative correlation was observed between SHBG and ABW, both in controls (P less than 0.05) and hirsute patients (P less than 0.01). The hirsute patient population was subdivided into two groups: nonobese (group 2; 60 +/- 1 kg; n = 35) and obese (group 3; 96 +/- 2 kg; n = 22). Plasma androgens, T/SHBG (an index of free T) and E2 in groups 2 and 3 (T: 75 +/- 4, 81 +/- 7; DHT: 24 +/- 2, 28 +/- 3; T/SHBG: 85 +/- 7, 105 +/- 11; delta 4A: 203 +/- 13, 155 +/- 16; DHA: 663 +/- 83, 521 +/- 49; E2: 6.1 +/- 1.0, 5.8 +/- 0.9) were similar; yet SHBG in group 3 (0.75 +/- 0.04) was significantly lower than in group 2 (1.0 +/- 0.01). Inverse correlations between SHBG and ABW, % IBW, and ABW/H2 were observed in group 2 but not in group 3. We conclude that a negative relationship exists between SHBG and the body size in nonobese women and that in hirsute patients, obesity leads to a further lowering of SHBG through mechanism(s) probably independent of androgens.
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PMID:Sex-hormone-binding globulin in clinically hyperandrogenic women: association of plasma concentrations with body weight. 720 37

Dehydroepiandrosterone (DHEA) has been reported to exert antiglucocorticoid activity. When administered to obese, hypercorticosteronemic Zucker rats, it causes a diminution of food intake and a reduction in their rate of weight gain. This experiment was conducted to evaluate whether this biologic effect could be ascribed to chronic adrenal insufficiency. Obese and lean Zucker rats were treated with DHEA as a food supplement for 28 days. Upon sacrifice, organ weights and serum chemistries were measured, along with neurotransmitter levels in regions of the hypothalamus. Results showed that although the obese animals gained weight more slowly, had lower insulin levels, and ate less, their serum glucose, corticosterone, and ACTH levels were not different from control. Hypothalamic neurotransmitters in the obese rat were unaffected by chronic DHEA treatment. We concluded that, although DHEA clearly affects Zucker weight gain, it does not induce chronic adrenal insufficiency.
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PMID:The effect of DHEA given chronically to Zucker rats. 753 42

Primary empty sella syndrome (ESS) is an anatomo-radiological picture characterized by the presence of an arachnoid herniation filled with liquor that compresses the pituitary against the sellar wall. ESS occurs particularly in obese, hypertensive, cephalalgic women. It is often asymptomatic but may be associated with ophthalmologic, neurologic and non-characterizing endocrine disorders. We report here 43 cases of primary ESS observed and assessed in our Departments of Internal Medicine from June 1983 to May 1993. The following endocrinological diagnostic procedures were carried out: hormonal (RIA) basal profile: FT3, FT4, TSH, PRL, ACTH, FSH, LH, 8.00 a.m. and p.m., blood cortisol, aldo, PRA, DHEA-S, FTe, E2, P, PTH, CT, and calcemia and phosphoremia; provocative tests: TRH, GnRH, etc.; inhibition tests: high dose dexamethasone. Clinical, neurologic (skull radiographs, sellar stratigraphy, computed tomography scan and magnetic resonance), and ophthalmologic (fundus, visual fields) assessments were also made. Our findings fit with the data in the literature concerning common symptoms of ESS, associated endocrinopathies and other illness. We found obesity (62.7%), oligo-amenorrhea (16.6%), galactorrhea (14.6%), hyperPRL (11.6%), hypopituitarism (9.3%), hypogonadism (4.6%), diabetes insipidus (2.3%), (micro-)polycystic ovary syndrome (19%), hyperACTH (2.3%). In 9.3% of the cases, endocrinopathy referred to pituitary adenomas. Moreover, we noted a high frequency of psychological disorders, to our knowledge not previously reported in the literature, including anxiety or dysthymic disorders with altered behavior (chiefly oral compulsion). We also make the hypothesis that obesity (occurring in 62.7% of our patients) and hypertension (62.7%) may be related to hypothalamic alterations.
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PMID:[43 cases of primary empty sella syndrome: a case series]. 761 55

Sex steroid hormones may be involved in determining body fat distribution in men. Recent evidence suggests that insulin may be an important regulator of sex hormones metabolism in men. Few data, however, are available on the relationship of dehydroepiandrosterone sulphate (DHEA-SO4), a major secretory product of the adrenal gland, to regional distribution of body fat or to insulin levels in men. We therefore examined the association of DHEA-SO4, total testosterone and free testosterone to waist-to-hip ratio (WHR) and to subscapular-to-triceps ratio (STR) in 34 obese, otherwise healthy men. In addition, we examined the relation between these sex steroid hormones and insulin response to an oral glucose tolerance test. DHEA-SO4 was significantly positively related to STR and significantly negatively related to insulin area. These associations remained significant after adjustment for age and obesity. Using multiple linear regression, DHEA-SO4 was independently related to both STR and insulin area. Without claiming any causality in the observed associations, we conclude that, in obese men, high DHEA-SO4 levels are related to centralized adiposity, while low DHEA-SO4 levels are related to hyperinsulinemia.
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PMID:Dehydroepiandrosterone sulphate, body fat distribution and insulin in obese men. 771 92

Polycystic ovary (PCO) syndrome is strongly associated with insulin resistance and the accompanying adverse metabolic profile. To distinguish the mechanisms of this association, we determined the interactions of PCO with obesity and the influence of ameliorating direct androgenic actions via short-term treatment with the antiandrogen flutamide. Insulin sensitivity was determined by the hyperinsulinemic euglycemic clamp in groups of lean and obese PCO women and weight-matched controls. Compared with control values, insulin-mediated glucose utilization in PCO women was significantly lower in lean (1.96 +/- 0.17 v 1.24 +/- 0.10, P < .01) and obese (1.23 +/- 0.18 v 1.03 +/- 0.09 mmol/m2/min, P < .01) subjects. ANOVA indicated that the effects of obesity and androgenicity are independent and additive. In both lean and obese PCO women, treatment with flutamide for 1 or 3 months markedly improved the clinical and biochemical androgenic features, but did not significantly influence the overall insulin sensitivity. A large disparity between individuals in the response to treatment correlated significantly with a simultaneous reduction in plasma levels of dehydroepiandrosterone sulfate (DHEA-S). Thus in women, PCO and obesity exert synergistic effects on insulin resistance. The decreased insulin sensitivity is mediated via indirect androgenic actions or nonandrogenic mechanisms. In some individuals, a direct effect of androgens might have been masked by a decrease in DHEA-S levels.
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PMID:Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome. 772 77

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

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 steroid hormone intermediate, DHEA, has been proposed as a therapeutic agent for the treatment of obesity. Its effects on lipogenesis, substrate cycling, peroxisome proliferation, mitochondrial respiration, protein synthesis, and thyroid hormone function have been reported. The results of these studies suggest that the antiobesity function of DHEA is not simply one of inhibiting fat synthesis and deposition but is one of affecting a number of pathways that contribute to the maintenance of the isoenergetic state rather than the promotion of positive energy balance.
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PMID:Is dehydroepiandrosterone an antiobesity agent? 846 83

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


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