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Vito Angelo Giagulli - One of the best experts on this subject based on the ideXlab platform.
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origin and significance of plasma androsterone glucuronide levels a parameter of adrenal androgen secretion and hepatic 5 alpha reductase activity
The Journal of Clinical Endocrinology and Metabolism, 1993Co-Authors: Vito Angelo Giagulli, R Giorgino, Alex VermeulenAbstract:To evaluate the reliability of plasma androsterone glucuronide (ADTG) as a parameter of Androgenicity at the target tissue level, we studied the origin of ADTG in women, by measuring the plasma conversion rate of different possible precursors as well as by measuring ADTG levels in ovariectomized women and women with Addison's disease. In women, ADTG levels reflect essentially adrenal androgen secretion, dehydroepiandrosterone sulfate (DHEAS) being the major precursor, accounting for 70%-80% of ADTG levels. As estimated from the ADTG/DHEAS ratio in hirsute women (increased peripheral 5 alpha-reductase) and hyperthyroid women (increased hepatic 5 alpha-reductase), it appears that hepatic 5 alpha-reductase is a major determinant of the conversion of precursors to plasma ADTG. In men, plasma testosterone and DHEAS appear to contribute to a comparable extent to plasma ADTG levels, as suggested by data obtained in orchidectomized men and men with Addison's disease. In accordance with the role of DHEAS as a prec...
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physiopathology of plasma androstanediol glucuronide
The Journal of Steroid Biochemistry and Molecular Biology, 1991Co-Authors: A. Vermeulen, Vito Angelo GiagulliAbstract:Abstract Plasma androstanediol-glucuronide (ADG) is considered by many authors to be a highly reliable parameter of peripheral Androgenicity. Recently, several authors have questioned the reliability of the ADG levels as a parameter of Androgenicity. Our data obtained by continuous infusion experiments showed that in women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma ADG, accounting for almost the totality of circulating ADG. As expected, in view of its precursors, ADG levels decrease significantly with age. Dexamethasone causes a significant decrease of these levels, whereas in women with Addison's disease the levels are only 20% of normal levels; ovariectomy hardly influences ADG levels. Our data show that in women with moderate hirsutism, plasma ADG levels are no more often increased than the other androgens. In virilizing syndromes ADG levels are higher than expected from precursor levels, suggesting an increased 5α-reductase activity. In hyperthyroidism as well as in euthyroid women with isolated suppressed thyroid stimulating hormone, ADG levels are increased without any sign of virilism. In men, ADG levels have testosterone as a major precursor, but the adrenals contribute to ±30% of ADG levels. After transdermal dihydrotestosterone gel, free androstanediol levels increased by a factor of 40, but ADG levels were only increased by a factor of 4, suggesting that the skin is not very effective in conjugating androstanediol. It is concluded that ADG levels in women reflect essentially adrenal precursor levels as well as 5α-reductase activity in peripheral tissues inclusive of the liver.
A. Vermeulen - One of the best experts on this subject based on the ideXlab platform.
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Reflections concerning biochemical parameters of Androgenicity
Aging Male, 2004Co-Authors: A. VermeulenAbstract:Due to the highly variable concentration of sex hormone binding globulin (SHBG) and the many factors affecting it, the evaluation of the androgen status may require the measurement of a parameter of bioactive plasma testosterone. As, however, no practical, clinical useful direct method for measurement of plasma androgen bioactivity is available, indirect biochemical parameters are used. All have their limitations and pitfalls. In this paper are discussed some of the factors influencing the values obtained with different methods (direct measurement of free testosterone by analog radioimmunoassay, dialysis, ammonium sulfate precipitation, free testosterone index, calculated free and bioavailable testosterone), all of which may explain the variability of data reported in the literature. It is concluded that, whereas determination of bioavailable testosterone by dialysis or ammonium sulfate precipitation of SHBG-bound testosterone is work-intensive and not really suitable for clinical routine, while direct measurement of free testosterone by analog immunoassay yields unreliable results, only the free testosterone index and calculated bioavailable testosterone are adapted for clinical routine. The limitations of the free testosterone index, a dimensionless parameter which does not reflect a defined bioavailable testosterone concentration, are discussed. As the same measurements of testosterone and SHBG required for determination of the free testosterone index permit the calculation of bioavailable testosterone, which yields a defined androgen concentration, it is advisable to prefer the latter over the free testosterone index, which should no longer be used.
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physiopathology of plasma androstanediol glucuronide
The Journal of Steroid Biochemistry and Molecular Biology, 1991Co-Authors: A. Vermeulen, Vito Angelo GiagulliAbstract:Abstract Plasma androstanediol-glucuronide (ADG) is considered by many authors to be a highly reliable parameter of peripheral Androgenicity. Recently, several authors have questioned the reliability of the ADG levels as a parameter of Androgenicity. Our data obtained by continuous infusion experiments showed that in women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma ADG, accounting for almost the totality of circulating ADG. As expected, in view of its precursors, ADG levels decrease significantly with age. Dexamethasone causes a significant decrease of these levels, whereas in women with Addison's disease the levels are only 20% of normal levels; ovariectomy hardly influences ADG levels. Our data show that in women with moderate hirsutism, plasma ADG levels are no more often increased than the other androgens. In virilizing syndromes ADG levels are higher than expected from precursor levels, suggesting an increased 5α-reductase activity. In hyperthyroidism as well as in euthyroid women with isolated suppressed thyroid stimulating hormone, ADG levels are increased without any sign of virilism. In men, ADG levels have testosterone as a major precursor, but the adrenals contribute to ±30% of ADG levels. After transdermal dihydrotestosterone gel, free androstanediol levels increased by a factor of 40, but ADG levels were only increased by a factor of 4, suggesting that the skin is not very effective in conjugating androstanediol. It is concluded that ADG levels in women reflect essentially adrenal precursor levels as well as 5α-reductase activity in peripheral tissues inclusive of the liver.
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clinical review 24 androgens in the aging male
The Journal of Clinical Endocrinology and Metabolism, 1991Co-Authors: A. VermeulenAbstract:IN CONTRAST to the situation in women, where the menopause marks the end of the fertile period, in men fertility persists into old age. Nevertheless old age in men is accompanied by clinical signs, such as a decrease in muscle and bone mass, decrease in sexual hair growth, and decreased libido and sexual activity, suggesting decreased virility. These clinical signs are supported by histological evidence for a decreased Leydig mass and function. Evidence for decreased plasma testosterone in elderly men As to biochemical evidence for decreased Androgenicity in elderly men, 25 yr ago the blood production rate of testosterone was reported to be decreased, which at least partially is caused by a decrease of the metabolic clearance. Whether or not aging is also associated with a decrease in plasma testosterone concentrations has long been highly controversial. Indeed, a large series of publications in the 1960s and early 1970s reporting decreased plasma testosterone concentrations in elderly
R Giorgino - One of the best experts on this subject based on the ideXlab platform.
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lower Androgenicity is associated with higher plasma levels of prothrombotic factors irrespective of age obesity body fat distribution and related metabolic parameters in men
Metabolism-clinical and Experimental, 1997Co-Authors: Giovanni De Pergola, Vito De Mitrio, M Sciaraffia, Nicola Pannaccuilli, Antonio Minenna, Francesco Giorgino, Mariella Petronelli, Ester Laudadio, R GiorginoAbstract:Abstract The purpose of this study was to examine the relationships between androgenic status and plasma levels of both prothrombotic and antithorombotic factors in men, irrespective of obesity, body fat distribution, and metabolic parameters. Sixty-four apparently healthy men, 40 with a body mass index (BMI) greater than 25 kg/m2 (overweight and obese [OO]) and 24 non-obese controls with a BMI less than 25, were selected and evaluated for (1) plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) antigen, PAI-1 activity, fibrinogen, von Willebrand factor (vWF) antigen, vWF activity, and factor VII (FVII) as the prothrombotic factors; (2) plasma levels of tissue plasminogen activator (TPA) antigen, protein C, and antithrombin III as the antithrombotic factors; (3) fasting plasma concentrations of insulin and glucose and the lipid pattern (triglycerides [TG] and total and high-density lipoprotein [HDL] cholesterol) as the metabolic parameters; and (4) free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), and sex hormone—biding globulin (SHBG) serun levels as the parameters of Androgenicity. Body fat distribution was evaluated by the waist to hip ratio (WHR). In OO and non-obese subjects taken together, plasma levels of PAI-1 antigen, fibrinogen, and FVII were inversely associated with FT (r = .255, P
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origin and significance of plasma androsterone glucuronide levels a parameter of adrenal androgen secretion and hepatic 5 alpha reductase activity
The Journal of Clinical Endocrinology and Metabolism, 1993Co-Authors: Vito Angelo Giagulli, R Giorgino, Alex VermeulenAbstract:To evaluate the reliability of plasma androsterone glucuronide (ADTG) as a parameter of Androgenicity at the target tissue level, we studied the origin of ADTG in women, by measuring the plasma conversion rate of different possible precursors as well as by measuring ADTG levels in ovariectomized women and women with Addison's disease. In women, ADTG levels reflect essentially adrenal androgen secretion, dehydroepiandrosterone sulfate (DHEAS) being the major precursor, accounting for 70%-80% of ADTG levels. As estimated from the ADTG/DHEAS ratio in hirsute women (increased peripheral 5 alpha-reductase) and hyperthyroid women (increased hepatic 5 alpha-reductase), it appears that hepatic 5 alpha-reductase is a major determinant of the conversion of precursors to plasma ADTG. In men, plasma testosterone and DHEAS appear to contribute to a comparable extent to plasma ADTG levels, as suggested by data obtained in orchidectomized men and men with Addison's disease. In accordance with the role of DHEAS as a prec...
Shuki Mizutani - One of the best experts on this subject based on the ideXlab platform.
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a highly specific heterologous enzyme immunoassay for 5α androstane 3α 17β diol 17 glucuronide androstanediol 17g and developmental patterns of urinary androstanediol 17g excretions
Steroids, 2002Co-Authors: Toshikazu Onishi, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, H Takei, Akira Kambegawa, Shuki MizutaniAbstract:We established a highly specific enzyme immunoassay (EIA) for 5α-androstane-3α, 17β-diol 17-glucuronide (androstanediol-17G). Rabbit antisera raised against 5α-androstane-3α, 11α, 17β-triol 17-glucuronide 11-glutaryl bovine serum albumin and a heterologous tracer of androstanediol-17G conjugated with horseradish peroxidase at the glucuronic acid group were used. The EIA showed excellent specificity: there were no remarkable cross-reactivities with related androgens. The assay range for urine samples was 0.3–30 ng/ml. Recoveries of standards added to samples were 100–108%. Intra-assay and inter-assay coefficients of variation were 2.9–4.4% and 5.7–7.9%, respectively. The EIA was applied to urine samples of 407 males and 322 females to determine developmental patterns and normal ranges of androstanediol-17G excretions in 11 age groups (0 y, 1 y, 2–3 y, 4–5 y, 6–7 y, 8–9 y, 10–11 y, 12–13 y, 14–15 y, 16–17 y, and over 18 y). Urinary androstanediol-17G/creatinine (androstanediol-17G/Cre) ratios in both sexes were high in infancy, tended to decrease during childhood, and began to increase near adolescence. While androstanediol-17G/Cre ratio in girls increased at 8–9 y and reached a plateau during adolescence, that in boys increased at 10–11 y and continued to increase throughout adolescence. Androstanediol-17G/Cre ratios in girls were higher than those in boys at 6–7 y (P < 0.05) and at 8–9 y (P < 0.01). Androstanediol-17G/Cre ratios in boys were higher than those in girls at 12–13 y and at older ages (P < 0.01). These developmental patterns are parallel to age-related changes in Androgenicity and serum androstanediol-17G, suggesting that urinary androstanediol-17G/Cre ratio could be a good marker for Androgenicity in childhood.
Cathy C Lee - One of the best experts on this subject based on the ideXlab platform.
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effect of oral phytoestrogen on Androgenicity and insulin sensitivity in postmenopausal women
Diabetes Obesity and Metabolism, 2012Co-Authors: Cathy C Lee, Josephine Z Kasavubu, C J Bloem, Lijung LiangAbstract:Aim: The aim of this study was to determine and compare the effect of treatment with transdermal oestrogen and phytoestrogen on insulin sensitivity and sex hormone-binding globulin (SHBG) levels in healthy postmenopausal women. Methods: Forty-three healthy postmenopausal women aged 68 ± 7( mean± SD) years who were not receiving hormonal replacement therapy completed a 3 month randomized drug therapy study. The participants were randomized to one of four groups: 0.05 mg or 0.1 mg transdermal oestrogen/day, or 40 or 80 mg oral phytoestrogen (Promensil)/day insulin sensitivity was indirectly measured using the quantitative insulin sensitivity check index (QUICKI). SHBG, total testosterone, oestradiol, and fasting glucose and insulin levels for calculation of insulin sensitivity were obtained at baseline and at monthly intervals during the 3 months of therapy. Results: In healthy nondiabetic postmenopausal women, the rate of change in QUICKI was significantly different between the red clover based phytoestrogen and transdermal oestrogen groups, so that after three months of therapy, QUICKI with red clover based phytoestrogen therapy was lower than that in the transdermal oestrogen group, p = 0.01. Red clover based phytoestrogen therapy was not associated with any changes in SHBG levels whereas transdermal estrogen therapy significantly increased SHBG levels, p = 0.05. Conclusions: In contrast to transdermal oestrogen therapy, oral phytoestrogen therapy does not decrease Androgenicity and is associated with a decrease in insulin sensitivity. These effects are similar to those of raloxifene and consistent with phytoestrogen’s selective oestrogen
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Androgenicity and obesity are independently associated with insulin sensitivity in postmenopausal women
Metabolism-clinical and Experimental, 2004Co-Authors: Cathy C Lee, Josephine Z Kasavubu, Mark A SupianoAbstract:Abstract An increase in Androgenicity may contribute to the development of insulin resistance in postmenopausal women. Increased Androgenicity in women has been found to be associated with the development of type 2 diabetes. In addition, obesity and central obesity are associated with greater Androgenicity. Insulin sensitivity, Androgenicity, and body composition were characterized in 34 nondiabetic postmenopausal women age 72 ± 1 years (mean ± SEM) to test the hypothesis that Androgenicity is a predictor of insulin sensitivity independent of measures of obesity. Androgenicity was measured using levels of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and free androgen index (FAI). Insulin sensitivity (SI) was determined from a frequently sampled intravenous glucose tolerance test. Body composition measures included body mass index (BMI) and dual energy x-ray absorptiometry measurements of total and central fat mass. SI was found to be associated with total fat mass (r = −.51, P = .002), central fat mass (r = −.62, P = .0001), BMI (r = −.55, P = .0008), SHBG levels (r = .65, P = .0001), and FAI (r = −.41, P = .01). SHBG levels were inversely correlated with central fat mass (r = −.59, P = .0002). Using multiple regression, SHBG and central fat mass were the only significant independent predictors of SI, accounting for 50% of its variance (r = .71, P = .0001); total fat mass, BMI, total and free testosterone, DHEA-S, androstenedione, and FAI did not enter the model. We conclude that there is a significant association between insulin sensitivity and Androgenicity in postmenopausal women that is independent of obesity. Interventions to decrease Androgenicity may therefore be useful in improving insulin sensitivity in postmenopausal women.