androstane-3-17-diol-glucuronide and Obesity

The effects of subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) injection on androgenic markers in obese women have not previously been studied.. Five normal-weight [body mass index (BMI)=18.5-24.9 kg/m²], five obese (BMI=30-39.9 kg/m²) and five extremely obese (BMI≥40 kg/m²) women were recruited for this prospective experimental study in which 104 mg DMPA-SC was administered at baseline and 12 weeks later. Serum levels of total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 3α-androstanediol glucuronide and sex hormone-binding globulin (SHBG) were quantified by immunoassay methods at baseline and at 13 and 26 weeks following the first injection; free T was calculated.. At baseline, obese women had lower levels of A and SHBG and higher total and free T levels than normal-weight women. There were a statistically significant decrease in the levels from baseline to week 26 among all three BMI classes for A, total T and SHBG (p≤.03) and an increase from baseline to week 26 in weight (p=.02). In addition, there was a statistically significant decrease in DHEAS from baseline to week 13 among all three BMI classes (p=.01), which was not sustained at week 26 (p>.1). Overall, the three groups responded similarly to all changes at week 13, and there were no statistically significant differences between groups at any time point (p≥.06).. DMPA-SC use in normal-weight, obese and extremely obese women can decrease serum androgen markers.

Topics: Adult; Androgen Antagonists; Androgens; Androstane-3,17-diol; Androstenedione; Biomarkers; Body Mass Index; Contraceptive Agents, Female; Dehydroepiandrosterone Sulfate; Drug Implants; Female; Humans; Medroxyprogesterone Acetate; Obesity; Obesity, Morbid; Sex Hormone-Binding Globulin; Subcutaneous Tissue; Testosterone; Time Factors; Young Adult

We examined interaction of sex steroid hormones and obesity with regard to insulin resistance (IR) and type 2 diabetes (T2D) by using nationally representative data from the US.. Data of 1461 men aged ≥20years who participated in the Third National Health and Nutrition Examination Survey were analyzed. Multiplicative interaction was calculated by cross-product interaction terms in multivariable logistic regression models. Additive interaction was assessed by the relative excess risk due to interaction (RERI).. After adjusting for demographic and lifestyle covariates, the odds of IR were greatest among obese men with low free testosterone and high androstanediol glucuronide. Multiplicative interactions for total testosterone, free testosterone, and free estradiol index (FEI) were statistically significant with central obesity but not with overweight and obesity regarding to T2D (P<0.05). Significant additive interactions with obesity or central obesity were detected for total testosterone (RERI=2.75, 95% CI=0.92,4.59), SHBG (RERI=5.71, 95% CI=0.77,10.64), and FEI (RERI=-9.96, 95% CI=-19.18,-0.74) with regard to IR, beta-cell dysfunction, and T2D.. Our findings add to the evidence suggesting that low testosterone and high estradiol may be associated greater risks of IR and T2D by interacting with overall and central obesity in adult men.

Topics: Adult; Aged; Androstane-3,17-diol; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Estradiol; Humans; Insulin Resistance; Logistic Models; Male; Middle Aged; Nutrition Surveys; Obesity; Obesity, Abdominal; Overweight; Prevalence; Risk; Testosterone; United States; Waist Circumference; Young Adult

This study has evaluated the behaviour of 3alpha-androstanediol glucuronide (3alpha-diol G) in 170 women of whom 85 had polycystic ovary syndrome (PCOS), 35 had idiopathic hirsutism (IH) and 50 had regular cycles (control group). Of the women with PCOS, 45 were hirsute (PCOS-H) and 40 were non hirsute (PCOS-NH). Women in the control group were not hirsute. Hirsutism was assessed by the same physician using the Ferriman-Gallway score. The body mass index (BMI) was estimated in all of the women. Plasma concentrations of 3alpha-diol G were elevated only in hirsute patients, both with PCOS and with IH. Even in PCOS-NH, concentrations of 3alpha-diol G were higher compared with controls (P < 0.001), but significantly lower (P < 0.001) than those of the PCOS-H and of the IH groups. The behaviour of 3alpha-diol G was not affected by BMI.

Topics: Adolescent; Adult; Androstane-3,17-diol; Case-Control Studies; Female; Hirsutism; Humans; Hyperandrogenism; Obesity; Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

Topics: Adult; Androgen Antagonists; Androstane-3,17-diol; Androstenedione; Cholesterol; Dehydroepiandrosterone Sulfate; Female; Flutamide; Humans; Hyperlipidemias; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Liver Function Tests; Obesity; Polycystic Ovary Syndrome; Testosterone; Triglycerides

Prostate-specific antigen (PSA) is present at very low concentrations in female serum, but it can now be measured with highly sensitive immunoassays. We have found that in female tissues the PSA gene is regulated by steroid hormones through the action of steroid hormone receptors. Thus, we examined whether female serum PSA is associated with hyperandrogenic states. Serum PSA levels were compared between 22 hirsute women with a Ferriman-Gallwey score higher than 8 and 50 women without hirsutism. The results show that PSA levels were higher in hirsute women in comparison with controls. In hirsute women, levels of PSA and 3 alpha-androstanediol glucuronide (3 alpha-AG), a specific metabolite of androgen action, showed a significant positive correlation, whereas PSA and 3 alpha-AG showed a significant negative correlation with patient age. Receiver operating characteristic (ROC) analysis revealed that 3 alpha-AG was a slightly better marker of androgen excess than PSA. We conclude that female serum PSA may be a new biochemical marker of androgen action in females.

Topics: Adolescent; Adult; Aging; Androgens; Androstane-3,17-diol; Biomarkers; Female; Hirsutism; Humans; Middle Aged; Obesity; Prostate-Specific Antigen; Reference Values; Testosterone

Plasma levels of androstane-3alpha,17beta-diol glucuronide (3alpha-DIOL-G) and androsterone glucuronide (ADT-G) as well as testosterone and adrenal C19 steroid concentrations were measured in a sample of 80 men in whom visceral adipose tissue (AT) accumulation was also determined by computed tomography. Plasma 3alpha-DIOL-G concentrations showed significant positive correlations with total body fat mass (r = 0.31; P < 0.05) and percent body fat (r = 0.28; P < 0.05). Furthermore, plasma 3alpha-DIOL-G levels were significantly associated with visceral adipose tissue accumulation (r = 0.41; P < 0.0005) as well as fasting plasma insulin (r = 0.35; P < 0.005) and glycemic and insulinemic responses to an oral glucose load (r = 0.39; P < 0.0005 and r = 0.32; P < 0.005, respectively). However, associations between 3alpha-DIOL-G and plasma glucose-insulin homeostasis indexes were no longer significant after adjustment for visceral AT area. ADT-G levels were not significantly associated with any of the adiposity variables. Subjects matched for abdominal sc AT area but with either low or high levels of visceral AT area showed significant differences in 3alpha-DIOL-G concentrations (P < 0.05), whereas subjects with low or high levels of abdominal sc AT but similar levels of visceral AT had similar 3alpha-DIOL-G concentrations. Among men with high testosterone levels, subjects with reduced 3alpha-DIOL-G concentrations had lower visceral adipose tissue accumulation than subjects with increased 3alpha-DIOL-G levels. The present results indicate that plasma 3alpha-DIOL-G, but not ADT-G, is a steroid correlate of visceral obesity. Excess visceral adipose tissue and/or concomitant alterations in insulin levels or in vivo insulin action could be responsible for the increased 3alpha-DIOL-G formation observed in this condition.

Topics: Adipose Tissue; Adult; Androstane-3,17-diol; Androsterone; Blood Glucose; Body Composition; Glucose Tolerance Test; Humans; Insulin; Male; Obesity; Testosterone; Viscera

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)

Topics: Adult; Androgens; Androstane-3,17-diol; Androsterone; Body Mass Index; Humans; Luteinizing Hormone; Male; Middle Aged; Obesity; Testosterone

Severe obesity is known to reduce either dehydroepiandrosterone circulating levels or growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. The present study was undertaken to evaluate the possibility of a relationship between the circulating levels of IGF-1 and those of dehydroepiandrosterone sulphate (DHEAS) in 25 fertile obese women. A logarithmic transformation of the values of non-normally distributed variables was performed before statistical analysis. We found a significant positive correlation between DHEAS and IGF-1 (r = 0.615, P < 0.01). In addition, stepwise multiple regression analysis showed that IGF-1 maintained a strong positive relationship with DHEAS (P < 0.01) when adjusted for other variables such as age, body mass index (BMI), waist:hip ratio (WHR) and insulin levels (adjusted R2 = 0.373; P < 0.01). These findings suggest that IGF-1 may independently influence the DHEAS circulating levels. ADG (5 alpha-androstan-3 alpha, 17 beta-diol-glucuronide) was also positively correlated to IGF-1 (r = 0.436, P < 0.05). However, when ADG concentrations were adjusted for DHEAS levels, this metabolite was not significantly correlated with IGF-1, thus excluding a direct influence of IGF-1 on the 5-alpha-reductase activity. Therefore, although our data represent only a preliminary study, they seem to suggest a possible influence of IGF-1 on circulating levels of DHEAS in obese women.

Topics: Adult; Androstane-3,17-diol; Body Constitution; Body Mass Index; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Obesity; Radioimmunoassay; Regression Analysis

The aim of the study was to investigate whether the absence of increased 5 alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels.. As in hyperandrogenicity there generally exists evidence for increased 5 alpha-reductase activity, we measured, as parameters of 5 alpha-reductase activity, plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women.. Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women.. Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis.. Compared to controls, mean free testosterone levels were increased (P less than 0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P less than 0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P less than 0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P less than 0.01), in the normal range in obese hirsute, and decreased in obese women (P less than 0.01).. These results show that, despite the presence of higher free testosterone levels, neither 5 alpha-reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Androstane-3,17-diol; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Obesity; Testosterone

To determine whether hyperinsulinemia can directly reduce serum sex hormone-binding globulin (SHBG) levels in obese women with the polycystic ovary syndrome, six obese women with this disorder were studied. Before study, ovarian steroid production was suppressed in each woman by the administration of 7.5 mg of a long-acting GnRH agonist, leuprolide depot, im, on days -56, -28, and 0. This resulted in substantial reductions in serum concentrations of testosterone (from 1.72 +/- 0.29 nmol/L on day -56 to 0.32 +/- 0.09 nmol/L on day 0), non-SHBG-bound testosterone (from 104 +/- 16 pmol/L on day -56 to 19 +/- 5 pmol/L on day 0), androstenedione (from 7.25 +/- 1.65 nmol/L on day -56 to 2.78 +/- 0.94 nmol/L on day 0), estrone (from 371 +/- 71 pmol/L on day -56 to 156 +/- 29 pmol/L on day 0), estradiol (from 235 +/- 26 pmol/L on day -56 to 90 +/- 24 pmol/L on day 0), and progesterone (from 0.28 +/- 0.12 nmol/L on day -56 to 0.08 +/- 0.02 nmol/L on day 0). Serum SHBG levels, however, did not change (18.8 +/- 2.8 nmol/L on day -56 vs. 17.8 +/- 2.6 nmol/L on day 0). While continuing leuprolide treatment, the women were administered oral diazoxide (300 mg/day) for 10 days to suppress serum insulin levels. Diazoxide treatment resulted in suppressed insulin release during a 100-g oral glucose tolerance test (insulin area under the curve, 262 +/- 55 nmol/min.L on day 0 vs. 102 +/- 33 nmol/min.L on day 10; P less than 0.05) and deterioration of glucose tolerance. Serum testosterone, androstenedione, estrone, estradiol, and progesterone levels did not change during combined diazoxide and leuprolide treatment. In contrast, serum SHBG levels rose by 32% from 17.8 +/- 2.6 nmol/L on day 0 to 23.5 +/- 2.0 nmol/L on day 10 (P less than 0.003). Due primarily to the rise in serum SHBG levels, serum non-SHBG-bound testosterone levels fell by 43% from 19 +/- 5 pmol/L on day 0 to 11 +/- 4 pmol/L on day 10 (P = 0.05). These observations suggest that hyperinsulinemia directly reduces serum SHBG levels in obese women with the polycystic ovary syndrome independently of any effect on serum sex steroids.

Topics: Adult; Androstane-3,17-diol; Androstenedione; Diazoxide; Estradiol; Estrone; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Insulin; Insulin Resistance; Leuprolide; Obesity; Polycystic Ovary Syndrome; Progesterone; Sex Hormone-Binding Globulin; Testosterone