Androstanediol Glucuronide Research Articles

Androgen UDP-glucuronyl transferase activity is found primarily in liver in the rat.

UDP-glucuronyl transferase (UDPGT) activity was determined for androgens in tissue minces and microsomal fractions from the liver and extrahepatic tissues (kidney, skin, prostate, and preputial glands) of the male rat. Liver microsomes showed the highest UDPGT activity with each of the androgens tested (Vmax = 7, 3, and 10 nmol/minute/mg protein for testosterone, androsterone, and androstanediol, respectively). UDPGT activity (Vmax) for androstanediol in the liver was 10(2)-fold higher than in the kidney and 10(3)-fold higher than in the skin and prostate. UDPGT activity for androgens was not detected in microsomes from preputial glands. Furthermore, no body site distribution was found for androgen UDPGT activity in skin microsomes. The Michaelis-Menten constant (Km) for UDPGT in liver microsomes was 20.4, 12.2, and 2.2 microM, respectively, for testosterone, androstanediol, and androsterone. Kidney microsomes showed a Km of 19.4 and 26.9 microM, respectively, for androstanediol and androsterone. The Km for testosterone was very high in the kidney (138 microM), suggesting that it was a poor substrate. In microsomes from the skin and prostate, the Km was very high (range 43-162 microM) for all three androgen substrates, suggesting that these androgens were not the preferred substrates for UDPGT in these tissues. These results indicate that the liver was the main site of androgen UDPGT activity and the skin and prostate formed little, if any, androgen glucuronides. These results suggest that androstanediol glucuronide was formed primarily in the liver and may not be a reliable marker of peripheral androgen metabolism.

Plasma 3 alpha-androstanediol glucuronide in normal children and in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Monitoring therapy for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase is difficult, although plasma determinations of 17 alpha-hydroxyprogesterone (17OHP), delta 4-androstenedione (delta 4A) and testosterone are helpful. We have studied the usefulness of monitoring plasma 3 alpha-androstanediol glucuronide (3 alpha-AG) in group of 24 CAH patients aged from birth to 18 years. For comparison, normal values for age and pubertal stage were determined in a control group of 115 girls and 118 boys. Mean plasma levels were higher during the first year of life, decreased to a nadir between 1 and 4 years, and increased steadily thereafter, there was also a significant increase with pubertal stage. In 24 pairs of blood samples obtained at the time of venopuncture and 2 h after, 3 alpha-AG levels did not change (p > 0.05) demonstrating that 3 alpha-AG levels were not affected by stress. In the patients with CAH, positive correlations between plasma 3 alpha-AG and delta 4A (females, r = 0.73; males, r = 0.98), 17OHP (females, r = 0.58; males, r = 0.84) and testosterone (females, r = 0.83; males, r = 0.97) were observed. Concordance between 3 alpha-AG and delta 4A was observed in 90% of all samples, and in 91% between 3 alpha-AG and testosterone. Our study demonstrates that 3 alpha-AG is a valid marker of control and its determination appears to be a reliable tool to monitor CAH.

A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion of dehydroepiandrosterone sulfate

To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol l-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3α-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 ± 1.5, 6.8 ± 1.8, and 6.9 ± 2.1 μmol/L for B, P, and M, respectively) and urinary excretion (8.8 ± 9.8, 9.4 ± 11.2, 8.0 ± 8.3 gmmol/d) of DHEAS remained unaffected. Considering the clear increments ( P < .01) in urinary C-peptide excretion with diet P (20.4 ± 10.3 nmol/d) versus diets B and M (12.6 ± 5.1 and 13.2 ± 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.

Hormones and Prostate Cancer: Where Do We Go From Here?

A striking phenomenon in prostate cancer epidemiology is that the prevalence of latent prostate tumors in most populations is similar (7), but the rates for clinical prostate cancer in U.S. men are 30-50 times higher than those for Asian men (7). Reasons for these disparities are unclear, although previous studies (7-5) have suggested racial differences in dietary fat intake, circulating levels of testosterone, intraprostatic activity of 5-alpha reductase (the enzyme that converts testosterone to the more potent dihydrotestosterone [DHT]), and polymorphisms of the androgen receptor (AR) gene (the intracellular receptor that binds DHT to form the DHT-AR complex that then binds to DNA to activate cell proliferation). Other than age, race, and a family history of prostate cancer, risk factors for prostate cancer are unknown (7). There are compelling reasons to believe that hormones, especially androgens, play a central role in prostate carcinogenesis. The growth and maintenance of the prostate are dependent on androgens (4), prostate cancer regresses following ablative or antiandrogen therapy (5), and testosterone can induce prostate cancer in laboratory rodents (6). However, epidemiologic data addressing hormonal hypotheses are limited and conflicting (7). In this issue of the Journal, Gann et al. (8) report their findings from a nested case-control study, using sera collected prior to prostate cancer diagnosis from a cohort of male physicians. In this study, higher levels of circulating testosterone and lower levels of estradiol and sex hormone-binding globulin (SHBG), a protein that binds about 56% of the circulating testosterone (9), are associated with increased risks of prostate cancer, while no association is found with DHT (the principal androgen within the prostate) or 3-alpha androstanediol glucuronide (a terminal metabolite of DHT that is used as an indirect measure of intraprostatic 5-alpha reductase activity) (9). Prospective nested case-control studies of this type provide better data for the tests of hormonal hypotheses than do casecontrol studies. Because blood was collected before the diagnosis of cancer, the possible impact of disease on hormonal levels is less profound and a temporal relationship can be established. To date, there are only five studies in which prediagnostic sera were used to examine the relationships of circulating hormones with subsequent prostate cancer risk (8,10-13). Results from these studies are inconsistent; positive associations were reported with androstenedione in one study, with testosterone-DHT ratio in two, and (weakly) with luteinizing hormone in one. Of these, Gann et al. is the largest and the first study to evaluate the role of 5-alpha reductase activity, using plasma levels of 3-alpha androstanediol glucuronide as a proxy measure. Although Gann et al. provide data consistent with a role for testosterone, a recent study by Nomura et al. (70), using a similar approach in a Japanese-American cohort in Hawaii, did not confirm this finding. The inconsistent results in these two well-designed studies may reflect, in part, the difficulties of measuring serum/plasma hormones in epidemiologic investigations. Sensitivity, specificity, and reliability of hormonal assays developed for clinical use need to be improved before they can be used for epidemiologic studies. The numbers of study subjects in most nested case-control studies are relatively small (<100) and the observed case-control differences are less than 15%, so that any potential noise, such as intra- and inter-person and laboratory variation, may influence hormonal assessment and case-control comparisons, leading to inconsistenci es between studies (14). To better interpret the case-control results, we need additional data on the reproducibility of hormonal assays, interrelationships among hormones, and factors influencing circulating levels of hormones.

Androstanediol glucuronide in patients with pancreatic cancer and in those with chronic pancreatitis.

The differential diagnosis between pancreatic cancer and chronic pancreatitis is extremely difficult. Beside CA19-9 level determinations, many tests have been tried with the aim to facilitate this distinction. Serum androgen levels have been used for this purpose. To further explore the value of androgen markers in differentiating pancreatic cancer from chronic pancreatitis we determined the serum levels of androstanediol glucuronide and of androgens in the two groups of patients and compared them with CA19-9 levels. A total of 25 males were entered into the study. Of these, 13 patients had pancreatic cancer and 12 chronic pancreatitis. They were comparable as to their body weight and age. Patients with pancreatic cancer had significantly lower serum testosterone, dihydrotestosterone and androstanediol glucuronide levels, but not testosterone/dihydrotestosterone ratios when compared to patients with chronic pancreatitis. Only androstanediol glucuronide and dihydrotestosterone serum concentrations had such a small overlap between the two groups that could be used for differentiation, their sensitivity and specificity being comparable to those of CA19-9 levels. The present study has shown for the first time that serum androstanediol glucuronide levels in male patients with pancreatic cancer are significantly lower than in those patients with chronic pancreatitis. Furthermore, the sensitivity and specificity of serum andorstanediol glucuronide levels which can be used to differentiate between pancreatic cancer and chronic pancreatitis are comparable to those of CA19-9.

Alterations in androgen conjugate levels in women and men with alopecia

Objective To assess levels of androgen metabolites thought to reflect, at least in part, peripheral androgen activity in women with androgenic alopecia and men with premature balding in an effort to determine if a common abnormality exists. Design Prospective study in various groups of women and men. Setting Reproductive Endocrine Clinic at our university medical center. Patients Ten normal ovulatory female controls and 50 hyperandrogenic women divided on the basis of hirsutism and alopecia as follows: [1] 8 hirsute women with androgenic alopecia; [2] 12 nonhirsute women with androgenic alopecia; [3] 18 hirsute women without androgenic alopecia; and [4] 12 nonhirsute women without androgenic alopecia. Ten normal men and 10 young premature balding men matched for age and weight also were compared. Intervention Blood was obtained from all subjects. Main Outcome Measure Comparison of blood hormone levels in the various groups. Results Serum T, androstenedione, and DHEAS were similarly elevated in hyperandrogenic women with and without alopecia, compared with controls. The female groups were then divided on the basis of hirsutism. Hirsute groups with and without alopecia had similarly elevated levels of unconjugated 3α-androstanediol, 3α-androstanediol glucuronide, 3α-androstanediol sulfate, androsterone glucuronide, and androsterone sulfate compared with controls. In the nonhirsute groups, androgenic alopecia patients were compared with hyperandrogenic females and cycling controls. The androgenic alopecia patients had elevated levels of 3α-androstanediol (0.75 ± 0.12 versus 0.46 ± 0.1 and 0.41 ± 0.1 nmol/L), 3α-androstanediol sulfate (200 ± 31 versus 79.6 ± 6 and 67.0 ± 4.0 nmol/L), elevated ratios of 3α-androstanediol sulfate:3α-androstanediol (267 ± 49 versus 170 ± 20 and 164 ± 49 nmol/L), elevated ratios of 3α-androstanediol sulfate:3α-androstanediol glucuronide (32.2 ± 6 versus 10.8 ± 1 and 10.0 ± 1) and lower ratios of 3α-androstanediol glucuronide:3α-androstanediol glucuronide (8.3 ± 1.8 versus 17 ± 1.7 and 15.2 ± 1.6 nmol/L). In men the premature balding group had lower levels of 3α-androstanediol glucuronide compared with the male controls (29.8 ± 4.4 versus 15.2 ± 1.6 nmol/L). Also, the ratio of 3α-androstanediol glucuronide:3α-androstanediol was significantly decreased, whereas the ratio of 3α-androstanediol sulfate:3α-androstanediol glucuronide was elevated. Conclusions These data provided evidence confirming that enhanced 5α-reductase activity occurs in androgenic alopecia but also suggests that a disorder of androgen conjugation, favoring sulfurylation over glucuronidation, may be a characteristic feature of scalp hair loss.

A twin study of polycystic ovary syndrome

To examine the role of genetic and environmental factors in polycystic ovary syndrome (PCOS) by using the classic twin model. Outpatient clinic of the Royal Hospital for Women, Paddington, Sydney, New South Wales, Australia. A group of 19 monozygotic (MZ) and 15 dizygotic (DZ) twin pairs identified from the national twin register. Ultrasound, clinical, and biochemical parameters were used to define PCOS. Eleven pairs of twins (5 MZ, 6 DZ pairs) were scan-discordant (i.e., one twin had scan-PCOS and the co-twin did not). Model-fitting analysis suggested that fasting insulin level, androstanediol glucuronide, and body mass index (BMI) were significantly influenced by genetic factors. This study suggests that PCOS is not the result of a single autosomal genetic defect, but rather environmental factors, perhaps both intrauterine and extrauterine, are involved in the pathogenesis of this disorder or that PCOS may be an X-linked disorder or the result of polygenic factors. However, fasting insulin level, androstanediol glucuronide, and BMI did appear to be under significant genetic influence.

Re-examination of the effect of hCG on plasma levels and renal excretion of dehydroepiandrosterone sulfate in healthy males

To reinvestigate the effect of hCG on circulating and urinary dehydroepiandrosterone sulfate (DHEAS), a hCG stimulation test (5000 IU administered i.m. at 8.30 h on 3 consecutive days) was performed in 6 healthy males (aged 24 to 35 years). Blood specimens and 24-h urine samples were collected immediately before the first and directly after the last hCG administration. Contrary to previous findings in normal men, the present study revealed significant DHEAS responses after testicular stimulation with hCG: plasma DHEAS increased from 7.9 ± 2.3 to 9.6 ± 2.2 μmol/L ( P < 0.05) and urinary DHEAS from 5.7 ± 3.6 to 9.3 ± 5.2 μmol/day ( P < 0.05). There was also a marked rise ( P < 0.05) in the urinary excretion of total 17-ketosteroid sulfates. Clear increases of unconjugated plasma dehydroepiandrosterone as well as of circulating and renally excreted androstenedione and testosterone definitely confirmed an adequate Leydig cell stimulation. Significant post-hCG changes were additionally observed for plasma and urinary 3α-androstanediol glucuronide (149% and 79% increases, respectively) and for urinary cortisol (21% decrease). Significant correlations were found for the post-hCG percent increases of plasma androstenedione versus plasma DHEAS ( r = 0.86) and for the percent increases of plasma testosterone versus urinary DHEAS ( r = 0.98), indicating that the extent of gonadal androgen elevations in the circulation of normal men is a determinant of DHEAS increases in blood or urine. These findings provide an explanation for the frequently observed sex differences for DHEAS in adults. In addition, the data suggests that the DHEAS rise during puberty in boys could possibly be modulated by the secretory activity of the testes.

Clinical relevance of testosterone and dihydrotestosterone metabolism in women

Androgens are part of normal female physiology. When they are secreted in excess or when they cause unwanted symptoms such as hirsutism and male-pattern baldness, the term hyperandrogenism is used. In many hyperandrogenic women, there is no well-defined hormonal abnormality, but the women are simply on one end of a normal spectrum of androgen secretion and cutaneous androgen sensitivity. To be active in the skin, testosterone must be converted to dihydrotestosterone by the enzyme 5 alpha-reductase. Androgen sensitivity is determined, in part, by 5 alpha-reductase activity in the skin. This is a localized phenomenon, and there is no generalized increase in 5 alpha-reductase activity in these women. Dihydrotestosterone can be converted to glucuronide and sulfate conjugates, including androstanediol glucuronide. These androgen conjugates have been proposed to be serum markers of cutaneous androgen metabolism, but recent evidence indicates that they arise from adrenal precursors and are more likely to be markers of adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the best medical treatment of cutaneous hyperandrogenism. 5 alpha-Reductase inhibitors have recently been approved for the treatment of benign prostatic hyperplasia, and research is currently underway to determine their effectiveness in treating hirsutism and male-pattern baldness.

Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men

We have investigated the role of steroid hormones as coronary risk factors in Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3α-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/1; P<0.005, of DHEAS 8.0 vs 5.8 μmol/1; P<0.001, of 3αAdiolG 18.3 vs 8.4 nmol/1; P<0.001, ofandrostenedione 5.7 vs 5.1 nmol/1; P<0.02, and of cortisol 426 vs 358 nmol/1; P<0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/1; P=0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/1; P=0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P=0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r=0.267; P<0.01) and DHEA (r=0.282; P<0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3α-AdiolG (r=−0.400; P<0.001) and cortisol (r=−0.281; P<0.01) levels in the gemfibozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocorticol function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.

11 3 α ANDROSTANEDIOL GLUCURONIDE AS A HARKER OF ANDROGENIC ACTIVITY IN GIRLS WITH PREMATURE PUBARCHE

Previous reports have postulated that 3 androstanediol glucuronide(3α AG)constitutes a marker of the 5 reductase activity in peripheral tissues. We studied the serum levels of androgens and their metabolites in 20 girls with premature pubarche (PP). EC X: 6.6±2.3 years, and in a control group of 12 girls, 5 of them prepubertal and the other 7 pubertal. 17 hidroxiprogesterone (17OHP), Androstenedione (Δ 4A), dehidroepiandrosterone sulfate (DS), testosterone (T)and 3 AG were determined by RIA. All patients showed pubic hair Tanner grade II-III. Besides pubic hair, 13 girls had one or more associated androgenic signs like acne: or face. trunk or limbs hair. Serum T and 17OHP levels were in prepubertal range in girls with PP except in one that showed basal 17OHP of 2 ng/ml and a response to ACTH stimulation of 20, which lead to a diagnosis of non classical 21OHlase deficiency. The elevated 3α AG levels found in PP agree with the pubertal levels of its precursors Δ4A and DS. The high 3α AG/4A ratio found in PP associated with other androgenic signs suggests and enhanced peripheral 5 reductase activity in those patients.

Serum 3α-androstanediol glucuronide measurements in children with congenital adrenal hyperplasia

To determine the value of 3 alpha-androstanediol glucuronide (3-AG) measurements in children with congenital adrenal hyperplasia, we compared serum 3AG, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) levels and 24-h urinary 17-ketosteroid (17-KS) excretion in 42 female children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, including 27 with the simple virilizing and 15 with the salt-losing form. Their mean age was 74.5 +/- 48.5 months (range, 6-194 months). Twenty-four-hour urinary 17-KS excretion and serum 3-AG, A, T, DHT and 17-OHP levels were measured in the patients. The values were less than the mean + 2 SD of the control group in 63%, 74%, 67%, 69%, 60% and 31% of the patients, respectively. Serum 3-AG levels correlated with 24-h urinary 17-KS excretion (r = 0.66) and plasma A (r = 0.80), 17-OHP (r = 0.56), T (r = 0.79) and DHT (r = 0.62) levels. We conclude that serum 3-AG is a useful metabolic index in the management of children with congenital adrenal hyperplasia.

Pathogenesis of the decreased androgen levels in obese men.

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)

Serum levels of androstanediol glucuronide, total testosterone, and free testosterone in hirsute women

To determine the serum levels of androstanediol glucuronide (3 alpha-diol G), total T, and free T in hirsute and nonhirsute women. Controlled clinical study. Hirsute women with oligomenorrhea, hirsute women with regular ovulatory cycles, and nonhirsute women with regular cycles were selected. Serum levels of 3 alpha-diol G, total T, and free T were measured in 8 hirsute with oligomenorrhea and 11 hirsute women with regular ovulatory cycles and compared with 20 nonhirsute women with regular cycles (control group). Serum 3 alpha-diol G was also measured during the follicular, periovulatory, and luteal phases in hirsute women with regular cycles. Serum levels of 3 alpha-diol G did not change during the menstrual cycle, in addition we observed that there was no difference between the levels of 3 alpha-diol G, total T, and free T in hirsute women with regular cycles when compared with normal women. These three serum androgens were elevated only in the hirsute women with oligomenorrhea. Besides, there was better correlation between total T and free T (r = 0.81) than total T and 3 alpha-diol G (r = 0.49) or free T and 3 alpha-diol G (r = 0.66). The findings suggest that serum 3 alpha-diol G does not provide additional benefit as a marker of hirsutism than serum total or free T.

The Clinical Usefulness of 3a‐Androstanediol Glucuronide in Premenopausal Women with Hirsutism

A biochemical parameter correlating with the clinical assessment of the severity of hirsutism and changing appropriately with the clinical response to treatment would be extremely useful. Preliminary reports of androstanediol glucuronide indicated that it was a peripherally-derived androgen and had a high correlation with clinical gradings of hirsutism. More recent reports have cast doubts on this association. This paper presents an evaluation of the clinical usefulness of androstanediol in 121 consecutive premenopausal patients with hirsutism. Androstanediol had a positive correlation with the clinical grading of hirsutism (p < 0.02) and the BMI (p < 0.01) but a negative correlation with age (p < 0.01). After adjustment for the effects of age and BMI there was no significant association between the degree of hirsutism and the level of androstanediol.

The Impact of a Pure Anti-Androgen (Flutamide) on LH, FSH, Androgens and Clinical Status in Idiopathic Hirsutism

Service d'Endocrinologie et des Maladies de la Reproduction, Hopital Bicêtre, Kremlin Bicêtre, France

Longitudinal study of maternal plasma bioavailable testosterone and androstanediol glucuronide levels during pregnancy

The aim of this study to evaluate during normal pregnancy plasma bioavailable testosterone and androstanediol glucuronide levels. Bioavailable testosterone, androstanediol glucuronide and SHBG levels were evaluated every 4 weeks from week 6 to week 38 in 10 normal pregnant women. We also measured plasma oestradiol, oestriol, delta 4-androstenedione, 17-hydroxyprogesterone, progesterone and testosterone. The mean bioavailable testosterone levels were within the range of non-pregnant women but with an increasing trend until delivery. Androstanediol glucuronide had increased at weeks 6 and 8, decreased at week 14, remained low at week 30, and increased again at week 34. SHBG was significantly correlated with testosterone, oestradiol and oestriol. No correlation could be established between androstanediol glucuronide and any other parameter. Bioavailable testosterone (non-SHBG bound testosterone) represents the sum of free testosterone plus albumin bound testosterone. The increase in testosterone concentrations with decreased albumin levels during pregnancy, could suggest reduced metabolic clearance of testosterone throughout pregnancy. No correlation was established between the decrease in androstanediol glucuronide and increase in progesterone, suggesting that the decrease in androstanediol glucuronide is not a consequence of the inhibitory effect of progesterone on 5 alpha-reductase activity.

Adrenal androgens and testosterone as coronary risk factors in the Helsinki Heart Study

We investigated the role of adrenal androgens, cortisol, testosterone and sex-hormone binding globulin (SHBG) as coronary risk factors using a nested case-control design. The study population consisted of 62 cases with cardiac endpoints and 97 controls on placebo during the last 4 years in the Helsinki Heart Study. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, androstanediol glucuronide, cortisol, testosterone, and SHBG at the first annual visit of the 5-year study period were determined by radioimmunoassays. The only significant difference was found in DHEAS, with cases having higher levels than controls ( P < 0.04). DHEAS levels were positively associated with smoking ( P < 0.001), alcohol consumption ( P < 0.04) and triglyceride levels ( P < 0.002) and with systolic ( P < 0.04) and diastolic ( P < 0.006) blood pressures, and negatively associated with age ( P < 0.01) and HDL-cholesterol ( P < 0.03). The association between DHEAS and the CHD risk was studied using logistic regression analyses with the classical risk factors - age, smoking, blood pressure, and lipid levels — as covariates in the models. Studies of the joint effects of age and DHEAS disclosed that the risk associated with elevated DHEAS was confined to older men (odds ratio (OR) 7.3, 95% CI 2.3–23.3). A similar analysis with smoking revealed that the DHEAS-related risk was mainly found in smokers (OR 3.4, 95% CI 1.5–8.2). One possible explanation for these results is that some form of mild steroid biosynthetic defect of the adrenals or functional adrenal hyperplasia associated with high DHEAS levels increases the CHD risk in this population.

Reference values for androstanediol glucuronide

Journal Article Reference values for androstanediol glucuronide Get access M André, M André Search for other works by this author on: Oxford Academic Google Scholar J Valsamis J Valsamis Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 40, Issue 1, 1 January 1994, Page 162, https://doi.org/10.1093/clinchem/40.1.162a Published: 01 January 1994

Androgen Metabolism in Men Receiving Finasteride before Prostatectomy

Oral administration of finasteride, a 5α-reductase inhibitor, affects intraprostatic androgens by suppressing dihydrotestosterone and increasing testosterone. This study was designed to determine the correlation of these effects of finasteride with changes in serum dihydrotestosterone, testosterone and androstanediol glucuronide. In a double blind, placebo-controlled study, 27 men with symptomatic benign prostatic hyperplasia were treated with placebo or 1 or 5mg. per day finasteride for 6 to 8 weeks before transurethral resection of the prostate. There was no significant change in serum testosterone in any group, or in serum dihydrotestosterone or androstanediol glucuronide in the placebo group. There was a decrease in serum dihydrotestosterone by 66 ± 4% and 70 ± 8% (p = 0.32), and of serum androstanediol glucuronide by 78 ± 3% and 86 ± 3% (p = 0.012) in the 1 and 5mg. finasteride groups, respectively. Intraprostatic dihydrotestosterone in the placebo group decreased from 18.6 ± 1.4nmol./kg. to 3.8 ± 1.0nmol./kg. and 1.7 ± 0.7nmol./kg. with 1mg. and 5mg. finasteride, respectively (p = 0.049 between 1mg. and 5mg. finasteride). Intraprostatic testosterone in the placebo group increased from 1.1 ± 0.2nmol./kg. to 7.6 ± 1.0nmol./kg. and 8.3 ± 0.7nmol./kg. with 1mg. and 5mg. finasteride, respectively (no significant difference between 1mg. and 5mg. finasteride). Serum and intraprostatic dihydrotestosterone correlated (p = 0.002). There was no correlation between intraprostatic dihydrotestosterone and serum androstanediol glucuronide. We conclude that 5mg. of finasteride cause greater inhibition of intraprostatic 5α-reductase than 1mg. and that serum dihydrotestosterone is a better marker of intraprostatic dihydrotestosterone than androstanediol glucuronide.