Serum Androstanediol Glucuronide Research Articles

Determination of serum androstanediol glucuronide reference range intervals in a cohort of healthy belgian subjects

Determination of serum androstanediol glucuronide reference range intervals in a cohort of healthy belgian subjects

Testosterone and androstanediol glucuronide among men in NHANES III

BackgroundMost of the androgen replacement therapies were based on serum testosterone and without measurements of total androgen activities. Whether those with low testosterone also have low levels of androgen activity is largely unknown. We hence examined the association between testosterone and androstanediol glucuronide (AG), a reliable measure of androgen activity, in a nationally representative sample of US men.MethodsCross-sectional analysis was based on 1493 men from the Third National Health and Nutrition examination Survey (NHANES III) conducted from 1988 to 1991. Serum testosterone and AG were measured by immunoassay. Kernel density was used to estimate the average density of serum AG concentrations by quartiles of testosterone.ResultsTestosterone was weakly and positively correlated with AG (correlation coefficient = 0.18). The kernel density estimates show that the distributions are quite similar between the quartiles of testosterone. After adjustment for age, the distributions of AG in quartiles of testosterone did not change. The correlation between testosterone and AG was stronger in men with younger age, lower body mass index, non-smoking and good self-rated health and health status.ConclusionsSerum testosterone is weakly correlated with total androgen activities, and the correlation is even weaker for those with poor self-rated health. Our results suggest that measurement of total androgen activity in addition to testosterone is necessary in clinical practice, especially before administration of androgen replacement therapy.

Dutasteride reduces alcohol's sedative effects in men in a human laboratory setting and reduces drinking in the natural environment.

Preclinical studies support the hypothesis that endogenous neuroactive steroids mediate some effects of alcohol. The aim of this study was to examine the effect of dutasteride inhibition of 5α-reduced neuroactive steroid production on subjective responses to alcohol in adult men. Using a within-subject factorial design, 70 men completed four randomly ordered monthly sessions in which pretreatment with 4 mg dutasteride or placebo was paired with a moderate dose of alcohol (0.8 g/kg) or placebo beverage. The pharmacologic effect of dutasteride was measured by an assay of serum androstanediol glucuronide. Self-reports of alcohol effects were obtained at 40-min intervals following alcohol administration using the Biphasic Alcohol Effects Scale (BAES) and the Alcohol Sensation Scale (SS). We used linear mixed models to examine the effects of dutasteride and alcohol on BAES and SS responses and the interaction of dutasteride with the GABRA2 alcohol dependence-associated polymorphism rs279858. We also examined whether exposure to dutasteride influenced drinking in the weeks following each laboratory session. A single 4-mg dose of dutasteride produced a 70 % reduction in androstanediol glucuronide. Dutasteride pretreatment reduced alcohol effects on the BAES sedation and SS anesthesia scales. There was no interaction of dutasteride with rs279858. Heavy drinkers had fewer heavy drinking days during the 2 weeks following the dutasteride sessions and fewer total drinks in the first week after dutasteride. These results provide evidence that neuroactive steroids mediate some of the sedative effects of alcohol in adult men and that dutasteride may reduce drinking, presumably through its effects on neuroactive steroid concentrations.

Orale Kontrazeptiva und Androgenisierungserscheinungen

Androgenisierungserscheinungen der Haut können aufgrund einer Hyperandrogenämie, einer vermehrten lokalen Androgenbildung in der Haut oder wegen einer „Hypersensitivität” der Haut gegenüber Androgenen entstehen. Wichtigster pathogenetischer Faktor ist neben einer Erhöhung der Serumkonzentration des gesamten und freien Testosterons eine verstärkte lokale Aktivität der 5α-Reduktase, zu deren Diagnose das Serum-Androstandiolglucuronid jedoch nicht geeignet ist. Alle östrogendominanten Ovulationshemmer bewirken bei 60 - 80 % der Frauen mit Akne und Seborrhö eine Besserung, wobei etwa die Hälfte des Therapieerfolgs auf einen Plazeboeffekt zurückgeführt werden kann. Vermutlich führt die Teilnahme an einer Studie zu einer sorgfältigeren Hautpflege und Vermeidung aknefördernder Faktoren. Die günstige Wirkung der oralen Kontrazeptiva beruht auf einer Senkung der ovariellen und adrenalen Produktion der Androgene und Androgenpräkursoren, einer Erhöhung des SHBG sowie auf einem lokalen Effekt des Ethinylestradiols und der Gestagene, wobei unterschiedliche Mechanismen zum Tragen kommen können. Bei einer androgenetischen Alopezie läßt sich mit Ovulationshemmern, die ein antiandrogen wirksames Gestagen enthalten, bei längerer Behandlung in vielen Fällen eine Besserung erreichen. Bei Frauen mit Hirsutismus sind orale Kontrazeptiva weniger wirksam, doch wird in schweren Fällen nicht selten unter einer längeren Therapie mit einer Kombination von Ethinylestradiol und hohen Dosen von Cyproteronacetat ein günstiger Effekt beobachtet. Präparate, die ein Gestagen mit androgenen Eigenschaften in zu hoher Dosierung enthalten, sind nicht nur weniger wirksam, sondern können sogar bei prädisponierten Frauen Androgenisierungserscheinungen verursachen. Gelegentlich wird aber auch zu Beginn einer Behandlung mit oralen Kontrazeptiva ein leichter diffuser Haarausfall oder eine vorübergehende Verstärkung einer bestehenden Akne beobachtet. Wenn es nach dem Absetzen eines Ovulationshemmers zu einer Akne oder einem Haarausfall kommt, so verschwinden die Symptome meist nach einiger Zeit.

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.

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.

Serum androstanediol glucuronide in women with facial hirsutism

Measurement of serum 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) has been proposed as a useful biochemical marker of peripheral androgen metabolism. Is 3 alpha-diol G a useful biochemical marker of peripheral androgen metabolism and does it correlate with degree of facial hirsutism? Our purpose was to assess possible correlation between serum 3 alpha-diol G and degree of facial hirsutism and to compare serum 3 alpha-diol G levels with levels of other commonly measured serum androgens. Twenty-three consecutive women with facial hirsutism were studied, and serum concentrations of 3 alpha-diol G, testosterone (total, free, and biologically active portions), dehydroepiandrosterone sulfate, and androstenedione were measured. There was no correlation between serum 3 alpha-diol G levels and degree of facial hirsutism. There was a correlation between levels of 3 alpha-diol G and dehydroepiandrosterone sulfate (p less than 0.01), biologically active testosterone (p = 0.01), free free testosterone (p less than 0.02), and androstenedione (p less than 0.05). Serum 3 alpha-diol G concentrations have no correlation with degree of facial hirsutism and do not provide additional information over the commonly measured androgens.

Monthly cyproterone acetate in the treatment of hirsute women: clinical and laboratory effects

Cyproterone acetate given as a single intramuscular dose of 300 mg monthly for 6 months resulted in significant reduction of hirsutism without appreciable side effects. This regimen resulted in decreased levels of luteinizing hormone (LH) and estradiol in the eight women studied. No significant changes were observed in total serum testosterone (T) levels, however, there was a reduction in sex hormone binding globulin (SHBG), resulting in lowered SHBG-bound T, and an increase in non-SHBG-T over this time. Serum androstanediol glucuronide levels decreased in three of four women, although not to normal levels.

Serum androstanediol glucuronide concentrations in normal and hirsute women and patients with thyroid dysfunction.

There is currently much interest in measurements of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (AdiolG) as a marker of peripheral androgen metabolism. We have therefore developed an assay to measure serum AdiolG levels and report that mean concentrations in hirsute (2.9 +/- 1.9 nmol/l, mean +/- SD, n = 15) and non-hirsute (1.9 +/- 0.6 nmol/l, n = 7) women with polycystic ovaries do not differ significantly from concentrations in normal women (2.2 +/- 0.8 nmol/l, n = 20). However, a correlation was found between serum AdiolG levels and Body Mass Index (r = 0.48, P less than 0.05) for women with polycystic ovaries, suggesting that weight may be an important factor in determining concentrations of this steroid conjugate. Serum AdiolG levels were significantly reduced in hypothyroid women (0.6 +/- 0.4 nmol/l, n = 5) and women receiving oral contraceptive therapy (0.6 +/- 0.4 nmol/l, n = 28) but increased in hyperthyroid women (4.0 +/- 0.6 nmol/l, n = 5). The results from this study do not support the hypothesis that serum AdiolG levels provide a marker of peripheral androgen metabolism in hirsute women and show that it is essential to exclude from such investigations any women with thyroid abnormalities or receiving oral contraceptive therapy.

Clinical usefulness of plasma androstanediol glucuronide measurements in women with idiopathic hirsutism.

Serum androstanediol glucuronide (3 alpha-diol G), a metabolite of the active androgens dihydrotestosterone and androstanediol, was elevated in 28 consecutive women with idiopathic hirsutism (IH). The mean 3 alpha-diol G level in the women with IH was 487 +/- 192 (+/- SD) ng/dL compared to 119 +/- 37 ng/dL in normal women (n = 50), and only 1 patient had a value overlapping with the normal range. Since 3 alpha-diol G appears to be formed entirely in target organs and has a long serum half-life, we studied its clinical usefulness by following women with IH during treatment. In 15 of 17 women with IH treated for 1-4 yr with glucocorticoids, contraceptives, or spironolactone, serum 3 alpha-diol G levels changed concordantly with clinical responses, in contrast to the poor concordance of serum testosterone (5 of 17), free testosterone (7 of 17), and androstenedione (7 of 17). Specifically, in IH patients treated with spironolactone, serum testosterone, free testosterone, and androstenedione levels changed little, yet clinical improvement frequently occurred, and this improvement was reflected by concomitantly lowered 3 alpha-diol G levels. Further, in 4 IH patients, discontinuation of effective therapy resulted in prompt increases in serum 3 alpha-diol G as harbingers of worsening hair growth. We, thus, conclude that serum 3 alpha-diol G measurements are clinically useful in evaluating hirsute women and correlate with the clinical responses to therapy.

Evidence for the importance of peripheral tissue events in the development of hirsutism in polycystic ovary syndrome.

Hirsutism can occur in the presence of normal or near normal levels of serum testosterone, unbound testosterone (uT), dehydroepiandrostene sulfate, androstenedione, and dihydrotestosterone. However, we have found that serum androstanediol glucuronide (3 alpha-diol G) is markedly increased in idiopathic hirsutism and it serves as an excellent marker of peripheral androgen metabolism and action. In the present work, we studied 12 hirsute (H) and 12 nonhirsute (NH) patients with polycystic ovary syndrome (PCO) and 13 age and weight matched controls in order to determine if differences in sex steroid levels or peripheral tissue androgen events were associated with hirsutism. Serum unbound estradiol levels and LH-FSH ratios were similar in both groups of women with PCO, and both were significantly higher than levels in controls (P less than 0.05). Whereas serum testosterone, uT, and androstenedione were elevated in both H-PCO and NH-PCO patients compared to controls, the levels in these two groups were similar. Serum dehydroepiandrostene sulfate was higher in PCO patients compared to controls, but H-PCO patients had slightly higher levels than NH-PCO patients. Serum delta 5-androstenediol was also slightly higher in H-PCO compared to NH-PCO patients. Dihydrotestosterone was normal and unconjugated; 3 alpha-diol was higher than normal in both groups of patients with PCO, although H-PCO patients had higher levels than NH-PCO patients. Compared to these relatively minor changes between the PCO patient groups, serum 3 alpha-diol G was markedly elevated in H-PCO patients (approximately 10-fold), yet normal in NH-PCO patients (P less than 0.01). The ratios of serum 3 alpha-diol G-uT were similar in NH-PCO patients and controls, but were elevated in H-PCO patients (P less than 0.01). These data indicate that: 1) women with PCO have increased circulating androgen levels regardless of the presence or absence of hirsutism; and 2) the presence of hirsutism is not only a function of circulating androgen levels, but may also be determined by events in peripheral tissues.