androstane-3-17-diol-glucuronide and androsterone-glucuronide

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17β-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Topics: Acneiform Eruptions; Adolescent; Adult; Amenorrhea; Androstane-3,17-diol; Androsterone; Combined Modality Therapy; Electroacupuncture; Exercise; Female; Humans; Hyperandrogenism; Menstrual Cycle; Motor Activity; Oligomenorrhea; Polycystic Ovary Syndrome; Severity of Illness Index; Testosterone; Time Factors; Young Adult

Quantification of steroidal glucuronide conjugates by the indirect methods of immunoassay and GC-MS/MS may underestimate some conjugates since hydrolysis is needed in sample processing. In the present work, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous direct quantification of androsterone glucuronide, etiocholanolone glucuronide, and androstan-3α, 17β diol 17-glucuronide in postmenopausal women's serum. The quantification limits are 0.1ng/mL for 3α-diol-17G and 4ng/mL for both ADT-G and Etio-G, respectively, with an extraction from 200μL serum while the total run time is less than 6min for all three glucuronides. In this method, solid phase extraction is used for sample preparation. The assay has been validated in compliance with EndoCeutics SOPs and FDA guidelines for bioanalytical method development and validation. The recovery of glucuronides in stripped serum is consistent with that in unstripped serum, where the average difference in stripped and unstripped is less than 10%. A linear regression model fits well the standard curves of all three compounds with R≥0.99 where the weighting factor is 1/X. Interday accuracy and CV for all levels of QCs are within the range of 15% in both stripped and unstripped serum while all calibration curves are within the range of 6% except for LLOQs, which are within the range of 9%. Other parameters have also been assessed such as selectivity, matrix, lipemic and hemolysis effects as well as stabilities in solution and matrix. Incurred sample reanalysis has been performed with a result of over 93% within 20% of the original values. This reliable, sensitive and fast method is ready for large-scale clinical sample assays.

Topics: Androstane-3,17-diol; Androsterone; Chromatography, High Pressure Liquid; Female; Humans; Limit of Detection; Postmenopause; Tandem Mass Spectrometry

Because the exclusive source of sex steroids (at least estrogens) after menopause is recognized to be dehydroepiandrosterone (DHEA), this study examines the interindividual variability of serum DHEA and its metabolites as well as the contribution of the ovary to global sex steroid physiology in postmenopausal women.. Serum levels of DHEA and 11 of its metabolites were measured by gas or liquid chromatography/mass spectrometry in 442 intact and 71 ovariectomized postmenopausal women aged 42 to 74 years.. With a mean ± SD concentration of 2.03 ± 1.33 ng/mL, serum DHEA in intact postmenopausal women is highly variable with 5th and 95th centiles at 0.55 and 4.34 ng/mL, respectively, for a 7.9-fold difference. A comparable variability is observed for the 11 metabolites of DHEA. The 22.3% higher serum DHEA in intact compared with ovariectomized women is accompanied by parallel differences for all the other steroids, thus indicating that all sex steroids originate from circulating DHEA in postmenopausal women with no direct secretion of active estrogens or androgens by the postmenopausal ovary.. The 7.9-fold difference between low and high serum DHEA levels provides an explanation for the lack of signs of hormone deficiency in some women, whereas most of them have symptoms or signs. The approximately 20% contribution of the ovary to the total pool of DHEA with no direct secretion of estrogens or androgens in the circulation could possibly explain the reported negative effect of oophorectomy on longevity, especially from coronary heart disease events.

Topics: Adult; Aged; Androstane-3,17-diol; Androstenediol; Androstenedione; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Estradiol; Estrone; Female; Humans; Middle Aged; Ovariectomy; Ovary; Postmenopause; Statistics, Nonparametric; Testosterone

Men with higher endogenous 5alpha-reductase activity may have higher prostate cancer risk. This hypothesis raises two questions: (a) Could racial differences in 5alpha-reductase activity explain the observed racial differences in prostate cancer risk? and (b) Could a man reduce his activity level by modifying his lifestyle? To address these questions, we measured two hormonal indices of 5alpha-reductase activity [serum levels of androstane-3alpha-17beta-diol glucuronide (3alpha-diol G) and androsterone glucuronide (AG)] in healthy, older African-American, white, and Asian-American men, who are at high, intermediate, and low prostate cancer risk, respectively. We also examined associations between these metabolite levels and such lifestyle characteristics as body size and physical activity as well as select aspects of medical history and family history of prostate cancer. Men included in this cross-sectional analysis (n = 1054) had served as control subjects in a population-based case-control study of prostate cancer we conducted in California, Hawaii, and Vancouver, Canada and provided information on certain personal attributes and donated blood between March 1990 and March 1992. In this study, concentrations of 3alpha-diol G declined significantly with age and increased significantly with body mass index. Mean levels of 3alpha-diol G, adjusted for age and body mass index, were 6.1 ng/ml in African-Americans, 6.9 ng/ml in whites and 4.8 ng/ml in Asian-Americans. These differences were statistically significant (African-Americans versus whites: P < 0.01; whites versus Asian-Americans: P < 0.001). Concentrations of AG decreased significantly with age, but only in whites, and were unrelated to any of the reported personal attributes. Mean levels of AG, adjusted for age, were 44.1 ng/ml in African-Americans, 44.9 ng/ml in whites, and 37.5 ng/ml in Asian-Americans (Asian-Americans versus whites, P < 0.001). In conclusion, older African-American and white men have similar levels of these two indices of 5alpha-reductase activity, and these levels are higher than those of older Asian-American men. This difference may be related to the lower prostate cancer risk in Asian-Americans.

Topics: Age Distribution; Aged; Aged, 80 and over; Aging; Analysis of Variance; Androstane-3,17-diol; Androsterone; Asian People; Biomarkers; Black People; British Columbia; California; Case-Control Studies; Cholestenone 5 alpha-Reductase; Hawaii; Humans; Life Style; Male; Middle Aged; Oxidoreductases; Population Surveillance; Prostatic Neoplasms; Reference Values; Risk Assessment; Risk Factors; Sensitivity and Specificity; White People

Familial correlation analyses were used to evaluate the familial aggregation of plasma androgens and androgen glucuronides (testosterone (TESTO), dihydrotestosterone (DHT), androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G), and androsterone glucuronide (ADT-G)) in 505 members of 99 white families and 296 members of 111 black families participating in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Each of these four measures was determined by RIA after separation of conjugated and unconjugated steroid using C18 column chromatography. All participants were sedentary prior to being including in this study. Significant spouse correlations, as well as parent-offspring and sibling correlations, were found for TESTO, DHT, 3 alpha-DIOL-G, and ADT-G in the white sample, suggesting that common familial environments and genes contribute to the familial resemblance. In the black sample, significant sibling and parent-offspring correlations were found for all four phenotypes, while the spouse correlation was marginally significant for 3 alpha-DIOL-G and not significant for TESTO, DHT, and ADT-G. The non-significance of spouse correlations in the black individuals may be due to the small number of spouse pairs. The maximal heritability estimates of TESTO, DHT, 3 alpha-DIOL-G, and ADT-G were 69%, 87%, 74%, and 56% for white individuals and 70%, 73%, 62%, and 48% for black individuals respectively. Sex differences in heritability estimates were found in the white individuals, but they were less dramatic in the black individuals. In conclusion, plasma levels of androgens and androgen glucuronides are highly heritable in both white individuals and black individuals. There are notable sex differences in the white individuals.

Topics: Adolescent; Adult; Aged; Androgens; Androstane-3,17-diol; Androsterone; Black People; Dihydrotestosterone; Exercise; Female; Humans; Male; Radioimmunoassay; Sex Factors; Statistics, Nonparametric; Testosterone; White People

There are few reports of the change in sex hormone levels accompanying a weight change in men, although an excessive decline in testosterone (TESTO) has been described as an associate of stress-induced weight loss. Plasma levels of cortisol, TESTO, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), androsterone glucuronide (ADT-G), and androstane-3alpha, 17beta-diol glucuronide (3alphaDIOL-G) were measured in seven pairs of sedentary male monozygotic twins (age, 21.0 +/- 0.8 years; body mass index [BMI], 26.2 +/- 5.5 kg/m2) before and after 93 days of standardized submaximal (50% to 55% maximum oxygen consumption) cycle-ergometer exercise. A total energy deficit of 244 +/- 9.7 MJ induced significant changes (P < .0001) in body weight ([BW] -5.0 +/- 2.2 kg) and body fatness measures. Plasma TESTO and DHEA-S increased and 3alphaDIOL-G decreased. The increase in TESTO was a significant inverse correlate of loss in all measures of body fat, particularly central adiposity (r = -.58 to -.86, P < .001, fat loss-adjusted). Lower postexercise levels of 3alphaDIOL-G correlated positively with decreased body composition measures (r = .65 to .68, P < .01). The increase in plasma TESTO accompanying the loss of abdominal visceral fat (AVF) was greater in men with lower fasting insulin levels (P < .0001). The baseline within-twin-pair resemblance in TESTO and 3alphaDIOL-G (intraclass correlation coefficients [ICC] = .83 and .78, respectively, P < .01) was lost with intervention. Cortisol, DHEA-S, and ADT-G developed within-twin-pair similarity (ICC adjusted for fat loss: cortisol, .72; ADT-G, .62, P < .05; DHEA-S, .85, P < .002). We conclude that a steroid profile characterized by high TESTO and low androgen metabolite levels accompanied the changes in body composition and body fat distribution generated by the exercise-induced negative energy balance. Furthermore, these changes were characterized by a significant resemblance within identical-twin pairs.

Topics: Adult; Androstane-3,17-diol; Androsterone; Body Composition; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Energy Metabolism; Exercise; Humans; Hydrocortisone; Insulin; Male; Steroids; Testosterone; Twins, Monozygotic; Weight Loss

An analysis of the data collected in the Quebec Overfeeding Study of identical twins was undertaken to determine any evidence of a genotype effect on plasma levels of adrenal and gonadal steroids arising from long term positive energy balance. Plasma levels of sex hormone-binding globulin (SHBG), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), androsterone glucuronide, androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-DIOL-G), and cortisol were measured in 12 pairs of young, sedentary, male monozygotic twins before and after 100 days of overfeeding. The dietary energy excess of 4.2 MJ/day (1000 Cal), 6 days a week, resulted in a total positive energy balance of 353 MJ (84,000 Cal). Overfeeding induced significant changes (P < 0.0001) in body weight and other measures of body composition. Within-twin pair resemblance was observed at baseline in all steroids, except cortisol [intraclass correlation range: DHEA-S, 0.50 (P < 0.05); DHT, 0.77 (P < 0.001)] and was lost with overfeeding, except for DHT and SHBG (P < 0.05). SHBG levels fell and 3 alpha-DIOL-G rose with the gain in body fatness. The change in testosterone was a significant correlate of the change in upper body fat (r = -0.48; P < 0.05). The change in 3 alpha-DIOL-G correlated positively with increases in all measures of central adiposity (r = 0.52; P < 0.01). A decrease in DHEA-S occurred with a higher, but not with a lower, gain in abdominal visceral fat (P < 0.05). Thus, analysis of adrenal and gonadal steroids and of conjugated metabolites before and after overfeeding in monozygous twins supports the idea that there is a genotype effect on steroid circulating steroid levels and that these blood levels are correlated with the pattern of body fat distribution. Moreover, the baseline within-twin pairs similarity in steroid levels was attenuated by prolonged positive energy balance and body fat gain.

Topics: Adipose Tissue; Adrenal Cortex Hormones; Adult; Androstane-3,17-diol; Androsterone; Body Composition; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Eating; Energy Intake; Food; Gonadal Steroid Hormones; Humans; Hydrocortisone; Insulin; Male; Sex Hormone-Binding Globulin; Testosterone; Twins, Monozygotic

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

A method is described for the differential extraction of unconjugated androgens (testosterone and dihydrotestosterone) and glucuronidated androgens (androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide) from human serum using solid-phase, gravity-flow extraction columns. In this method, 100-microL aliquots of serum are loaded onto the normal-phase columns, unconjugated androgens are eluted with ethyl ether, and glucuronides are eluted with ethyl ether containing 2% acetic acid. Glucuronide eluates are washed with 1% aqueous acetic acid to remove cross-reacting steroid sulfates. Assays of sera for the four steroids were performed using standard radioimmunoassay methodology, except for androsterone glucuronide. This steroid was assayed with a novel radioimmunoassay method that employees a tritiated, unconjugated androsterone tracer and an anti-dehydroepiandrosterone sulfate antiserum. The new method is well suited for the assay of conjugated and unconjugated steroids in large numbers of specimens, particularly where the sample volume is limited.

Topics: Adult; Aged; Androgens; Androstane-3,17-diol; Androsterone; Dihydrotestosterone; Humans; Hydrogen-Ion Concentration; Male; Radioimmunoassay; Reference Values; Testosterone; Tritium

To compare the peripheral versus the splanchnic contribution to the formation of 3 alpha-diol G.. Prospective study in various groups of women and men.. Reproductive Endocrine service of our University Medical Center.. Six normal ovulatory women, five hirsute women with polycystic ovary syndrome, and six normal men.. All subjects received IV dihydrotestosterone (DHT) infusions as well as percutaneous administration of DHT. Serum was obtained at multiple time points before and after each administration of DHT.. Comparison of serum levels of DHT, 3 alpha-androstanediol (3 alpha-diol), 3 alpha-diol G, and androsterone glucuronide in the three groups.. Steady-state levels of DHT were similar in the three groups and were also similar after the two different routes of administration. However, ratios of 3 alpha-diol G to DHT were significantly greater after percutaneous gel than after IV administration in all three groups. This also was the case for the ratio of unconjugated serum 3 alpha-diol to DHT. Levels of androsterone glucuronide were similar with the different routes of administration.. Using normal routes of administration and, in attempting to assess in vivo metabolism of DHT, our data confirm that the skin is the major site of unconjugated 3 alpha-diol and 3 alpha-diol G formation. Serum 3 alpha-diol G, therefore, appears largely to reflect skin DHT metabolism.

Topics: Administration, Cutaneous; Adolescent; Adult; Androstane-3,17-diol; Androsterone; Dihydrotestosterone; Female; Hirsutism; Humans; Infusions, Intravenous; Male; Middle Aged; Polycystic Ovary Syndrome; Prospective Studies; Reference Values; Splanchnic Circulation

Serum C19 conjugates, specifically 3 alpha-androstanediol glucuronide (3 alpha G), reflect peripheral androgen action through the action of 5 alpha-reductase activity. The origin of 5 alpha-reduced C19 conjugates has been controversial and it has been suggested that they are derived primarily from adrenal androgens. We examined concentrations of 3 alpha G, 3 alpha-androstanediol sulphate (3 alpha S), androsterone glucuronide (AoG) and androsterone sulphate (AoS) in 40 hirsute hyperandrogenic women. These patients were divided into four groups based upon individual, combined or normal concentrations of the adrenal androgens dehydroepiandrosterone (DHEAS) and 11 beta-hydroxy-androstenedione. Testosterone, unbound testosterone and androstenedione were similar in these groups. Serum 3 alpha G was equally high in all groups and was correlated significantly with hirsutism, while the other conjugates were not. Androsterone glucuronide was raised in all groups but was higher in patients with raised DHEAS. Serum 3 alpha S was raised in all groups and was higher where both adrenal androgens were raised. Serum AoS was highly correlated with DHEAS. Serum 3 alpha G was correlated with unbound testosterone and androstenedione but not with the adrenal androgens. The glucuronide conjugates were correlated with one another as were the sulphate conjugates but glucuronides and sulphates were not correlated. These data confirm ovarian and adrenal dependency of C19 conjugates. Serum 3 alpha G appears to reflect hirsutism most accurately and is least dependent on adrenal androgens in patients with mixed hyperandrogenism.

Topics: Adrenal Glands; Adult; Androgens; Androstane-3,17-diol; Androsterone; Female; Hirsutism; Humans; Hyperandrogenism; Substrate Specificity

The clinical utility of serum 3 alpha-androstanediol glucuronide level has been controversial. Among the concerns regarding its lack of utility has been the finding that suppression of serum 3 alpha-androstanediol glucuronide does not occur readily with treatment. We hypothesized that because the treatment of hirsutism requires a prolonged duration, a longer observation period is required for changes in serum 3 alpha-androstanediol glucuronide to be measured. Therefore, we studied the clinical and hormonal changes in 11 women treated for hirsutism with a gonadotropin-releasing hormone agonist (GnRH-a) for 1 year. A progressive reduction in Ferriman-Gallwey scores occurred, which was significant at 6 weeks and was maximal at 12 months. Serum 3 alpha-androstanediol glucuronide and another peripheral marker, androsterone glucuronide, also fell commensurately. While there was no correlation at 3 months, by 6 weeks a significant correlation had occurred between the suppression in Ferriman-Gallwey scores and the suppression of serum 3 alpha-androstanediol glucuronide and androsterone glucuronide. The suppression of these steroids also correlated with the suppression of non-sex hormone-binding globulin-bound testosterone. These data confirm that markers of peripheral androgen action, particularly serum 3 alpha-androstanediol glucuronide, reflect the clinical manifestation of hirsutism. However, it appears that modifications in peripheral androgen activity (presumably through 5 alpha-reductase activity) are time-dependent, and that serum markers reflect changes after 6 months of treatment.

Topics: Adult; Androstane-3,17-diol; Androsterone; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Testosterone; Triptorelin Pamoate

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

Recent reports have thrown doubt on the role of measurements of plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG) as a marker of peripheral androgen metabolism in women with polycystic ovarian syndrome and idiopathic hirsutism. It has been suggested that a plasma profile of C19 steroid glucuronides may be more informative. While preliminary data indicates that both 3 alpha-diolG and androsterone G (ADTG) may arise from adrenal steroid precursors, there have been no reports of C19 steroid glucuronides in women with non-classical, or late-onset congenital adrenal hyperplasia (NC-CAH), who constitute a significant proportion of the hirsute female population. We therefore measured plasma levels of 3 alpha-diolG, ADTG and dihydrotestosterone G (DHTG) before and following a standard Cortrosyn test in 15 symptomatic and 3 asymptomatic NC-CAH patients, 5 heterozygote carriers for 21-hydroxylase deficiency (NCHETS) and 18 normal women. The effects of chronic glucocorticoid (GCR) therapy (greater than 3 months) on the C19 steroid glucuronide profile in the symptomatic patients was also investigated. Baseline plasma levels of all 3 glucuronides were significantly (P less than 0.001) higher in symptomatic patients compared with either normals or NCHETS. However, the order of discrimination was ADTG greater than 3 alpha-diolG greater than DHTG. There were no significant differences between steroid glucuronide levels for NCHET and normal women and the C19 steroid glucuronide concentrations for the asymptomatic NC-CAH patients were greater than 2 SD above the normal means. Moderate clinical improvement was observed in all patients receiving oral GCR therapy and was accompanied by approx. 80% suppression of the plasma levels of all 3 C19 steroid glucuronides. This contrasts with a mean suppression of androstenedione of only 50%. However, plasma levels of the C19 steroid glucuronides were not significantly increased in response to a short ACTH stimulation test. This may be explained by the fact that the androgen glucuronides are thought to be peripherally formed metabolites derived from unconjugated glandular secreted androgen precursors and thus their synthesis at 60 min following adrenal stimulation may lag substantially behind that of their respective precursors. There were significant linear correlations between the levels of all 3 glucuronides, but neither correlated with Ferriman-Gallway scores, body mass index or 17-hydroxyprogesterone leve

Topics: Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Androstane-3,17-diol; Androsterone; Animals; Cross Reactions; Dihydrotestosterone; Female; Glucocorticoids; Heterozygote; Humans; Menopause; Rats

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

Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after the cutaneous application of androstenedione (A).. An A gel was applied for 6 days to the skin of normal women, male volunteers, and hirsute and nonhirsute patients with polycystic ovarian syndrome (PCOS). Blood samples were obtained at baseline and on day 6 of the A gel application. Blood samples were assayed for A, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide, and androsterone glucuronide. In three hirsute women, the protocol was followed before and after receiving an oral contraceptive (OC) and spironolactone 200 mg/d for 3 months.. The study was performed in the outpatient clinic of the Division of Reproductive Endocrinology and Infertility, Women's Hospital of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California.. A total of eight nonhirsute patients with PCOS, seven hirsute patients with PCOS, and six male volunteers were enrolled in the study. Five normal women served as a control group.. Serum A increased after 6 days by a similar magnitude in all groups. Serum androsterone glucuronide showed a significant increase from baseline only in the hirsute group (P < 0.03), whereas the increase in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide was not statistically significant.. The ratio of the increases in serum androsterone glucuronide over serum A was significantly higher in the hirsute group (P < 0.02). In the three hirsute patients who were placed on an OC and spironolactone, serum 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide decreased after 3 months and did not increase with application of the gel for another 6 days.. The cutaneous application of A provides a useful assessment of in vivo 5 alpha-reductase activity. However, because we found that A absorption varied considerably (30% to 62%), we suggest that this in vivo test may not provide more information than baseline determinations of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide. It may, however, be useful as a parameter for assessing the effectiveness of various treatment regimens for hirsutism.

Topics: Administration, Cutaneous; Adult; Androstane-3,17-diol; Androstenedione; Androsterone; Cholestenone 5 alpha-Reductase; Female; Gels; Hirsutism; Humans; Male; Oxidoreductases; Polycystic Ovary Syndrome

Hirsutism in women is often explained on the basis of abnormal peripheral androgen metabolism. To determine whether serum markers of ovarian, adrenal, or peripheral androgen production may be helpful determinants in the treatment of hirsutism and to compare the efficacy of treatment with dexamethasone or spironolactone, 20 hyperandrogenic hirsute patients were treated for up to 2 years. Eleven women who were selected on the basis of sensitivity to dexamethasone were treated with a daily dose of 0.37 mg dexamethasone and had androgen levels suppressed into the normal range. Although significant (P less than .05), Ferriman-Gallwey scores decreased only by 20%: 14.2 +/- 0.5 to 11.4 +/- 0.6. Nine other women received spironolactone 100 mg/day for 1 year and did not have significant changes in serum androgens, but had a significant (P less than .01) 47% reduction in the Ferriman-Gallwey score (15.2 +/- 0.8 to 8 +/- 0.8). Thus, with either treatment, the reduction in Ferriman-Gallwey scores did not correlate with the change in androgen levels. The patients treated with dexamethasone for 1 year then received spironolactone 100 mg/day together with dexamethasone for an additional year. Serum androgen levels did not change further, but the Ferriman-Gallwey scores decreased significantly (P less than .01) from 11.4 +/- 0.6 to 3.74 +/- 0.7 (-61%). These data suggest that serum androgens are not helpful in assessing response to the treatment of hirsutism and that despite normal androgen levels, only modest clinical improvement may be expected with dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Androgen Antagonists; Androgens; Androstane-3,17-diol; Androstenedione; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Dihydrotestosterone; Drug Combinations; Female; Hirsutism; Humans; Spironolactone; Testosterone

The plasma levels of pituitary hormones (LH, FSH and prolactin) as well as testosterone were determined in 62 patients treated with combined therapy using the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide and the antiandrogen Flutamide. Plasma radioimmunoassayable LH and FSH levels increased to 534% (p less than 0.01) and 150% (p less than 0.01) of control, respectively, during the first 5 days of treatment, while, afterwards, a marked inhibition was observed which remained constant at approximately 30-50% of control values during the whole period of treatment. All patients showed a decrease of plasma testosterone concentration to approximately 10% of control levels. Detailed determinations of plasma testicular and adrenal steroid levels were then performed in 15 patients. Our data indicate that, except for the blockade of testicular 17-hydroxyprogesterone secretion, the combined therapy has no effect on plasma C-21 steroid levels. However, adrenal C-19 steroids, namely dehydroepiandrosterone and its sulfate, androst-5-ene-3 beta, 17 beta-diol and androstenedione were decreased to approximately 50% of control values (p less than or equal to 0.01). The main testicular steroids, testosterone and dihydrotestosterone, which were increased during the first 10 days of combined administration, rapidly decreased and reached approximately 10% of control values at later time intervals. The present study extends our previous observations indicating that the combined antihormonal treatment affects both testicular and adrenal steroidogenesis. Moreover, we have demonstrated that, up to at least 2 years, this treatment, in addition to decreasing the serum levels of testicular androgens, causes an inhibition of the plasma levels of C-19 steroids from adrenal origin.

Topics: Adenocarcinoma; Adrenal Cortex Hormones; Androgens; Androstane-3,17-diol; Androstenediol; Androstenedione; Androsterone; Anilides; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Dehydroepiandrosterone; Flutamide; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Kinetics; Luteinizing Hormone; Male; Pregnenolone; Progesterone; Prolactin; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Plasma levels of androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diol-G) and androsterone glucuronide (ADT-G) have been found to be effective markers of C-19 steroid metabolism in periphery in man. The present study has been performed in order to study in castrated patients the effect of antiandrogen administered alone or in combination with aminoglutethimide (AG) on the metabolism of adrenal C-19 steroid. Ten castrated patients with prostatic cancer received flutamide (FLU) alone for 2 months and, afterwards, the combined therapy of FLU and AG for 2 months. Antiandrogen treatment alone reduces the levels of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone glucuronide (DHEA-G) and androstenedione (4-ene-dione) by 43, 34 and 38% (P less than or equal to 0.01) respectively while dehydroepiandrosterone (DHEA), androst-5-ene-3 beta,17 beta-diol (5-ene-diol) and androst-5-ene-3 beta,17 beta-diol-glucuronide (5-ene-diol-G) levels show a nonsignificant inhibition. In these patients, plasma 3 alpha-diol-G and ADT-G concentrations are nonsignificantly stimulated to 122 and 143%. Moreover, when patients were receiving the combined administration of FLU and AG, adrenal C-19 steroids were further inhibited while both 3 alpha-diol-G and ADT-G show a small but nonsignificant decrease. Our data indicate that the antiandrogen increases the formation and/or the metabolism of adrenal C-19 steroids into steroid glucuronides.

Topics: Aged; Aminoglutethimide; Androstane-3,17-diol; Androstanols; Androsterone; Anilides; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Flutamide; Glucuronates; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Urinary levels of the glucuronides of androsterone, aetiocholanolone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 beta-androstane-3 alpha, 17 beta-diol, were determined in twenty-two-post menopausal women both in spring and in autumn--winter. In sixteen women dehydroepiandrosterone sulphate plasma levels were also measured. Plasma DHAS levels as well as urinary metabolite excretion values were significantly higher in autumn--winter than in spring. This seasonal variability should be taken into account in long-term studies involving adrenal hormone levels, excretion or metabolism. Moreover this seasonal variability might be of relevance for the cyclical growth rate of hormone dependent tumours such as breast cancer.

Topics: Adrenal Cortex; Aged; Androgens; Androstane-3,17-diol; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Menopause; Middle Aged; Seasons