androstane-3-17-diol-glucuronide and Prostatic-Neoplasms

A randomised crossover dietary intervention study was performed to evaluate the effects of replacing meat protein in the diet with a soyabean product, tofu, on blood concentrations of testosterone, dihydrotestosterone, androstanediol glucuronide, oestradiol, sex hormone-binding globulin (SHBG), and the free androgen index (total testosterone concentration/SHBG concentration x 100; FAI). Forty-two healthy adult males aged 35-62 years were studied. Diets were isoenergetic, with either 150 g lean meat or 290 g tofu daily providing an equivalent amount of macronutrients, with only the source of protein differing between the two diets. Each diet lasted for 4 weeks, with a 2-week interval between interventions. Fasting blood samples were taken between 07.00 and 09.30 hours. Urinary excretion of genistein and daidzein was significantly higher after the tofu diet (P < 0.001). Blood concentrations of sex hormones did not differ after the two diets, but the mean testosterone:oestradiol value was 10% higher (P = 0.06) after the meat diet. SHBG was 3% higher (P = 0.07), whereas the FAI was 7% lower (P = 0.06), after the tofu diet compared with the meat diet. There was a significant correlation between the difference in SHBG and testosterone:oestradiol and weight change. Adjusting for weight change revealed SHBG to be 8.8% higher on the tofu diet (mean difference 3 (95% CI 0.7, 5.2) nmol/l; P = 0.01) and testosterone:oestradiol to be significantly lower, P = 0.049). Thus, replacement of meat protein with soyabean protein, as tofu, may have a minor effect on biologically-active sex hormones, which could influence prostate cancer risk. However, other factors or mechanisms may also be responsible for the different incidence rates in men on different diets.

Topics: Adult; Androstane-3,17-diol; Cross-Over Studies; Dietary Proteins; Dihydrotestosterone; Estradiol; Glycine max; Gonadal Steroid Hormones; Humans; Male; Meat; Middle Aged; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone

Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial.. In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3α-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples.. We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA.. Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.

Topics: Aged; Androgens; Androstane-3,17-diol; Arm; Biopsy; Case-Control Studies; Estradiol; Estrone; Humans; Kallikreins; Linear Models; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Sex Hormone-Binding Globulin; Testosterone

To elucidate the mechanism of the androgen deprivation therapy (ADT)-related decrease in lean body mass (LBM).. The LBM and blood samples were studied before and after 6 months of ADT in 72 patients with localized prostate cancer. The LBM was assessed using a foot-to-foot bioelectrical impedance analyzer.. Before ADT, the LBM correlated with none of the serum sex steroid levels; however, it correlated closely with serum 5α-androstane-3α,17β-diol glucuronide (Spearman's rank correlation coefficient = 0.409, P = .001) and insulin-like growth factor-1 (IGF-I, Spearman's rank correlation coefficient = 0.329, P = .005). After ADT, the LBM decreased by 0.9% (P = .036), and the serum testosterone and dihydrotestosterone had decreased by 96.8% and 94.3%, respectively (P <.001 for both), and the IGF-I had increased by 11.6% (from 19.9 to 22.2 nmol/L, P = .001). The serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels decreased after ADT by 9.8% (from 66.2 to 59.7 pg/mL, P = .008), and the post-treatment LBM correlated inversely with 1,25(OH)2D (Spearman's rank correlation coefficient = -0.343, P = .003). The post-treatment LBM was dissociated with 5α-androstane-3α,17β-diol glucuronide and IGF-I. The pretreatment and post-treatment LBMs both correlated inversely with serum sex hormone-binding globulin (P = .024 and P = .016, respectively).. The deficiency in androgen levels was suggested to be a link to the ADT-related decrease in LBM; the androgen metabolite 5α-androstane-3α,17β-diol glucuronide has a potential value for assessing the LBM in untreated men. IGF-I also promotes muscle building and is positively regulated during ADT. Sex hormone-binding globulin possibly accelerates the ADT-related decrease in LBM. Although the mechanism for the decrease in 1,25(OH)2D and its inverse correlation with LBM during ADT is unclear, 1,25(OH)2D might be a biomarker reflecting the ADT-related decrease in LBM.

Topics: Aged; Androgen Antagonists; Androstane-3,17-diol; Biomarkers; Body Composition; Body Mass Index; Calcitriol; Dihydrotestosterone; Electric Impedance; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Statistics, Nonparametric; Testosterone; Thinness

UDP glucuronosyltransferase 2B17 is present in the prostate, where it catalyzes the addition of glucuronic acid to testosterone and dihydrotestosterone and their metabolites androsterone and androstane-3α,17β-diol. Hence, changes in UGT2B17 gene expression may affect the capacity of the prostate to inactivate and eliminate male sex hormones. In this work, we identify a prevalent polymorphism, -155G/A, in the proximal promoter of the UGT2B17 gene. This polymorphism modulates UGT2B17 promoter activity, because luciferase-gene reporter constructs containing the -155A allele were 13-fold more active than those containing the -155G allele in prostate cancer LNCaP cells. The -155G/A polymorphism is contained within a putative binding site for the transcription factor Forkhead Box A1 (FOXA1). Using gene reporter, electromobility shift, and chromatin immunoprecipitation analyses, we show that FOXA1 binds to this site and stimulates the UGT2B17 promoter. Furthermore, down-regulation of FOXA1 in LNCaP cells substantially reduces UGT2B17 mRNA levels. The binding of FOXA1 and subsequent stimulation of the UGT2B17 promoter is greatly reduced in the presence of the -155G allele compared with the -155A allele. Consonant with its capacity to be stimulated by FOXA1, the UGT2B17 -155A allele, compared with the -155G allele, is associated with higher levels of circulating androstane-3α,17β-diol glucuronide. Although the initial phases of prostate cancer are androgen-dependent and UGT2B17 inactivates androgens, there was no association of the UGT2B17 -155G/A polymorphism with prostate cancer risk. In summary, this work identifies FOXA1 as an important regulator of UGT2B17 expression in prostate cancer LNCaP cells and identifies a polymorphism that alters this regulation.

Topics: Androstane-3,17-diol; Binding Sites; Cell Line, Tumor; Glucuronosyltransferase; Hepatocyte Nuclear Factor 3-alpha; Humans; Male; Minor Histocompatibility Antigens; Polymorphism, Genetic; Promoter Regions, Genetic; Prostatic Neoplasms

Androgens have been implicated in prostate tumorigenesis, but prospective studies have overall reported no association between circulating levels of androgens and risk of prostate cancer. However, some recent studies have shown that a high level of testosterone increase the risk of non-aggressive tumors but is associated with a decreased risk of aggressive tumors.. We prospectively measured plasma levels of total testosterone, androstanediol glucuronide (A-diol-g) and sex hormone binding globuline (SHBG) and calculated estimated levels of free testosterone, in a nested case-control study of 392 cases and 392 matched controls.. None of the studied hormones were significantly associated with prostate cancer risk in the full study group or in subgroups according to tumor aggressiveness. Odds ratios in the full study group, for top versus bottom quartile, was for total testosterone 1.25 (95% CI = 0.79-2.00; P(trend) = 0.51); free testosterone, 1.31 (95% CI = 0.82-2.07; P(trend) = 0.35); A-diol-g, 0.88 (95% CI = 0.59-1.33; P(trend) = 0.77); and for SHBG, 1.01 (95% CI = 0.64-1.58; P(trend) = 0.94).. We found no significant associations between androgen levels and risk of prostate cancer in this population-based, non-screened cohort.

Topics: Androgens; Androstane-3,17-diol; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Sex Hormone-Binding Globulin; Testosterone

African-Caribbean men have a risk of prostate cancer comparable to that of African-American men. To begin exploring potential risk factors for prostate cancer in these high-risk black subgroups, we conducted a pilot study in Brooklyn, New York, a community with large numbers of African-Americans and immigrants from Jamaica and Haiti.. Black men, 35 to 65 years of age, who were born in the United States, Jamaica, or Haiti were recruited in Brooklyn. The subjects' serum samples were analyzed for prostate-specific antigen (PSA) and the following hormones, which may be related to prostate cancer: testosterone, sex hormone-binding globulin, 3alpha-androstanediol glucuronide, insulin-like growth factor-1 (IGF-1), and IGF-binding protein-3 (IGFBP-3). Subgroup differences in PSA and hormonal levels, adjusted for relevant covariates, were explored using analysis of variance techniques.. For 3 months, we recruited 21 U.S.-born, 20 Jamaican-born, and 24 Haitian-born black men using various methods. The mean age-adjusted PSA level was 1.04 ng/mL in the U.S.-born men, 1.09 ng/mL in the Jamaican-born men, and 0.85 ng/mL in the Haitian-born men (P = 0.55). The mean age-adjusted hormone levels, as well as testosterone/sex hormone-binding globulin and IGF-1/IGFBP-3 ratios, also were not significantly different statistically across the subgroups.. It is feasible to conduct epidemiologic studies of prostate cancer in these high-risk black subgroups in Brooklyn. Our preliminary data suggest that the serum levels of PSA and potential hormonal risk factors are similar among U.S.-born, Jamaican-born, and Haitian-born black men. Larger follow-up studies are being planned to confirm these findings.

Topics: Adult; Aged; Androstane-3,17-diol; Black or African American; Emigration and Immigration; Ethnicity; Feasibility Studies; Genetic Predisposition to Disease; Gonadal Steroid Hormones; Haiti; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Jamaica; Male; Middle Aged; New York City; Patient Selection; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Sex Hormone-Binding Globulin; Testosterone; United States

To determine whether prediagnostic serum hormones are predictive of prostate cancer risk in a sample of men 40 to 70 years old at baseline.. Seventeen serum hormones, including androgens, estrogens, and adrenal and pituitary hormones, were measured at baseline (1987 to 1989) and used to predict incident prostate cancer by follow-up (1995 to 1997) using data from the Massachusetts Male Aging Study, a prospective, population-based random sample.. Seventy men (4%) of 1576 were diagnosed with prostate cancer between the baseline and follow-up periods (approximately 8 years). None of the hormones were associated with prostate cancer risk except for androstanediol glucuronide (AAG), which exhibited a nonlinear, inverse relationship with prostate cancer (P <0.003) when age, body mass index, alcohol use, dihydrotestosterone, and total prostate-specific antigen were controlled for. Men in the second, third, and fourth quartiles of AAG relative to the first were less likely to be diagnosed with prostate cancer, although only the comparison of the second versus the first achieved statistical significance (odds ratio 0.2, 99% confidence interval 0.04 to 0.6). No dose-response relationships were observed.. The lack of association with most hormones and the nonlinear association with AAG calls into question whether serum hormones collected during midlife are risk factors for prostate cancer.

Topics: Adrenal Cortex Hormones; Adult; Aged; Androgens; Androstane-3,17-diol; Estrogens; Follow-Up Studies; Humans; Male; Massachusetts; Middle Aged; Pituitary Hormones; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Sampling Studies

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

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.

Topics: Adult; Androgens; Androstane-3,17-diol; Anthropometry; Biomarkers; Cross-Sectional Studies; Diet; Diet, Vegetarian; England; Humans; Insulin-Like Growth Factor I; Luteinizing Hormone; Male; Meat; Prostatic Neoplasms; Risk Factors; Sex Hormone-Binding Globulin; Testosterone

We have investigated the contributions of three polymorphic markers in the SRD5A2 gene to prostate cancer in a group of Italian patients. We have genotyped cases and controls for a polymorphic (TA)n dinucleotide repeat and two functional substitutions, A49T and V89L, substituting respectively alanine with threonine at codon 49, and valine to leucine at codon 89. We found a substantially increased but not significant risk associated with the 49T mutation and a reduction of risk for the V89L substitution. In conclusion, we report on preliminary evidence for both increased and decreased risk associated with separate markers at this locus.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adenocarcinoma; Aged; Aged, 80 and over; Amino Acid Substitution; Androstane-3,17-diol; Codon; Dinucleotide Repeats; Ethnicity; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Italy; Male; Middle Aged; Mutation, Missense; Neoplasm Proteins; Polymorphism, Genetic; Prostatic Neoplasms; Risk

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

Topics: Adult; Aged; Androgens; Androstane-3,17-diol; Biomarkers; Blood Specimen Collection; Case-Control Studies; Cholestenone 5 alpha-Reductase; Dihydrotestosterone; Humans; Male; Middle Aged; Norway; Oxidoreductases; Prostatic Neoplasms; Risk Factors; Time Factors

Topics: Androstane-3,17-diol; Case-Control Studies; Cholestenone 5 alpha-Reductase; Gonadal Steroid Hormones; Humans; Male; Oxidoreductases; Prostatic Neoplasms; Reproducibility of Results; Testosterone

Sex steroids, particularly androgens, have been implicated in the pathogenesis of prostate cancer. Data from previous studies comparing circulating hormone levels in men with and without prostate cancer are difficult to interpret, since the studies were limited in size, hormone levels were analyzed in blood drawn after the diagnosis of cancer, nonrepresentative control subjects were used, and hormone and hormone-binding protein levels were not simultaneously adjusted.. We conducted a prospective, nested case-control study to investigate whether plasma hormone and sex hormone-binding globulin (SHBG) levels in healthy men were related to the subsequent development of prostate cancer.. Among participants in the Physicians' Health Study who provided plasma samples in 1982, we identified 222 men who developed prostate cancer by March 1992. Three hundred ninety control subjects, matched to the case patients on the bases of age, smoking status, and length of follow-up, were also identified. Immunoassays were used to measure the levels of total testosterone, dihydrotestosterone (DHT), 3 alpha-androstanediol glucuronide (AAG), estradiol, SHBG, and prolactin in the stored (at -82 degrees C) plasma samples. Correlations between individual hormone levels and between hormone levels and SHBG in the plasma of control subjects were assessed by use of Spearman correlation coefficients (r). Odds ratios (ORs) and 95% confidence intervals (CIs) specifying the prostate cancer risk associated with quartile levels of individual hormones, before and after adjustment for other hormones and SHBG, were calculated by use of conditional logistic regression modeling. Reported P values are two-sided.. No clear associations were found between the unadjusted levels of individual hormones or SHBG and the risk of prostate cancer. However, a strong correlation was observed between the levels of testosterone and SHBG (r = .55), and weaker correlations were detected between the levels of testosterone and the levels of both estradiol (r = .28) and DHT (r = .32) (all P < .001). When hormone and SHBG levels were adjusted simultaneously, a strong trend of increasing prostate cancer risk was observed with increasing levels of plasma testosterone (ORs by quartile = 1.00, 1.41, 1.98, and 2.60 [95% CI = 1.34-5.02]; P for trend = .004), an inverse trend in risk was seen with increasing levels of SHBG (ORs by quartile = 1.00, 0.93, 0.61, and 0.46 [95% CI = 0.24-0.89]; P for trend = .01), and a non-linear inverse association was found with increasing levels of estradiol (ORs by quartile = 1.00, 0.53, 0.40, and 0.56 [95% CI = 0.32-0.98]; P for trend = .03). No associations were detected between the levels of DHT or prolactin and prostate cancer risk; for AAG, a marker of 5 alpha-reductase activity, only suggestive evidence of a positive association was found. The results were essentially unchanged when case patients diagnosed within 4 years of plasma collection, case patients diagnosed with localized (i.e., nonaggressive) disease, or control subjects with elevated prostate serum antigen levels (> 2.5 ng/mL) were excluded from the analyses.. High levels of circulating testosterone and low levels of SHBG-both within normal endogenous ranges-are associated with increased risks of prostate cancer. Low levels of circulating estradiol may represent an additional risk factor. Circulating levels of DHT and AAG do not appear to be strongly related to prostate cancer risk.

Topics: Adult; Aged; Aged, 80 and over; Androstane-3,17-diol; Case-Control Studies; Dihydrotestosterone; Estradiol; Gonadal Steroid Hormones; Humans; Male; Middle Aged; Odds Ratio; Prolactin; Prospective Studies; Prostatic Neoplasms; Risk; Sex Hormone-Binding Globulin; Testosterone

We studied the relationship between circulating androsterone glucuronide, androstane-3 alpha, 17 beta-diol glucuronide and androstane-3 beta, 17 beta-diol glucuronide concentrations and adrenal as well as testicular C-19 steroids in men. Among the three 5 alpha-reduced steroid glucuronides, androsterone glucuronide is the predominant C-19 steroid glucuronide measured in plasma and its levels are markedly elevated compared to those of the non-conjugated steroid. The marked rise in testosterone during puberty was strongly correlated with the increase in both androsterone glucuronide and androstane-3 alpha, 17 beta-diol glucuronide, thus suggesting that testicular C-19 steroids are the main precursors of the steroid glucuronides. We also found that the presence of testicular androgen in plasma contributes to approx. 70% of plasma androsterone glucuronide and androstane-3 alpha, 17 beta-diol glucuronide. Our data suggest that the adrenal C-19 steroids remaining in circulation after castration in men are converted into potent androgen which are then glucuronidated by UDP-glucuronyltransferase. We also demonstrated that the human prostate cell line LNCaP is capable of converting to a large extent androstenedione into androsterone glucuronide. Our data further confirm that glucuronidation is a major pathway of steroid metabolism in steroid target tissues.

Topics: Adolescent; Adult; Aging; Androstane-3,17-diol; Androstenedione; Child; Child, Preschool; Dehydroepiandrosterone; Glucuronates; Humans; Male; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Sulfates; Tumor Cells, Cultured

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 testosterone and 3 alpha-androstanediol (3 alpha diol G) glucuronides together with plasma testosterone, 5 alpha-dihydrotestosterone (DHT), and delta 4-androstenedione (delta 4) were measured in 43 normal young men (18-36 yr old), 23 elderly men without clinically evident prostatic pathology (54-89 yr old), 68 elderly men with benign prostatic hyperplasia (BPH group; 54-91 yr old), and 26 elderly men with well differentiated cancer of the prostate (K group; 63-97 yr old). Plasma testosterone decreased slightly with age in all 3 elderly groups (from 591 to 438, 479, and 444 ng/100 ml, respectively). Plasma DHT, on the contrary, was significantly (P less than 0.01) higher in the BPH group than in the other three groups (68 vs. 30, 37, and 32 ng/100 ml, respectively). Plasma delta 4 was significantly lower (P less than 0.01) in the elderly K group than in all other groups (59 vs. 109, 83, and 78 ng/100 ml, respectively). Urinary testosterone glucuronide decreased with age in all 3 elderly groups (from 109 to 55, 38, and 44 micrograms/24 h, respectively) as a result of decreased androgen production rates with age. All 3 elderly groups also had decreased urinary 3 alpha diol G, from 194 to 123, 55, and 118 micrograms/24 h, respectively. The group of elderly patients with BPH had the lowest mean urinary 3 alpha diol G excretion together with the highest mean plasma DHT. This low urinary 3 alpha diol G excretion, which reflects a decrease in both androgen production and DHT metabolism, suggests a decrease in 3 alpha-hydroxysteroid dehydrogenase activity, which, in turn, could explain the increased DHT availability and tissue retention in most target organs. Moreover, the extent of these modifications in androgen metabolism specific to the BPH condition raises the question of an overall alteration of androgen metabolism in patients with BPH which could be the cause of the disease.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aging; Androstane-3,17-diol; Androstanols; Androstenedione; Dihydrotestosterone; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone