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Androgen Suppression (androgen + suppression)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Regulation of global gene expression in the bone marrow microenvironment by androgen: Androgen ablation increases insulin-like growth factor binding protein-5 expression

THE PROSTATE, Issue 15 2007
Chang Xu
Abstract BACKGROUND Prostate cancer frequently metastasizes to bone. Androgen suppression treatment is initially highly effective, but eventually results in resistant cancer cells. This study evaluates the effects of androgen suppression on the bone and bone marrow (BM). In particular we questioned whether the androgen therapy could adversely facilitate prostate cancer progression through an increase growth factor secretion by the bone microenvironment. METHODS Global gene expression is analyzed on mPEDB DNA microarrays. Insulin-like growth factor binding protein-5 (IGFBP5) is detected by immunohistochemistry in mouse tissues and its regulation measured by qPCR and Western blotting in human BM stromal cells. Effects of extracellular matrix-associated IGFBP5 on human prostate epithelial cells are tested in an MTS cell-growth assay. RESULTS Castration increases expression of 159 genes (including 4 secreted cytokines) and suppresses expression of 84 genes. IGFBP5 is most consistently increased and the increase in expression is reversed by testosterone administration. IGFBP5 protein is detected in vivo in osteoblasts, BM stromal cells, and endothelial cells. Primary human stromal cell cultures secrete IGFBP5. In vitro, treatment of immortalized human marrow stromal cells with charcoal-stripped serum increases IGFBP5 mRNA expression, which is reversed by androgen supplementation. IGFBP5 is incorporated into the extracellular matrix. Further, IGFBP5 immobilized on extracellular matrices of stromal cells enhances the growth of immortalized prostate epithelial cells. CONCLUSIONS Androgen suppressive therapy increases IGFBP5 in the BM microenvironment and thereby may facilitate the progression of prostate cancer. Prostate 67: 1621,1629, 2007. © 2007 Wiley-Liss, Inc. [source]

Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer

BJU INTERNATIONAL, Issue 11 2009
Roger S. Kirby
Hormonal therapy is the main recommended treatment for locally advanced and metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH) agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately leading to its de-sensitization and subsequent reduction of LH and testosterone levels. However, this reduction is accompanied by a well described increase or ,surge' in LH and testosterone levels, necessitating the concomitant administration of an antiandrogen to combat the potential effects of transient acceleration in cancer activity. Two pure GnRH antagonists have been developed, abarelix and degarelix, that are devoid of any agonist effect on the GnRH receptor and consequently do not result in testosterone flare. Abarelix was the first GnRH antagonist to be developed and was approved by the USA Food and Drug Administration in 2004 for the initiation of hormonal castration in advanced or metastasizing hormone-dependent prostate carcinoma, when rapid androgen suppression is necessary. Clinical data on both abarelix and degarelix show that they can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term. [source]

Duration of testosterone suppression and the risk of death from prostate cancer in men treated using radiation and 6 months of hormone therapy

CANCER, Issue 8 2007
Anthony V. D'Amico MD
Abstract BACKGROUND. The authors evaluated whether the duration of androgen suppression (AS) after the completion of hormone therapy (HT) was associated with the risk of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). METHODS. The study cohort was comprised of 220 men who received radiation therapy (RT) and 6 months of HT for prostate cancer between 1996 and 2005. The duration of AS was defined as the time to return to the baseline testosterone level after the completion of HT. Grays and Cox regression analyses were used to evaluate whether the duration of AS after the completion of HT was associated with the time to PCSM and ACM, respectively, after adjusting for known prognostic factors. RESULTS. An increasing duration of AS was associated with a decreased risk of PCSM (adjusted hazards ratio [HR], 0.89; P = .003) and ACM (HR, 0.94; P = .007). Men who had prostate cancer with Gleason scores from 8 to 10 had significantly lower cumulative incidence estimates of PCSM (P = .04) if the duration of AS plus the length of HT administration was ,2 years compared with <2 years. After a median follow-up of 6.1 years, the respective 5-year estimates were 0% and 38%. CONCLUSIONS. The duration of AS after 6 months of HT was associated with the risk of PCSM and ACM. This duration could be used to identify men who have prostate cancer with Gleason scores from 8 to 10 in whom 6 months of HT produces long-term testosterone suppression, which may provide the cancer-specific survival benefit observed with long-term HT. Cancer 2007. © 2007 American Cancer Society. [source]

Influence of body mass index on prostate-specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer

CANCER, Issue 8 2007
Jason A. Efstathiou MD
Abstract BACKGROUND Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. Whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. METHODS The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). RESULTS Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1,74.7) years and 27.4 (24.8,30.7) kg/m,2 respectively. In addition to an increasing PSA level (P = .006) and Gleason 8,10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6,8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.01,1.19; P = .026) after RT and AST. CONCLUSIONS After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all-cause mortality. Cancer 2007. © 2007 American Cancer Society. [source]

Locally advanced prostate cancer,biochemical results from a prospective phase II study of intermittent androgen suppression for men with evidence of prostate-specific antigen recurrence after radiotherapy

CANCER, Issue 5 2007
Nicholas Bruchovsky MD
Abstract BACKGROUND. Biochemical results from a prospective Phase II trial of intermittent androgen suppression for recurrent prostate cancer after radiotherapy were analyzed for correlations to the onset of hormone-refractory disease. METHODS. Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen (PSA) level after external beam irradiation of the prostate were treated intermittently with a 36-week course of cyproterone acetate and leuprolide acetate. Then, patients were stratified according to their serum PSA range at the start of each cycle and were followed with further biochemical testing until disease progression was evident. RESULTS. The mean PSA reduction was 95.2% irrespective of stratification group. A baseline serum PSA level <10 ,g/L and a serum PSA nadir ,0.2 ,g/L were associated with the longest time off treatment. The overall mean nadir PSA value in the progression group at 1.40 ± 0.19 ,g/L was 2.6-fold greater than the value of 0.55 ± 0.88 ,g/L in the no-progression group (P = .0002). Recovery of serum testosterone to a level of ,7.5 nmol/L was observed in 75%, 50%, 40%, and 30% of men in Cycles 1 to 4, respectively, and was sufficient to normalize the level of hemoglobin in each cycle, which dropped by an average of 10.8 g/L during treatment (P < .0001). CONCLUSIONS. The length of the off-treatment interval during cyclic androgen withdrawal therapy was related inversely to baseline and nadir levels of serum PSA. Nadir PSA was a powerful predictor of early progression to androgen independence. Cancer 2007 © 2007 American Cancer Society. [source]

Anti-androgens increase N-terminal pro-BNP levels in men with prostate cancer

CLINICAL ENDOCRINOLOGY, Issue 1 2008
Frances Dockery
Summary Objective, The aim of this study was to determine the effects of anti-androgens on left ventricular (LV) function and levels of N-terminal proB-type natriuretic peptide (NT-proBNP), a sensitive cardiac risk marker, in men with prostate cancer as these are widely used drugs in this condition, and evidence suggests that endogenous androgens are cardioprotective in men. Design and patients, Forty-three men (mean age 70·7 ± 6·2 years) with prostate cancer were randomized to goserelin (an LH-releasing hormone analogue) or bicalutamide (an androgen-receptor blocker) for 6 months; 20 men with a history of prostate cancer on no treatment were studied in parallel. Results, Mean changes in testosterone and oestradiol, respectively, from baseline to 6 months were ,88% and ,46% with goserelin, +50% and +44% with bicalutamide, and ,1% and ,9% for the ,no-treatment' group. Bicalutamide significantly increased NT-proBNP from baseline to 3 and 6 months (median value at baseline, 3 and 6 months: 55, 101 and 118 ng/l, respectively). Goserelin caused a significant increase from baseline to 3 months but not to 6 months (median value at baseline, 3 and 6 months: 66, 87 and 72 ng/l, respectively). No significant changes occurred in the ,no-treatment' cohort (median value at baseline 3 and 6 months: 60, 53 and 60 ng/l, respectively). No significant changes in LV function, blood pressure (BP), body mass index or waist,hip ratio occurred to account for the changes in NT-proBNP. Conclusion, Androgen receptor blockade and, to a lesser extent, androgen suppression cause an increase in NT-pro-BNP in men with prostate cancer. The significance is not clear but could imply an adverse effect on cardiovascular risk following hormonal manipulation. [source]