The Effect of Androgen-replacement Therapy on Prostate Growth: A Systematic Review and Meta-analysis

Size: px
Start display at page:

Download "The Effect of Androgen-replacement Therapy on Prostate Growth: A Systematic Review and Meta-analysis"

Transcription

1 EUROPEAN UROLOGY 64 (2013) available at journal homepage: Review Benign Prostatic Enlargement The Effect of Androgen-replacement Therapy on Prostate Growth: A Systematic Review and Meta-analysis Yuanshan Cui, Yong Zhang * Department of Urology, Beijing Tian-Tan Hospital, Capital Medical University, Beijing, China Article info Article history: Accepted March 24, 2013 Published online ahead of print on April 3, 2013 Keywords: Androgens Prostate Meta-analysis Randomized controlled trial Abstract Context: Androgen-replacement therapy (ART) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome. Urologists have been concerned about the possibility of ART causing prostate growth. Objective: To assess the relationship between ART and prostate growth. Evidence acquisition: A literature review was performed to identify all published randomized controlled trials (RCTs) of androgen treatment for hypogonadism. The search included the Medline, Embase, and Cochrane Controlled Trials Register databases. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Evidence synthesis: Results of 16 RCTs involving a total of 1030 patients were analyzed. Seven RCTs were short-term (<12 mo) and nine were long-term (12 36 mo) comparisons of ART with a placebo; ART was administered transdermally, orally, or by injection. Respective p values for injection, transdermal administration, and oral administration of short-term ART were as follows: PSA level: 0.07, 0.01, and 0.95; prostate volume: 0.70, 0.79, and 0.32; IPSS: 0.78, 0.98, and no oral; Q max :0.92,no transdermal, and Respective p values for injection, transdermal administration, and oral administration of long-term ART were as follows: PSA level: 0.42, 0.51, and 0.57; prostate volume: 0.35, 0.59, and 0.47; IPSS: 0.34, 0.32, and 0.97; Q max : 0.11, 0.63, and no oral. Neither short-term nor long-term ART showed significant changes in the four determinants of prostate growth investigated compared with placebo. Conclusions: This meta-analysis shows that regardless of the administration method, neither short-term nor long-term ART increases the risk of prostate growth. Further high-quality, prospective studies are required to confirm this observation. # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Beijing Tian-Tan Hospital affiliated Capital Medical University, No. 6 Tiantan Xi Li, Dong cheng District, Beijing , China. Tel / ; Fax: address: doctorzhy@126.com (Y. Zhang). 1. Introduction Androgen deficiency in the aging male has become a topic of increasing interest and debate worldwide. Cross-sectional and longitudinal data indicate that testosterone levels are reduced progressively with age and that a significant percentage of men aged >60 yr have serum testosterone levels that are below the lower limits of young adult men aged yr [1 3]. Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with advancing age and is characterized by a deficiency in serum testosterone levels, among other signs and symptoms [4,5]. LOH may result in significant detriment to quality of life and may adversely affect the function of multiple organ systems. Androgen-replacement therapy (ART) is a widely accepted treatment to prevent or ameliorate many of the /$ see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

2 812 EUROPEAN UROLOGY 64 (2013) [(Fig._1)TD$FIG] symptoms and conditions associated with LOH in aging men. Studies over the past decade have reported evidence of benefit of androgen treatment for multiple target organs of hypogonadal men, including short-term beneficial effects of testosterone in older men that are similar to those seen in younger men [6]. ART is most commonly administered by injection, by transdermal application, or orally. Sometimes a gradual increase in prostate volume concomitant with the progressive decline in testosterone level that occurs in middle age reflects the evolution of benign prostatic hyperplasia (BPH) [7]. It is well known that androgen plays an important role in the development of BPH; therefore, it has been suggested that ART may potentially promote prostate growth [8 11]. Many urologists are concerned that ART may accelerate prostate growth not only in cancer but also in benign disease. 2. Evidence acquisition 146 articles were identified including: Medline: 96 articles Embase: 50 articles Cochrane Controlled Trials Register: 0 18 relevant articles were included. 16 RCTs were included in the analysis: 7 RCTs compared androgen with a placebo over the short term ( 12 mo) and 9 RCTs compared androgen with a placebo over the long term (12-36 mo). On the basis of titles and abstracts, 128 articles were excluded. 2 articles lacked useful data. Fig. 1 A flow diagram of the study selection process. RCT = randomized controlled trial Search strategy The Medline (1966 to October 2012), Embase (1974 to October 2012), and Cochrane Controlled Trials Register databases were searched to identify randomized controlled trials (RCTs) that referred to the impact of ART on the prostate. We also searched the reference lists of the retrieved studies. The following search terms were used: androgen, prostate, and randomized controlled trials Inclusion criteria and trial selection RCTs that met the following criteria were included: (1) The study design included ART; (2) the study provided accurate data that could be analyzed, including the total number of subjects and the values of each determinant of prostate growth, such as prostate-specific antigen (PSA) levels, prostate volume, International Prostate Symptom Score (IPSS), and maximum flow rate (Q max ); and (3) the full text of the study could be accessed. When the same study was published in various journals or in different years, the most recent publication was used for the meta-analysis. If the same group of researchers studied a group of subjects with multiple experiments, then each study was included. A flow diagram of the study selection process is presented in Figure 1. each study was rated and assigned to one of the three following quality categories: A: If all quality criteria were adequately met, the study was deemed to have a low risk of bias. B: If one quality criterion or more were only partially met or were unclear, the study was deemed to have a moderate risk of bias. C: If one criterion or more were not met or not included, the study was deemed to have a high risk of bias. Differences were resolved by discussion among the authors Data extraction The following information was collected for each study: (1) the name of the first author and the publication year; (2) the study design and sample size; (3) the therapy that the patients received; (4) the country in which the study was conducted; (5) data on the four determinants of prostate growth (ie, PSA levels, prostate volume, IPSS, Q max ); and (6) the ART administration method and dosage Quality assessment The quality of the retrieved RCTs was assessed using the Jadad scale [12]. All the identified RCTs were included in the meta-analysis, regardless of the quality score. The methodological quality of each study was assessed according to how patients were allocated to the arms of the study, the concealment of allocation procedures, blinding, and data loss due to attrition. The studies were then classified qualitatively according to the guidelines published in the Cochrane Handbook for Systematic Reviews of Interventions v [13]. Based on the quality assessment criteria, 2.5. Statistical analysis and meta-analysis The meta-analysis of comparable data was carried out using RevMan v (Cochrane Collaboration, Oxford, UK) [13]. Changes in all four determinants of prostate growth were determined as differences between baseline (study entry) and study completion. We estimated the relative risk for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes pooled across studies by using the DerSimonian and Laird random-effects model [14]. We used a 95% confidence interval (CI). If the result of analysis showed p > 0.05, we considered the studies

3 EUROPEAN UROLOGY 64 (2013) homogeneous and so chose a fixed-effect model for metaanalysis. Otherwise, a random-effect model was used. We quantified inconsistency using the I 2 statistic, which describes the proportion of heterogeneity across studies that is not due to chance, thus describing the extent of true inconsistency in results across trials [15]. I 2 <25% reflects a small level of inconsistency and I 2 >50% reflects significant inconsistency Subgroup and sensitivity analysis To explore causes of inconsistency and subgroup treatment interactions, subgroup analyses were specified a priori according to the following factors: Participants: aged <65 or 65 yr; total testosterone level at baseline (testosterone level was considered low if <350 ng/dl or 12 nmol/l); if total testosterone was not available, then the lower limit of normal for bioavailable or free testosterone levels was used; if neither total nor free testosterone levels were available, then studies were classified according to PSA levels Interventions: testosterone formulation, route of administration Outcome characteristic: duration of follow-up (<12 mo vs 12 mo) Study quality measure: proportion of patients lost to follow-up (10% vs >10%), concealment of allocation, and blinding of patients. 3. Evidence synthesis 3.1. Characteristics of the individual studies The database search found 146 articles that could have been included in our meta-analysis. Based on the inclusion and exclusion criteria, 128 articles were excluded after reading the titles and abstracts of the articles. Two articles lacked useful data. In all, 16 articles [16 31], reporting data from a total of 16 RCTs, were included in the analysis: 7 RCTs compared androgen with a placebo over the short term (<12 mo), and 9 RCTs compared androgen with a placebo over the long term (12 36 mo). Three different administration methods were used: oral, transdermal, and injection (Fig. 1). The baseline characteristics of the studies included in our meta-analysis are listed in Table 1. Only four of the included studies had as their end points the same determinants of prostate growth measured in the present analysis (ie, prostate volume, IPSS, PSA levels, and Q max ). All 16 RCTs included in our analysis involved rigorous, periodic monitoring of patients, and treatment was withdrawn when there were indications suspicious for prostate cancer or other serious complications. Few patients suffered serious complications, and all patients who withdrew from treatment had returned to normal at long-term assessment. Five of the 16 RCTs [18,21,23,25,26] reported that the few patients with increased PSA levels on follow-up had undergone prostate biopsy (Table 3), and pathologic examination of biopsy specimens revealed benign histology. All 16 RCTs provided baseline PSA levels, prostate volume, IPSS, and Q max, and only one patient from the studies [29] suffered from BPH symptoms (Table 3). In addition, for all 16 RCTs, no patient had prostate enlargement at baseline, all patients had normal PSA levels at baseline (Table 3), and no patient underwent prostate biopsy at study entry Quality of the individual studies All 16 RCTs were double blinded, and all described the randomization processes used. All except Kenny et al. [22] included a power calculation to determine the optimal sample size, and seven used intention-to-treat analysis (Table 2). The level of quality of each identified study was A (Table 2). The funnel plot provided a qualitative estimation of publication bias of the studies, and no evidence of bias was found (Fig. 4) Short-term androgen replacement therapy versus placebo Prostate-specific antigen levels Six RCTs, representing 345 participants (170 in the androgen group and 175 in the control group), included PSA data [16,22,23,26,30,31] (Fig. 2). Three studies used injection for administration [16,22,23]; two used transdermal application [26,30]; and in one, treatment was given orally [31]. No heterogeneity was found among the trials (Fig. 2). For the three RCTs using injected treatments, the fixed-effects estimate of the SMD was 0.50 (95% CI, 0.04 to 1.05; p = 0.07) (Fig. 2). For the RCTs using transdermal application, the SMD was 0.30 (95% CI, ; p = 0.002) (Fig. 2). For the study in which treatment was given orally, the SMD was 0.02 (95% CI, 0.64 to 0.60; p = 0.95) (Fig. 2). This result suggests that ART was more likely to result in increased PSA levels than treatment with a placebo when administered transdermally Prostate volume changes Four RCTs [16,23,30,31], representing 103 participants (50 in the androgen group and 53 in the control group), included data on prostate volume changes (Fig. 2). Two trials used injection for administration [16,23], one used transdermal application [30], and one used oral delivery [31]. No heterogeneity was found between the RCTs in which treatment was given by injection (Fig. 2); the SMD was 0.95 (95% CI, 3.82 to 5.72; p = 0.70) (Fig. 2). For the study that used transdermal treatment application [30], the SMD was 0.40 (95% CI, 2.61 to 3.41; p = 0.79) (Fig. 2). For the study in which treatment was given orally [31], the SMD was 3.00 (95% CI, 2.96 to 8.96; p = 0.32) (Fig. 2). These results suggests that regardless of administration method, comparing androgen with a placebo revealed no apparent differences in prostate volume changes International Prostate Symptom Score changes Five RCTs [22 24,26,30], representing 346 participants (173 in the androgen group and 173 in the control group), included the data for changes in IPSS between groups (Fig. 2). Two trials used injection for administration of ART

4 814 Table 1 Study and patient characteristics Study Therapy in experimental group Therapy in control group Country Sample size T cut-off level for Experimental Control study entry Other inclusion criteria Exclusion of PSA levels, ng/ml Short-term or long-term ART Administration method Dosage Tenover, 1992 [16] T Placebo USA 6 7 TT 12.1 nmol/l Kenny et al., 2004 [22] T Placebo USA 6 5 BT 128 ng/dl Marks et al., 2006 [23] T Placebo USA TT 300 ng/dl Chiang et al., 2007 [24] T Placebo Taiwan TT 300 ng/dl Srinivas-Shankar et al., 2010 [26] T Placebo New Zealand TT 12 nmol/l No history disease, BMI kg/m 2 >4 Short-term I 100 mg/2 wk Folstein Mini-Mental State >4 Short-term I 200 mg/3 wk Exam scores Men with late-onset >10 Short-term I 150 mg/2 wk hypogonadism symptoms T deficiency, never took ART >4 Short-term Tr 50 mg/d Men with late-onset hypogonadism symptoms Page et al., 2011 [30] DHT Placebo USA TT normal IPSS <10 and a normal prostate TRUS Holmang et al., 1993 [31] T Placebo Sweden TT normal Men without urinary tract symptoms Sih et al., 1997 [17] T Placebo USA BT 60 ng/dl Snyder et al., 1999 [18] T Placebo USA TT 475 ng/dl Kenny et al., 2001 [19] T Placebo USA BT 4.44 nmol/l Normal liver function tests, PSA, and hematocrit Men with BMD of the lumbar spine below the mean for healthy young men Men with late-onset hypogonadism symptoms Wittert et al., 2003 [20] T Placebo Australia TT normal Men with late-onset hypogonadism symptoms Amory et al., 2004 [21] T Placebo USA TT 12.1 nmol/l Emmelot-Vonk et al., 2008 [25] T Placebo Netherlands TT 13.7 nmol/l Men with late-onset hypogonadism symptoms Men with late-onset hypogonadism symptoms Idan et al., 2010 [28] DHT Placebo Australia TT normal Men had no known prostate disease (cancer, disease requiring further treatment) Aversa et al., 2010 [27] T Placebo Italy TT 11 nmol/l Shigehara et al., 2011 [29] T Placebo Japan BT 11.8 pg/ml At least two symptoms of hypogonadism IPSS >7 and total prostate volume >20 ml >4 Short-term Tr 50 mg/d >2 Short-term Tr 7 mg/d >10 Short-term O 160 mg/d >4 Long-term I 200 mg/2 wk >4 Long-term Tr 6 mg/d >4 Long-term Tr 5 mg/d >5 Long-term O 80 mg 2/d >4 Long-term I 200 mg/2 wk >4.5 Long-term O 80 mg 2/d >4 Long-term Tr 70 mg/d >4 Long-term Tr 1000 mg/12 wk >2 Long-term I 250 mg/4 wk ART = androgen replacement therapy; BMD = bone mineral density; BMI = body mass index;dht = dihydrotestosterone; FTI = free testosterone index; I = injection; IPSS = International Prostate Symptom Score; O = oral; PSA = prostate-specific antigen; RCT = randomized controlled trial; SHBG = sex hormone-binding globulin; TT = total testosterone; BT = bioavailable testosterone; T = testosterone; Tr = transdermal; TRUS = transrectal ultrasound. EUROPEAN UROLOGY 64 (2013)

5 EUROPEAN UROLOGY 64 (2013) Table 2 Quality assessment of individual studies Study Allocation sequence generation Allocation concealment Blinding Loss to follow-up Calculation of sample size Statistical analysis ITT analysis Level of quality Tenover, 1992 [16] B A A 0 Yes ANOVA No A Kenny et al., 2004 [22] B A A 0 No ANOVA No A Marks et al., 2006 [23] B A A 21 Yes Paired t tests No A Chiang et al., 2007 [24] A A A 3 Yes ANOVA Yes A Srinivas-Shankar et al., 2010 [26] A A A 31 Yes ANCOVA Yes A Page et al., 2011 [30] A A A 4 Yes Wilcoxon rank-sum tests No A Holmang et al., 1993 [31] B A A 2 Yes Student t test No A Sih et al., 1997 [17] A A A 10 Yes Student t test No A Snyder et al., 1999 [18] A A A 12 Yes ANOVA Yes A Kenny et al., 2001 [19] A A A 24 Yes Paired t tests No A Wittert et al., 2003 [20] A A A 18 Yes Fisher exact test Yes A Amory et al., 2004 [21] A A A 13 Yes Student t test Yes A Emmelot-Vonk et al., 2008 [25] A A A 16 Yes Unpaired t tests Yes A Idan et al., 2010 [28] A A A 33 Yes Fisher exact test Yes A Aversa et al., 2010 [27] A A A 0 Yes ANOVA No A Shigehara et al., 2011 [29] B A A 6 Yes Student t test No A A = all quality criteria met (adequate), low risk of bias; ANCOVA = analysis of covariance; ANOVA = analysis of variance; B = one quality criterion or more only partly met (unclear), moderate risk of bias; C = one criterion or more not met (inadequate or not used), high risk of bias; ITT = intention-to-treat analysis. or placebo [22,23], and three used a transdermal method [24,26,30]. No heterogeneity was found between the trials using the injection method [22,23] (Fig. 2); the SMD was 0.46 (95% CI, 3.74 to 2.82; p = 0.78) (Fig. 2). Nor was there heterogeneity among the trials using transdermal application [24,26,30] (Fig. 2); the SMD was 0.02 (95% CI, 1.01 to 1.04; p =0.98)(Fig. 2). These results demonstrate that ART and placebo were similar in terms of the IPSS changes whether administered by injection or transdermally Maximum urine flow rate changes Only two RCTs [23,31], involving a total of 63 participants (32 in the androgen group and 31 in the control group), included Q max data (Fig. 2). Treatment was given by injection in one study [23] and orally in the other [31]. No heterogeneity was found between the trials (Fig. 2). The SMD was 0.22 (95% CI, 4.35 to 4.79) for the study using delivery by injection and 5.00 (95% CI, 0.96 to 10.96) for the study using oral delivery ( p = 0.28) (Fig. 2). Therefore, for either an injection or an oral administration method, androgen did not decrease Q max compared with placebo Long-term androgen replacement therapy versus placebo Prostate-specific antigen levels Nine RCTs [17 21,25,27 29] included PSA data for a total of 670 participants (255 in the androgen group and 315 in the control group) (Fig. 3). Three used injection [17,21,29] for administration, four used transdermal administration [18,19,27,28], and two gave treatments orally [20,25]. According to our analysis, no heterogeneity was found among the trials (Fig. 3). The SMDs were 0.15 (95% CI, 0.22 to 0.53; p = 0.42), 0.06 (95% CI, 0.23 to 0.12; p = 0.51), and 0.08 (95% CI, 0.36 to 0.20; p = 0.57) for ART administered by injection, transdermally, and orally, respectively (Fig. 3). These results indicate no apparent differences between ART and placebo in changes in PSA levels regardless of how the treatments were administered Prostate volume changes Four RCTs [21,25,27,28], representing a total of 402 participants (216 in the androgen group and 186 in the control group), included data on changes in prostate volume (Fig. 3). One study used injection [21] for administration, two used transdermal administration [27,28], and one administered treatment orally [25]. No heterogeneity was found among the trials (Fig. 3). Our analysis revealed that the SMD for injection was 4 (95% CI, 4.32 to 12.32; p =0.35), SMD for transdermal delivery was 0.42 (95% CI, 1.99 to 1.14; p = 0.59), and SMD for oral delivery was 1.20 ( ; p = 0.47) (Fig. 3). The result clarified that there was no difference between ART and a placebo in terms of prostate volume changes for all three administration methods International Prostate Symptom Score changes Six RCTs [18 20,25,28,29], representing 563 participants (286 in the androgen group and 277 in the control group), included data on IPSS changes (Fig. 3). One trial delivered treatment by injection [29], three used transdermal application [18,19,28], and two used oral delivery [20,25]. No heterogeneity was found among the trials (Fig. 3), and a fixed-effects model was chosen for the analysis. The SMDs were 2.70 (95% CI, 2.88 to 8.28; p = 0.34), 0.42 (95% CI, 0.41 to 1.24; p = 0.32), and 0.02 (95% CI, 1.11 to 1.15; p = 0.97) for administration by injection, transdermally, and orally, respectively (Fig. 3). Therefore, we concluded that androgen and a placebo were nearly the same in terms of the IPSS changes for all three methods of administration Maximum urine flow rate changes Only two RCTs [18,29], representing a total of 142 participants (68 in the androgen group and 74 in the control

6 816 [(Fig._2)TD$FIG] EUROPEAN UROLOGY 64 (2013) Fig. 2 Forest plots showing changes in (a) prostate-specific antigen levels, (b) prostate volume, (c) International Prostate Symptom Score, and (d) maximum urine flow rate in the short-term treatment studies. CI = confidence interval; IV = inverse; SD = standard deviation.

7 [(Fig._3)TD$FIG] EUROPEAN UROLOGY 64 (2013) Fig. 3 Forest plots showing changes in (a) prostate-specific antigen levels, (b) prostate volume, (c) International Prostate Symptom Score, and (d) maximum urine flow rate in the long-term treatment studies. CI = confidence interval; IV = inverse; SD = standard deviation.

8 818 [(Fig._4)TD$FIG] EUROPEAN UROLOGY 64 (2013) Fig. 4 Funnel plot of the studies represented in the meta-analysis. Although 16 articles are included, 15 symbols are shown because of overlap among the articles in reporting the determinants of prostate growth. MD = mean difference; SE = standard error. group), included Q max data (Fig. 3). One used an injection [29] method, and one used a transdermal method [18] of delivering treatment. No heterogeneity was found between the trials (Fig. 3). The SMD for the study using delivery by injection [29] was 3.70 (95% CI, 0.85 to 8.25) and 0.60 (95% CI, 3.04 to 1.84) for the study using transdermal application [18] ( p =0.74) (Fig. 3). Therefore, we concluded that for either an injection or a transdermal administration method, ART did not decrease the Q max compared with a placebo Subgroup analyses and sensitivity analysis According to the baseline data of PSA levels and the inclusion criteria for our studies, we divided the included studies into three groups for preplanned subgroup analyses: PSA 2 ng/ml, PSA 1 2 ng/ml, and PSA 1 ng/ml. There were no differences between the ART and placebo groups regarding the changes of the four determinants of prostate growth (Table 4). Subgroup analyses shows that all the results of determinants of prostate growth in the ART and placebo groups matched our findings (Table 4) except that ART using the transdermal administration method was more likely to increase PSA levels than treatment with a placebo ( p = ) in the group aged 65 yr (Table 4). Sensitivity analysis was performed by removing the studies for which generation of allocation sequence was inadequate. Our analysis indicated that short-term ART using the transdermal administration method was more likely to increase PSA levels than treatment with placebo ( p = 0.01) (Table 4). No differences were found between the ART and placebo groups in the long-term studies regarding changes in PSA levels ( p = 0.57), prostate volume ( p = 1.00), IPSS ( p = 0.41), or Q max ( p = 0.63) (Table 4) Discussion Prostate growth is dependent on the presence of androgens; conversely, antiandrogen and orchidectomy can decrease prostate volume in patients with BPH [9]. It has been suggested that ART may potentially increase prostate volume. Urologists have been concerned about the use of androgen supplementation due to the possibility of fueling prostate growth not only in cancer but also in benign disease. Resolving this question will inform methods of treating LOH accompanied by prostatic problems. In our analysis, short-term ART delivered by transdermal application was more likely to increase PSA levels than treatment with a placebo; therefore, we can state that PSA levels increased slightly over 12 mo in patients receiving treatment transdermally. This is not in accord with clinical manifestation, however. There are two possible reasons for this discrepancy. One is that skin expresses high 5a-reductase activity; therefore, testosterone gel applied to the skin achieves much higher dihydrotestosterone levels than a comparable dose of testosterone enanthate [32 34], which may increase PSA levels. The other is that PSA is sensitive to changes in the level of testosterone at low concentrations, when unbound receptors are available to respond to an increase in testosterone. With an increase in testosterone to eugonadal levels in the clinical setting, the receptors become saturated, and increasing the testosterone level further has no real effect on the level of PSA [35]. Some urologists think that testosterone has a linear effect on prostate growth, and prostate dysfunction as an adverse effect of this was the dominant theory in the past. Now there is a new paradigm: the saturation model of testosterone and the prostate [36]. This theory holds that testosterone s effect on the prostate reaches a saturation point well below the physiologic testosterone levels encountered in the clinical setting, beyond which additional testosterone does not have an increased effect. This theory is gaining traction in modern studies. In the study by Page et al. [30], for example, the inclusion criteria for patients receiving treatment transdermally included PSA level <2 ng/ml, which was lower than in other short-term studies (Table 1). Perhaps due to the relatively low level of testosterone, unbound receptors are available to respond, leading to increased PSA levels in the short term. Combined with the long-term ART trial data, we recognized that the PSA levels exhibited small increases associated with ART. However, there was no significant difference between the PSA levels of the two groups at baseline compared with the end of the trial. Therefore, we hypothesize that the PSA level increases slightly in the early stage of ART and then decreases to a relatively low level that is still higher than baseline and remains relatively stable for a long period during ART. Our study also evaluated the safety of long-term ART (12 36 mo) for prostate growth. All 16 RCTs included in our analysis involved rigorous, periodic monitoring of patients, and treatment was withdrawn when there were indications suspicious for prostate cancer or other serious complications. In addition, for all 16 RCTs, no patient had prostate enlargement at baseline, all patients had normal PSA levels at baseline, and no patient underwent prostate biopsy at study entry (Table 3). Consequently, long-term ART is safe in terms of prostate growth, although rigorous monitoring is indispensable. Our conclusion is based on the fact that

9 Table 3 Baseline data in our study Age, yr, median PSA, ng/ml Prostate volume, ml IPSS Maximum flow rate, ml/s TG PG TG PG TG PG TG PG Prostate volume determination Prostate biopsy at study entry Prostate biopsy during follow-up Tenover, 1992 [16] (0.4) 2.1 (0.4) 33 (4) 33 (4) Transabdominal US No No Kenny et al., 2004 [22] (0.71) 1.30 (0.78) 6.6 (5.8) 8.8 (6.4) NA No No Marks et al., 2006 [23] (0.89) 0.97 (1.55) 43.8 (9.94) 36.8 (6.51) 13.0 (8.14) 11.0 (7.74) 14.0 (7.48) 10.6 (7.27) Transabdominal US No Yes Chiang et al., 2007 [24] (6.9) 8.8 (5.9) NA No No Srinivas-Shankar (0.9) 1.5 (0.9) 7.0 (5.0) 5.9 (4.3) NA No Yes et al., 2010 [26] Page et al., 2011 [30] (0.4) 1.1 (0.6) 20.3 (4.6) 21.5 (4.2) 2.3 (1.7) 2.5 (2.8) TRUS No No Holmang et al., 1993 [31] (1.22) 0.72 (1.06) 24.6 (5.97) 22.1 (6.79) 15 (8.73) 17 (7.91) TRUS No No Sih et al., 1997 [17] (0.82) 1.5 (1.16) NA No No Snyder et al., 1999 [18] (1.1) 1.6 (1.0) 3.9 (2.5) 4.0 (2.3) 25.7 (5.4) 24.7 (6.1) NA No Yes Kenny et al., 2001 [19] (1.3) 2.0 (1.2) 9.3 (6.5) 9.0 (5.2) NA No No Wittert et al., 2003 [20] (0.8) 2.5 (1.2) 6.0 (4.0) 5.6 (5.1) NA No No Amory et al., 2004 [21] (0.8) 1.4 (1.1) 29 (11) 32 (14) TRUS No Yes Emmelot-Vonk (1.1) 1.7 (1.1) 28.3 (12.6) 28.0 (9.9) 6.3 (5.1) 6.7 (4.9) TRUS No Yes et al., 2008 [25] Idan et al., 2010 [28] (1.1) 1.5 (1.1) 28.6 (10.4) 29.3 (16.2) 5.4 (4.2) 6.2 (5.0) TRUS No No Aversa et al., 2010 [27] (0.4) 1.1 (0.5) 26 (3) 26.5 (2) TRUS No No Shigehara et al., 2011 [29] (0.53) 1.06 (0.53) 15.7 (8.7) 14.0 (10.1) 12.9 (5.6) 11.4 (4.9) TRUS No No IPSS = International Prostate Symptom Score; NA = not available; PG = placebo group; PSA = prostate-specific antigen; TG = androgen group; TRUS = transrectal ultrasound; US = ultrasound. Baseline data are expressed as mean (standard deviation). Yes indicates that few patients with increased PSA levels on follow-up had undergone prostate biopsy. EUROPEAN UROLOGY 64 (2013)

10 820 EUROPEAN UROLOGY 64 (2013) Table 4 The results of subgroup, sensitivity, and preplanned subgroup analysis PSA Prostate volume IPSS Maximum flow rate SMD (95% CI) p value SMD (95% CI) p value SMD (95% CI) p value SMD (95% CI) p value Age <65 yr 0.08 ( 0.24 to 0.08) 65 yr 0.23 ( ) Testosterone level Lower 0.15 ( ) Normal 0.10 ( 0.30 to 0.10) Testosterone assay types Gold standard * 0.05 ( 0.25 to 0.15) Not gold standard * 0.13 ( 0.01 to 0.27) Study quality (A level) ** Short-term 0.30 ( ) Long-term 0.04 ( 0.18 to 0.10) Serum PSA level PSA 2 ng/ml 0.41 ( 0.36 to 1.18) PSA 1 2 ng/ml 0.06 ( 0.07 to 0.20) PSA 1 ng/ml 0.14 ( 0.11 to 0.39) Duration of ART Short-term 0.30 ( ) Long-term 0.04 ( 0.17 to 0.10) ( 1.43 to 1.27) ( 0.59 to 1.23) ( 1.15 to 3.93) ( 0.54 to 0.83) ( 1.21 to 2.73) ( 1.55 to 1.44) ( 1.74 to 2.26) ( 1.26 to 1.72) ( 2.61 to 3.41) ( 1.39 to 1.39) ( to 12.55) ( 1.52 to 1.29) ( 1.09 to 3.49) ( 1.41 to 3.27) ( 1.39 to 1.39) ( 0.28 to 0.9) ( 1.84 to 1.03) ( 0.59 to 1.27) ( 0.54 to 0.81) ( 1.01 to 1.04) ( 0.39 to 0.95) ( 4.30 to 1.30) ( 0.19 to 1.07) ( 1.90 to 1.23) ( 1.00 to 0.95) ( 0.35 to 0.98) ( 1.61 to 2.28) ( 1.61 to 2.28) ( 1.13 to 2.92) ( 3.04 to 1.84) ( 1.79 to 2.52) ( 1.64 to 5.62) ( 1.64 to 5.62) ( 1.79 to 2.52) ART = androgen-replacement therapy; CI = confidence interval; IPSS = International Prostate Symptom Score; PSA = prostate-specific antigen; SMD = standardized mean difference. * Gold standard was tandem mass spectrometry and liquid chromatography. ** A level: all quality criteria were met (adequate), low risk of bias. ART has no adverse effect on prostate growth in patients without prostatic hyperplasia. Whether or not ART will increase the risk for prostate growth in patients with BPH needs further investigation in larger, high-quality studies. Current laboratory protocol to support a diagnosis of LOH is for a serum sample for total testosterone determination to be obtained between 7:00 AM and 11:00 AM [37]. It is generally agreed that a total testosterone level >12 nmol/l (350 ng/dl) does not require substitution [5], and that a free testosterone level <225 pmol/l (65 pg/ml) can provide supportive evidence for testosterone treatment [38]. The cohorts of 11 of the 16 studies in our meta-analysis were evaluated in accordance with the diagnosis standard (Table 1). Combined with our study, ART following this diagnosis standard dose not increase the risk of prostate growth. Inadequate data are available to determine the optimal serum testosterone level for efficiency and safety. For the present time, moderate to lower serum testosterone levels seem appropriate in young adult males and should be the therapeutic goal. Although different methods and dosages were used in the selected RCTs, supraphysiologic levels were avoided. This meta-analysis included findings from 16 doubleblinded RCTs. According to the quality-assessment scale that we developed, the quality of the individual studies in the meta-analysis was high. The results of this analysis are important from a scientific standpoint, and they apply to everyday clinical practice, particularly because data were analyzed by method of ART delivery. The results of the subgroup and sensitivity analyses are in accordance with our findings, indicating that our results are robust and reliable. Nevertheless, there are some limitations to our analysis. Data on prostate volume after short-term ART and on Q max were derived from a relatively small sample because cohort sizes of a few of the studies [16,17,22,31] were not large. Major limitations include heterogeneity in the populations examined (Table 1), androgen dosage used (Table 1), and baseline prostate status (with the exception of PSA levels) (Table 3). LOH is a clinical and biochemical syndrome that adversely affects the function of multiple organ systems. The presence of symptoms associated with LOH was not consistent across the included studies, and this may have contributed to the heterogeneous population. Although we

11 EUROPEAN UROLOGY 64 (2013) conducted subgroup and sensitivity analyses to assess the quality of the studies, the problem of heterogeneity still could not be completely avoided. Only four of the included studies had as their end points the same determinants of prostate growth measured in the present analysis (ie, prostate volume, IPSS, PSA levels, and Q max ). Although 15 of the 16 RCTs drew morning blood samples to measure testosterone levels, 11 of the 15 studies reported 6 measurement assay methods included tandem mass spectrometry-liquid chromatography, mass spectroscopy, chemiluminescent immunoassay, radioimmunoassay, fluoroimmunoassay, and electrochemiluminescence. It is generally known that the first method is the gold standard. Although the results of subgroup analysis by testosterone assay types (gold standard and not gold standard) matched our findings, this made inclusion of studies using different testosterone assays problematic and potentially influenced the results of the meta-analysis. 4. Conclusions This meta-analysis shows that regardless of the administration method, neither short-term nor long-term ART increases the risk of prostate growth. Further highquality, prospective studies are required to confirm this observation. Author contributions: Yong Zhang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Zhang. Acquisition of data: Zhang, Cui. Analysis and interpretation of data: Zhang, Cui. Drafting of the manuscript: Zhang, Cui. Critical revision of the manuscript for important intellectual content: Zhang, Cui. Statistical analysis: Zhang, Cui. Obtaining funding: None. Administrative, technical, or material support: Zhang. Supervision: Zhang. Other (specify): None. Financial disclosures: Yong Zhang certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. Acknowledgment statement: The authors thank Dragonfly Editorial for assisting in the preparation of this manuscript. References [1] Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab 2007;92: [2] Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86: [3] Wu FC, Tajar A, Pye SR, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors. J Clin Endocrinol Metab 2008;93: [4] Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 2009;55: [5] Morales A, Schulman CC, Tostain J, Wu FCW. Testosterone deficiency syndrome (TDS) needs to be named appropriately the importance of accurate terminology. Eur Urol 2006;50: [6] Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005;26: [7] Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB. Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54: [8] Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002;60: [9] Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT Study. Eur Urol 2010;57: [10] Fowler Jr JE, Whitmore Jr WF. Considerations for the use of testosterone with systemic chemotherapy in prostatic cancer. Cancer 1982;49: [11] McConnell JD. Prostatic growth: new insights into hormonal regulation. Br J Urol 1995;76(Suppl 1):5 10. [12] Jadad AR. Randomised controlled trials. London, UK: BMJ Publishing Group; [13] Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions, v.5.1. Cochrane Collaboration Web site. Updated March [14] DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7: [15] Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327: [16] Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992;75: [17] Sih R, Morlet JE, Kaiser FE, Perry III HM, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997;82: [18] Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999;84: [19] Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 2001;565: [20] Wittert GA, Chapman IM, Haren MT, Mackintosh, Coates P, Morley JE. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low normal gonadal status. J Gerontol A Biol Sci Med Sci 2003;587: [21] Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89: [22] Kenny AM, Fabregas G, Song C, Biskup B, Bellantonio S. Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. J Gerontol A Biol Sci Med Sci 2004;591:75 8.

12 822 EUROPEAN UROLOGY 64 (2013) [23] Marks LS, Mazer NA, Mostaghel E, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism. JAMA 2006;296: [24] Chiang HS, Hwang TIS, Hsui YS, et al. Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function. Int J Impot Res 2007;19: [25] Emmelot-Vonk MH, Verhaar HJJ, Pour HRN, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men. JAMA 2008;299: [26] Srinivas-Shankar U, Roberts SA, Connolly MJ, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010;95: [27] Aversa A, Bruzziches R, Francomano D, et al. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med 2010;7: [28] Idan A, Griffiths KA, Harwood DT, et al. Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease. Ann Intern Med 2010;153: [29] Shigehara K, Sugimoto K, Konaka H, et al. Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study. Aging Male 2011;14:53 8. [30] Page ST, Lin DW, Mostaghel EA, et al. Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomizedcontrolled trial. J Clin Endocrinol Metab 2011;96: [31] Holmang S, Marin P, Lindstedt G, Hedelin H. Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentration in eugonadal middleaged men. Prostate 1993;23: [32] Wang C, Berman N, Longstreth JA, et al. Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. J Clin Endocrinol Metab 2000;85: [33] Swerdloff RS, Wang C, Cunningham G, et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000;85: [34] Bhasin S, Travison TG, Storer TW, et al. Effect of testosterone supplementation with and without a dual 5a-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. JAMA 2012;307: [35] Polackwich AS, Ostrowski KA, Hedges JC. Testosterone replacement therapy and prostate health. Curr Urol Rep 2012;13: [36] Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55: [37] Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol 2003;58: [38] Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society Position Statement. J Clin Endocrinol Metab 2007;92:

Point-Counterpoint: Late Onset Hypogonadism (LOH)

Point-Counterpoint: Late Onset Hypogonadism (LOH) Point-Counterpoint: Late Onset Hypogonadism (LOH) We are Under-diagnosing and Treating Men with LOH LOH is a Non-existent Disease ~ Robert E. Donohue, MD Late Onset Hypogonadism LOH: underdx. & undertx

More information

Current Data and Considerations Novel Testosterone Formulations

Current Data and Considerations Novel Testosterone Formulations Current Data and Considerations Novel Testosterone Formulations 1 Hypogonadism: Treatment Safety and Prostate Health 2 Monitoring for Testosterone Therapy DRE 1,2 PSA Parameter Voiding/IPSS 1,2 Hemoglobin

More information

Increasing Awareness, Diagnosis, and Treatment of BPH, LUTS, and EP

Increasing Awareness, Diagnosis, and Treatment of BPH, LUTS, and EP Introduction to Enlarged Prostate E. David Crawford, MD Professor of Surgery (Urology) and Radiation Oncology Head, Urologic Oncology E. David Crawford Endowed Chair in Urologic Oncology University of

More information

6/14/2010. GnRH=Gonadotropin-Releasing Hormone.

6/14/2010. GnRH=Gonadotropin-Releasing Hormone. Male Androgen Replacement Mitchell Sorsby, MD June 19, 2010. QUESTION # 1 Which of the following is not a symptom associated with low T levels? a) decreased libido b) erectile dysfunction c) depression

More information

Testosterone Therapy in Men An update

Testosterone Therapy in Men An update Testosterone Therapy in Men An update SANDEEP DHINDSA Associate Professor of Medicine Director, Division of Endocrinology and Metabolism, Saint Louis University, St. Louis, MO Presenter Disclosure None

More information

Update on diagnosis and complications of adult and elderly male hypogonadism

Update on diagnosis and complications of adult and elderly male hypogonadism Hypoandrogenism in the elderly: to treat or not to treat? 12 th Italian AME Meeting; 6 th joint Meeting with AAC Bari november 10th Update on diagnosis and complications of adult and elderly male hypogonadism

More information

Managing Testosterone Deficiency: A Practical Guide. John Grantmyre MD Professor of Urology Dalhousie University

Managing Testosterone Deficiency: A Practical Guide. John Grantmyre MD Professor of Urology Dalhousie University Managing Testosterone Deficiency: A Practical Guide John Grantmyre MD Professor of Urology Dalhousie University 1 2 Case Study #1 A 59-Year-Old Man with Erectile Dysfunction 3 Case History Robert is a

More information

How to treat: TRT modalities and formulations

How to treat: TRT modalities and formulations How to treat: TRT modalities and formulations Paul PIETTE, PharmD Senior Research Fellow Clinique Antoine Depage - Belgium ppiette@besins-healthcare.com Bruges 2014, May 15 th Testosterone-replacement

More information

Does TRT Induce Prostate Cancer?

Does TRT Induce Prostate Cancer? Does TRT Induce Prostate Cancer? Prism VI, Bruges, Belgium 21-22November 2014 Herman Leliefeld, Urologist, Utrecht The Netherlands Does TRT Induce Prostate Cancer? Why is it a controversial topic? Is there

More information

Corporate Medical Policy Testosterone Pellet Implantation for Androgen Deficiency

Corporate Medical Policy Testosterone Pellet Implantation for Androgen Deficiency Corporate Medical Policy Testosterone Pellet Implantation for Androgen Deficiency File Name: Origination: Last CAP Review: Next CAP Review: Last Review: testosterone_pellet_implantation_for_androgen_deficiency

More information

Evidence based urology in practice: heterogeneity in a systematic review meta-analysis. Health Services Research Unit, University of Aberdeen, UK

Evidence based urology in practice: heterogeneity in a systematic review meta-analysis. Health Services Research Unit, University of Aberdeen, UK Version 6, 12/10/2009 Evidence based urology in practice: heterogeneity in a systematic review meta-analysis Mari Imamura 1, Jonathan Cook 2, Sara MacLennan 1, James N Dow 1 and Philipp Dahm 3 for the

More information

The association of time of day and serum testosterone concentration in a large screening population

The association of time of day and serum testosterone concentration in a large screening population Original Article TIME OF DAY AD SERUM TESTOSTEROE LEVEL I A LARGE SCREEIG POPULATIO CRAWFORD et al. Authors from the USA reviewed semen samples for their ational Prostate Cancer Awareness screening programme.

More information

Impact of 5-Alpha Reductase Inhibitors Treatment for Benign Prostatic Hyperplasia on Erectile Dysfunction: A Meta-Analysis

Impact of 5-Alpha Reductase Inhibitors Treatment for Benign Prostatic Hyperplasia on Erectile Dysfunction: A Meta-Analysis International Journal of Clinical Urology 2017; 1(1): 1-6 http://www.sciencepublishinggroup.com/j/ijcu doi: 10.11648/j. ijcu.20170101.11 Review Article Impact of 5-Alpha Reductase Inhibitors Treatment

More information

The Evolution of Combination Therapy. US men eligible for BPH treatment * with projected population changes

The Evolution of Combination Therapy. US men eligible for BPH treatment * with projected population changes The Management of BPH & The Impact of Combination Therapy Results Combination of Avodart and Tamsulosin (CombAT) Medical Therapy of Prostate Symptoms (MTOPS) Dr. Jack Barkin, md, fics, facs, dabu, Mcert

More information

Testosterone Replacement Alone for Testosterone Deficiency Syndrome Improves Moderate Lower Urinary Tract Symptoms: One Year Follow-Up

Testosterone Replacement Alone for Testosterone Deficiency Syndrome Improves Moderate Lower Urinary Tract Symptoms: One Year Follow-Up pissn: 2287-4208 / eissn: 2287-4690 World J Mens Health 2013 April 31(1): 47-52 http://dx.doi.org/10.5534/wjmh.2013.31.1.47 Original Article Testosterone Replacement Alone for Testosterone Deficiency Syndrome

More information

Testosterone Substitution and the Prostate

Testosterone Substitution and the Prostate European Urology Supplements European Urology Supplements 4 (2005) 16 23 Testosterone Substitution and the Prostate E. David Crawford* University of Colorado Health Sciences Center, 1665 N. Ursula Street,

More information

PRISM Bruges June Herman Leliefeld Urologist. The Netherlands

PRISM Bruges June Herman Leliefeld Urologist. The Netherlands PRISM Bruges 25-26 June 2015 Herman Leliefeld Urologist The Netherlands Guidelines EAU 2015: a rich source of Knowledge! Epidemiology/ Aetiology / Pathology Diagnostic evaluation Disease management Follow-Up

More information

HYPOGONADISM DEFINITION: PRODUCTION OF SEX HORMONES AND GERM CELLS IS INADEQUATE (ENDOCRINE SOCIETY)

HYPOGONADISM DEFINITION: PRODUCTION OF SEX HORMONES AND GERM CELLS IS INADEQUATE (ENDOCRINE SOCIETY) HYPOGONADISM DEFINITION: PRODUCTION OF SEX HORMONES AND GERM CELLS IS INADEQUATE (ENDOCRINE SOCIETY) DEFECT OF THE REPRODUCTIVE SYSTEM THAT RESULTS IN LACK OF FUNCTION OF THE GONADS (Wikipedia) REDUCTION

More information

Chapter 4: Research and Future Directions

Chapter 4: Research and Future Directions Chapter 4: Research and Future Directions Introduction Many of the future research needs listed in the 1994 Agency for Health Care Policy and Research (AHCPR) clinical practice guideline Benign Prostatic

More information

PCa Commentary. Prostate Cancer? Where's the Meat? - A Collection of Studies Supporting the Safety of Its Use. Seattle Prostate Institute CONTENTS

PCa Commentary. Prostate Cancer? Where's the Meat? - A Collection of Studies Supporting the Safety of Its Use. Seattle Prostate Institute CONTENTS Volume 70 July - August 2011 PCa Commentary SEATTLE PROSTATE INSTITUTE CONTENTS TESTOSTERONE REPLACEMENT in Hypogonadal Men with Treated and Untreated Prostate Cancer? 1 TESTOSTERONE REPLACEMENT in Hypogonadal

More information

A dro r gen e R e R p e lac a e c m e e m n e t t T her e a r p a y Androgen Replacement Therapy in the Aging O j b ecti t ve v s Male

A dro r gen e R e R p e lac a e c m e e m n e t t T her e a r p a y Androgen Replacement Therapy in the Aging O j b ecti t ve v s Male Androgen Replacement Therapy in the Aging Male Thomas J. Walsh, MD, MS Department of Urology University of California, San Francisco Objectives 1. List 3 effects of androgens on normal male physiology.

More information

The Relationship between Prostate Inflammation and Lower Urinary Tract Symptoms: Examination of Baseline Data from the REDUCE Trial

The Relationship between Prostate Inflammation and Lower Urinary Tract Symptoms: Examination of Baseline Data from the REDUCE Trial european urology 54 (2008) 1379 1384 available at www.sciencedirect.com journal homepage: www.europeanurology.com Benign Prostatic Hyperplasia The Relationship between Prostate Inflammation and Lower Urinary

More information

The Journal of International Medical Research 2012; 40:

The Journal of International Medical Research 2012; 40: The Journal of International Medical Research 2012; 40: 899 908 Comparison of α-blocker Monotherapy and α-blocker Plus 5α-Reductase Inhibitor Combination Therapy Based on Prostate Volume for Treatment

More information

PREVALENCE OF PROSTATE CANCER AMONG HYPOGONADAL MEN WITH PROSTATE-SPECIFIC ANTIGEN LEVELS OF 4.0 ng/ml OR LESS

PREVALENCE OF PROSTATE CANCER AMONG HYPOGONADAL MEN WITH PROSTATE-SPECIFIC ANTIGEN LEVELS OF 4.0 ng/ml OR LESS ADULT UROLOGY PREVALENCE OF PROSTATE CANCER AMONG HYPOGONADAL MEN WITH PROSTATE-SPECIFIC ANTIGEN LEVELS OF 4.0 ng/ml OR LESS ABRAHAM MORGENTALER AND ERNANI LUIS RHODEN ABSTRACT Objectives. To determine

More information

ISSN: (print), (electronic)

ISSN: (print), (electronic) http://informahealthcare.com/tam ISSN: 1368-5538 (print), 1473-0790 (electronic) Aging Male, 2014; 17(3): 147 154! 2014 Informa UK Ltd. DOI: 10.3109/13685538.2014.908460 ORIGINAL ARTICLE Performance of

More information

INTEROBSERVER VARIATION OF PROSTATIC VOLUME ESTIMATION WITH DIGITAL RECTAL EXAMINATION BY UROLOGICAL STAFFS WITH DIFFERENT EXPERIENCES

INTEROBSERVER VARIATION OF PROSTATIC VOLUME ESTIMATION WITH DIGITAL RECTAL EXAMINATION BY UROLOGICAL STAFFS WITH DIFFERENT EXPERIENCES Clinical Urology International Braz J Urol Official Journal of the Brazilian Society of Urology DIGITAL RECTAL EXAMINATION BY UROLOGICAL STAFFS Vol. 30 (6): 466-471, November - December, 2004 INTEROBSERVER

More information

Alectinib Versus Crizotinib for Previously Untreated Alk-positive Advanced Non-small Cell Lung Cancer : A Meta-Analysis

Alectinib Versus Crizotinib for Previously Untreated Alk-positive Advanced Non-small Cell Lung Cancer : A Meta-Analysis Showa Univ J Med Sci 30 2, 309 315, June 2018 Original Alectinib Versus Crizotinib for Previously Untreated Alk-positive Advanced Non-small Cell Lung Cancer : A Meta-Analysis Ryo MANABE 1, Koichi ANDO

More information

How Do New Data from Clinical Trials Allow Us to Optimise the Assessment and Treatment of Patients with Benign Prostatic Hyperplasia?

How Do New Data from Clinical Trials Allow Us to Optimise the Assessment and Treatment of Patients with Benign Prostatic Hyperplasia? available at www.sciencedirect.com journal homepage: www.europeanurology.com How Do New Data from Clinical Trials Allow Us to Optimise the Assessment and Treatment of Patients with Benign Prostatic Hyperplasia?

More information

The population of subjects which was statistically analyzed was the Intent-to-Treat population

The population of subjects which was statistically analyzed was the Intent-to-Treat population Study No.: ARIB3003 (Year 1) Title: A Randomized, Double-Blind, Placebo-Controlled, Two-Year Parallel-Group Study of the Efficacy and Safety of GI198745 in the Treatment and Modification of Progression

More information

Testim 1 Gel: Review of Clinical Data

Testim 1 Gel: Review of Clinical Data European Urology Supplements European Urology Supplements 4 (2005) 24 30 Testim 1 Gel: Review of Clinical Data Tom A. McNicholas* Department of Urology, Lister Hospital, Corey s Mill Lane, Stevenage, Hertfordshire

More information

EUROPEAN UROLOGY 58 (2010)

EUROPEAN UROLOGY 58 (2010) EUROPEAN UROLOGY 58 (2010) 551 558 available at www.sciencedirect.com journal homepage: www.europeanurology.com Prostate Cancer Prostate Cancer Prevention Trial and European Randomized Study of Screening

More information

EFFICACY AND SAFETY OF TESTOSTERONE THERAPY FOR LATE-ONSET HYPOGONADISM: AN UPDATE

EFFICACY AND SAFETY OF TESTOSTERONE THERAPY FOR LATE-ONSET HYPOGONADISM: AN UPDATE EFFICACY AND SAFETY OF TESTOSTERONE THERAPY FOR LATE-ONSET HYPOGONADISM: AN UPDATE Matthew Ho, PGY-2 Department of Urologic Sciences University of British Columbia OBJECTIVES 1. Review the characteristics

More information

American Journal of Internal Medicine

American Journal of Internal Medicine American Journal of Internal Medicine 2016; 4(3): 49-59 http://www.sciencepublishinggroup.com/j/ajim doi: 10.11648/j.ajim.20160403.12 ISSN: 2330-4316 (Print); ISSN: 2330-4324 (Online) The Effect of Dose-Reduced

More information

2. The effectiveness of combined androgen blockade versus monotherapy.

2. The effectiveness of combined androgen blockade versus monotherapy. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer Blue Cross and Blue Shield Association, Aronson N, Seidenfeld J Authors' objectives

More information

Androderm patch, AndroGel packets and pump, Axiron solution, First- Testosterone, First-Testosterone MC, Fortesta gel, Testim gel, Vogelxo

Androderm patch, AndroGel packets and pump, Axiron solution, First- Testosterone, First-Testosterone MC, Fortesta gel, Testim gel, Vogelxo Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.31 Subject: Testosterone Topical Page: 1 of 9 Last Review Date: September 23, 2016 Testosterone topical

More information

BIOCHEMICAL TESTS FOR THE INVESTIGATION OF COMMON ENDOCRINE PROBLEMS IN THE MALE

BIOCHEMICAL TESTS FOR THE INVESTIGATION OF COMMON ENDOCRINE PROBLEMS IN THE MALE Authoriser: Moya O Doherty Page 1 of 7 BIOCHEMICAL TESTS FOR THE INVESTIGATION OF COMMON ENDOCRINE PROBLEMS IN THE MALE The purpose of this protocol is to describe common tests used for the investigation

More information

Take-Home Messages: Androgens

Take-Home Messages: Androgens Take-Home Messages: Androgens Anthony J. Bella MD, FRCSC Greta and John Hansen Chair in Men s Health Research Division of Urology, Department of Surgery University of Ottawa SUMMARY SLAMS Symposium Clinical

More information

Testosterone Therapy and the Prostate. Frans M.J. Debruyne Professor of Urology The Netherlands

Testosterone Therapy and the Prostate. Frans M.J. Debruyne Professor of Urology The Netherlands Testosterone Therapy and the Prostate Frans M.J. Debruyne Professor of Urology The Netherlands TRT- Risks Prostate ( Cancer, BPH )? Cardiac? Lipids? Polycythemia Sleep apnea Gynecomastia Edema Testosterone

More information

Prof Dato Dr TAN Hui Meng University of Malaya, Kuala Lumpur University of Pennsylvania, USA

Prof Dato Dr TAN Hui Meng University of Malaya, Kuala Lumpur University of Pennsylvania, USA Prof Dato Dr TAN Hui Meng University of Malaya, Kuala Lumpur University of Pennsylvania, USA Prevailing context Increase number of men who are potential candidates for Testosterone Replacement Therapy

More information

testosterone and LH concentrations in the morning ( hours) and evening ( hours).

testosterone and LH concentrations in the morning ( hours) and evening ( hours). Original Article SERUM TESTOSTERONE AND LH IN HEALTHY MEN BOYCE et al. Are published normal ranges of serum testosterone too high? Results of a cross-sectional survey of serum testosterone and luteinizing

More information

Men Getting Older Will Testosterone Keep Him Young?

Men Getting Older Will Testosterone Keep Him Young? Men Getting Older Will Testosterone Keep Him Young? Alvin M. Matsumoto, M.D. Associate Director, GRECC V.A. Puget Sound Health Care System Professor, Department of Medicine Division of Gerontology and

More information

Systematic Review & Course outline. Lecture (20%) Class discussion & tutorial (30%)

Systematic Review & Course outline. Lecture (20%) Class discussion & tutorial (30%) Systematic Review & Meta-analysisanalysis Ammarin Thakkinstian, Ph.D. Section for Clinical Epidemiology and Biostatistics Faculty of Medicine, Ramathibodi Hospital Tel: 02-201-1269, 02-201-1762 Fax: 02-2011284

More information

Benign Prostatic Hyperplasia. Jay Lee, MD, FRCSC Clinical Associate Professor University of Calgary

Benign Prostatic Hyperplasia. Jay Lee, MD, FRCSC Clinical Associate Professor University of Calgary Benign Prostatic Hyperplasia Jay Lee, MD, FRCSC Clinical Associate Professor University of Calgary Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied,

More information

Endocrine Update Mary T. Korytkowski MD Division of Endocrinology University of Pittsburgh

Endocrine Update Mary T. Korytkowski MD Division of Endocrinology University of Pittsburgh Endocrine Update 2016 Mary T. Korytkowski MD Division of Endocrinology University of Pittsburgh Disclosure of Financial Relationships Mary Korytkowski MD Honoraria British Medical Journal Diabetes Research

More information

R. Charles Welliver, Jr.,* Herbert J. Wiser, Robert E. Brannigan, Kendall Feia, Manoj Monga and Tobias S. K ohler

R. Charles Welliver, Jr.,* Herbert J. Wiser, Robert E. Brannigan, Kendall Feia, Manoj Monga and Tobias S. K ohler Sexual Function/Infertility Validity of Midday Total Testosterone Levels in Older Men with Erectile Dysfunction R. Charles Welliver, Jr.,* Herbert J. Wiser, Robert E. Brannigan, Kendall Feia, Manoj Monga

More information

Combination Drug Therapy for Benign Prostatic Hyperplasia (BPH)

Combination Drug Therapy for Benign Prostatic Hyperplasia (BPH) The Annals of African Surgery www.sskenya.org Combination Drug Therapy for Benign Prostatic Hyperplasia (BPH) Author: Oliech J.S. FRCS, Affiliation: Department of Surgery, University of Nairobi. P.O. Box

More information

Testosterone Therapy in Men with Hypogonadism

Testosterone Therapy in Men with Hypogonadism Testosterone Therapy in Men with Hypogonadism (Endocrine Society 2018 Guideline) Ngwe Yin, MD Assistant Clinical Professor of Medicine, UCSF Fresno Medical Education Program Disclosures None Objective

More information

GUIDELINES ON. Introduction. G.R. Dohle, S. Arver, C. Bettocchi, S. Kliesch, M. Punab, W. de Ronde

GUIDELINES ON. Introduction. G.R. Dohle, S. Arver, C. Bettocchi, S. Kliesch, M. Punab, W. de Ronde GUIDELINES ON Male Hypogonadism G.R. Dohle, S. Arver,. Bettocchi, S. Kliesch, M. Punab, W. de Ronde Introduction Male hypogonadism is a clinical syndrome caused by androgen deficiency. It may adversely

More information

Testosterone Injection / Implant

Testosterone Injection / Implant Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Testosterone Injection / Implant Page: 1 of 9 Last Review Date: December 5, 2014 Testosterone

More information

Sexual Dysfunction. Jae Il Kang, Byeong Kuk Ham, Mi Mi Oh, Je Jong Kim, Du Geon Moon. DOI: /kju

Sexual Dysfunction. Jae Il Kang, Byeong Kuk Ham, Mi Mi Oh, Je Jong Kim, Du Geon Moon.  DOI: /kju www.kjurology.org DOI:10.4111/kju.2011.52.6.416 Sexual Dysfunction Correlation between Serum Total Testosterone and the AMS and IIEF Questionnaires in Patients with Erectile Dysfunction with Testosterone

More information

Testosterone Replacement Therapy for Hypogonadism: Learning Objectives. What Is the Evidence? Is It Safe? Case Study. Case Study contd.

Testosterone Replacement Therapy for Hypogonadism: Learning Objectives. What Is the Evidence? Is It Safe? Case Study. Case Study contd. 4 4:4pm Testosterone Therapy: Examining the Evidence SPEAKER Culley Carson, MD Presenter Disclosure Information The following relationships exist related to this presentation: Culley Carson, MD: Consultant

More information

An Idea Whose Time Has Come-Male Health Programs: An Opportunity For Clinical Expansion and Better Health

An Idea Whose Time Has Come-Male Health Programs: An Opportunity For Clinical Expansion and Better Health An Idea Whose Time Has Come-Male Health Programs: An Opportunity For Clinical Expansion and Better Health KEVIN R. LOUGHLIN MD,MBA Harvard Medical School Boston, MA THE WEAKER SEX-MALES LIFE EXPECTANCY

More information

Cochrane Pregnancy and Childbirth Group Methodological Guidelines

Cochrane Pregnancy and Childbirth Group Methodological Guidelines Cochrane Pregnancy and Childbirth Group Methodological Guidelines [Prepared by Simon Gates: July 2009, updated July 2012] These guidelines are intended to aid quality and consistency across the reviews

More information

Male Menopause: Disease or Pseudoscience? March 4, 2015 story: FDA to require warning on labels of testosterone products.

Male Menopause: Disease or Pseudoscience? March 4, 2015 story: FDA to require warning on labels of testosterone products. Male Menopause: Disease or Pseudoscience? March 4, 2015 story: FDA to require warning on labels of testosterone products. 3-30-2015; web William E. Winter, MD University of Florida Departments of Pathology

More information

Testosterone treatment in the aging male: myth or reality?

Testosterone treatment in the aging male: myth or reality? Published 19 March 2012, doi:10.4414/smw.2012.13539 Cite this as: Testosterone treatment in the aging male: myth or reality? Nicole Nigro, Mirjam Christ-Crain Department of Endocrinology University Hospital

More information

Tobias S. Kohler, MD, MPH, FACS Southern Illinois University School of Medicine AUA SMSNA Program May 7, 2016

Tobias S. Kohler, MD, MPH, FACS Southern Illinois University School of Medicine AUA SMSNA Program May 7, 2016 Tobias S. Kohler, MD, MPH, FACS Southern Illinois University School of Medicine AUA SMSNA Program May 7, 2016 Abbvie Researcher/Consultant/Grant Funding Boston Scientific Researcher/Consultant/Grant Funding

More information

TRT and localized protate cancer

TRT and localized protate cancer TRT and localized protate cancer Frans M. J. Debruyne Professor of Urology PRISM BRUGES Increased risk of prostate cancer with TRT? Prostate cancer Testosterone and Prostate Cancer There appears to be

More information

Keywords: Position statement, expert opinion, hypogonadism, men, testosterone, calculated bioavailable testosterone

Keywords: Position statement, expert opinion, hypogonadism, men, testosterone, calculated bioavailable testosterone The Aging Male, December 2007; 10(4): 211 216 WORKSHOP REPORT Functional testosterone: Biochemical assessment of hypogonadism in men Report from a multidisciplinary workshop hosted by the Ontario Society

More information

Although the test that measures total prostate-specific antigen (PSA) has been

Although the test that measures total prostate-specific antigen (PSA) has been ORIGINAL ARTICLE STEPHEN LIEBERMAN, MD Chief of Urology Kaiser Permanente Northwest Region Clackamas, OR Effective Clinical Practice. 1999;2:266 271 Can Percent Free Prostate-Specific Antigen Reduce the

More information

Alpha-BlockerTherapy Can Be Withdrawn in the Majority of Men Following Initial CombinationTherapy with the Dual 5a-Reductase Inhibitor Dutasteride

Alpha-BlockerTherapy Can Be Withdrawn in the Majority of Men Following Initial CombinationTherapy with the Dual 5a-Reductase Inhibitor Dutasteride European Urology European Urology 44 (2003) 461 466 Alpha-BlockerTherapy Can Be Withdrawn in the Majority of Men Following Initial CombinationTherapy with the Dual 5a-Reductase Inhibitor Dutasteride J.

More information

Testosterone supplementation in the aging male: Which questions have been answered?

Testosterone supplementation in the aging male: Which questions have been answered? The Aging Male, March 2005; 8(1): 31 38 Testosterone supplementation in the aging male: Which questions have been answered? WALTER KRAUSE 1, ULRICH MUELLER 2, & ALLAN MAZUR 3 1 Department of Andrology,

More information

Introduction to systematic reviews/metaanalysis

Introduction to systematic reviews/metaanalysis Introduction to systematic reviews/metaanalysis Hania Szajewska The Medical University of Warsaw Department of Paediatrics hania@ipgate.pl Do I needknowledgeon systematicreviews? Bastian H, Glasziou P,

More information

Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy

Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy ORIGINAL ARTICLE Vol. 41 (6): 1167-1171, November. December, 2015 doi: 10.1590/S1677-5538.IBJU.2014.0528 Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy

More information

Hypogonadism 4/27/2018. Male Hypogonadism -- Definition. Epidemiology. Objectives HYPOGONADISM. Men with Hypogonadism. 95% untreated.

Hypogonadism 4/27/2018. Male Hypogonadism -- Definition. Epidemiology. Objectives HYPOGONADISM. Men with Hypogonadism. 95% untreated. Male Hypogonadism -- Definition - Low T, Low Testosterone Hypogonadism -...a clinical syndrome that results from failure of the testes to produce physiological concentrations of testosterone due to pathology

More information

Late onset Hypogonadism. Dr KhooSay Chuan Department of Urology Penang General Hospital

Late onset Hypogonadism. Dr KhooSay Chuan Department of Urology Penang General Hospital Late onset Hypogonadism Dr KhooSay Chuan Department of Urology Penang General Hospital Late onset hypogonadism(loh) Definition LOH age associated testoteronedeficiency syndrome (TDS) Male menopause, andropause,

More information

HHS Public Access Author manuscript Int J Impot Res. Author manuscript; available in PMC 2015 September 01.

HHS Public Access Author manuscript Int J Impot Res. Author manuscript; available in PMC 2015 September 01. Testosterone Therapy and Mortality Risk Michael L. Eisenberg, MD 1, Shufeng Li, MS 2, Danielle Herder, MD 3, Dolores J. Lamb, PhD 4, and Larry I. Lipshultz, MD 4 1 Assistant Professor, Departments of Urology

More information

What is indirect comparison?

What is indirect comparison? ...? series New title Statistics Supported by sanofi-aventis What is indirect comparison? Fujian Song BMed MMed PhD Reader in Research Synthesis, Faculty of Health, University of East Anglia Indirect comparison

More information

Therapeutic Strategies for Managing BPH Progression

Therapeutic Strategies for Managing BPH Progression european urology supplements 5 (2006) 997 1003 available at www.sciencedirect.com journal homepage: www.europeanurology.com Therapeutic Strategies for Managing BPH Progression John M. Fitzpatrick a, *,

More information

Testosterone Injection and Implant

Testosterone Injection and Implant Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.33 Subject: Testosterone Injection Implant Page: 1 of 10 Last Review Date: December 8, 2017 Testosterone

More information

Cochrane Bone, Joint & Muscle Trauma Group How To Write A Protocol

Cochrane Bone, Joint & Muscle Trauma Group How To Write A Protocol A p r i l 2 0 0 8 Cochrane Bone, Joint & Muscle Trauma Group How To Write A Protocol This booklet was originally produced by the Cochrane Renal Group to make the whole process of preparing a protocol as

More information

Significance of Serum Testosterone for Prostate-Specific Antigen (PSA) Elevation and Prediction of Prostate Cancer in Patients with PSA Above 10 ng/ml

Significance of Serum Testosterone for Prostate-Specific Antigen (PSA) Elevation and Prediction of Prostate Cancer in Patients with PSA Above 10 ng/ml www.kjurology.org DOI:10.111/kju.010.51.1.81 Urological Oncology Significance of Serum Testosterone for Prostate-Specific Antigen (PSA) Elevation and Prediction of Prostate Cancer in Patients with PSA

More information

The reality of LOH-symptoms

The reality of LOH-symptoms The reality of LOH-symptoms PRISM IV Bruges, Belgium September 25-26, 2014 Dr. Herman Leliefeld Androsmannenkliniek The Netherlands The reality of LOH symptoms male external & internal genitalia Testosterone

More information

The QUOROM Statement: revised recommendations for improving the quality of reports of systematic reviews

The QUOROM Statement: revised recommendations for improving the quality of reports of systematic reviews The QUOROM Statement: revised recommendations for improving the quality of reports of systematic reviews David Moher 1, Alessandro Liberati 2, Douglas G Altman 3, Jennifer Tetzlaff 1 for the QUOROM Group

More information

Meta-analyses: analyses:

Meta-analyses: analyses: Meta-analyses: analyses: how do they help, and when can they not? Lee Hooper Senior Lecturer in research synthesis & nutrition l.hooper@uea.ac.uk 01603 591268 Aims Systematic Reviews Discuss the scientific

More information

School of Dentistry. What is a systematic review?

School of Dentistry. What is a systematic review? School of Dentistry What is a systematic review? Screen Shot 2012-12-12 at 09.38.42 Where do I find the best evidence? The Literature Information overload 2 million articles published a year 20,000 biomedical

More information

Testosterone Injection and Implant

Testosterone Injection and Implant Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.33 Subject: Testosterone Injection Implant Page: 1 of 10 Last Review Date: November 30, 2018 Testosterone

More information

MALE HYPOGONADISM: CHOOSING THE APPROPRIATE THERAPY. Michael S. Irwig, M.D. Director, Center for Andrology Division of Endocrinology & Metabolism

MALE HYPOGONADISM: CHOOSING THE APPROPRIATE THERAPY. Michael S. Irwig, M.D. Director, Center for Andrology Division of Endocrinology & Metabolism MALE HYPOGONADISM: CHOOSING THE APPROPRIATE THERAPY Michael S. Irwig, M.D. Director, Center for Andrology Division of Endocrinology & Metabolism Disclosures Aromatase inhibitors & clomiphene citrate are

More information

Agomelatine versus placebo: A meta-analysis of published and unpublished trials

Agomelatine versus placebo: A meta-analysis of published and unpublished trials Agomelatine versus placebo: A meta-analysis of published and unpublished trials (Protocol for a systematic review, Ulm, January 17, 2011) Markus Kösters, Andrea Cipriani, Giuseppe Guaiana, Thomas Becker

More information

Testosterone Oral Buccal Nasal. Android, Androxy, Methitest, Natesto, Striant, Testred. Description

Testosterone Oral Buccal Nasal. Android, Androxy, Methitest, Natesto, Striant, Testred. Description 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.32 Subject: Testosterone Oral Buccal Nasal Page: 1 of 10 Last Review Date: March 17, 2017 Testosterone Oral Buccal Nasal Description

More information

Testosterone Injection and Implant

Testosterone Injection and Implant Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.33 Subject: Testosterone Injection Implant Page: 1 of 10 Last Review Date: March 17, 2017 Testosterone

More information

Cancer. Description. Section: Surgery Effective Date: October 15, 2016 Subsection: Original Policy Date: September 9, 2011 Subject:

Cancer. Description. Section: Surgery Effective Date: October 15, 2016 Subsection: Original Policy Date: September 9, 2011 Subject: Subject: Saturation Biopsy for Diagnosis, Last Review Status/Date: September 2016 Page: 1 of 9 Saturation Biopsy for Diagnosis, Description Saturation biopsy of the prostate, in which more cores are obtained

More information

Serum Prostate-Specific Antigen as a Predictor of Prostate Volume in the Community: The Krimpen Study

Serum Prostate-Specific Antigen as a Predictor of Prostate Volume in the Community: The Krimpen Study european urology 51 (2007) 1645 1653 available at www.sciencedirect.com journal homepage: www.europeanurology.com Benign Prostatic Hyperplasia Serum Prostate-Specific Antigen as a Predictor of Prostate

More information

Testosterone Replacement Therapy & Monitoring in HIV Infected Men. Adam B. Murphy, MD, MBA, MSCI October 29, 2014

Testosterone Replacement Therapy & Monitoring in HIV Infected Men. Adam B. Murphy, MD, MBA, MSCI October 29, 2014 Testosterone Replacement Therapy & Monitoring in HIV Infected Men Adam B. Murphy, MD, MBA, MSCI October 29, 2014 Acknowledgement Ramona Bhatia MD (HIV Research Fellow, First Author) Chad Achenbach MD (HIV

More information

Evaluating the results of a Systematic Review/Meta- Analysis

Evaluating the results of a Systematic Review/Meta- Analysis Open Access Publication Evaluating the results of a Systematic Review/Meta- Analysis by Michael Turlik, DPM 1 The Foot and Ankle Online Journal 2 (7): 5 This is the second of two articles discussing the

More information

Testosterone Oral Buccal Nasal. Android, Androxy, Methitest, Natesto, Striant, Testred. Description

Testosterone Oral Buccal Nasal. Android, Androxy, Methitest, Natesto, Striant, Testred. Description 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.32 Subject: Testosterone Oral Buccal Nasal Page: 1 of 10 Last Review Date: November 30, 2018 Testosterone Oral Buccal Nasal

More information

Testosterone Oral Buccal Nasal. Android, Androxy, Methitest, Natesto, Striant, Testred. Description

Testosterone Oral Buccal Nasal. Android, Androxy, Methitest, Natesto, Striant, Testred. Description 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.32 Subject: Testosterone Oral Buccal Nasal Page: 1 of 10 Last Review Date: June 24, 2016 Testosterone Oral Buccal Nasal Description

More information

CHAPTER 6. M.D. Eckhardt, G.E.P.M. van Venrooij, T.A. Boon. hoofdstuk :49 Pagina 89

CHAPTER 6. M.D. Eckhardt, G.E.P.M. van Venrooij, T.A. Boon. hoofdstuk :49 Pagina 89 hoofdstuk 06 19-12-2001 09:49 Pagina 89 Urethral Resistance Factor (URA) Versus Schäfer s Obstruction Grade and Abrams-Griffiths (AG) Number in the Diagnosis of Obstructive Benign Prostatic Hyperplasia

More information

Testosterone and the Prostate

Testosterone and the Prostate Testosterone and the Prostate E. David Crawford, MD Professor of Surgery (Urology) and Radiation Oncology Head, Urologic Oncology E. David and Vicki M. Crawford Endowed Chair in Urologic Oncology University

More information

Cochrane Breast Cancer Group

Cochrane Breast Cancer Group Cochrane Breast Cancer Group Version and date: V3.2, September 2013 Intervention Cochrane Protocol checklist for authors This checklist is designed to help you (the authors) complete your Cochrane Protocol.

More information

PROTOCOL. Francesco Brigo, Luigi Giuseppe Bongiovanni

PROTOCOL. Francesco Brigo, Luigi Giuseppe Bongiovanni COMMON REFERENCE-BASED INDIRECT COMPARISON META-ANALYSIS OF INTRAVENOUS VALPROATE VERSUS INTRAVENOUS PHENOBARBITONE IN GENERALIZED CONVULSIVE STATUS EPILEPTICUS PROTOCOL Francesco Brigo, Luigi Giuseppe

More information

Can men on AS be treated with testosterone?

Can men on AS be treated with testosterone? Can men on AS be treated with testosterone? Professor Bertrand Tombal, MD, PhD Cliniques universitaires Saint-Luc Université catholique de Louvain Brussels, Belgium Conflicts of interest PI or member steering

More information

Screening for prostate cancer (Review)

Screening for prostate cancer (Review) Ilic D, Neuberger MM, Djulbegovic M, Dahm P This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 1 http://www.thecochranelibrary.com

More information

Meta Analysis. David R Urbach MD MSc Outcomes Research Course December 4, 2014

Meta Analysis. David R Urbach MD MSc Outcomes Research Course December 4, 2014 Meta Analysis David R Urbach MD MSc Outcomes Research Course December 4, 2014 Overview Definitions Identifying studies Appraising studies Quantitative synthesis Presentation of results Examining heterogeneity

More information

Disclosures. Learning Objectives. Effects of Hormone Therapy on the Metabolic Syndrome and Cardiovascular Disease. None

Disclosures. Learning Objectives. Effects of Hormone Therapy on the Metabolic Syndrome and Cardiovascular Disease. None Effects of Hormone Therapy on the Metabolic Syndrome and Cardiovascular Disease Micol S. Rothman, MD Associate Professor of Medicine Endocrinology, Diabetes and Metabolism Clinical Director Metabolic Bone

More information

Literature Scan: Drugs for BPH

Literature Scan: Drugs for BPH Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119

More information

PROSPERO International prospective register of systematic reviews

PROSPERO International prospective register of systematic reviews PROSPERO International prospective register of systematic reviews High-dose chemotherapy followed by autologous haematopoietic cell transplantation for children, adolescents and young adults with first

More information

α-blocker Monotherapy and α-blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia; 10 Years Long-Term Results

α-blocker Monotherapy and α-blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia; 10 Years Long-Term Results www.kjurology.org http://dx.doi.org/10.4111/kju.2012.53.4.248 Voiding Dysfunction α-blocker Monotherapy and α-blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia;

More information

/04/ /0 Reprinted from Vol. 172, , August 2004 THE JOURNAL OF UROLOGY

/04/ /0 Reprinted from Vol. 172, , August 2004 THE JOURNAL OF UROLOGY 0022-5347/04/1722-0658/0 Reprinted from Vol. 172, 658 663, August 2004 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright 2004 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000132389.97804.d7

More information

Supplementary Online Content

Supplementary Online Content Supplementary Online Content Tsai WC, Wu HY, Peng YS, et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with chronic kidney disease: a systematic

More information

Systematic reviews and meta-analyses of observational studies (MOOSE): Checklist.

Systematic reviews and meta-analyses of observational studies (MOOSE): Checklist. Systematic reviews and meta-analyses of observational studies (MOOSE): Checklist. MOOSE Checklist Infliximab reduces hospitalizations and surgery interventions in patients with inflammatory bowel disease:

More information