To identify and characterize the most frequently cited articles published in Journals dedicated to Urology over the last 50 years. A Pubmed search was performed of all articles published in the 13 most cited urological journals between 1955 and 2009. Articles with more than 100 citations were identified as "classic", and were analyzed further. Of 97 554 articles published during this time, 1239 articles were cited more than 100 times. The most common topic among classic articles was prostate cancer and prostate-specific antigen (33.5%), followed by bladder cancer and benign prostatic hyperplasia. A further analysis was performed for the 50 most frequently cited articles ("top-50").

Androgen deprivation therapy reduces prostate cancer (PCa) tumour growth; however, disease relapse often ensues independently of androgen stimulation, producing androgen-refractory tumours with increased invasion, proliferation, and malignancy. Androgens downregulate epidermal growth factor receptor (EGFR) in normal prostate but not in PCa. Thus, loss of EGFR regulation and altered signalling may, in part, explain the transition of prostate tumours from androgen dependent to androgen independent. Studies in animal models, PCa cell lines, and tumour specimens suggest that androgens modulate prostate growth and function through mechanisms that involve 'cross-talk' between androgen receptor (AR) and growth factor receptor signalling pathways. The objective of this review is to discuss the paradoxical relationship between androgen regulation of EGFR in normal prostate and PCa. We reviewed the literature from mid-1980s through 2009 to assess the relationship between androgens and EGFR function in modulating the growth of normal prostate and PCa. Loss of androgen regulation of EGFR in PCa may be responsible for increased tumour growth, invasion, and metastasis, with important implications on the clinical management of PCa. We advance the hypothesis that a molecular switch, responsible for downregulating EGFR expression by androgens in the normal prostate, is either lost or modified in PCa.British Journal of Cancer advance online publication, 3 November 2009; doi:10.1038/sj.bjc.6605376 www.bjcancer.com.

Background. Current screening instruments for hypogonadism lack adequate specificity and diagnostic accuracy. A new self-administered questionnaire of hypogonadism symptoms is being developed to address this need. The process for questionnaire development and results from the first (qualitative) phase are presented. Methods. Qualitative interviews were conducted based on a new conceptual model of hypogonadism and according to standards for questionnaire development. An item pool was generated from focus groups and in-depth interviews with two groups of hypogonadal patients, treated (N = 26) and untreated (N = 26), and age-equivalent controls (N = 28). Standardized scoring of the qualitative interviews was used to confirm conceptual domains in the model and to generate questionnaire items for further validation. Results. Key domains identified in both patients and controls included:(a) physical function;(b) bodily signs and symptoms;(c) sexual function and libido;(d) sleep function;(e) mood and affective function;(f) memory and cognitive function. The final domain is distress or bother associated with hypogonadism symptoms. This domain was only relevant to the patient groups. Conclusions. The first stage in the design of a new hypogonadism screener has been completed. Seven domains were identified and draft items were developed in each domain according to current standards of patient-reported outcomes.

ABSTRACT Introduction. The most widely used method for measuring free testosterone (FT) is by analog immunoassay (aFT); however, this assay has been criticized as unreliable based on laboratory studies in small groups of men. Calculated FT (cFT), derived from total testosterone (TT) and sex-hormone binding globulin (SHBG) values has been recommended in its place. There are limited data comparing aFT and cFT in clinical populations. Aim. The purpose of this study was to compare aFT with cFT in a population of ambulatory men in a clinical setting. Methods. Medical records were reviewed for 100 randomly selected men in a urology practice, yielding 140 test results complete for TT, aFT, and SHBG. Calculated FT was determined via an online calculator. Comparisons were made with Pearson rank coefficients. Main Outcome Measures. Pearson rank correlation between aFT and cFT. Results. Mean patient age was 52.3 +/- 14.3 years (range 24-80). Mean TT was 443.0 +/- 208.3 ng/dL (range 110-1276). Mean aFT was 1.22 +/- 0.54 ng/dL (range 0.24-3.8) and mean cFT 9.4 +/- 4.5 ng/dL (range 1.8-27.8). Mean SHBG was 34.2 +/- 19.5 nmol/L (range 9-127). A strong correlation was observed for aFT and cFT (r = 0.88, P < 0.0001), particularly at low concentrations. Significant correlations were also noted between aFT and TT (r = 0.73, P < 0.0001), and between cFT and TT (r = 0.82, P < 0.0001). Numerical values for aFT were approximately one-eighth of the values obtained for cFT. Neither aFT nor cFT correlated with SHBG. Conclusions. A strong correlation was observed between aFT and cFT in this clinical population of ambulatory men. Different sets of reference values must be applied for each of these tests. Moreno SA, Shyam A, and Morgentaler A. Comparison of free testosterone results by analog radioimmunoassay and calculated free testosterone in an ambulatory clinical population. J Sex Med **;**:**-**.

There has been a recent dramatic shift in our understanding of the relationship between androgens and prostate cancer (PCa). Whereas for several decades it had been assumed that higher serum testosterone (T) concentrations would lead to ever-greater PCa growth, current literature indicates that PCa growth is unaffected by changes in serum T throughout most of the naturally occurring range. A Saturation Model has been proposed to explain how prostate tissue can be exquisitely sensitive to changes in serum T at the very low end of the concentration range, but appears indifferent to such changes above the near-castrate range. This has special applicability to T-deficient men, since this means that T therapy may not be nearly as risky as once assumed. Indeed, one of the more interesting changes over the last several years has been the growing acceptance of the use of T therapy in men with a prior history of PCa, with early data indicating minimal risk of cancer recurrence or progression. Provocative new evidence suggests that it is not high serum T that is problematic for PCa, but low serum T that is associated with worrisome cancer features and outcomes, such as high Gleason score, advanced stage of presentation, and increased risk of biochemical recurrence after surgery. It will be interesting to see what changes will occur in this rapidly changing field over the next several years.

ABSTRACT Introduction. As testosterone (T) has been shown to influence wound healing, and serum T declines in the age group at risk for Peyronie's disease (PD), we explored the possibility that low serum T may be associated with PD. Aim. The purpose of this study was to evaluate the relationship between serum T concentrations and features of PD. Methods. Medical records were reviewed for 121 consecutive patients with PD seen over a 2-year period. All patients were assessed for sociodemographic data, medical history, comorbid medical conditions, findings on physical examination, and severity of curvature. Laboratory testing included serum concentrations of total testosterone (TT) and free testosterone (FT). Testosterone deficiency (TD) was defined as TT values less than 300 ng/dL and/or FT less than 1.5 ng/dL. Main Outcome Measures. Prevalence of TD in men with PD and correlation of TT and FT with severity of curvature and plaque size. Results. Mean patient age was 53.9 +/- 10.6 years (range 28-77). Penile curvature was 50.2 +/- 23.6 degrees (range 10-120). Mean TT was 411.6 +/- 203.6 ng/dL (range 69-877), and mean FT was 1.12 +/- 0.58 ng/dL (range 0.13-5.06). Low T was identified in 29.5% by TT alone and in 74.4% overall. Severity of curvature was greater for men with TD compared with men with normal T (54.3 vs. 37.1 degrees, P = 0.006). Men with low FT had greater penile curvature than men with normal FT (37.5 vs. 55.9 degrees, respectively, P = 0.003). Severity of penile curvature correlated significantly with FT (r =-0.314, P = 0.016) and estradiol/T (r = 0.476, P = 0.0001) but not TT (r =-0.199, P = 0.138). Conclusions. This pilot study suggests a possibly important relationship between low T and PD. Further prospective studies are needed to confirm this relationship. Moreno SA, and Morgentaler A. Testosterone deficiency and Peyronie's disease: Pilot data suggesting a significant relationship. J Sex Med **;**:**-**.

CONTEXT: Androgens are vital for growth and maintenance of the prostate; however, the notion that pathologic prostate growth, benign or malignant, can be stimulated by androgens is a commonly held belief without scientific basis. Therefore, the current prostatic guidelines for testosterone therapy (TT) appear to be overly restrictive and should be reexamined. OBJECTIVE: To review the literature addressing the possible relationship between testosterone and prostate cancer (PCa) and to summarize the main aspects of this issue. EVIDENCE ACQUISITION: A Medline search was conducted to identify original articles, review articles, and editorials addressing the relationship between testosterone and the risk of PCa development, as well as the impact of TT on PCa development and its natural history in men believed to be cured by surgery or radiation. EVIDENCE SYNTHESIS: Serum androgen levels, within a broad range, are not associated with PCa risk. Conversely, at time of PCa diagnosis, low rather than high serum testosterone levels have been found to be associated with advanced or high-grade disease. The available evidence indicates that TT neither increases the risk of PCa diagnosis nor affects the natural history of PCa in men who have undergone definitive treatment without residual disease. These findings can be explained with the saturation model (which states that prostatic homeostasis is maintained by a relatively low level of androgenic stimulation) and with the observation that exogenous testosterone administration does not significantly increase intraprostatic androgen levels in hypogonadal men. It must, however, be recognized that the literature remains limited regarding the effect of TT on PCa risk. Nonetheless, the current European Association of Urology guidelines state that in hypogonadal men who were successfully treated for PCa, TT can be considered after a prudent interval. CONCLUSIONS: Although no controlled studies have yet been performed and there is a paucity of long-term data, the available literature strongly suggests that TT neither increases the risk of PCa diagnosis in normal men nor causes cancer recurrence in men who were successfully treated for PCa. Large prospective studies addressing the long-term effect of TT are needed to either refute or corroborate these hypotheses.

INTRODUCTION: Testosterone (T) therapy has long been considered contraindicated in men with prostate cancer (PCa). However, the traditional view regarding the relationship of T to PCa has come under new scrutiny, with recent reports suggesting that PCa growth may not be greatly affected by variations in serum T within the near-physiologic range. AIM: This report details the clinical and prostate-specific antigen (PSA) response of a man with untreated PCa treated with T therapy for 2 years. METHODS: Measurements of serum PSA, total and free T concentrations were obtained at regular intervals at baseline and following initiation of T therapy. MAIN OUTCOME MEASURE: Serum PSA during T therapy. RESULTS: An 84-year-old man was seen for symptoms of hypogonadism, with serum total T within the normal range at 400 ng/dL, but with a reduced free T of 7.4 pg/mL (radioimmunoassay [RIA], reference range 10.0-55.0). PSA was 8.5 ng/mL, and 8.1 ng/mL when repeated. Prostate biopsy revealed Gleason 6 cancer in both lobes. He refused treatment for PCa, but requested T therapy, which was initiated with T gel after informed consent regarding possible cancer progression. Serum T increased to a mean value of 699 ng/dL and free T to 17.1 pg/mL. PSA declined to a nadir of 5.2 ng/mL at 10 months, increased slightly to 6.2 ng/mL at 21 months, and then declined to 3.8 ng/mL at 24 months after addition of dutasteride for voiding symptoms. No clinical PCa progression was noted. CONCLUSION: A decline in PSA was noted in a man with untreated PCa who received T therapy for 2 years. This case provides support for the notion that PCa growth may not be adversely affected by changes in serum T beyond the castrate or near-castrate range.

PURPOSE: Pertinent literature regarding the potential use of testosterone therapy in men with prostate cancer is reviewed and synthesized. MATERIALS AND METHODS: A literature search was performed of English language publications on testosterone administration in men with a known history of prostate cancer and investigation of the effects of androgen concentrations on prostate parameters, especially prostate specific antigen. RESULTS: The prohibition against the use of testosterone therapy in men with a history of prostate cancer is based on a model that assumes the androgen sensitivity of prostate cancer extends throughout the range of testosterone concentrations. Although it is clear that prostate cancer is exquisitely sensitive to changes in serum testosterone at low concentrations, there is considerable evidence that prostate cancer growth becomes androgen indifferent at higher concentrations. The most likely mechanism for this loss of androgen sensitivity at higher testosterone concentrations is the finite capacity of the androgen receptor to bind androgen. This saturation model explains why serum testosterone appears unrelated to prostate cancer risk in the general population and why testosterone administration in men with metastatic prostate cancer causes rapid progression in castrated but not hormonally intact men. Worrisome features of prostate cancer such as high Gleason score, extracapsular disease and biochemical recurrence after surgery have been reported in association with low but not high testosterone. In 6 uncontrolled studies results of testosterone therapy have been reported after radical prostatectomy, external beam radiation therapy or brachytherapy. In a total of 111 men 2 (1.8%) biochemical recurrences were observed. Anecdotal evidence suggests that testosterone therapy does not necessarily cause increased prostate specific antigen even in men with untreated prostate cancer. CONCLUSIONS: Although no controlled studies have been performed to date to document the safety of testosterone therapy in men with prostate cancer, the limited available evidence suggests that such treatment may not pose an undue risk of prostate cancer recurrence or progression.