Antti Kaipia

Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST Study)

INTRODUCTION Addition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels. AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant. METHODS A multicenter, multinational, double-blind, placebo-controlled study of 173 men, 45-80 years, nonresponders to treatment with different PDE5-Is, with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double-blind, placebo-controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory. Main Outcomes Measures.  Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question). RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5-Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5-I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤ 3 ng/mL.

Chemical castration and anti-androgens induce differential gene expression in prostate cancer.

Endocrine therapy by castration or anti‐androgens is the gold standard treatment for advanced prostate cancer. Although it has been used for decades, the molecular consequences of androgen deprivation are incompletely known and biomarkers of its resistance are lacking. In this study, we studied the molecular mechanisms of hormonal therapy by comparing the effect of bicalutamide (anti‐androgen), goserelin (GnRH agonist) and no therapy, followed by radical prostatectomy. For this purpose, 28 men were randomly assigned to treatment groups. Freshly frozen specimens were used for gene expression profiling for all known protein‐coding genes. An in silico Bayesian modelling tool was used to assess cancer‐specific gene expression from heterogeneous tissue specimens. The expression of 128 genes was > two‐fold reduced by the treatments. Only 16% of the altered genes were common in both treatment groups. Of the 128 genes, only 24 were directly androgen‐regulated genes, according to re‐analysis of previous data on gene expression, androgen receptor‐binding sites and histone modifications in prostate cancer cell line models. The tumours containing TMPRSS2–ERG fusion showed higher gene expression of genes related to proliferation compared to the fusion‐negative tumours in untreated cases. Interestingly, endocrine therapy reduced the expression of one‐half of these genes and thus diminished the differences between the fusion‐positive and ‐negative samples. This study reports the significantly different effects of an anti‐androgen and a GnRH agonist on gene expression in prostate cancer cells. TMPRSS2‐ERG fusion seems to bring many proliferation‐related genes under androgen regulation. Copyright

High-Intensity Physical Activity, Stable Relationship, and High Education Level Associate with Decreasing Risk of Erectile Dysfunction in 1,000 Apparently Healthy Cardiovascular Risk Subjects

INTRODUCTION Erectile dysfunction (ED) is especially common in men with cardiovascular diseases (CVDs). However, the data are scarce concerning populations without manifested CVD. AIM The aim of this study was to describe factors associated with ED, especially those associated with decreasing risk of ED, in men with cardiovascular risk factors but without CVD, diabetes, or chronic renal disease. METHODS In 2004 to 2007, a cross-sectional population-based sample of men 45 to 70 years old in two rural towns in Finland was collected. Men with previously diagnosed CVD, diabetes, or kidney disease were not invited to the study. In total 1,000 eligible men with cardiovascular risk factors, i.e., central obesity, high scores in the Finnish Diabetes Risk Score, high blood pressure, antihypertensive medication, or family history of coronary heart disease, myocardial infarction, or stroke, were included in the analysis. Questionnaires, clinical measurements, and laboratory tests were obtained. The prevalence of ED was studied comparing the means, and risk factors were studied using multivariate logistic regression analysis. MAIN OUTCOME MEASURES The rate of ED was defined by the International Index of Erectile Function short form (IIEF-5) and by two questions (2Q) about the ability to achieve and to maintain an erection. RESULTS The prevalence of ED was 57% or 68% using IIEF-5 or 2Q, respectively. Age (odds ratio [OR]: up to 9.16; 95% confidence interval [CI], 5.00-16.79; P < 0.001), smoking (OR: 1.41; 95% CI, 1.04-1.91; P = 0.028), depressive symptoms (OR: 4.04 for moderate and severe; 95% CI,1.22-13.45; P = 0.001), high-intensity physical activity (OR: 0.50; 95% CI, 0.29-0.86; P = 0.045), high education (OR: 0.52; 95% CI, 0.33-0.83; P = 0.013), and stable relationship (OR: 0.43; 95% CI, 0.21-0.88; P = 0.046) were associated with ED. CONCLUSIONS In apparently healthy men with cardiovascular risk factors, decreasing risk of ED is associated with high-intensity physical activity, stable relationship, and high education level.

Goserelin and bicalutamide treatments alter the expression of microRNAs in the prostate.

Although endocrine therapy has been used for decades, its influence on the expression of microRNAs (miRNAs) in clinical tissue specimens has not been analyzed. Moreover, the effects of the TMPRSS2:ERG fusion on the expression of miRNAs in hormone naïve and endocrine‐treated prostate cancers are poorly understood.

Expression of Luteinizing Hormone Receptors in the Mouse Penis

The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of the present study is to investigate the expression of the LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting, and quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at M(r) = 97.4 and 78 kd. Quantitative RT-PCRs confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis; thus, it may directly regulate functions of penile tissue.

Penile cancer in Scandinavia: Current practice and future perspectives

Department of Urology, Aarhus University Hospital, Aarhus, Denmark, Department of Urology, Copenhagen University Hospital, Copenhagen, Denmark, Department of Urology, Orebro University Hospital, Orebro, Sweden, Department of Urology, Skane University Hospital, Malmo€, Sweden, Department of Surgery, Satakunta Central Hospital, Pori, Finland, Department of Urology, Helsinki University Hospital, Helsinki, Finland, Department of Surgery, St. Olavs University Hospital of Trondheim, Norway, Department of Urology, Haukeland University Hospital, Bergen, Norway, and Surgical Division, The National University Hospital of Iceland, Reykjavik, Iceland

Stage-specific mortality and survival trends of prostate cancer patients in Finland before and after introduction of PSA

Abstract Background: The early diagnosis and right treatment strategy of localized prostate cancer (PCa) remains problematic. In order to characterize the survival of PCa patients, we compared patients’ all-cause and cancer-specific mortalities between pre- and post-PSA periods by stage in Finland. Material and methods: All PCa cases diagnosed in Finland between 1985 and 2013 (N = 91,329) were identified from the Finnish Cancer Registry (FCR). PCa stage at diagnosis was defined as localized, local node positive or metastasized. Standardized mortality ratios (SMRs), and relative and cause-specific survival were assessed by stage and introduction of PSA testing. The main limitation was the high proportion of men with unknown stage (28%). Results: A clear decreasing trend in the SMR of PCa patients was evident when pre- and post-PSA eras were compared: for localized PCa, the SMR was 1.43 (95%CI 1.38–1.48) in 1985–1989 and 0.98 (95%CI 0.95–1.01) in 2000–2004, and for metastasized PCa, the SMRs were 4.51 (95%CI 4.30–4.72) and 3.01 (95%CI 2.89–3.12), respectively. Difference between cause-specific and relative survival was pronounced in localized PCa in post-PSA period: 10-year relative survival was 94.6% (95%CI 91.4–97.8) and cause-specific 84.2% (95%CI 82.9–85.5%). In metastasized PCa the difference was not that significant. Conclusions: From 1985 to 2009, the SMR among men diagnosed with PCa decreased significantly in Finland. Among men with localized PCa, the SMR decreased even below that of the Finnish male population. This and the increased difference between relative and cause-specific survival reflects most likely selection of men to opportunistic PSA testing. The results highlight the importance of caution in the use of PSA testing in healthy men.

Management of Prolonged Urinary Leakage at the Urethro-Vesical Anastomosis

Urinary leakage at the urethrovesical anastomosis is a rare but troublesome complication after radical prostatectomy. Usually, the anastomosis is almost watertight when tested during the operation and small leakages typically seal off in a few days. We describe 3 cases with postoperative urinary leakage where we have utilized a simple procedure of replacing the standard Foley catheter with another catheter with extra side fenestrations close to the anastomosis. Side fenestrations provide efficient drainage at the anastomosis area leading to a rapid resolution of the leakage. The method described represents an effective and low-risk solution to a potentially harmful complication.

Erectile dysfunction cannot be used in primary screening of pre-diabetes.

We hypothesized that erectile dysfunction is associated with impaired fasting glucose and impaired glucose tolerance and could be used in primary screening of pre-diabetes. Although erectile dysfunction is known to be closely associated with diabetes, we demonstrate that it is not associated with pre-diabetes in 926 apparently healthy men.

Side-fenestrated catheter decreases leakage at the urethrovesical anastomosis after robot-assisted laparoscopic radical prostatectomy.

Abstract Objective. The aim of this study was to analyse whether a side-fenestrated urinary catheter can decrease the frequency of anastomotic leakage after robot-assisted laparoscopic radical prostatectomy (RALP). Material and methods. Two-hundred and fifty patients with localized prostate cancer undergoing RALP were randomized into standard and side-fenestrated catheter groups in a prospective randomized study. The catheter was fenestrated at the site of the anastomosis to improve drainage. A cystogram was taken at 7 ± 2 days postoperatively to verify the watertightness of the anastomosis. The patients were monitored for 3 months. Results. The study included 106 patients with the standard and 108 patients with the fenestrated catheter. Leakage at the urethrovesical anastomosis was found in 13/106 (12.3%) of the standard and 5/108 (4.6%) of the side-fenestrated catheter patients (p = 0.044). Discomfort induced by the catheter and urinary leakage beside the catheter did not differ between the groups. The clinical and pathological characteristics and complications were equal between the groups. Conclusions. The side-fenestrated catheter decreased leakage rates at the urethrovesical anastomosis after RALP.