Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population P.N. Mukhopadhyaya1, A. Acharya1, Y. Chavan1, S.S. Purohit1 and A. Mutha2 1Medical Genetics Division, geneOmbio Technologies, Pashan, Pune, Maharashtra, India2Diabetes Care and Research Foundation, Rasta Peth, Pune,
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Stesura sevesoComparison of tamsulosin vs tamsulosin/sildenafil
effectiveness in the treatment of erectile dysfunction
in patients affected by type III chronic prostatitis
Ubaldo Cantoro, Francesco Catanzariti, Vito Lacetera, Luigi Quaresima,
Giovanni Muzzonigro, Massimo Polito
Institute of Urology, Polytechnic University of Marche, Azienda O.U. Ospedali Riuniti, Ancona, Italy.
Aim: We evaluated the effectiveness of tamsulosin monotherapy versus tamsulosin plus
sildenafil combination therapy on erectile dysfunction (ED) in young patients with type
III chronic prostatitis and ED by using symptom score scales.
Materials and methods: 44 male patients were divided into 2 groups: the first group
(20 patients) was treated with tamsulosin 0,4 mg monotherapy and the second one
(24 patients) was treated with tamsulosin 0,4 mg plus sildenafil 50 mg combination therapy.
"International Prostate Symptom Score" (IPSS), "National Institute of Health Chronic Prostatitis
Symptom Index" (NIH-CPSI) and "International Index of Erectile Function" (IIEF-5) were inves-
tigated in each group of patients, and scores calculated during the first medical examination. Both
groups were treated with tamsulosin once daily for 60 days, while sildenafil 50 mg was given on
demand (at least 2 times per week) for 60 days. During the second medical examination IPSS,
NIH-CPSI and IIEF-5 scores were analyzed once more. Afterwards, the alterations of scores
among medical examinations in each group and between both groups were statistically compared.
Results: The age average of the 44 cases included was 32.04 ± 3.15 years. Both groups present a
statistically significant decrease, between the first and the second medical examination, in IPSS,
NIH-CPSI scores and statistically significant increase in IIEF-5 score. In addition, there is no sta-
tistically significant difference, in all scores, between mono and combination therapy.
Conclusions: tamsulosin monotherapy, as well as a combination therapy (tamsulosin plus silde-
nafil) has an improving effect on symptoms and on ED in patients with type III prostatitis. In the
near future alpha-blockers monotherapy could be used in the treatment of chronic prostatitis and
ED cases instead of phosphodiesterase type 5 (PDE-5) inhibitors combination therapy.
KEY WORDS: Chronic prostatitis; Erectile dysfunction; Tamsulosin; Sildenafil.
Submitted 8 April 2013; Accepted 30 April 2013 No conflict of interest declared INTRODUCTION
The aim of this study is to evaluate the effectiveness of
abdominal, pelvic, genital pain, obstructive or irritative tamsulosin in patients affected by Low Urinary Tract LUTS and by the absence of urinary tract infection (1).
Symptoms (LUTS) and erectile dysfunction (ED), and Many studies showed its association with painful prema- also to compare this monotherapy with one combined ture ejaculation and with erectile dysfunction. CP/CPPS with sildenafil, belonging to phosphodiesterase type 5 occurs frequently in young patients and is one of the organ- (PDE-5) inhibitors drug class, which are the recom- ic causes of erectile dysfunction (ED) in this age range. mended first-line treatment for ED.
Therefore, a common pathogenic mechanism for these Type III chronic prostatitis or Chronic prostatitis/chronic two diseases is likely to exist (2).
pelvic pain syndrome (CP/CPPS) is characterized by Adult-old patients LUTS affected have two times higher Archivio Italiano di Urologia e Andrologia 2013; 85, 3 U. Cantoro, F. Catanzariti, V. Lacetera, L. Quaresima, M. Giovanni, M. Polito risk to develop ED, since the prevalence of LUTS is of During the first medical examination, all patients were 72.2% in males affected also by ED and of 37.7% in subjected to "International Prostate Symptom Score" (IPSS), males with no ED (3).
"National Institute of Health Chronic Prostatitis Symptom Literature data show that ED associates with the severity Index" (NIH-CPSI) and "International Index of Erectile of LUTS but, although studies pointed out a correlation Function" (IIEF-5). Both groups were treated with tamsu- between CP/CPPS and ED, they do not provide with any losin for 60 days; sildenafil 50 mg was taken when need- explication of pathogenic mechanisms (4).
ed before a sexual intercourse (at least 2 times per week) Many pathogenic mechanism were investigated to find and for 60 days by the second group. During the second an explanation to ED in young patients affected by medical examination, 60 days later, all patients were sub- CP/CPPS. Any connection with hypogonadism neither jected again to IPSS, NIH-CPSI and IIEF-5.
other endocrine disorders were found, except for a study We considered mild patients' symptoms with IPSS score which, unlike controls, found higher levels of testos- between 0-7 and NIH-CPSI between 0-14; moderate terone in patients with CP/CPPS (5).
respectively between 8-19 and 15-29 and severe between Another study found an association with hypogonadism, 20-35 and > 30. We considered mild patients' erectile due to the fact that patients took opioids for long periods dysfunction with IIEF-5 score between 17-21, mild- because of LUTS severity (6). Vascular diseases and arteri- moderate between 12-16, moderate between 8-11 and al insufficiency are well known causes of ED, even though severe between 5-7.
they are uncommon in young patients (7). Anyway, one We statistically evaluated a potential difference in IIEF-5 study pointed out alterations in the peripheral arterial tone scores according to the symptomatic severity of IPSS and in patients with CP/CPPS (8), due to a endothelial vascu- NIH-CPSI and in the last two questionnaires scores lar dysfunction mediated by nitric oxide (9).
according to IIEF-5 severity. Moreover, the arterial flow can be compromised from the Therefore, we statistically evaluated the differences of outside by spastic contractions of pelvic floor (10). It is questionnaires scores means between the two medical known muscle relaxant therapies can have positive examinations in each group and between the two groups. effects on ED (11).
For the statistic analysis we used Graphpad Prism 5 pro- Occlusive vessel disease is a condition which frequently gram. In addition to the descriptive statistic modes occurs in old patients, also in presence of penile fibrosis.
(mean, standard deviation), oneway ANOVA, Kruskal- Therefore, also this pathogenic mechanism is uncommon Wallis, Mann-Whitney and Student t test were used for a in young patients. Although ED psychogenic cause was statistic evaluation. The results were analyzed with a sig- not adequately investigated in patients with CP/CPPS, a nificance level of P < 0.05.
relation may exist since often patients affected by painfulsyndromes also suffer from stress, anxiety and maladaptiveresponses to stressful events ("catastrophizing") (12).
Table 1 shows the mean of questionnaires analyzed and the
mean of patients' figures. According to IPSS questionnaire,
MATERIALS AND METHODS
4 patients presented mild symptoms, 26 moderates and 14 Our study analyzed a number of 44 patients who were severe; according to NIH-CPSI questionnaire 6 patients examined at our Clinic because affected by type III chron- presented mild symptoms, 29 moderates, 9 severe; accord- ic prostatitis associated with erectile dysfunction since at ing to IIEF-5 questionnaire 8 patients suffered from mild least 6 months. All patients were sexually active. We erectile dysfunction, 17 mild-moderate, 13 moderate, 6 excluded from the study all patients affected by infections severe. We confronted IIEF-5 score means of patients with of the urinary system, neoplasia, congenital disorders, mild, moderate and severe symptoms according to IPSS previous surgeries, urolithiasis and hyperactive bladder.
and we did not notice any statistically difference: ANOVA None of the included patients used PDE-5 in the past.
(p = 0,87) and Kruskal-Wallis (p = 0.92) (Table 2). None of the examined patients presented side effects due Moreover, there is no statistically difference between IPSS to the use of alpha-blockers and PDE-5. Patients wereexamined through anamnesis, which is a clinical examwith neurological evaluation of the pelvic floor and rectal examination, uroflowmetry, suprapubic ultrasound evalu-ation of post-void residual, trans-rectal prostate ultra- General characteristics sound, total PSA, microscopic and cultural exams of urine and mean symptom scores of the cases. and semen and urethral secretion after prostate massage.
The 44 patients were divided into 2 groups: the firstgroup (20 patients) was treated with monotherapy, tam- Age (year)
sulosin 0.4 mg, the second one (24 patients) was treated with a combination therapy, tamsulosin 0.4 mg plus sildenafil 50 mg. Patients assignment to one group or the other was random. The average age of patients included in the study is 32.04 ± 3.15 years. None of patients was affected by BPH; prostate volume range was between 15 and 25 ml. Both uroflowmetry parameters and post-void residuals were not pathological.
Archivio Italiano di Urologia e Andrologia 2013; 85, 3 Comparison of tamsulosin vs tamsulosin/sildenafil effectiveness in the treatment of erectile dysfunction in patients affected by type III chronic prostatitis in IIEF-5 score (Table 6 -7). We did not notice, in 60days, a statistically relevant difference, between the two The effect of IPSS level on mean IIEF-5 score. therapy groups, in all questionnaires score, IIEF-5 Mean IIEF-5 score
included (Table 8).
Alterations in IPSS, IIEF-5, NIH-CPSI, IPSS-QOL between visit Kruskal-Wallis P = 0.92 1 and visit 2 in Group 1 treated with tamsulosin 0,4 mg. The effect of IIEF-5 level on mean IPSS score. Mean IPSS score
13.25 ± 1.17 ANOVA P = 0.43 Alterations in IPSS, IIEF-5, NIH-CPSI, IPSS-QOL between visit 14.48 ± 0.96 Kruskal-Wallis P = 0.61 1 and visit 2 in Group 2 treated with tamsulosin 0,4 mg plus sildenafil 50 mg. The effect of NIH-CPSI level on mean IIEF-5 score. Mean IIEF-5 score
Alterations in IPSS, IIEF-5, NIH-CPSI, IPSS-QOL between Kruskal-Wallis P = 0.25 Group 1 and Group 2 after 60 days. The effect of IIEF-5 level on mean NIH-CPSI score. All cases
19.08 ± 0.56 Kruskal-Wallis P = 0.26 C prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a syndrome characterized by pain (abdom- inal, pelvic, genital), obstructive and irritative LUTS inabsence of infection (1), causing Quality Of life (QOL)decrease (13).
Although it is known that type III chronic prostate asso- score means of patients with mild, mild-moderate, moder- ciates with erectile dysfunction, it is still less clear the ate, severe erectile dysfunction: ANOVA (p = 0,43) and etiophatogenesis implied in these two nosological enti- Kruskal-Wallis (p = 0,61) (Table 3). We did not notice any ties. Great part of clinical studies examine old patients statistically difference even through the comparison of with LUTS and ED, but also with concomitant BPH and IIEF-5 scores according to NIH-CPSI mild, moderate and obstruction of urine flow. Still few are studies which severe symptoms: ANOVA (p = 0,12), Kruskal-Wallis investigate the presence of ED in younger patients affect- (p = 0,25) (Table 4); any difference also in NIH-CPSI scores ed by type III chronic prostatitis in absence of BPH and according to IIEF-5: ANOVA (p = 0,18), Kruskal-Wllis (p = 0,26) (Table 5). The most supported theory explaining the common We noticed, inside each therapy group, a statistically rel- pathogenic mechanism of LUTS and concomitant ED, evant decrease, between the first medical examination independently from BPH, points out there is a hyperac- and 60 days later, in IPSS, IPSS-QOL and NIH-CPSI tivity of autonomic nervous system and endothelial score. We also pointed out a statistically relevant increase alterations due to the effects on nitric oxide – cyclic Archivio Italiano di Urologia e Andrologia 2013; 85, 3 U. Cantoro, F. Catanzariti, V. Lacetera, L. Quaresima, M. Giovanni, M. Polito monophosphate guanosine e alterations in Rho-kinase 6. Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002; 3:377-84. Some studies already evaluated the effectiveness of 7. Gonen M, Kalkan M, Cenker A, et al. Prevalence of premature alpha-blockers in treating erectile dysfunction associated ejaculation in Turkish men with chronic pelvic pain syndrome. with LUTS (15-16), but it was not compared with PDE- J Androl. 2005; 26:601-3. 5 inhibitors and, as stated above, the patients examinedwere old people with concomitant BPH.
8. Shoskes DA, Prots D, Karns J, et al. Greater endothelial dysfunc-tion and arterial stiffness in men with chronic prostatitis/chronic In our study, after 60 days of therapy, each group showed pelvic pain syndrome-a possible link to cardiovascular disease. statistically relevant improvements in questionnaires J Urol. 2011; 186:907-10. scores: IPSS, IPSS-QOL, IIEF-5, NIH-CPSI.
In other words, tamsulosin, as well as the combination 9. Rubinshtein R, Kuvin JT, Soffler M, et al. Assessment of endothe- therapy of tamsulosin and sildenafil, improved both lial function by non-invasive peripheral arterial tonometry predictslate cardiovascular adverse events. Eur Heart J. 2010; 31:1142-8. LUTS and ED. Sixty days after the therapy, we did notstress out any statistically relevant difference in question- 10. Shoskes DA, Berger R, Elmi A, et al. Muscle tenderness in men naires scores between the two groups, despite a PDE-5 with chronic prostatitis/chronic pelvic pain syndrome: the chronic inhibitors treatment in the second group. Moreover, prostatitis cohort study. J Urol. 2008; 179:556-60. there is no correlation between LUTS severity (classified 11. Anderson RU, Wise D, Sawyer T, et al. Sexual dysfunction in according to IPSS and NIH-CPSI), ED rate and vice men with chronic prostatitis/chronic pelvic pain syndrome: improve- versa. These results suggest tamsulosin may improve ED ment after trigger point release and paradoxical relaxation training. and chronic prostatitis symptoms, reducing the spasm of J Urol. 2006; 176:1534-8. prostate smooth muscle, the associated inflammation 12. Nickel JC, Tripp DA, Chuai S, et al. Psychosocial variables affect and improving prostate and penis blood flow.
the quality of life of men diagnosed with chronic prostatitis/chronic Anyway, our study has several limitations; it does not have pelvic pain syndrome. BJU Int. 2008; 101:59-64. a placebo control arm and it is circumscribed. We are also 13. McNaughton Collins M, Pontari MA, O'Leary MP, et al. Quality persuaded other studies are needed for evaluating of life is impaired in men with chronic prostatitis: the Chronic monotherapy and combination therapy for a longer peri- Prostatitis Collaborative Research Network. J Gen Intern Med. od than 60 days. Moreover, patients' randomization does 2001; 16:656-62. not guarantee a complete randomness: patients' assign-ment to one study group or the other was made through 14. Rosen RC, Wei JT, Althof SE, et al. Association of sexual dysfunc-tion with lower urinary tract symptoms of BPH and BPH medical ther- their alternated insertion in one of the two groups. apies: results from the BPH registry. Urology. 2009; 73:562-566. 15. Kirby RS, Andersen M, Gratzke P, et al. A combined analysis of double-blind trials of the efficacy and tolerability of doxazosin-gas- LUTS severity in young patients suffering from type III trointestinal therapeutic system, doxazosin standard and placebo inpatients with benign prostatic hyperplasia. BJU Int. 2001; 87:192-200. chronic prostatitis does not correlate with the severity ofED and vice versa. Tamsulosin therapy for the treatment 16. De Rose AF, Carmignani G, Corbu C, et al. Observational mul- of young patients with type III chronic prostatitis togeth- ticentric trial performed with doxazosin: evaluation of sexual effects er with erectile dysfunction has the same effectiveness of on patients with diagnosed benign prostatic hyperplasia. Urol Int. the most expensive combination therapy (tamsulosin 2002; 68:95-98. and sildenafil). We are persuaded in the future thecheaper therapy with alpha-blocker will be used inCP/CPPS and ED affected patients.
Ubaldo Cantoro, MD (Corresponding Author) Resident in Urology 1. Schaeffer AJ, Datta NS, Fowler JEJ, et al. Overview summary statement. Diagnosis and management of chronic prostatitis/chronic Francesco Catanzariti, MD pelvic pain syndrome (CP/CPPS). Urology. 2002; 60:1-4. Resident in Urologyfracatanzariti@libero.it 2. Costabile RA, Steers WD. How can we best characterize the rela- Vito Lacetera, MD tionship between erectile dysfunction and benign prostatic hyperpla- Urologist, Resident in Urology sia? J Sex Med. 226; 3:676-681. 3. Carson CC. Combination of phosphodiesterase-5 inhibitors and Luigi Quaresima, MD alpha-blockers in patients with benign prostatic hyperplasia: treat- Resident in Urology ments of lower urinary tract symptoms, erectile dysfunction, or both? BJU Int. 2006; 97:39-43. Giovanni Muzzonigro MDProfessor of Urology and Chief Institute of Urology, Resident in Urology 4. Shiri R, Ha¨kkinen JT, Hakama M, et al. Effect of lower urinary tract symptoms on the incidence of erectile dysfunction. J Urol.
2005; 174:205-209. Massimo Polito, MDUrologist, Resident in Urology 5. Dimitrakov J, Joffe HV, Soldin SJ, et al. Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain Institute of Urology, A.O. Ospedali Riuniti syndrome. Urology. 2008; 71:261-6. Via Conca 71 - I-60020 Ancona, Italy Archivio Italiano di Urologia e Andrologia 2013; 85, 3
A WECKMAN and others Autophagy in the endocrine Autophagy in the endocrine glands Andrea Weckman, Antonio Di Ieva, Fabio Rotondo1, Luis V Syro2, Leon D Ortiz3, Kalman Kovacs1 and Michael D Cusimano Division of Neurosurgery, Department of Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario,Canada 1Division of Pathology, Department of Laboratory Medicine, St Michael's Hospital, University of Toronto, Toronto,