Benign prostatic hyperplasia (BPH) is one of the common cause of lower urinary tract symptoms (LUTS) in aging men. Voiding symptoms have been related to obstruction of the bladder outlet. However, it is well recognized that voiding symptoms may or may not correlate with underlying pathophysiology. Erectile dysfunction (ED) and LUTS are interrelated, Men with LUTS have a higher incidence of ED, and LUTS themselves represent an independent risk factor for ED, resulting in significant negative impact on quality of life. The pathophysiology of LUTS secondary to BPH and ED are not completely understood, even though several determinants are shared by these two clinical entities. The current standard of care in men with symptomatic LUTS secondary to BPH is treatment with 5-alpha-reductase inhibitors either alone or in combination with alpha-blockers and transurethral surgery is reserved for those who have failed medical therapy.
Phosphodiesterase type 5 inhibitors (PDE5-Is) were approved for the treatment of ED, but they have been also found highly effective in blunting LUTS in men with or without ED. PDE5-Is causes relaxation of bladder neck and prostate by increasing nitric oxide in smooth muscle, facilitating voiding phase of micturation cycle. They also exert potent anti-inflammatory effects on prostate therefore reducing fibrosis and overgrowth. All these beneficial effects help in reducing symptoms due to prostatic enlargement.
We carried out a prospective Comparative study, with the aim to compare the efficacy and safety of daily administration tamsulosin 0.4 mg versus tadalafil 5 mg.
MATERIALS AND METHODS
This study was a prospective comparative randomised study conducted in the Department of Urology SKIMS Srinagar J AND K India between August 2018 and July 2020.
- Male patient with age >40 years and diagnosed with symptomatic benign prostate hyperplasia.
- Patient already on alpha-blockers
- Chronic kidney disease
- Bilateral hydro-ureteronephrosis
- Bladder calculi
- Bladder diverticula.
A total of 92 patients were randomly assigned to two groups using a computer-based method. Groups I and II had 45 and 47 patients, respectively. Two patients from Group I and three patients from Group II did not follow and were excluded from the study. Patients in Group I received 0.4 mg of tamsulosin and Group II patients received 5 mg tadalafil. Patients were advised to take drugs at bedtime.
All patients were properly evaluated before enrolling them for study. Detailed history, general physical examination with abdominal examination, examination of external genitalia and digital rectal examination was done in each case. Neurological examination was done to exclude any neurological deficit.
Investigations done include urine analysis, urine culture, baseline investigations including renal function tests, abdominal ultrasound, serum prostate-specific antigen, and uroflowmetry.
All patients were explained about the International Prostate Symptom Score (IPSS) and the IPSS scoring sheet was provided to quantify the severity of LUTS and Sexual Health Inventory for Men (SHIM) scoring to access ED. SHIM score signifies sexual health of patients, five questions were asked in each patient, and each question carries a score of 1–5. Score varies from 5 to 25. Score 22–25 meaning no ED, 17–21 mild ED, 12–16 mild to moderate ED, 8–11 moderate ED, and 5–7 severe ED.
Patients were assessed at baseline, 3 months, and at 6 months after receiving treatment. Treatment efficacy was measured by a change in Qmax, post void residual urine (PVR), IPSS score, and SHIM score at 3 months and 6 months.
Data was analysed using SPSS ver. 15.0 software. Student’s t-test, and univariate logistic regression analysis were used for statistical assessment of results and a value of P < 0.05 was considered statistically significant.
Baseline parmeters of patients in Group I and Group II [Table 1]
- Age: Mean age of patients in group 1 was 60.4 SD8.74 with range from 42-78 years and in group II Mean age of patients was 62.66 SD8.89 With range from 42-80 years.
- Prostate size: The mean prostate size of patients in Group I was 35.32 (Sd 9.79) with a range from 16 to 50 and in Group II, the mean prostate size was 32.20 (SD: 9.26) with a range from 18 to 48
- Post voidal residual urine (PVRU): Mean PVRU of patients in Group I was 64.76(SD 45.84) with a range from 15 to 200, while in patients in Group II, the mean PVRU was 78.5 (SD: 55.02), with a range from 0 to 220
- Qmax: The mean Qmax of patients in Group I was 11.44 (SD 4.49) with a range from 2.9 to 22.1, while in patients in Group II, the mean Qmax was 12.46 (SD 4.54) with a range from 3.9 to 23.1
- IPSS score: The mean IPSS SCORE of patients in Group I was 16.84 (SD: 4.88) with a range from 4 to 25, while in Group II, the mean IPSS score was 15.62 (SD 4.78) with a range from 3 to 21
- SHIM Score: The mean Shim score of patients in Group I was 15.5 (SD: 5.12) with a range from 8 to 25, while in patients in Group II, the mean SHIM score was 15.8 (SD 4.89) with a range from 7 to 25.
Parameters of patients in Group I and Group II at 3 months after receiving tamsulosin 0.4 mg in Group 1 and tadalafil 5 mg in Group II [Table 2]
- Post voidal residual urine (PVRU): Mean PVRU at 3 months of patients in Group I was 29.22 (SD: 10.82) with a range from 0 to 71 and in Group II, mean PVRU at 3 months was 33.52 (SD: 13.94) with a range from 0 to 80.
- Qmax: Mean Qmax at 3 months of patients in Group I was 18.44 (SD 3.80) with a range from 9.6 to 23.2 and in Group II, mean Qmax at 3 months was 17.19 (SD: 3.54) with a range from 9.8 to 22.8
- IPSS SCORE: Mean IPSS score at 3 months of patients in Group I was 12.60 (SD: 3.14) with a range from 4 to 18 and in Group II, mean IPSS score at 3 months was 11.62 (SD: 3.64) with a range from 3 to 17.
- SHIM SCORE: Mean SHIM score at 3 months of patients in Group I was 16.2 (SD: 4.12) with a range from 7 to 25 and in group II, mean SHIM score at 3 months was 21.9 (SD: 4.89) with a range from 12 to 25.
Parameters of patients in Group I and Group II at 6 months after receiving tamsulosin 0.4 mg in Group 1 and tadalafil 5 mg in Group II [Table 3]
1. Post voidal residual urine (PVRU): Mean PVRU at 6 months of patients in Group I was 17.52 (SD: 6.94) with a range from 0 to 52. and in Group II, mean PVRU at 6 months was 20.22 (SD 7.82) with a range from 0 to 60
2. Qmax: Mean Qmax at 6 months of patients in Group I was 20.88 (SD 3.38) with a range from 12.5 to 24.6 and in Group II, mean Qmax at 6 months was 18.92 (SD: 3.44) with a range from 13.2 to 25.5
3. IPSS SCORE: Mean IPSS score at 6 months of patients in Group I was 9.62 (SD: 3.84) with a range from 3 to 13, and in Group II, the mean IPSS score at 6 months was 10.6 (SD: 3.54) with a range from 3 to 15
4. SHIM SCORE: Mean SHIM score at 6 months of patients in Group I was 16.3 (SD: 5.31) with a range from 8 to 22 and in Group II, the mean SHIM score at 6 months was 22.1 (SD: 4.93) with a range from 14 to 25.
The role of medical therapy in prostatomegaly with LUTS has been supported by the certain limitations of prostatectomy, which include significant early and late complications of the surgical procedure and significant re-treatment rate. Treatment of symptomatic BPH has evolved from surgical therapy to medical therapy. Depending on weight of prostate either combination therapy with 5a-reductase inhibitors with a-adrenergic antagonists or alpha-blocker alone is used in clinical practice guidelines. Several long-term studies such as MTOPS and ComBAT have demonstrated the superiority of combination therapy over monotherapy in preventing disease progression.
a-adrenergic blockers use in the treatment of LUTS is based on the hypothesis that LUTS due to bladder outlet obstruction is mediated by a1 adrenoceptors associated with prostatic smooth muscle, since smooth muscles are dominant constituents of BPH, accounting for around 40% of the area density of the hyperplastic prostate, signifying the role of a-blockers in BHP.
The rationale for the use of PDEIs in the treatment of LUTS and BPH was based on data showing the frequent occurrence of both ED and LUTS in men as they age. This raised the possibility of a common underlying mechanism contributing to both processes, which, in turn, raised the possibility of new treatment options that might affect both processes. The pathophysiologic link between these conditions is not yet clear. It is likely that there is an overlap between the roles of each of these candidate mechanisms, and an ultimate effect leading to smooth muscle relaxation in the prostate bladder neck or erectile tissues appears to be crucial.
We conducted this study to compare the efficacy of tamsulosin and tadalafil in men with BHP with LUTS by measuring a change in Qmax, PVR (post void residual urine), IPSS score, and SHIM score at 3 months and 6 months after receiving tamsulosin 0.4 mg in Group I and tadalafil 5 mg in Group II with respect to baseline score in these two groups.
In our study, tamsulosin 0.4 mg was found to improve Qmax, PVR, and IPSS score more than tadalafil 5 mg, but the difference was statistically insignificant. Pogula et al., Abrams et al., and Lepor et al. stated in their studies that patients treated with tamsulosin experienced a greater increase in peak urinary flow.
In our study, almost all patients with BHP with LUTS had some degree of ED (mild to severe). We found that patients taking tadalafil 5 mg had statistically significant improvement in overall SHIM score compared to patients taking tamsulosin 0.4 mg. Vedamurthy Reddy Pogula et al. reported patient taking tadalafil 5 mg had an increase in mean SHIM score at 3 months compared to tamsulosin 0.4 mg. Lee et al. observed that after 12 weeks of tadalafil treatment, IIEF-5 scores had increased from baseline by 47.8%. Sebastianelli et al. reported in their study that from baseline to 12 week, all the subjects showed a significant improvement of International Index of Erectile Function (IIEF), but tadalafil achieved the same improvements of IIEF when compared to combination alpha-blocker and tadalafil.
When both groups were compared, tadalafil showed statistically similar improvements in Qmax, PVRU, and IPSS score, but statistically significant improvement was observed with tadalafil in SHIM score compared with tamsulosin in treating LUTS secondary to BPH. Our study provides evidence that once-daily tadalafil 5 mg is well tolerated and can be considered for the treatment of LUTS secondary to BPH, especially in patients with ED.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
1. Chapple CR, Wein AJ, Abrams P, Dmochowski RR, Giuliano F, Kaplan SA, et al Lower urinary tract symptoms revisited:A broader clinical perspective Eur Urol 2008 54 563–9
2. de la Rosette JJ, Witjes WP, Schäfer W, Abrams P, Donovan JL, Peters TJ, et al Relationships between lower urinary tract symptoms and bladder outlet obstruction;Results from the ICS-“BHP” study group Neurol Urodyn 1998 17 99–108
3. Barbosa JA, Muracca E, Nakano É, Assalin AR, Cordeiro P, Paranhos M, et al Interactions between lower urinary tract symptoms and cardiovascular risk factors determine distinct patterns of erectile dysfunction:A latent class analysis J Urol 2013 190 2177–82
4. McVary KT Erectile dysfunction and lower urinary tract symptoms secondary to BPH Eur Urol 2005 47 838–45
5. McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al Update on AUA guideline on the management of benign prostatic hyperplasia J Urol 2011 185 1793–803
6. McVary KT, Roehrborn CG, Kaminetsky JC, Auerbach SM, Wachs B, Young JM, et al Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia J Urol 2007 177 1401–7
7. Gacci M, Andersson KE, Chapple C, Maggi M, Mirone V, Oelke M, et al Latest evidence on the use of phosphodiesterase type 5 inhibitors for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia Eur Urol 2016 70 124–33
8. Vignozzi L, Gacci M, Cellai I, Morelli A, Maneschi E, Comeglio P, et al PDE5 inhibitors blunt inflammation in human BPH:A potential mechanism of action for PDE5 inhibitors in LUTS Prostate 2013 73 1391–402
9. Lepor H Medical treatment of benign prostatic hyperplasia Urology 1993 42 483–501
10. Marberger M The MTOPS study:New findings, new insights, and clinical implications for the management of BPH Eur Urol 2006 5 628–33
11. Roehrborn CG, Siami P, Barkin J, Damiao R, Major-Walker K, Nandy I, 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 57 123–31
12. Caine M, Perlberg S, Meretyk S A placebo- controlled double –Blind study of the effectas of phenoxybenzamine in benign prostatic obstruction Br J Urol 1978 50 551–4
13. Shapiro E, Hartanto V, Lepor H The Response to alfa blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle Prostate 1992 21 297–307
14. Pogula VR, Kadiyala LS, Gouru VR, Challa SR, Byram R, Bodduluri S Tadalafil vs. tamsulosin
in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia:A prospective, randomized study Cent European J Urol 2019 72 44–50
15. Lepor H, Williford WO, Barry MJ, Haakenson C, Jones K The impact of medical therapy on bother due to symptoms, quality of life and global outcome, and factors predicting response. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group J Urol 1998 160 1358–67
16. Schulman CC, Cortvriend J, Jonas U, Lock TM, Vaage S, Speakman MJ Tamsulosin
, the first prostate-selective alpha 1A-adrenoceptor antagonist. Analysis of a multinational, multicentre, open-label study assessing the long-term efficacy and safety in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin
Study Group Eur Urol 1996 29 145–54
17. Abrams P, Schulman CC, Vaage S Tamsulosin
, a selective alpha 1c-adrenoceptor antagonist:A randomized, controlled trial in patients with benign prostatic 'obstruction'(symptomatic BPH). The European Tamsulosin
Study Group Br J Urol 1995 76 325–36
18. Lee JY, Park SY, Jeong TY, Moon HS, Kim YT, Yoo TK, et al Combined tadalafil and a-blocker therapy for benign prostatic hyperplasia in patients with erectile dysfunction:A multicenter, prospective study J Androl 2012 33 397–403
19. Sebastianelli A, Spatafora P, Frizzi J, Saleh O, Sessa M, De Nunzio C, et al Tadalafil 5 mg alone or in combination with tamsulosin
0.4 mg for the management of men with lower urinary tract symptoms and erectile dysfunction:Results of a prospective observational trial J Clin Med 2019 8 1126