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ORIGINAL ARTICLE |
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Year : 2022 | Volume
: 35
| Issue : 4 | Page : 2081-2086 |
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Tadalafil versus tadalafil with sildosin in the management of symptomatic benign prostatic hyperplasia
Mohamed A Selim, Mohamed K Omar, Mohamed Y. M. Mohamed, Ahmed A. G. El-Din
Department of Urology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
Date of Submission | 28-Aug-2022 |
Date of Decision | 14-Sep-2022 |
Date of Acceptance | 27-Sep-2022 |
Date of Web Publication | 04-Mar-2023 |
Correspondence Address: Mohamed Y. M. Mohamed Shebin El-Kom, Menoufia Egypt
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/mmj.mmj_294_22
Objectives To compare the safety and efficacy of tadalafil versus tadalafil with silodosin in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH) and their effect on erectile function. Background Lower urinary tract symptoms and erectile dysfunction are two commonly associated conditions in patients with BPH and lead to worsening of the quality of life in the male population. For such cases, alpha-blockers and phosphodiesterase five inhibitors are used. Patients and methods A total of 100 men, having lower urinary tract symptoms owing to BPH with moderate and severe international prostatic symptom score (IPSS), were randomly divided into four equal groups of 25 patients each. The IPSS and International index of erectile function-5 (IIEF-5) were scored for all patients together with measuring postvoid residual urine (PVR) and maximum urine flow rate (Q-MAX) at the first visit and then follow-up was done on the third, sixth, and 12th weeks, with same parameters added to inquiry about any adverse effects. Results Tadalafil monotherapy statistically improved IPSS, IIEF, and Q-MAX, with P value less than 0.001 in groups I and III. Moreover, it showed a statistically significant reduction in PVR in the same groups, with P value less than 0.001. The same findings were in groups II and IV receiving the combination therapy, with P value less than 0.001, with numerically better results in all aspects of the study. Conclusion All patients tolerated both protocols of treatment with no statistically significant adverse effects. The combination therapy was superior to monotherapy in all aspects regarding IPSS, IIEF, PVR, and Q-MAX.
Keywords: benign prostatic hyperplasia, erectile dysfunction, lower urinary tract symptoms, sildosin, tadalafil
How to cite this article: Selim MA, Omar MK, Mohamed MY, El-Din AA. Tadalafil versus tadalafil with sildosin in the management of symptomatic benign prostatic hyperplasia. Menoufia Med J 2022;35:2081-6 |
How to cite this URL: Selim MA, Omar MK, Mohamed MY, El-Din AA. Tadalafil versus tadalafil with sildosin in the management of symptomatic benign prostatic hyperplasia. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:2081-6. Available from: http://www.mmj.eg.net/text.asp?2022/35/4/2081/371021 |
Introduction | | |
Evidence of a strong link between Lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and sexual dysfunction has been elucidated with negative effects on patient's quality of life [1].
α1-adrenergic receptors at the level of the bladder neck, the proximal urethra, and the prostate are responsible for the dynamic component of bladder outlet obstruction in patients with BPH, and their blockade leads to the relaxation of smooth muscle tissue at both sites, with consequent relief of symptoms [2].
Phosphodiesterase inhibitors type 5 (PDE5Is) can relax the prostate and bladder neck smooth muscle. This effect is associated with an increase in nitric oxide signaling from nerve fibers close to the muscle fibers [3].
PDE5Is inhibitors similarly work to block the catalytic action of the enzyme that degrades cGMP, the downstream effector of the erection mediator nitric oxide, which then facilitates the signal transductional mechanisms of corpus cavernosal smooth muscle relaxation required for penile erection [4].
The current study compared tadalafil alone and the combination with silodosin aiming to find if the monotherapy is equal to or nearly as effective as the combination therapy in the management of two conditions, which would be more compliant and economic for the patient.
Patients and methods | | |
The study was carried out at Menoufia University hospitals as a prospective randomized trial from January 2021 to January 2022, after the institutional ethics committee approval. Written informed consent was obtained from each participant. A total number of 100 patients with LUTS owing to BPH with moderate international prostatic symptom score (IPSS) scores of 8–19 and severe IPSS scores of 20–35 and prostate size of 50–80 g were included in the study.
The study excluded patients with contraindications to alpha-blockers or tadalafil, prostate cancer, neurogenic bladder, stone bladder, bladder tumors, refractory retention, hematuria of prostate origin or any indication for surgical intervention, clinically significant cardiovascular disorders, hepatic and or renal insufficiency, or cataract surgery planned during the study period.
The sample size was estimated based on a previous study done by Yoshida et al.[5], who reported that percentages of adverse drug reactions that occurred with silodosin and tadalafil were 23.4 and 8.4%, respectively. The minimum calculated sample was 93 patients, with a final sample size calculated to be 102 patients after adding nine patients the for dropout rate (10% of the calculated sample).
Randomization of patients was done using 102 opaque envelopes, 51 containing tadalafil 5 mg once daily label and 51 tadalafil with silodosin 8 mg once daily label. The envelopes were given to patients with severe or moderate LUTS, allocating the patients into four groups: group I patients with moderate LUTS received tadalafil 5 mg once daily alone, group II patients with moderate LUTS received tadalafil 5 mg once daily with silodosin 8 mg once daily, group III patients with severe LUTS received tadalafil 5 mg once daily alone, and group IV patients with severe LUTS received tadalafil 5 mg once daily with silodosin 8 mg once daily.
Before treatment and at the first visit, detailed medical history was obtained from each patient, including personal history (name, age, and residency); special habits of medical importance (sports, smoking, and masturbation); assessment of BMI; marital status; sexual history [including an inquiry about morning erection as a good sign to exclude – if present – any organic cause of erectile dysfunction (ED)] being assessed by International index of erectile function-5 (IIEF-5) score; assessment of LUTS by IPSS; detailed past medical history including an inquiry about diabetes mellitus, hypertension, and hepatic or cardiovascular diseases; and detailed past surgical history.
Physical and genitourinary examination and evaluation were also done through general examination including vital signs, abdominal examination, neurological examination, and digital rectal examination; laboratory evaluation by complete blood count, total and free prostate-specific antigen, complete urine analysis, and serum creatinine; imaging studies, including ultrasonographic assessment of prostate size (either pelviabdominal or transrectal), ultrasonographic assessment of postvoid residual urine (PVR), ascending cystourethrogram when indicated in patients with a history of previous endoscopic maneuvers, and uroflowmetry studies using Q-MAX, which were measured for all patients before treatment; and pressure flow studies, when indicated.
Follow-up visits were scheduled for patients in the third, sixth, and 12th weeks of treatment. Patients were followed up for the IPSS score (being the primary end point of the study); IIEF score; adverse effects of medications, especially headache and myalgia, which are the most common reported adverse effects; and PVR and Q-MAX, which were measured as indicators for bladder outlet obstruction.
Statistical analysis
Two patients dropped out of the protocol, so data were collected, tabulated, and statistically analyzed for 100 patients using an IBM-compatible personal computer with Statistical Package for the Social Sciences (SPSS) version 28 (IBM Corp., Armonk, New York, USA). Two types of statistical analysis were performed: descriptive statistics and analytic statistics. analysis of variance test was used for comparison of quantitative variables between more than two groups of normally distributed data, whereas the Kruskal–Wallis test was used for comparison of quantitative variables between more than two groups of not normally distributed data. Whenever any of the expected cells were less than five, Fisher's exact test was used to study the association between qualitative variables. Significant test results were quoted as two-tailed probabilities. The significance of the obtained results was judged at the 5% level (P > 0.05).
Results | | |
A statistically significant decrease in IPSS score was noted in all groups with more decrease (regarding the mean IPSS) seen in groups II and IV. Group III showed an initial decrease in the third week and then a stationary course till the 12th week [Table 1]. | Table 1: Comparison between studied groups in the international prostatic symptom score
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There was a statistically significant increase in the mean of Q-MAX score, being higher in groups II and IV, and increasing with treatment all over the follow-up visits. Groups I and III showed initial improvement and thereafter showed a stationary course [Table 2].
A statistically significant decrease in the mean of PVR, being higher in groups II and IV, was noted. Groups I and III showed an initial improvement and then showed an almost stationary course [Table 3]. | Table 3: Comparison between studied groups according to postvoid residual urine
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All groups showed a statistically significant initial improvement in IIEF score at third week then maintained improvement throughout the follow-up visits on treatment when compared with the baseline [Table 4]. There was no statistically significant difference between groups regarding complications, which were almost absent by the end of the study [Table 5]. | Table 4: Comparison between studied groups in the international index of erectile function score
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Discussion | | |
PDE5Is represent the gold standard for the treatment of ED. Moreover, PDE5Is are proved to be effective also for the treatment of LUTS in several clinical trials, as they were found to be able to increase oxygenation and blood supply, reduce intraprostatic inflammation, and reduce the smooth muscle tone of the lower urinary tract. PDE5 was demonstrated to be highly expressed not only in penile corpora cavernosa but also in the male bladder, urethra, and prostate [6].
A few literature-based studies compared the efficacy of tadalafil monotherapy against the combination therapy with silodosin in the management of patients with the two aforementioned conditions: which one would be effective and add to patient compliance, safety, and amelioration of his/her quality of life.
There was no statistically significant difference among the four groups regarding age, smoking, BMI, or comorbidities (diabetes mellitus and hypertension).
The current study showed that there was a statistically significant decrease in IPSS score noted in all groups with more decrease seen in groups II and IV. Group III showed an initial decrease in the third week then a stationary course till the 12th week, with the P value less than 0.001 in all groups, which is the primary end point of the work.
Combination therapy with tadalafil 5 mg and tamsulosin 0.4 mg (n = 50) was compared with tadalafil 5 mg monotherapy (n = 25) by Sebastianelli et al.[7] Compared with baseline, after 12 weeks, total IPSS changed (combination vs. tadalafil: −7 vs. −5.2, P = 0.08). IPSS significantly improved in both groups.
Mahajan et al.[8] demonstrated that the change in total IPSS from baseline to fourth week in the silodosin group was statistically very highly significant (P < 0.001), and the percentage difference between baseline and at end of fourth week was 38.474 ± 10.736%. Change in total IPSS at end of the fourth week in the tadalafil group was statistically very highly significant (P < 0.001), and the percentage difference was 32.322 ± 7.996%. Comparing percentage differences, combination therapy was very highly significant in improving total IPSS from baseline (P < 0.001). This matches with the result of the study by Yoshida et al.[5] where both silodosin and tadalafil significantly reduced the IPSS, but the reduction by silodosin was more statistically significant than that by tadalafil.
Our current findings regarding PVR clearly revealed that there was a statistically significant decrease in the mean PVR, being higher in groups II and IV, and groups I and III showed initial improvement and thereafter showed an almost stationary course.
These results were compatible with Singh et al.[9] who compared tadalafil alone and silodosin alone and illustrated that there was a significant improvement in PVR (mean = 64.33 ± 40.95, 33.52 ± 18.94; P = 0.001) with alpha-blockers alone. There was also a significant improvement in PVR (mean = 55.33 ± 32.27, 28.22 ± 10.82; P = 0.001) with the PDE5I group alone.
The current study showed that there was a statistically significant increase in the mean Q-MAX score being higher in groups II and IV and in increasing with treatment all over the follow-up visits. Groups I and III showed initial improvement and thereafter showed a stationary course.
Singh et al.[9] concluded that alpha-blockers are quite capable of improving the Q-MAX (mean = 13.45 ± 2.97 and 17.44 ± 3.50, respectively; P = 0.000). Moon et al.[10] in their study had shown similar results, where the mean (11.2 and 14.7, respectively, P < 0.0001). PDE5I group were capable of improving the Q-MAX (mean = 13.36 ± 5.28 and 17.38 ± 4.62, respectively; P = 0.000).
Contrary to that, Yoshida et al.[5] found that the maximum urine flow rate showed no significant change from baseline to the eight week of treatment for tadalafil but silodosin achieved a statistically significant improvement from baseline (P = 0.0146).
The current study showed that there was an initial improvement in IIEF score in the third week and then kept improving throughout follow-up. The same finding was noted by Sebastianelli et al. [7], who stated that IIEF improvement was similar between the two treatment arms: tadalafil monotherapy vs. combination therapy (+5.7 vs. +6.1, respectively; P = 0.255).
In the present study, we found that there was no statistically significant difference between groups regarding complications, which were almost absent by the end of the study. The study by Gnyawali et al.[11] showed that drug-related adverse effects such as headache, dizziness, postural hypotension, and myalgia were comparable between the two groups and not statistically significant.
LUTS/BPH and ED are two worldwide problems, mostly associated and common in men at and after the age of 50 years. Therefore, large-scale, multicenter, placebo-controlled studies are needed to further assess the long-term safety and effectiveness of tadalafil and alpha-blockers in management. Moreover, this study focused only on the erectile function of patients under trial assessed by IIEF-5. Ameliorating ejaculatory and orgasmic functions surely add to the quality of life.
Conclusion | | |
Tadalafil monotherapy exhibited satisfactory improvement in all parameters of management protocol, with an acceptable safety profile. However, the combination therapy was numerically and statistically superior to monotherapy in all aspects with an improvement of IPSS, IIEF, PVR, and Q-MAX.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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