
==== Front
J Adv Pharm Technol Res
J Adv Pharm Technol Res
JAPTR
J Adv Pharm Technol Res
Journal of Advanced Pharmaceutical Technology & Research
2231-4040
0976-2094
Wolters Kluwer - Medknow India

JAPTR-15-161
10.4103/JAPTR.JAPTR_87_24
Original Article
Comparing monotherapy with tadalafil or tamsulosin in men with benign prostatic hyperplasia: A case–control study
Fawzi Hayder Adnan
Akram Saif Nabeel 1
Talib Aya Fawzi 2
Alwan Mustafa Hasan 3
Yasir Luma Amer 4
Department of Pharmacy, Al-Mustafa University College, Baghdad, Iraq
1 Department of Surgery, Al-Mahmodiya General Hospital, Baghdad, Iraq
2 Department of Clinical Pharmacy, College of Pharmacy, Uruk University, Baghdad, Iraq
3 Department of Pharmaceutic, College of Pharmacy, Ashur University, Baghdad, Iraq
4 Department of Biochemistry, College of Medicine, Mustansiriyah University, Baghdad, Iraq
Address for correspondence: Dr. Hayder Adnan Fawzi, Department of Pharmacy, Al-Mustafa University College, Baghdad, Iraq. E-mail: hayder.adnan2010@gmail.com
Jul-Sep 2024
22 7 2024
15 3 161165
06 3 2024
06 6 2024
29 5 2024
Copyright: © 2024 Journal of Advanced Pharmaceutical Technology & Research
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Benign prostatic hyperplasia (BPH) is a chronic disorder that inflicts severe symptoms on middle-aged men. The current study compared the effects of tadalafil and tamsulosin on urological parameters after 3 and 6 months of therapy. A retrospective case–control study was conducted, in which 100 patients with moderately severe BPH were divided into two groups based on their treatment: 50 patients were given tamsulosin 0.4 mg/day and group 50 patients were administered tadalafil 5 mg daily. All patients continued therapy for approximately 6 months, and their urological parameters were assessed at baseline and after 3 and 6 months. There was no significant difference in the overall effect on the International Prostate Symptom Score at the end of the study using two-way ANOVA analysis (P = 0.448). The intercourse number was significantly improved by tadalafil compared to tamsulosin (P < 0.001). The prostatic-specific antigen, postvoiding residual, and prostatic volumes were not significantly different between tadalafil and tamsulosin (P = 0.198, 0.163, and 0.183, respectively). In conclusion, tadalafil, 5 mg once daily, appears to have similar efficacy to tamsulosin, with significant improvement in the patient’s erectile function. Tadalafil can be used for 6 months for moderate-to-severe lower urinary tract symptoms.

Benign prostatic hyperplasia
sexual dysfunction
tadalafil
tamsulosin
==== Body
pmcINTRODUCTION

Benign prostatic hyperplasia (BPH) affects the quality of life (QoL) of older men and requires frequent medical attention and expensive treatment.[1] An increase in both stromal and glandular epithelial cells in the transition zone of the prostate is characteristic of BPH. In addition, prominent, isolated prostatic nodules form due to hyperplasia.[2] BPH is associated with multiple underlying causes, with the prostate playing a significant but possibly overemphasized role in the pathophysiology of these conditions.[3]

The α1-blockers are characterized by a fast onset of action, excellent pharmacological activity, and minimum side effects; as such, they are typically considered the first-line drug treatment for male lower urinary tract symptoms (LUTS). The α1-blockers reduce prostate tone by blocking the action of noradrenaline on prostate smooth muscle cells.[4] According to controlled studies, α1-blockers showed improvement in International Prostate Symptom Score (IPSS) around 30%–40% and boost peak flow rates by 25%;[56] there are up to 50% IPSS improvements and increases of up to 40% in peak flow rates documented in open-label studies.[7] The α1-blockers can mitigate storage and void LUTS. Although short-term studies have not found an association between prostate size and α1-blocker efficacy, α1-blockers appear more effective in patients with smaller prostates.[7891011] In addition, it has been shown that the effectiveness of α1-blockers does not change with age.[7]

The only medication from the phosphodiesterase inhibitor five inhibitors (PDE5Is) that have been granted an official license for treating male LUTS with or without erectile dysfunction (ED) is tadalafil 5 mg once daily. Treatment with PDE5Is appears to be most beneficial for younger men with a lower body mass index and more severe LUTS.[12] PDE5Is decrease detrusor, prostate, and urethral smooth muscle tone because of increased intracellular cyclic guanosine monophosphate.[13] In addition, PDE5Is appear to improve lower urinary tract blood flow and oxygenation with long-term use.[14] PDE5Is possess anti-inflammatory activities.[15]

To the best of our knowledge, this is the most extended (6 months follow-up) study that compared monotherapy with tadalafil to tamsulosin using not only patients’ subjective measurement (IPSS) but also uro-specific parameters (prostatic-specific antigen [PSA] and postvoiding residual [PVR]). In addition, the findings came from the use of a lower (and approved) dose of tadalafil 5 mg daily, while most trials used 10–20 mg when compared to tamsulosin. Therefore, these extended findings allow us to use tadalafil 5 mg daily longer than previously reported (i.e., 6 months instead of 3 months). At the same time, all our patients had moderate-to-severe LUTS, making the use of tadalafil more attractive to patients, especially for initial therapy, since it has fewer side effects and, at the same time, improves erectile dysfunction that the disease itself can cause, side effects of drugs, or the natural aging process of the individual, thus improving the quality of life and possibly enhancing the patients’ medication compliance. The current study investigates the efficacy of tadalafil as a monotherapy for treating moderate-to-severe BPH compared to tamsulosin monotherapy.

METHODS

Study design

A retrospective case–control study, in which 100 patients with moderately severe BPH (diagnosed based on the EAU Guidelines[16]) were divided into two groups based on their treatment: 50 patients were given tamsulosin 0.4 mg/day and 50 patients were administered tadalafil 5 mg daily. All patients continued therapy for approximately 6 months, and their urological parameters were assessed at baseline and after 3 and 6 months.

Sample size

G * Power version 3 was used with a calculated sample of 100 patients (with an effect size of 0.30 and 89.7% power, with a noncentrality parameter of 2.93).

Study setting

The study was performed at the outpatient clinic of the Department of Surgery, Al-Mahmodiya General Hospital. The study was conducted from September 2021 to the end of September 2022.

Inclusion criteria

BPH patients with LUTS and age above or equal to 45 years.

Exclusion criteria

The exclusion criteria for the study include patient’s noncompliance, acute urinary retention, neurological bladder dysfunction, bladder neck contraction, urethral stricture, bladder stones, active infections of the urinary tract, prostatic malignancy, prostatectomy, any condition that affects urinary function (such as chronic kidney dysfunction, severe heart conditions, and liver disorders), and patients who are taking other medication for BPH.

Measurement of study parameters

All patients had their PSA level, PVR volume, and prostatic volume measured at baseline, after 3 months, and after 6 months. To assess PSA fluorescence immunoassay using AFIAS, PSA (Avant Medical, Netherlands) and prostatic volume were measured using a Mindray® Z60 ultrasound machine. The IPSS score, International index of erectile function (IIEF) score, and number of intercourses per month were taken from each patient at baseline, after 3 months, and after 6 months to assess the severity of PSA and erectile dysfunction.

Ethical consideration

The institutional research committee of the Al-Mustafa University College (ethical code: A321, date: October 1, 2023). All participants in this study provided informed written consent.

Statistical analysis

Two-way ANOVA was used to assess the statistical significance between both arms of the treatment across follow-up periods, i.e., baseline, 3, and 6 months in a 3 × 2 model (two treatments against three follow-up periods) was used to determine the between-groups P value. In addition, the post hoc Bonferroni method was used, and the independent t-test was used to assess the difference between both groups in age. The analysis was carried out using GraphPad Prism 9.2. (GraphPad Software, Boston, Massachusetts USA, www.graphpad.com) Moreover, a P value is considered to be significant if <0.05.

RESULTS

Two-way ANOVA was used to assess the effect of patient treatment throughout the study period. Although the IPSS was significantly higher in the tamsulosin group at baseline, at 3 months, and after 6 months, no significant differences were observed in the overall effect using two-way ANOVA analysis (P = 0.448). The intercourse number was significantly improved by tadalafil compared with tamsulosin (P < 0.001), as illustrated in Table 1 and Figure 1.

Figure 1 Assessment of International Prostate Symptom Score (a), and number of intercourses (b)

Table 1: Assessment of age, International Prostate Symptom Score, and intercourse number

Variables	Tadalafil	Tamsulosin	P	
Number	55	45	-	
Age (years)	66.3±9.6	64.2±7.8	0.225	
IPSS				
    Baseline	21.5±3.3	23.4±2.8	0.004	
    3 months	12.8±1.8	15.0±2.3	<0.001	
    6 months	10.4±1.9	12.0±2.0	<0.001	
Number of intercourses per month				
    Baseline	4.2±1.7	3.5±2.0	0.054	
    3 months	17.8±2.9	3.6±3.0	<0.001	
    6 months	21.4±4.1	3.7±3.1	<0.001	
Data presented as mean±SD. IPSS: International Prostate Symptom Score, SD: Standard deviation

PSA, PVR, and prostate volume were not significantly different between tadalafil and tamsulosin (P = 0.198, 0.163, and 0.183, respectively), as illustrated in Table 2 and Figure 2.

Figure 2 Assessment of prostatic-specific antigen (a), postvoiding residual (b), and prostate volume, (c) throughout the study period

Table 2: Assessment of uro-specific parameters (prostatic-specific antigen, postvoiding residual, and prostate volume)

	Tadalafil	Tamsulosin	P	
    Number	55	45	-	
    Age (years)	62.0±9.7	64.7±12.6	0.228	
PSA				
    Baseline	3.8±1.5	4.9±1.9	0.002	
    3 months	3.1±1.2	4.1±1.5	<0.001	
    6 months	2.9±1.1	3.7±1.2	0.001	
PVR (mL)				
    Baseline	82.3±22.9	95.2±30.8	0.019	
    3 months	43.0±13.3	51.2±19.1	0.013	
    6 months	36.9±12.6	43.8±15.9	0.016	
Prostate volume (mL)				
    Baseline	55.2±8.9	70.9±23.1	<0.001	
    3 months	49.7±9.2	66.6±21.4	<0.001	
    6 months	48.0±8.7	64.0±20.7	<0.001	
PSA: Prostatic-specific antigen, PVR: Postvoiding residual

DISCUSSION

In the present study, tadalafil, after 6 months of treatment, showed a similar reduction in the IPSS score compared to tamsulosin, and uro-specific parameters (PSA, PVR, and prostate volume) showed no significant difference between tadalafil and tamsulosin. We used two-way ANOVA to assess the statistical differences, in which the baseline value was adjusted, and the term of interaction was calculated, resulting in no significant difference despite the lower tadalafil value than tamsulosin. Regarding sexual dysfunction, tadalafil showed significantly better outcomes (number of monthly intercourses) than tamsulosin.

In a recent randomized controlled trial (RCT) involving 183 Iranian patients, the inclusion criteria were age ≥45 years, IPSS ≥12, history of erectile dysfunction, and a large prostate, similar to our study. After 3 months of treatment, PSA and PVR between 20 mg tadalafil and 0.4 mg tamsulosin showed no difference. However, the total IPSS score and Qmax were significantly better with tamsulosin than with tadalafil. In addition, the IIEF score was significantly better with tadalafil than with tamsulosin.[17] These results partially agree with our findings; the discrepancy compared to our findings may be related to differences in methodology, as the current study lasted 6 months, compared to 3 months for Karami et al.,[17] and the dose of tadalafil was not the same.

Another study by Singh et al., a 3-month prospective open-label RCT involving 133 patients treated with tadalafil (10 mg daily) and 0.4 mg daily tamsulosin had similar inclusion criteria to the present study; in all groups, IPSS was improved, reduction in PVR, and improved quality of life. However, tamsulosin was significantly better than tadalafil in the total IPSS, and while similar to our findings, no significant difference in PVR was observed.[18] In addition, similar to our results, a significant improvement in erectile dysfunction was observed with tadalafil.[18]

A meta-analysis of seven studies involving 1601 individuals found a lack of statistical significance between tadalafil and tamsulosin in enhancing the clinical outcomes, regarding IPSS, voiding, storage, QoL, and PVR. However, tadalafil seems to improve erectile dysfunction better than tamsulosin.[19] This finding agrees with the results of the current study.

Limitations

This research used many exclusion criteria to limit the confounding effect. However, the impact of the omitted conditions on the clinical outcome of tadalafil or tamsulosin treatment in men with BPH should be investigated more thoroughly. Furthermore, the number of participants was limited; we encourage future research with more participants, including BPH patients of varying severity levels. This study included a single ethnic group (Arabic population).

CONCLUSION

Tadalafil, 5 mg once daily, appears to have similar efficacy to tamsulosin, with significant improvement in the patient’s erectile function. Tadalafil can be used for 6 months for moderate-to-severe LUTS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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