Comparison of the Efficacy and Safety of Alfuzosin and Tamsulosin In

Joodi A Jalo (2020): Effect of selective and nonselective alpha blocking agents in Iraqi patients with BPH Oct 2020 Vol. 23 Issue 14

Comparison of the efficacy and safety of alfuzosin and tamsulosin in relieving lower urinary tract symptoms in Iraqi patients with benign prostatic hyperplasia (BPH): Observational case reference study

Mohammed Ridha Joodi A. Jalo*M.B.ch.B/ FICMS (uro.)

1. Department of Surgery, College of Medicine ,University of Babylon, Hilla, Iraq

*Corresponding author

Dr. Mohammed Ridha Joodi A. Jalo Department of Surgery, College of Medicine, University of Babylon, Hilla, Iraq. E-mail: [email protected] Phone number: 009647809113938

Abstract

Background:The main stay in non-surgical management of benign prostatic hyperplasia (BPH) includes the use of “5-alpha reductase inhibitors” which act by inhibition of the production of dihydroxy testosterone, the active metabolite of testosterone with high affinity to androgen receptors. In addition selective and non-selective alpha receptors inhibitors are also used in the medical treatment of BPH. The basis behind using of alpha blocker is that a substantial proportion of prostatic enlargement is due to stromal hyperplasia containing a principal element of smooth muscle fibers that produce dynamic obstruction. Objectives: The current study was aiming at comparing the effect of selective and nonselective alpha blocking agents, tamsulosin and alfuzosin on size of prostate and “lower urinary tract symptoms” in a sample of Iraqi patients with BPH. Patients and methods: The current observational case reference study was conductedat the department of urology at Al-Hilla teaching hospital, Babylon province, Iraq. The work with this study started on September the 1st 2018 through July the 15th 2019. Three groups were included each one enrolled 20 patients with a diagnosis of BPH. The first group included patients who were recently diagnosed to have symptomatic BPH (n = 37) and are on no medical treatment or surgical intervention till time of starting the study. The second group included 45 patients already on medical treatment with the non-selective alfuzosin alpha blocking agent and the third group included 41 patients on the selective tamsulosin alpha blocking agent. Patients were included based on taking the treatment for at least one month duration. Results: The mean size of the prostate gland of patients within groups 1 and 2 was significantly less than that belonging to control category (P< 0.05). However, there has beeninsignificant variation in the mean size of the prostate gland between group 1 and group 2 (P> 0.05). Moreover, the mean IPSS of patients within groups 1 and 2 was significantly less than that belonging to control group (P< 0.05). However, there has been an insignificant variation in mean IPSS between group 1 and group 2 (P> 0.05).Conclusion: Based on data obtained from the current study and some previous reports, both alfuzosin and tamsulosin appear to be equally effective and safe in treating lower urinary tract symptoms in patients with BPH.

Keywords: alfuzosin, tamsulosin, lower urinary tract symptoms, BPH, Iraq

How to cite this article: Joodi A Jola MR (2020: Comparison of the efficacy and safety of alfuzosin and tamsulosin in relieving lower urinary tract sysmtoms in Iraqu with benign prostatic hyperplasia (BPH): Observational case reference study, Ann Trop Med & Public Health; 23(S14): SP231434. DOI: http://doi.org/10.36295/ASRO.2020.231434

Introduction

One of the common medical conditions affecting elderly men is benign prostatic hyperplasia (BPH)(1). The disease is a form of a benign growth and hyperplasia affecting both glandular epithelium and stromal elements leading to enlargement of prostate size in different shapes and configuration with resultant “lower urinary tract symptoms” in

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231434

Joodi A Jalo (2020): Effect of selective and nonselective alpha blocking agents in Iraqi patients with BPH Oct 2020 Vol. 23 Issue 14

significant proportion of elderly men (2).The etiology of the disease is rarely understood; however, a number of risk factors have identified in association with BPH (3).

The prevalence of this condition has been observed to increase markedly with age based on observational epidemiological studies (4, 5) and autopsy studies (6). On the other hand it has been demonstrated that the size of the prostate gland becomes more with increasing age (7, 8). The association between incidence of BPH and race is not clear and researches with this regards have shown conflicting data. Some reports favored higher incidence rate among black race in comparison with white race (9); others denied such an observation and suggested lower incidence rate in Asian men in comparison with white race (10). Genetic predisposition has been suggested by some authors based on observation of BPH in relatively young men with lower urinary tract symptoms necessitating surgical intervention since follow reveals that their siblings are at much higher risk of developing BPH in comparison with general population (11).Some reports have shown that dietary habits may be associated with higher or lower risk of developing BPH (12-14).

The molecular mechanism that underlies the development of BPH is till now incompletely understood; however, the role of androgens and estrogens is well established (15 -17). In normal physiological conditions, the regulation of prostate growth and function is greatly determined by sex steroid hormones. Both androgen and estrogen receptors have been found to be expressed by prostatic cells (17, 18). Nevertheless the variation in the level of expression of these receptors between normal prostate and BPH is controversial (17, 18). However, evidences for the role of androgen and estrogen signaling in the pathogenesis of BPH are supported by both animal experimental studies and studies on human being (17-10).

Therefore, the main stay in non-surgicaltherapy of BPH include the use of “5-alpha reductase inhibitors” which act by inhibition of the production of dihydroxy testosterone, the active metabolite of testosterone with high affinity to androgen receptors (21). In addition selective and non-selective alpha receptors inhibitors are also used in the medical management of BPH. The basis behind using alpha blocker is that a substantial proportion of prostatic enlargement is due to stromal hyperplasia containing principal element of smooth muscle fibers that produce dynamic obstruction (22).

The current study aims to comparing the effect of selective and nonselective alpha blocking agents, tamsulosin and alfuzosin on size of prostate and “lower urinary tract symptoms” in a sample of Iraqi patients with BPH.

Patients and Methods

The current observational case reference study was conductedat the department of urology at Al-Hilla teaching hospital, Babel province, Iraq. The work with this study started on September the 1st 2018 through July the 15th 2019. Three groups were included each one enrolled 20 patients with a diagnosis of BPH. The first group included patients who were recently diagnosed to have symptomatic BPH (n = 37) and are on no medical treatment or surgical intervention till time of starting the study. The second group included 45 patients already on medical treatment with the non-selective alfuzosin

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231434

Joodi A Jalo (2020): Effect of selective and nonselective alpha blocking agents in Iraqi patients with BPH Oct 2020 Vol. 23 Issue 14

alpha blocking agent and the third group included 41 patients on the selective tamsulosin alpha blocking agent. Patients were included based on taking the treatment for at least one month duration.

The main variables included in the current study included ultrasound assessment of size of prostate, age of patients, serum prostatic specific antigen (PSA), “International Prostate Symptom Score (IPSS), serum testosterone, serum estrogen and serum testosterone to estrogen ratio.

The study was approved by the ethical approval committee of the institute and every patient was informed about the aim and the procedure of the current study and all patients gave verbal consent.

The statistical workup was based on the statistical package for social science (SPSS) provided by (IBM, Chicago, USA, version 23). Qualitative variables were presented as number and percentage. The quantitative variables were presented as mean, range and standard deviation. One way ANOVA was used to assess difference in mean values among groups followed by post-hoc LSD test. The significance level was set at P ≤ 0.05.

Results

The characteristics of individualsparticipating in this study are demonstrated in table 1. Therewas no significant difference in mean age among groups (P> 0.05), 74.24 ±7.27 versus 75.09 ±6.93 versus 73.90 ±8.71 years, for control group, group 1 (patients on the non-selective alpha blocker, alfuzosin) and group 2 (patients on the selective alpha blocker, tamsulosin) respectively. There has been however, significant variation in mean prostate size among groups. The mean size of prostate gland of patients within group 1 was significantly lower than that of control group, 43.47 ±8.12 ml versus 45.65 ±5.60 ml, respectively (P< 0.05). Similarly, the mean size of prostate gland of patients within group 2 has been significantly less than that belonging to control group, 42.46 ±5.37 ml versus 45.65 ±5.60 ml, respectively (P< 0.05). However, there has been insignificant variation in mean size of prostate gland between group 1 and group 2 (P> 0.05). Moreover, there was significant difference in mean IPSS among groups. The mean IPSS of patients within group 1 was significantly lower than that of control group, 18.09 ±4.87 versus 22.95 ±5.19, respectively (P< 0.05). Similarly, the mean IPSS of patients within group 2 was significantly lower than that of control group, 17.61 ±4.59 versus 22.95 ±5.19, respectively (P< 0.05). However, there was no significant difference in mean IPSS between group 1 and group 2 (P> 0.05). Added to that, there has beeninsignificant variation in mean serum testosterone, serum estrogen and mean testosterone to estrogen ratio among groups (P> 0.05). Furthermore, there has been insignificant variation in mean serum PSA among groups (P> 0.05), as shown in table 1.

Table 2 showed the correlation of IPSS to other characteristics of patients enrolled in the study. The IPSS showed no significant correlation to any of patients characteristics within all enrolled groups (P> 0.05), as outlined in table 2.

Table 1:Characteristics of patients with benign prostatic hyperplasia (BPH) enrolled in this study presented according to groups

Control group Group 1 Group 2 Characteristic n = 37 n = 45 n = 41

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231434

Joodi A Jalo (2020): Effect of selective and nonselective alpha blocking agents in Iraqi patients with BPH Oct 2020 Vol. 23 Issue 14

Age (Years)

74.24 ±7.27 75.09 ±6.93 73.90 ±8.71 Mean ±SD A A A Range 61 -87 61 -87 61 -87

Size (ml)

45.65 ±5.60 43.47 ±8.12 42.46 ±5.37 Mean ±SD A B B Range 35 -55 32 -58 33 -53

IPSS

22.95 ±5.19 18.09 ±4.87 17.61 ±4.59 Mean ±SD A B B Range 15 -31 10 -26 10 -26

Estrogen (pg/ml)

38.39 ±7.68 37.47 ±9.62 38.54 ±7.92 Mean ±SD A A A Range 24.3 -51.3 23.3 -51.3 23.3 -50.3

Testosterone (nmol/L)

14.39 ±0.71 14.31 ±0.67 14.58 ±0.72 Mean ±SD A A A Range 13.31 -15.71 13.31 -15.71 13.31 -15.71

Testosterone/ Estrogen

106.54 ±24.09 111.52 ±30.82 108.41 ±28.28 Mean ±SD A A A Range 75.66 -153.68 72.8 -171.96 75.33 -181.32

PSA (ng/ml)

5.61 ±2.70 5.13 ±0.55 5.75 ±2.61 Mean ±SD A A A Range 3.02 -11.57 3.89 -6.17 3.04 -11.59 SD: Standard deviation; PSA: Prostatic specific antigen; IPSS: International prostate symptom score; capital letters represent the level of significance in such a way that similar letters denote no significant difference at P> 0.05; whereas, different letters indicate significant difference at P ≤ 0.05; the statistical test used was one way ANOVA followed by post hoc LSD multiple comparison test

Table 2:Correlation of “international prostate symptom score (IPSS)” to age of patients, size of prostate gland, serum prostatic antigen (PSA) and serum hormonal levels in control group and study groups

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231434

Joodi A Jalo (2020): Effect of selective and nonselective alpha blocking agents in Iraqi patients with BPH Oct 2020 Vol. 23 Issue 14

Control group Group 1 Group 2 n = 37 n = 45 n = 41 Characteristic r P r P r P 0.667 0.968 0.962 Age (years) -0.073 -0.006 -0.008 NS NS NS 0.548 0.521 0.968 Size (ml) 0.102 0.098 0.007 NS NS NS 0.508 0.092 0.197 Estrogen (Pg/ml) 0.104 0.254 0.206 NS NS NS 0.456 0.516 0.980 Testosterone (nmol/L) -0.126 0.099 0.004 NS NS NS 0.418 0.197 0.288 Testosterone/ Estrogen 0.131 -0.196 -0.170 NS NS NS 0.632 0.586 0.934 PSA -0.081 0.083 -0.013 NS NS NS PSA: Prostatic specific antigen; NS: not significant at P> 0.05

Discussion The current study was aiming at evaluating the role, efficacy and safety of alpha blocking agents, selective and nonselective, namely alfuzosin and tamsulosin, as medical treatment of “lower urinary tract symptoms” in Iraqi patients with BPH. It was shown, according to results of this study, that both selective and nonselective alpha blocking agents were effective in reducing the suffering of patients with BPH as it is evident from the significant reduction in mean IPSS. However, both drugs produced nearly the magnitude of effect because of lack of significant difference in mean IPSS between group 1 (alfuzosin group) and group 2 (tamsulosin group). In addition, no relevant adverse effects were reported up on using either drug.

Benign prostatic hyperplasia is a progressive disorder principally characterized by an aggravation of symptoms with the progress of time and also the development of serious outcomes such as the need for BPH-related surgery in a number of patients and acute urinary retention (23, 24). A crucial role is played by the sympathetic nervous system in regulating the myogenic tone of the bladder outflow. For that reason, urinary outflow resistance is partly due this system activity. The alpha blockerstamsulosin, alfuzosin, terazosin or doxazosin are capable or reducing bladder outlet resistance, which resultsinsubstantialalleviation of “lower urinary tract symptoms”and ease of urinary flow in patients with symptomatic benign prostatic hyperplasia (25). A number of previous reports have givenclues for the efficacy and safety of alpha blockers in treating “lower urinary tract symptoms” in patients with BPH and that these agents are the most frequent primary steps in treating these manifestations (26). Newer drugs such as tamsulosin and alfuzosin tend to showbetter selectivity for the bladder and prostate, although all alpha-blocking agents provide comparable levels of efficacy for managing lower urinary tract manifestation.Tamsulosin (in 0.4 mg once daily dose) and Alfuzosin (in a single daily dose of 10 mg) yield better tolerance than terazosin and doxazosinbecause of lower risk of postural hypotension (27). Comparable

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231434

Joodi A Jalo (2020): Effect of selective and nonselective alpha blocking agents in Iraqi patients with BPH Oct 2020 Vol. 23 Issue 14

effect of alfuzosin and tamsulosin has been shown by previous authors (23, 28, 29) in accordance with findings of the current study. Both alfuzosin and tamsulosin can be given at therapeutic dose from start, therefore, they can be used to treat acute urinary retention in patients with BPH; however, this characteristic cannot be offered by other alpha blocking agents such as terazosin and doxazosin(30).

The current study failed to demonstrate significant adverse effects in association with the use of alfuzosin or tamsulosin. Dizziness was the most frequentlyreportedadverse effect with alfuzosin, as recorded by previous reports (31, 32). Ejaculatory problems have been recorded by some previous authors (32); however, this was not the case with the current study.

Based on data obtained from current study and some previous reports, both alfuzosin and tamsulosin appears to be equally effective and safe in treating lower urinary tract symptoms in patients with BPH.

Conclusion

Conflict of interest

There has been no conflict of interest of any kind with the author of this work.

Ethical Approval

All the variable information consents of the patients and control groups were taken after explaining the purpose of the study to the patients, Those who refused to participate in the study were excluded. The study was formally approved the research plan by the ethical committee board at the Babylon health directorate.

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