INTRODUCTION
Benign prostatic hyperplasia (BPH) describes a common condition in old age in which there is a benign enlargement of the prostate gland.[1] BPH may lead to bladder outlet obstruction, initially inducing lower urinary tract symptoms (LUTS).[1,2] About 70% of men under the age of 80 years are affected by LUTS.[3] LUTS include storage and voiding, the severity of which can be assessed using the International Prostate Symptom Score (IPSS).[4,5] BPH can be treated using surgical therapies, for example, transurethral resection of the prostate or medical therapies (e.g., α1-Adrenoceptor antagonists [α-blockers], 5α-reductase inhibitors, or a combination).[6] However, α-blockers are the drugs of choice for LUTS secondary to BPH (LUTS/BPH).[7] Alpha 1-adrenoceptor is additionally divided into three subtypes α 1a, α 1b, and α 1d, α 1a being the most predominant in patient with BPH (up to 85%).[8,9] Alpha-blockers relax prostatic smooth muscles thus relieving LUTS/BPH.[8]
Uroselective drugs, such as tamsulosin, that specifically target α 1a-receptors have an advantage over the other less selective α-blockers, especially in reducing serious side effects such as hypotension. Due to their high selectivity, these drugs have low-cardiovascular side effects and virtually no intervention with the activity of antihypertensive agents. Tamsulosin (0.4 mg) daily proved to be favorably safe, effective, and well-tolerated.[8,10-15] However, tamsulosin is known to cause ejaculatory dysfunction.[16,17] This side effect has a significant impact on the patients’ quality of life.[18-21] Several studies were conducted to assess the efficacy of modified dosage of tamsulosin into either lowering the dose (0.2 mg) or using it intermittently to alleviate ejaculatory issues, showed a potential improvement for the medication’s overall effectiveness.[18,22-24]
The aim of this study is to assess the influence of using full dose of tamsulosin (0.4 mg) every other day in reducing LUTS secondary to BPH on patients living in Eastern province in Saudi Arabia as a trial to increase the drug safety (in terms of reducing the drug side effects, especially retrograde ejaculation) while maintaining the efficacy in relieving the patients’ symptoms and its impact on the patients’ quality of life.
MATERIALS AND METHODS
This prospective study was conducted in King Faisal University’s Health Care Center between January 2015 and April 2015. Patients who participated in this study were suffering from LUTS due to BPH and were using 0.4 mg tamsulosin daily to relieve their symptoms but complained from no ejaculate or low-volume ejaculate. Exclusion criteria involved IPSS ≥18, postvoid residual volume (PVR) >400 ml, and any conditions affecting the function of the bladder neck either medical or surgical, renal or hepatic impairment, significant cardiovascular disease, central nervous or cerebrovascular system disease, diabetes mellitus, or allergic reactions to α-adrenoceptor blockers. The baseline assessment involves medical history and evaluation of ejaculatory function, IPSS, quality of life assessed using global satisfaction, vital signs, physical examination including digital rectal examination, renal function, abdominopelvic ultrasound, and PVR estimation.
During the study, patients consented to take 0.4 mg tamsulosin intermittently every other day, and to proceed with their sexual activities on the days they did not take the drug in. The baseline assessment was repeated and recorded after 3 months from starting the treatment. The adverse event and patients’ compliance with the drug were analyzed. Patients who developed aggravation of their symptoms were excluded and returned to their standard dose.
RESULTS
In the beginning, 30 patients were enrolled in the study with the mean age of 55.5 ± 6.4 years. Out of these 30 patients, a total of 5 (16.7%) were excluded from the study due to the following reasons: incomplete follow-up in the clinic in three patients and worsening of the symptoms of BPH in the remaining two patients. Ultimately, 25 patients remaining matched the predefined criteria and carried on the intermittent dose of tamsulosin, 0.4 mg every other day.
In the start of our study, the mean baseline IPSS for the 25 patients was 6.6 ± 1 and the baseline PVR was 87.6 ± 15.1 ml. Then, after 3 months of follow-up, the mean IPSS increased to 7.3 ± 1.1, and the mean PVR increased to 100.4 ± 15.1 ml. Statistical analysis for these two parameters showed a statistically significant difference (P = 0.0001) [Table 1].
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Table 1: Analysis of intermittent tamsulosin therapy before and after
Before our study, 17 out of the 25 patients (68%) have reported symptoms of no ejaculate at all, and the rest of eight patients (32%) have reported low-volume ejaculate. All of these, 17 patients have shown either dissatisfaction with these symptoms or neutral satisfactions (2 or 3 respectively) as per the global satisfaction rate.
After the trial of the intermittent dose of tamsulosin, in the 17 patients who had no ejaculation, all of them (100%) plus 3 out of the 8 (37.5%) who had low-volume ejaculation have reported improvements in their ejaculatory volume. Hence overall, 20 out of the total number of 25 patients (80%) reported improvement in their ejaculation. Analysis with the Chi-square test of independence has revealed a significant relationship between the intermittent dosing and the recovery of abnormal ejaculation (P = 0.0001). Moreover, in regard to the global satisfaction rate, all of the 20 patients showing improvement in their ejaculatory volume have stated that they are either satisfied or very satisfied with their conditions (4 or 5, respectively) [Figures 1 and 2].
Figure 1: Summary of the trial
Figure 2: Before and after the trial
DISCUSSION
Alpha-blockers are the first line of medical treatments for LUTS/BPH. Drugs, such as tamsulosin, are highly selective blockers to α 1a-receptors in the prostate gland. Tamsulosin is advantageous over the other less selective α-blockers in terms of cardiovascular side effects reduction such as decreased hypotension. And therefore, it is the drug of choice in the treatment of LUTS/BPH.[8,10-12] However, tamsulosin has been noted to impact ejaculation negatively and can cause low-volume ejaculate or no ejaculate.[13-15] This side effect has been found to be dose-dependent, i.e., more prevalent with higher doses.[16] To reduce this side effect while maintaining the drug’s safety and efficacy, tamsulosin dose manipulation studies were conducted. Dose adjustment was in terms of either dose reduction (0.2 mg) or intermittent dosing.
Several studies have investigated the safety and efficacy of using daily 0.2 mg dose for relieving LUTS with less side effects. Kim et al.[18] studied 138 male patients over 50 years of age with LUTS and found that the use of low-dose treatment of tamsulosin for 3 months showed significant improvement in both IPSS and quality of life. However, the study revealed an incidence of de novo ejaculatory discomfort of 10.2% at 1 month and 6.0% at 3 months and thereafter concluded that low-dose tamsulosin did not show any significant impact on ejaculatory function. On the other hand, Park et al.[24] studied 146 patients who were administered tamsulosin 0.2 mg daily over the course of 1 year. The study found significant improvement in all efficacy parameters, including reduction in total IPSS mean by 41.1% and a mean increase of Qmax by 4.56 mL/s. Only 0.6% of the 146 patients showed ejaculatory dysfunction and adverse events occurred in 6.2%. The study concluded that low dosing was well-tolerated and effective in improving LUTS and urinary flow. Finally, Kim et al.[25] conducted a large cross-sectional study with a total sample of 2574 patients to evaluate efficacy and treatment satisfaction with low-dose tamsulosin. However, despite the improvement with low-dose tamsulosin in IPSS and satisfaction in 63.4% of the patients that the study showed, dissatisfaction was reported in 36.5% of the patients. The reasons for dissatisfaction included efficacy problems (84.66%) and side effects (3.72%). Compared to these studies, our study revealed that the patients who recovered from ejaculatory dysfunction were more satisfied with using an intermittent dose of tamsulosin than with the standard dose.
In the other forms of dose manipulation, and in concordance with our study, two studies from Turkey investigated the safety and efficacy of using intermittent tamsulosin therapy. In the first study, Goktas et al.[22] included 405 patients with LUTS, of which 30 patients had abnormal ejaculation and were studied subsequently in another phase. The study reported that intermittent dosing provided comparable improvements for abnormal ejaculation. Of the 30 patients, 19 (63.3%) have recovered from abnormal ejaculation expressed as retrograde ejaculation, low-volume ejaculate, and no ejaculate. Of importance note that the majority of recovery in ejaculatory function was observed in the patients with retrograde ejaculation. Namely, 12 out of the 19 (63%) who recovered had retrograde ejaculation. These patients have reported a significant improvement in their ejaculation after intermittent tamsulosin dosing. In the second study, Yanardag et al.[23] studied 140 patients for intermittent tamsulosin therapy in two phases. In the first phase, patients received 0.4 mg of tamsulosin daily for 3 months. Moreover, in the second phase, the responders to tamsulosin were divided randomly into three groups – Group 1 continued the standard dose of 0.4 mg tamsulosin daily, Group 2 was given intermittent tamsulosin dose, i.e., 0.4 mg every other day, and Group 3 discontinued tamsulosin. For patients in Groups 1 and 2, there were no statistically significant differences among them at 6 months for IPSS, maximum or average urine flow, or residual urine. Nevertheless, it was noted that 9.6% of patients in the standard dosing group (Group 1) have suffered from retrograde ejaculation and only 2.9% of patients in the intermittent dosing group (Group 2). These two studies go in agreement with our study, where recovery of ejaculatory dysfunction was in 17 (100%) patients that reported no ejaculate, and in 3 out of 8 (37.5%) patients that reported low ejaculate.
In our study, we explored the safety and efficacy of using intermittent doses of tamsulosin (0.4 mg every other day) in patients with LUTS who were also suffering from abnormal ejaculation. In all 25 patients, after 3 months of intermittent therapy, mean IPSS and mean PVR have increased and showed a statistically significant difference compared to the initial baseline. However, out of the 25 patients studied, 20 patients (80%) expressed improvement in ejaculatory function and were more satisfied with the intermittent therapy than with the standard dose as shown by their global satisfaction and improved quality of life, and despite their significant increase in IPSS and PVR. In those 20 patients, recovery was in all 17 (100%) patients with no ejaculate and in 3 out of 8 (37.5%) patients with low ejaculate. According to these results, we can conclude that the intermittent therapy is more effective in patients complaining from absent ejaculation.
CONCLUSION
In patients suffering from LUTS/BPH and complaining from abnormal ejaculation, especially absent ejaculate, intermittent tamsulosin therapy (0.4 mg/every other day) is well-tolerated and shows a potential advantage in their recovery. Even with the significant change in IPSS and PVR after applying the intermittent tamsulosin therapy, most patients show a higher overall satisfaction with the treatment compared to the standard dose (0.4 mg/daily). A study on a larger scale is still needed to confirm our results.
Informed consent
Written and oral informed consent was obtained from all individual participants included in this study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this manuscript.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
We would like to thank the participants who were all contributed samples to the study.
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