|Year : 2015 | Volume
| Issue : 1 | Page : 56-59
Role of once-daily tadalafil in men with concomitant erectile dysfunction and symptomatic benign prostatic hyperplasia: A prospective randomized placebo-controlled study
Sunder Goyal1, Snigdha Goyal2, Isha Saini3
1 Department of Surgery, Kalpana Chawla Government Medical College, Karnal, Haryana, India
2 Department of Pathology, Dr. Ram Manohar Lohia Postgraduate Institute of Medical, Sciences, New Delhi, India
3 Department of Surgery, Life Line Clinical and Diagnostic Centre, Karnal, Haryana, India
|Date of Web Publication||5-Jun-2015|
Dr. Sunder Goyal
Department of Surgery, Kalpana Chawla Government Medical College, Karnal, Haryana
Source of Support: None, Conflict of Interest: None
Background: Majority of men over age 50 are sexually active and sex is an important part of overall quality of life. Both benign prostatic hyperplasia (BPH) with lower urinary tract symptoms-BPH (BPH-LUTS) and erectile dysfunction (ED) are often found in this age group simultaneously. Pathophysiological mechanisms for both these diseases are almost common. All males presenting with LUTS should be assessed for sexual dysfunction and viceversa. The aim of this study is to evaluate the effects of once-daily tadalafil on erectile function in men with ED and benign prostatic hypertrophy with LUTS. One drug for treatment of both diseases and better patient's compliance are important issues for proper management.
Materials and Methods: We did a study of 60 men. All patients were divided in two groups: 30 in group A who were given tadalafil 5 mg (megalis-5 mg of Macleods Pharmaceutical Company) and 30 patients in group B who were on placebo (plain sugar pills) for 12-week. This was a randomized, placebo-controlled study of once-daily tadalafil, which was carried out in men with BPH-LUTS in a rural Medical College of Northern India during June 2009 to November 2011.
Results: International index of erectile function-erectile function (IIEF-EF) domain score improvements from baseline with 5 mg once-daily tadalafil were significantly greater throughout the study for tadalafil groups versus placebo (all P ≤ 0.001). International Prostate Symptom Score (IPSS) improvements from baseline to end point were significantly greater with 5 mg tadalafil dose versus placebo (all P < 0.05).
Conclusion: There are encouraging results with tadalafil. It was used in 30 patients who were suffering with both ailments of BPH and LUTS simultaneously and is effective in both diseases.
Keywords: Benign prostatic hyperplasia and lower urinary tract symptoms, erectile dysfunction, International index of erectile function-erectile function, International prostate symptom score, tadalafil
|How to cite this article:|
Goyal S, Goyal S, Saini I. Role of once-daily tadalafil in men with concomitant erectile dysfunction and symptomatic benign prostatic hyperplasia: A prospective randomized placebo-controlled study. Indian J Health Sci Biomed Res 2015;8:56-9
|How to cite this URL:|
Goyal S, Goyal S, Saini I. Role of once-daily tadalafil in men with concomitant erectile dysfunction and symptomatic benign prostatic hyperplasia: A prospective randomized placebo-controlled study. Indian J Health Sci Biomed Res [serial online] 2015 [cited 2019 Sep 16];8:56-9. Available from: http://www.ijournalhs.org/text.asp?2015/8/1/56/158236
| Introduction|| |
Men with benign prostatic hyperplasia (BPH) mostly suffer from lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, intermittency, nocturia, straining, incomplete emptying, or weak urinary stream. Incidence of BPH increase with advancing age. Usually severity of BPH symptomology have got no direct relation with prostate size. , Severity of clinical symptoms of BPH may depend on the tone of smooth muscle in prostate and bladder neck (BN). , The pathophysiological mechanism for both diseases (BPH-LUTS and erectile dysfunction [ED]) is common and adds further melancholy to ageing men. ,, α 1A -adeno receptors affect the tone of smooth muscle of human prostate as noted in vitro study.  Nitric oxide-cyclic guanosine monophosphatase causes smooth muscle relaxation in corpus cavernosal tissue and in the bladder neck, the urethra and the prostate.  PDE5 is a drug of choice to treat both LUTS and ED due to common pathophysiology.  Majority of men over age 50 are sexually active and sex is an important part of overall quality of life (QoL). One should assess sexual dysfunction in patients with BPH-LUTS. 
| Materials and Methods|| |
This study was carried out in men suffering with BPH-LUTS and ED in a rural Medical College of Northern India during June 2009 to November 2011. Study was discussed with the Institutional Ethical Committee as this drug was already in use. Sixty men (at least 50 years old) suffering with BPH-LUTS and ED who gave their informed consent were included in the study. All the participants were divided in two groups of 30 each. Group A: Case group, who were given tadalafil 5 mg (Megalis-5 mg of Macleods Pharmaceutical Company) for 12 weeks at bed time post cabal and group B: Control group, who were given placebo (plain sugar pills) for 12-week. Inclusion criteria was sexually active men with living wives who suffered with BHP-LUTS and ED. Eligible men were at least 50 years old with an IPSS-13 or higher and peak urinary flow rate (Qmax)-4 to15 ml/s. The exclusion criteria were spinal cord injury, prostatitis, a history of prostate or bladder cancer, bladder neck or urethral stricture and contraindication to tadalafil. Patient on drug like alpha1-adrenoceptor antagonists or any other treatment for ED were also excluded from the study.
International index of erectile function-erectile function (IIEF-EF) domain score was used to study changes in EF while the changes in BPH-LUTS were assessed with the help of International prostate symptom score (IPSS). Peak urinary flow rate (Q max ) and postvoid residual volume were also assessed in both groups. 
Assessments of IPSS (total score) and IIEF-5 scores were carried out at week 0 (baseline), week 12 after treatment initiation. Comparisons were made between IPSS and IIEF-5 scores before treatment (week 0), at the completion of treatment (week 12).
The quality of life was also assessed at the base and at 12 weeks. Responses were measured on a scale from 0 to 6, from delighted to terrible.
Data were expressed as means ± standard deviations. Student's t-test was used to compare IIEF-5 and IPSS scores before and after treatment. Differences with P < 0.05 were considered significant.
| Results|| |
Patient characteristics are shown in [Table 1]. The mean age of the participants was 59 ± 6.26 years, and the mean disease duration was 5.51 ± 2.47 months. Blood tests as luteinizing hormone, follicle stimulating hormone, prostatic specific antigen, prolactin and testosterone were within normal range.
International index of erectile function-erectile function domain score improvements from baseline with 5 mg once-daily tadalafil were significantly greater throughout the study for tadalafil groups versus placebo (all P ≤0.001). IPSS improvements from baseline to end point were significantly greater with 5 mg tadalafil dose versus placebo (all P <0.05) [Table 2].
Improvement was also observed for Q max. Urinary flow measurements demonstrated that those patients receiving tadalafil had a significantly (P < 0.0001) higher increase at 12 weeks from baseline in mean Q max than those receiving placebo.
The percentage of patient's QoL (delighted, pleased or satisfied) for the rest of their lives increased from 5% to 25% in tadalafil group and only from 5% to 8% in placebo group.
Postvoid residual volume before tadalafil was 138.53 ± 14.65 ml and after 12 weeks therapy was significantly lower 54 ± 3.93 ml.
Safety and tolerability
Once daily tadalafil was well tolerated, and the most commonly reported adverse events (headache, back pain, dyspepsia, and myalgia) were consistent with those reported in previous studies of once-daily tadalafil in men with BPH or ED.
| Discussion|| |
Men with signs of BPH suffer with LUTS, such as urinary frequency, urgency, intermittence, nocturia, straining, incomplete emptying or a weak urinary stream. LUTS increase with age and incidence is about 55% in men of age 50 years or older. Most of the drugs, which are being used to treat BPH can cause unwanted side-effects such as dizziness, low blood pressure, retrograde ejaculation and sexual dysfunction. Various reports of ED incidence, pathophysiology and treatment have shown a possible link between BPH LUTS and ED.
How BPH and its LUTS are associated with ED is not clear. According to a few studies, the sympathetic nervous system is hyperactive in animals and men with BPH-associated urinary tract symptoms. Nerve fibers in the sympathetic nervous system send out signals that have an impact on stress and stress-related symptoms. An increase in these signals may result in over-activity in the sympathetic nervous system, which is associated with erectile problems.
Many studies suggest that ED drugs may be beneficial in treating BPH symptoms. Reasons for this benefit are not clear. ED drugs block the phosphodiesterase-5 (PDE-5) enzyme, which is present in high level in the bladder muscles and prostate. Thus ED drugs relax the arteries and increase blood to flow into the penis and they may also cause small blood vessels in the prostate and bladder to open up and enhance blood flow thus could improve urinary symptoms. Another possibility is that in older men with BPH-LUTS, the nerve signals to the brain, prostate, and bladder may not function properly. Drugs for ED may block those abnormal signals and thus improve BPH symptoms.
The following three observations are the support for using tadalafil for BPH: First, with increasing age there is the combined occurrence of BPH with LUTS and ED; second, smooth muscle relaxation in the lower urinary tract are affected by PDE5 inhibitor; and third, various clinical trials have demonstrated that PDE5 inhibitors such as tadalafil is successful in treating LUTS and ED.  Four possible pathophysiologic mechanisms that may explain a potential role of PDE5-inhibitor therapy in LUTS have been described in literature. PDE5 inhibitors facilitate smooth muscle relaxation by inhibiting the breakdown of cyclic guanosine monophosphate. Cyclic guanosine monophosphate subsequently phophorylates several other targets and results in smooth muscle relaxation. Effects and expression of PDE5 have been shown in the bladder, prostate and urethra.  PDE5 inhibitors like tadalafil has shown good result in treating BPH-LUTS.  Tadalafil also causes engorgement of cavernous sinuses and increases the length of flaccid penis and thus helps in formation better stream of urine.
Various studies in literature have shown that once daily 5 mg tadalafil produces good results for patients with BHP with LUTS and showed clinical and statistical efficacy. , Dmochowski et al., concluded that tadalafil is useful for both ED and for bladder outlet obstruction symptoms due to BPH.  Treatment with tadalafil once daily for LUTS secondary to BPH demonstrated no negative effect on bladder function as measured by detrusor pressure at maximum urinary flow rate or on any other urodynamic parameter assessed.  Porst et al., reported that IPSS decreased significantly with all tadalafil doses and clinical significant improvement was observed in maximum flow rate and post void residual urine (it was there in our study).  Roehrborn et al., studied the effectiveness of tadalafil, a PDE5 inhibitor, in patients with LUTS secondary to BPH compared to placebo. The results show no significant change of peak urinary flow (Qmax) or voiding efficiency, but there was good improvement in the obstructive symptom due to BPH.  McVary et al., reported in their study that tadalafil once daily was well tolerated and revealed statistically significant symptomatic improvement for LUTS/BPH. Tadalafil also improved EF in men with LUTS and ED.  Rajiv et al., suggested that for men ≥50 years old, chances of development of sexual dysfunction decreases with the use of α-blocker use. They observed this relationship in each of the five domains of sexual function, including EF, ejaculatory function, sexual drive, sexual problem assessment, and overall sexual satisfaction. Patient who showed improvement in LUTS with α-blocker treatment were less likely to develop sexual dysfunction. 
Our study showed that 5 mg once-daily tadalafil is equally effective in men suffering with both ED as well as for BPH-LUTS as in other studies, which also support the use of once-daily tadalafil in men with ED and signs and symptoms of BPH. Further studies are required to assess:
- How long these effects of once-daily tadalafil on obstructive signs and symptoms of BPH are maintained and can this drug avoid urinary retention in future
- Whether tadalafil can stop the proliferation of prostatic stromal cells thus can reduce the prostatic size and thus controls subsequent prostatic growth.
| Conclusion|| |
The majority of men over age 50 are sexually active and sex is a vital part of overall QoL. Once-daily dosing of tadalafil 5 mg for 12 weeks demonstrated statistically remarkable efficacy in the treatment of BPH-LUTS and ED in men with both BPH-LUTS and ED. Safety results were comparable with other tadalafil studies.
| References|| |
Lepor H. Pathophysiology of lower urinary tract symptoms in aging male prostate. Rev Urol 2005;7:83.
Andersson KE, Gratzke C. Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat Clin Pract Urol 2007;4:368-78.
Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol 2008;15:193-9.
Porst H, McVary KT, Montorsi F, Sutherland P, Elion-Mboussa A, Wolka AM, et al.
Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia. Eur Urol 2009;56:727-35.
Rosen R, Altwein J, Boyle P, Kirby RS, Lukacs B, Meuleman E, et al.
Lower urinary tract symptoms and male sexual dysfunction: The multinational survey of the aging male (MSAM-7). Eur Urol 2003;44:637-49.
Braun MH, Sommer F, Haupt G, Mathers MJ, Reifenrath B, Engelmann UH. Lower urinary tract symptoms and erectile dysfunction: Co-morbidity or typical "Aging Male" symptoms? Results of the "Cologne Male Survey". Eur Urol 2003;44:588-94.
Marshall I, Burt RP, Chapple CR. Noradrenaline contractions of human prostate mediated by alpha 1A-(alpha 1c-) adrenoceptor subtype. Br J Pharmacol 1995;115:781-6.
McVary K. Lower urinary tract symptoms and sexual dysfunction: Epidemiology and pathophysiology. BJU Int 2006;97 Suppl 2:23-8.
Gonzalez RR, Kaplan SA. Tadalafil for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia. Expert Opin Drug Metab Toxicol 2006;2:609-17.
Mouli S, McVary KT. PDE5 inhibitors for LUTS. Prostate Cancer Prostatic Dis 2009;12:316-24.
Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A dose finding study. J Urol 2008;180:1228-34.
Gales BJ, Gales MA. Phosphodiesterase-5 inhibitors for lower urinary tract symptoms in men. Ann Pharmacother 2008;42:111-5.
Dmochowski R, Roehrborn C, Kraus S, Klise S. Changes in bladder outlet obstruction index in men with signs and symptoms of benign prostatic hyperplasia treated with tadalafil. J Urol 2009;181:1924.
Dmochowski R, Roehrborn C, Kraus S, Xu L, Kaminetsky J, Kraus S. Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: A randomized, placebo controlled 12-week clinical trial. J Urol 2010;183:1092-7.
Roehrborn CG, Kaminetsky JC, Auerbach SM, Montelongo RM, Elion-Mboussa A, Viktrup L. Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment. BJU Int 2010;105:502-7.
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.
Kumar R, Nehra A, Jacobson DJ, McGree ME, Gades NM, Lieber MM, et al.
Alpha-blocker use is associated with decreased risk of sexual dysfunction. Urology 2009;74:82-7.
[Table 1], [Table 2]