Evaluation and Management of Male LUTS: From Evidence to Clinical Practice
Male LUTS describe a range of symptoms that include storage, voiding and post-micturition symptoms. Strongly associated with ageing, LUTS are bothersome symptoms that can impair the quality of life of male patients. Typically, LUTS are linked to benign prostatic hyperplasia (BPH), but a host of other causes may be at play.1
Dr Kaplan urged the audience to take a holistic approach when it comes to LUTS management. The reason for this is that there is increasing evidence to show that male patients with obesity and metabolic syndrome have higher rates of LUTS compared with those without these conditions.2-5
Role of α1-blockers in male LUTS
Greater understanding of the distribution of α1-adrenoreceptors and the various subtypes in the prostate, urethra, bladder and spinal cord has led to the clinical development and use of α1-blockers in the treatment of male LUTS.6 The blocking of α1a- and α1d-adrenoreceptor subtypes by these drugs is particularly beneficial in LUTS and therefore, it is hardly surprising that all the currently available α1-blockers are similarly efficacious.6 In general, α1-blockers are considered first-line treatment for male LUTS due to their rapid onset of action, good efficacy and low rate and severity of adverse events.1
Doxazosin in a controlled-release gastrointestinal therapeutic system (GITS)
Doxazosin in standard formulation (doxazosin-S) is effective in improving LUTS associated with BPH. To initiate, start with doxazosin-S 1 mg daily, and double the dose every 7–14 days to a maximum dose of 8 mg daily until urinary flow rate or LUTS is controlled. This is done so that therapeutically effective doses can be reached while avoiding first-dose side effects.7
The doxazosin GITS is designed to improve the pharmacokinetic profile of doxazosin-S, thus enabling a simplified dosing schedule. The GITS technology permits a higher initial daily dose (4 mg daily) so that therapeutic plasma levels can be reached more rapidly while avoiding first-dose side effects. At the same time, doxazosin GITS provides a more uniform plasma concentration with minimal peak-to-trough concentration.7
Efficacy in LUTS associated with BPH. One study reported that following a 2-week run-in, there were significantly more patients on doxazosin GITS who perceived an improvement in LUTS after Day 1 through to Day 14 compared with placebo. The benefits of doxazosin GITS were seen as early as Day 3 of treatment – doxazosin GITS was associated with significantly greater improvement in the International Prostate Symptom Score (IPSS) and the proportion of patients with IPSS improvement of 30% or more, as well as improvement in maximum urine flow rate (Qmax) and proportion of patients with 3 mL or more improvement in Qmax.8
Efficacy in men with symptomatic BPH and erectile dysfunction (ED). Kirby et al9 reported that among those with symptomatic BPH and ED at baseline, doxazosin GITS did not negatively affect sexual function (Figure 1).
Long-term efficacy in LUTS. The study by Chung et al15 demonstrated that doxazosin GITS provided significant improvements in IPSS, Qmax, post-void residual (PVR) urine volume and quality of life that were sustained over a treatment period of 12 months.
Efficacy vs active comparators. Compared with tamsulosin, doxazosin GITS demonstrated a significantly more rapid onset of efficacy16; and was better for reducing the frequency of nocturia, as well as improving the quality of sleep and quality of life.17 Recently, a systematic review of α1-blockers found that doxazosin could reduce IPSS significantly more than tamsulosin and alfluzosin.18
Overactive bladder (OAB) and LUTS
Most men with LUTS have OAB as well.1 For such patients, a study by Dr Kaplan and his team found that a significantly greater proportion of patients treated with the combination of tolterodine extended release (ER) and tamsulosin reported treatment benefit compared with monotherapy of tolterodine ER, tamsulosin or placebo.19
Mirabegron, a β3-agonist, is an emerging therapy for the treatment of OAB. It relieves OAB symptoms by promoting smooth muscle relaxation in the bladder.1,20 The most common side effect of mirabegron is hypertension. In October 2015, the Medicines and Healthcare Products Regulatory Agency of the United Kingdom21 noted that cases of severe hypertension (including hypertensive crisis associated with cerebrovascular and cardiac events) have been reported with mirabegron. Mirabegron is contraindicated in patients with severe uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg, or both). Blood pressure should be measured before starting treatment and monitored regularly during treatment, especially in patients with hypertension.21
It is important to take a holistic approach when it comes to managing LUTS. Factors such as patients’ general health and well-being, age, and treatment affordability and ease of use, should be taken into consideration when initiating therapy. The majority of currently available treatment options are similar in terms of efficacy, but the emergence of side effects with each option is an important determinant of patients’ adherence to long-term treatment.
- The European Association of Urology Guidelines on the Management of Non-neurogenic Male Lower Urinary Tract Symptoms (LUTS). Available at: http://uroweb.org/wp-content/uploads/EAU-Guidelines-Non-Neurogenic-Male-LUTS-Guidelines-2015-v2.pdf. Accessed 13 Jan 2016.
- Mondul AM, et al. J Urol 2014;191(3):715–721.
- Gacci M, et al. BJU Int 2015;116(2):271–277.
- Gacci M, et al. BJU Int 2015;115(1):24–31.
- Pashootan P, et al. BJU Int 2015;116(1):124–130.
- Schwinn DA, et al. Mayo Clin Proc 2004;79(11):1423–1434.
- Chung M, et al. Br J Clin Pharmacol 1999;48(5):678–687.
- Roehrborn CG, et al. Eur Urol 2005;48(3):445–452.
- Kirby RS, et al. BJU Int 2005;95(1):103–109.
- MIMS.com. Concise prescribing information for Cialis. Available at: http://mims.com/Malaysia/drug/info/Cialis/?type=BRIEF. Accessed 18 Jan 2016.
- Roehrborn CG, et al. J Urol 2008;180(4):1228–1234.
- Braunholtz DA, et al. J Clin Epidemiol 2001;54(3):217–224.
- Menezes P, et al. PLoS One 2011;6(7):e21824.
- Glina S, et al. J Sex Med 2015;12(1):129–138.
- Chung BH, Hong SJ. BJU Int 2006;97(1):90–95.
- Chung MS, et al. Int J Clin Pract 2011;65(11):1193–1199.
- Zhang K, et al. Urology 2011;78(3):636–640.
- Yuan J, et al. Curr Med Res Opin 2013;29(3):279–287.
- Kaplan SA, et al. JAMA 2006;296(19):2319–2328.
- MIMS.com. Full prescribing information for Betmiga. Available at: http://mims.com/Malaysia/drug/info/Betmiga/?type=full#Indications. Accessed 18 Jan 2016.
- Medicines and Healthcare products Regulatory Agency. Drug Safety Update 2015;9(2):2.