Alpha blockers (ABs) and 5-alpha reductase inhibitors, the most prescribed drugs for LUTS/BPH treatment, are burdened with sexual side effects like ejaculatory dysfunction and reduced or lost libido. Phosphodiesterase type 5 inhibitors (PDE5is) are the standard treatment of ED. However, several trials proved their effectiveness also on LUTS relief, allowing the approval of daily tadalafil 5 mg for the treatment of LUTS/BPH, alone or in combination with tamsulosin. Indeed, a favorable additive effect compared with monotherapies has been recognized for both LUTS (improvement of International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax)) and sexual function (increase of International Index of Erectile Function (IIEF) score).2
In our systematic review carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA statement), we aimed to assess the efficacy and safety of tadalafil alone or in combination with tamsulosin for the treatment of patients presenting LUTS/BPH and ED.
In 2007, McVary et al. published the results of the first randomized clinical trial (RCT) on the use of tadalafil to treat LUTS due to BPH,3 comparing placebo for 12 weeks with daily tadalafil 5 mg for 6 weeks and a dose escalation to 20 mg for the subsequent 6 weeks. Along with the improvement of ED, LUTS assessed by IPSS significantly improved in tadalafil arm at 6 (− 2.8 vs. − 1.2 IPSS points) and 12 weeks (− 3.8 vs. − 1.7). Several subsequent trials confirmed the efficacy of all tadalafil doses for LUTS/BPH, and a post hoc analysis on 581 men by Porst et al. proved that daily 5 mg tadalafil offered the best risk-benefit profile, both for urinary and sexual function.4 A significant impact of tadalafil on uroflowmeter parameters (e.g.: Qmax) has not been observed in all of the trials. Nevertheless, recently Matsukawa et al. reported the 12 months outcomes from a prospective urodynamic study on 94 men with LUTS/BPH treated with daily tadalafil 5 mg. The authors found that Qmax significantly increased by 2.9 mL/s at 12-month follow-up (p < 0.001), and detrusor overactivity and baseline diagnosed at cystometry in 49 men was no longer detected after 3 months of treatment in 15 patients (30.6%; p = 0.02), and in 22 at the end of the trial (44.9%, p < 0.001).5
Tamsulosin has been used in several trials as a comparator with tadalafil. In 2012 Oelke et al. compared, in a 12-week RCT, 171 men treated tadalafil 5 mg, 168 with tamsulosin 0.4 mg, and 172 with placebo.
Total IPSS significantly improved in both tadalafil (− 6.3 from baseline; Δplacebo= − 2.1; p = 0.001) and tamsulosin arms (− 5.7 from baseline; Δplacebo = − 1.5; p = 0.023). A significant improvement of Qmax was observed in both tadalafil (2.4 mL/s; p = 0.009) and tamsulosin (2.2 mL/s; p = 0.014) groups.6 In 2019, Pogula et al. compared tadalafil 5 mg with tamsulosin 0.4 mg in a 12-week RCT, enrolling 50 men with LUTS/BPH in each group. Total IPSS score was improved from baseline in both groups, without a statistically significant difference between the two treatment arms (tadalafil vs. tamsulosin: − 0.62 vs. − 2.76; p = 0.438). Qmax was improved in both groups too, compared with baseline; nevertheless, men in the tamsulosin group experienced a statistically significant improvement compared with tadalafil (tadalafil vs tamsulosin: + 2.4 vs. + 4; p = 0.002).7
In the last years, thanks to emerging evidence, the association of tadalafil and tamsulosin have been approved for the treatment of LUTS. Indeed, combination therapy with tadalafil 5 mg and tamsulosin 0.4 mg compared with tadalafil 5 mg monotherapy allowed a significant and similar improvement of total (combination vs tadalafil: − 7 vs. − 5.2, p = 0.08), voiding, storage (−3 vs. − 3.1, p = 0.08), and QoL (− 1.8 vs. − 1.3, p = 0.3) IPSS, but better outcomes in terms of Qmax (+ 4.2 vs. + 2.2, p = 0.027) and voiding IPSS (− 3.5 vs. − 2; p = 0.006) was significantly better in the combination arm. The incidence of treatment-emergent adverse effects (TEAEs) was numerically but not significantly higher in the combination group (22% vs. 16%, p = 0.07), with headache, nasopharyngitis, back pain, and dizziness being the most frequent.8 According to our reports, a combination of daily tadalafil 5 mg and tamsulosin 0.4 mg showed an improvement of LUTS relief when compared to monotherapy with both the single drugs, retaining a good compliance and safety profile, despite a slight increase of TEAEs.
Written by: Arcangelo Sebastianelli, MD, and Mauro Gacci, MD, Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, Careggi University Hospital, Florence, Italy
- Gacci, Mauro, Ian Eardley, Francois Giuliano, Dimitris Hatzichristou, Steven A. Kaplan, Mario Maggi, Kevin T. McVary, Vincenzo Mirone, Hartmut Porst, and Claus G. Roehrborn. "Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia." European urology 60, no. 4 (2011): 809-825.
- Gacci, Mauro, Giovanni Corona, Matteo Salvi, Linda Vignozzi, Kevin T. McVary, Steven A. Kaplan, Claus G. Roehrborn et al. "A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia." European urology 61, no. 5 (2012): 994-1003.
- McVary, Kevin T., Claus G. Roehrborn, Jed C. Kaminetsky, Stephen M. Auerbach, Barton Wachs, Jay M. Young, Anne Esler, Gregory D. Sides, and Bela S. Denes. "Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia." The Journal of urology 177, no. 4 (2007): 1401-1407.
- Porst, Hartmut, Kevin T. McVary, Francesco Montorsi, Peter Sutherland, Albert Elion-Mboussa, Anne M. Wolka, and Lars Viktrup. "Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia." European urology 56, no. 4 (2009): 727-736.
- Matsukawa, Yoshihisa, Shun Takai, Tsuyoshi Majima, Yasuhito Funahashi, Naoto Sassa, Masashi Kato, Tokunori Yamamoto, and Momokazu Gotoh. "Objective impacts of tadalafil on storage and voiding function in male patients with benign prostatic hyperplasia: 1-year outcomes from a prospective urodynamic study." World journal of urology 37, no. 5 (2019): 867-872.
- Oelke, Matthias, François Giuliano, Vincenzo Mirone, Lei Xu, David Cox, and Lars Viktrup. "Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial." European urology 61, no. 5 (2012): 917-925.
- Pogula, Vedamurthy Reddy, Lalith Sagar Kadiyala, Vijayabhaskar Reddy Gouru, Sivasankar Reddy Challa, Ranadheer Byram, and Sudeep Bodduluri. "Tadalafil vs. tamsulosin in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a prospective, randomized study." Central European journal of urology 72, no. 1 (2019): 44.
- Sebastianelli, Arcangelo, Pietro Spatafora, Jacopo Frizzi, Omar Saleh, Maurizio Sessa, Cosimo De Nunzio, Andrea Tubaro et al. "Tadalafil 5 mg alone or in combination with tamsulosin 0.4 mg for the management of men with lower urinary tract symptoms and erectile dysfunction: results of a prospective observational trial." Journal of clinical medicine 8, no. 8 (2019): 1126.