Tadalafil, phosphodiesterase 5 inhibitor, is comparably effective to improve male lower urinary tract symptoms (LUTS) as alpha-adrenergic antagonist. Thus, tadalafil or alpha-adrenergic antagonist is usually used as the first line drug for male LUTS. 
Dutasteride, a 5-alpha reductase inhibitor, has widely used to keep improving LUTS and benign prostatic enlargement (BPE). Several studies have shown the combination treatment with alpha-adrenergic antagonist and dutasteride is effective for patient with LUTS/BPE. However, there was no research to identify the effect of combination therapy with dutasteride and tadalafil.
The aim of this study was to investigate the efficacy of dutasteride add-on therapy to tadalafil in patients with LUTS/BPE and to compare with combination therapy with alpha-adrenergic antagonist and dutasteride.

The primary objective of the present study was to assess whether dutasteride add-on therapy improved the International Prostate Symptom Score (IPSS). Based on a projected difference of 4.0 in the change from baseline in IPSS, with an SD=7, a significant level of =0.05, two-sided, and a power of 90%, 44 evaluable patients were required. A prospective study was conducted in consecutive 49 patients with BPE who had not been satisfied with tadalafil monotherapy for more than 3 months. Inclusion criteria were prostate volume (PV) ≥30 ml and IPSS ≥8 or QOL index ≥3 under administration of tadalafil without anticholinergic agent. Before and 24 weeks after dutasteride (0.5 mg daily) add-on treatment with tadalafil, we assessed IPSS, OABSS (overactive bladder symptom score), serum PSA and testosterone, and uroflowmetry (UFM) to compare these parameters before and after dutasteride add-on therapy.
　We previously conducted a research of dutasteride add-on therapy to alpha-adrenergic antagonist from December 2009 to November 2011 on the same inclusion criteria [1]. We compared the efficacy of dutasteride add-on therapy to tadalafil and alpha-adrenergic antagonist using a propensity-score matching analysis
 The mean values of intra- and inter-group were statistically compared using t-test and Wilcoxon signed ranks test, with P<0.05 considered to indicate statistical significance. Propensity scores were calculated for each patient using multivariate logistic regression analysis including the following covariates: age, PV, and IPSS before dutasteride add-on.

Of 49 patients, 3 (6%) discontinued dutasteride during the study period and 46 were finally analyzed. Dutasteride add-on therapy to tadalafil significantly improved IPSS (from 16.4 ± 5.2 to 13.3 ± 6.4) and IPSS-QOL (from 4.0 ± 1.2 to 3.3 ± 1.1), and reduced PV from 55 ± 26 to 39 ± 22 ml. Total OABSS (from 6.2 ± 3.2 to 5.7 ± 2.8) and UFM parameter (maximum and average flow rate) or postvoid residual were not changed after dutasteride therapy. In 27 (59%) patients who was diagnosed with OAB based on OABSS, total OABSS tend to be improved from 7.3 ± 1.8 to 6.2 ± 2.7 (P=0.06). Serum PSA was decreased by 52% (from 5.7 ± 4.8 to 3.0 ± 2.9, ng/ml) and serum testosterone was not changed (from 427 ± 148 to 450 ± 162, ng/dl).
Propensity-score matching identified 42 matched pairs of patients. The improvement rate of IPSS (-20% vs -27%) and reduction rate of PV (-29% vs -28%) were similar between patients treated with dutasteride add-on therapy to tadalafil and alpha-adrenergic antagonist.

There were few published data that investigated the clinical efficacy of the combination therapy with tadalafil and 5-alpha reductase inhibitor including dutasteride and finasteride. This study indicates that the combination therapy with tadalafil and dutasteride is comparably effective to improve LUTS as the combination therapy with alpha-adrenergic antagonist and dutasteride. However, the add-on effect of dutasteride to tadalafil was not shown in UFM parameters. We do not have any clear explanation for this observation, but the number of patients might be too small to statistically prove the improvement of UFM parameters. The limitation of this study is a short-term follow-up period. Another limitation is the lack of data on sexual function.

Dutasteride add-on therapy to tadalafil for patients with LUTS and BPE is comparably effective as the combination therapy with alpha adrenergic antagonist and dutasteride.

Neurourol Urodyn . 2013 Nov;32(8):1123-7.