Urodynamic and Symptomatic Improvement After Treatment With Silodosin in Men With Symptoms Secondary to Benign Prostatic Hyperplasia: Relationship Between Efficacy and Retrograde Ejaculation
Claus G. Roehrborn, MD1, Herbert Lepor, MD2, Steven A. Kaplan, MD3, Weining Volinn, MS4, Lawrence A. Hill, RPh, PharmD4.
1UT Southwestern Medical Center, Dallas, TX, USA, 2NYU School of Medicine, New York, NY, USA, 3Weill Medical College, Cornell University, New York, NY, USA, 4Watson Laboratories, Inc., Salt Lake City, UT, USA.
BACKGROUND: Smooth muscle relaxation in the bladder neck and prostate through blockade of alpha-1A-adrenoceptors is thought to be a central mechanism by which alpha-blockers improve urine flow and symptoms secondary to benign prostatic hyperplasia (BPH). Retrograde ejaculation (RE), a common adverse effect of some alpha-blockers, is believed to result from alpha-1A-adrenoceptor blockade in the male genital tract. We examined whether the occurrence of RE in patients receiving the highly alpha-1A-selective adrenoceptor antagonist silodosin is associated with increased improvement in symptoms or flow rate.
METHODS: In two US phase 3 studies, patients (age >50 yr) with moderate to severe BPH-related symptoms (IPSS ≥13; peak flow rate [Qmax] of 4 to 15 ml/sec; voided volume >125 ml; postvoid residual <250 ml) received 8 mg silodosin or placebo once daily for 12 weeks. In this secondary analysis, changes in IPSS and Qmax from baseline to week 12 (last observation carried forward) were analyzed separately in patients who experienced RE and those who did not. Treatment effects between groups were compared by analysis of covariance.
RESULTS: Of 466 patients who received silodosin, 131 (28.1%) experienced RE (SIL+RE) and 335 experienced no RE (SIL-RE); 457 patients received placebo. All three groups had similar baseline values for IPSS and Qmax. Compared with patients receiving placebo, patients in both SIL+RE and SIL-RE groups showed significant improvement (P<.02) in IPSS and Qmax after 12 weeks of treatment. Mean improvement in IPSS and Qmax was greater in the SIL+RE than in the SIL-RE group (Table). Although the difference in Qmax improvement for SIL+RE vs SIL-RE was not significant at the pre-specified significance level (5%), it would have been significant at a 10% significance level.
CONCLUSIONS: Overall, retrograde ejaculation related to silodosin treatment was indicative of greater improvement in symptoms and Qmax. The mean difference between SIL+RE and SIL-RE for Qmax was clinically meaningful. Superior alpha-1A-mediated relaxation of smooth muscle in the genital and lower urinary tracts may result in both RE as an adverse effect and greater efficacy in “unobstructing” urinary flow.
|Mean (SD)||Placebo||SIL−RE||P value|
SIL−RE vs placebo
|Baseline||21.3 (4.9)||21.0 (5.1)||22.2 (5.0)|
|Change from baseline (CFB) to wk 12 (last observation carried forward [LOCF])||−3.5 (5.8)||−6.1 (6.4)||<.0001||−7.2 (7.2)||<.0001||.3856|
|Baseline||8.9 (2.8)||8.6 (2.6)||8.9 (2.4)|
|CFB to wk 12 (LOCF)||1.5 (4.4)||2.4 (4.3)||.0184||3.1 (4.8)||.0003||.0699|