Symptomatic and urodynamic responses in patients with reduced or no seminal emission during silodosin treatment for LUTS and BPH

C G Roehrborn, S A Kaplan, H Lepor, W Volinn, C G Roehrborn, S A Kaplan, H Lepor, W Volinn

Abstract

Data from phase 3 studies (NCT00224107, NCT00224120) of silodosin for treatment of BPH symptoms were analyzed to examine the relationship between treatment efficacy and occurrence of abnormal ejaculation. Men aged ≥50 years with International Prostate Symptom Scores (IPSS) ≥13 and peak urinary flow rates (Qmax) of 4-15 ml s(-1) received placebo or silodosin 8 mg once daily for 12 weeks. Silodosin-treated patients were stratified by absence or presence of 'retrograde ejaculation' (RE). Groups were compared using analysis of covariance (for change from baseline) and responder analyses. Of the 466 patients receiving silodosin, 131 (28%) reported RE and 335 (72%) did not; 4 of the 457 patients receiving placebo (0.9%) reported RE. Most RE events in silodosin-treated patients (110/134; 82%) were reported as 'orgasm with absence of seminal emission.' Silodosin-treated patients with (+) and without (-) RE showed significant improvement in IPSS, Qmax and quality of life versus placebo (P<0.02). RE+ patients versus RE- patients experienced numerically greater improvement, but differences were not statistically significant (P>0.05). For RE+ patients, the odds of achieving improvement of ≥3 points in IPSS and ≥3 ml s(-1) in Qmax by study end were 1.75 times those for RE- patients (P=0.0127). Absence of seminal emission may predict superior treatment efficacy of silodosin in individual patients.

Figures

Figure 1
Figure 1
Mean changes from baseline in total IPSS (a), IPSS irritative subscore (b), IPSS obstructive subscore (c), Qmax (d) and QoL (e) by ejaculation status. Error bars indicate 95% confidence intervals. Abbreviations: BL, baseline; IPSS, International Prostate Symptom Score; LOCF, last observation carried forward; Qmax, peak urinary flow rate; QoL, quality of life; RE, retrograde ejaculation.
Figure 2
Figure 2
Patient response to silodosin treatment by ejaculation status. A patient was considered a responder if he experienced a 30% improvement in IPSS and Qmax or both an improvement in IPSS by at least 3 points and an improvement in Qmax by at least 3 ml s−1. Analyses were based on changes from baseline to week 12 (LOCF). IPSS, International Prostate Symptom Score; LOCF, last observation carried forward; Qmax, peak urinary flow rate; RE, retrograde ejaculation.

References

    1. Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008;15:193–199.
    1. Chapple CR. A comparison of varying alpha-blockers and other pharmacotherapy options for lower urinary tract symptoms. Rev Urol. 2005;7 (Suppl 4:S22–S30.
    1. American Urological Association Practice Guidelines Committee Results of the Treatment Outcomes AnalysesIn: Guideline on the management of benign prostatic hyperplasia (BPH). American Urological Association Education and Research, Inc., Chapter 3, 2006. Available at: .
    1. Djavan B, Marberger M. A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol. 1999;36:1–13.
    1. Andersson KE, Gratzke C. Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat Clin Pract Urol. 2007;4:368–378.
    1. Wilt TJ, Mac DR, Rutks I. Tamsulosin for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2003;1:CD002081.
    1. Lepor H. Long-term evaluation of tamsulosin in benign prostatic hyperplasia: placebo-controlled, double-blind extension of phase III trial. Tamsulosin Investigator Group. Urology. 1998;51:901–906.
    1. Narayan P, Lepor H. Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia. Urology. 2001;57:466–470.
    1. Hellstrom WJ, Sikka SC. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J Urol. 2006;176:1529–1533.
    1. Michel MC. Alpha1-adrenoceptors and ejaculatory function. Br J Pharmacol. 2007;152:289–290.
    1. Tatemichi S, Tomiyama Y, Maruyama I, Kobayashi S, Kobayashi K, Maezawa A, et al. Uroselectivity in male dogs of silodosin (KMD-3213), a novel drug for the obstructive component of benign prostatic hyperplasia. Neurourol Urodyn. 2006;25:792–799.
    1. Yoshida M, Homma Y, Kawabe K. Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia. Expert Opin Investig Drugs. 2007;16:1955–1965.
    1. Kobayashi S, Tomiyama Y, Tatemichi S, Hoyano Y, Kobayashi M, Yamazaki Y. Effects of silodosin and tamsulosin on the urethra and cardiovascular system in young and old dogs with benign prostatic hyperplasia. Eur J Pharmacol. 2009;613:135–140.
    1. Tatemichi S, Kobayashi K, Maezawa A, Kobayashi M, Yamazaki Y, Shibata N. Alpha1-adrenoceptor subtype selectivity and organ specificity of silodosin (KMD-3213)] Yakugaku Zasshi. 2006;126 (Spec no:209–216.
    1. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: Pooled results of 2 phase 3 studies. J Urol. 2009;181:2634–2640.
    1. Kawabe K, Yoshida M, Homma Y. Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int. 2006;98:1019–1024.
    1. Takao T, Tsujimura A, Kiuchi H, Matsuoka Y, Miyagawa Y, Nonomura N, et al. Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Int J Urol. 2008;15:992–996.
    1. Kobayashi K, Masumori N, Hisasue S, Kato R, Hashimoto K, Itoh N, et al. Inhibition of seminal emission is the main cause of anejaculation induced by a new highly selective alpha1A-blocker in normal volunteers. J Sex Med. 2008;5:2185–2190.
    1. Barry MJ, Williford WO, Chang Y, Machi M, Jones KM, Walker-Corkery E, et al. Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients. J Urol. 1995;154:1770–1774.

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