Safety and Efficacy of Tamsulosin in the Treatment of Painful Ejaculation: a Randomized, Double-Blind, Placebo-Controlled Study
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International Journal of Impotence Research (2006) 18, 527–533 & 2006 Nature Publishing Group All rights reserved 0955-9930/06 $30.00 www.nature.com/ijir ORIGINAL ARTICLE Safety and efficacy of tamsulosin in the treatment of painful ejaculation: a randomized, double-blind, placebo-controlled study MR Safarinejad Urology and Nephrology Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran We evaluate the efficacy and safety of tamsulosin a selective a1A-receptor antagonist in patients with painful ejaculation (PE) as a sole entity. A total of 118 men with PE were included in the study. Patients were randomly assigned to receive 0.4 mg oral daily tamsulosin (group 1, n ¼ 59) or placebo (group 2, n ¼ 59), during a 6-week period for each agent. Pretreatment evaluation included history and physical examination, International Index of Erectile Function (IIEF) and a visual analog scale (VAS) for pain. The efficacy of two treatments was assessed every 2 weeks during treatment, and at the end of the study using responses to IIEF, VAS evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. In all, 104 patients (88%) completed the whole treatment schedule. Pain resolved in 16 and 13% of the patients treated with tamsulosin and placebo, respectively (P ¼ 0.1). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 12 and 10 at 6-week treatment in groups 1 and 2, respectively (P ¼ 0.08). The VAS after tamsulosin and placebo decreased from 5.7 and 5.8 to 5.1 and 5.5, respectively (P ¼ 0.1). The mean weekly intercourse episodes increased from pretreatment values of 1.8 and 1.6 to 1.9 and 1.7, for tamsulosin and placebo, respectively (P ¼ 0.08). Mean number of adverse events was 11 for tamsulosin and 5 for placebo (Po0.05). Tamsulosin is no better than placebo in improvement of PE as a sole entity. International Journal of Impotence Research (2006) 18, 527–533. doi:10.1038/sj.ijir.3901466; published online 16 March 2006 Keywords: painful ejaculation; treatment; tamsulosin; ejaculation disorders Introduction infectious, psychological or neurological diseases are associated with the symptoms. The pain is Painful ejaculation (PE) is an uncommon problem refractory to conventional analgesics and several that may have psychological or organic causes. neuropathic pain therapies. The proposed theory for Although ejaculatory pain in the general male etiology of this problem in men is that pelvic floor population is considered to be 1%,1 it is presented muscle and/or bladder neck spasm are key to the a serious problem for 88–91% of men who experi- development of this condition. 2,3 4,5 ence it. It can be caused by prostatectomy, a Three a1-adrenoceptor subtypes a1A, a1B and a1D 6 7,8 19 history of prostatitis, pelvic radiation, lower exist. Another a1-adrenoceptor subtype with a urinary tract symptoms (LUTS) diagnosed with low-affinity prazosin adrenoceptor termed a1L also 9,10 19 clinical benign prostatic hyperplasia (BPH), exists. a1-receptors predominate in the prostate chronic pelvic pain disorder,11 and neuroleptics.12–18 gland, prostatic capsule, prostatic urethra and On the other hand, PE as a sole entity is rare, and bladder.20 Electrophysiological study of prostate its etiology often remains unknown. No urogenital, and smooth muscles have shown that the a1A and a1L-adrenoceptor subtype predominates in the prostate capsule and it is responsible for mediating smooth muscle tone.21–25 Another study demon- Correspondence: Dr MR Safarinejad, Urology and Ne- strates that a -adrenoceptors in the human detrusor phrology Research Center, Shaheed Beheshti University of 1 are of the a1D and, to a lesser extent, the a1A Medical Sciences, PO Box 19395-1849, Tehran, Iran. 26 E-mail: [email protected] subtypes. Tamsulosin is an a1-adrenoceptor an- Received 12 December 2005; revised 19 January 2006; tagonist that exhibits selectivity for a1A – and, accepted 13 February 2006; published online 16 March somewhat lesser extent, a1D – over a1B-adrenocep- 2006 tors.26–29 In addition, tamsulosin has 12 times Safety and efficacy of tamsulosin in the treatment of painful ejaculation MR Safarinejad 528 greater affinity for a1-adrenoceptors in the human eligible for study. Age limits were selected to prostate than in the aorta in contrast to prazosin, exclude men from the study who might have helped which has comparable affinity for those in the from a-blocker therapy for symptoms associated prostate and aorta.30 This can be referred to as with BPH. Only patients without any obvious receptor pharmacological uroselectivity.31 organic, psychogenic, neurogenic, infectious and A randomized, placebo-controlled, multi-center drug-induced causes of PE, and serum PSA level of clinical trial studying the efficacy of tamsulosin in p4 ng/ml were included in the study. We presumed treating patients with chronic prostatitis/chronic that for preventing bias in study protocol, the pelvic pain syndrome (CP/CPPS) has demonstrated patients had to have adequate frequency of inter- improvement in pain using tamsulosin.11 Also course, therefore only patients with possible sexual tamsulosin was superior to placebo in providing intercourse equal or greater than one per week were symptomatic relief in men with CP/CPPS in few included. studies.11,32 Case reports have also suggested tam- Patients with chronic or acute bacterial and sulosin to be effective in alleviating PE in clinically nonbacterial prostatitis, CPPS, prostatodynia, abnor- depressed patients.33 Given the aforementioned mal digital rectal examination (DRE), bacteriuria postulated theory for the origin of PE and the within 3 months of screening, any urogenital uroselectivity of tamsulosin, we decided to test its disease, prior prostate or pelvic surgery or pelvic potential therapeutic effect on PE as a sole entity. To radiotherapy, a history of another chronic pain our knowledge this is the first double-blind placebo disorder or using any therapy for chronic pelvic controlled study on the efficacy of tamsulosin for pain disorders such as central analgesic agents, a treating PE in patients without any urogenital, history of active genital herpes within the previous infectious, psychological or neurological causes. year, a history of genitourinary cancer, inflammatory bowel disease, abnormal serum chemistries or complete blood count, history of allergy to a- Materials and methods adrenergic antagonists or hypersensitivity to tamsu- losin, postural hypotension, cancer diagnosed within 5 years of baseline, finasteride use within Study design 3 months, or cardiac, endocrine, or neurological This study comprised 118 married men (aged 21–40 disorders, were excluded. Medications known to years) with PE as a sole entity. All patients gave their cause PE (such as imipramine, desipramine, clomi- written informed consent to participate in the study pramine, protriptyline, amoxapine, fluoxetine and after procedures, and possible side effects were venlafaxine) or interference with the study drug or explained to them. All couples were in a stable influence the symptom of PE (such as a-adrenergic relationship for at least 6 months. The primary blocking drugs, a-adrenergic agents, drugs with diagnostic criterion was pain or discomfort during anticholinergic activity, antispasmodics or muscle or immediately after ejaculation in more than 90% relaxants, parasympathomimetics or cholinomi- of coitus for at least 3 months in the previous 6 metics, nonsteriodal anti-inflammatory drugs, anti- months. biotics, warfarin, cimetidine, herbal medications and intravesical bacillus Calmette-Guerin) were not Evaluations permitted. All patients underwent preliminary assessment, including a medical and sexual history, physical examination, and structured interview diagnostic of Medical treatment mental and physical disorders. To be able to exclude The patients were randomly assigned to either group organic causes, urine analysis, urine culture, urine of 59 subjects each. Each eligible patient was given a cytology, semen culture, and expressed prostatic randomization number using an interactive voice secretions analysis were done and serum chemis- response system, which followed a randomization tries, serum prostate-specific antigen (PSA) level, table generated by the method of random permuted and complete blood count were measured. We used blocks. Persons who were geographically and oper- ligase chain reaction to screen for Chlamydia in ationally independent from the study investigator urethral urine samples and excluded men whose did the randomization of the study. Group 1 was tests yielded positive results. All patients had given 0.4 mg tamsulosin (Omnic, Yamanouchi Eur- undergone cystoscopy to exclude lower urinary tract ope, The Netherlands) orally daily for 6 weeks. pathology. Group 2 received a similar regimen of placebo. The placebo capsules were a starch compound with the same color and size of tamsulosin. All the men were Inclusion/exclusion criteria asked not to consume alcoholic drinks within 6 h of Men 40 years old or younger diagnosed with PE and sexual activity. Treatment was administered in a with negative urine and semen cultures and normal randomized sequence that remained unknown to expressed prostatic secretions at baseline were the patient and to the physician. International Journal of Impotence Research Safety and efficacy of tamsulosin in the treatment of painful ejaculation MR Safarinejad 529 Table 1 International index of erectile