Combining Programmed Intracavernous PGE1 Injections and Sildenafil on Demand to Salvage Sildenafil Nonresponders

MALE AND FEMALE SEXUAL FUNCTION AND DYSFUNCTION; ANDROLOGY

relation between CRP levels and FSFI score (r ⫽ ⫺0.32, P ⫽ 0.02). Investigation of female sexuality is suggested for patients with the metabolic syndrome. Editorial Comment: The metabolic syndrome is an important risk factor for cardiovascular disease. The metabolic syndrome, as defined by the National Institutes of Health, consists of 3 or more of the following abnormalities—waist circumference greater than 102 cm in men and 88 cm in women, serum triglyceride level 150 mg/dl (1.69 mmol/l) or greater, high density lipoprotein cholesterol level less than 40 mg/dl (1.04 mmol/l) in men and 50 mg/dl (1.29 mmol/l) in women, blood pressure 130/85 mm Hg or greater and serum glucose level 110 mg/dl (6.1 mmol/l) or greater.1 These timely data by Esposito et al provide an organic basis for FSD. Data on treatment of the metabolic syndrome along with any positive effect on FSD are welcome. Allen D. Seftel, M.D. 1. National Institutes of Health: Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Washington, D. C.: United States Department of Health and Human Services, NIH Publication No. 01-3670, 2001

Chronic Treatment With Tadalafil Improves Endothelial Function in Men With Increased Cardiovascular Risk G. M. ROSANO, A. AVERSA, C. VITALE, A. FABBRI, M. FINI AND G. SPERA, Cardiovascular Research Unit, Department of Medical Sciences, San Raffaele—Roma, Rome, Italy Eur Urol, 47: 214 –222, 2005 OBJECTIVE: Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the study was to evaluate whether chronic therapy (4 weeks) with TAD improves endothelial function in patients with increased cardiovascular risk and whether this effect is sustained after discontinuation of therapy. METHODS: We randomized 32 patients with increased cardiovascular risk to receive either TAD 20 mg on alternate days or matching placebo (PLB) for 4 weeks. Patients underwent evaluation of brachial artery flow-mediated dilation (FMD), nitrite/nitrate and endothelin-1 plasma levels at baseline, at the end of treatment period and after two-weeks follow-up. RESULTS: At 4 weeks, FMD was significantly improved by TAD (from 4.2 ⫹/⫺ 3.2 to 9.3 ⫹/⫺ 3.7%, p ⬍0.01 vs. baseline), but was not modified by PLB (from 4.1 ⫹/⫺ 2.8 to 4.0 ⫹/⫺ 3.4%, p ⫽ NS). At 6 weeks the benefit in FMD was sustained in patients that received TAD (9.1 ⫹/⫺ 3.9% vs. 4.2 ⫹/⫺ 3.2%, p ⫽ 0.01 vs. baseline; 9.1 ⫹/⫺ 3.9% vs. 9.3 ⫹/⫺ 3.7%, vs. 4 weeks, p ⫽ NS) while no changes in FMD were observed in patients randomized to PLB. Also, compared to baseline, a net increase in nitrite/nitrate levels (38.2 ⫹/⫺ 12.3 vs. 52.6 ⫹/⫺ 11.7 and 51.1 ⫹/⫺ 3.1, p ⬍0.05) and a decrease in endothelin-1 levels (3.3 ⫹/⫺ 0.9 vs. 2.9. ⫹/⫺ 0.7 and 2.9 ⫹/⫺ 0.9, p ⬍0.05) was found both at four and six-weeks after TAD; these changes were inversely correlated as shown by regression analysis (adjusted R2 ⫽ 0.81, p ⬍0.0001). CONCLUSIONS: Chronic therapy with TAD improves endothelial function in patients with increased cardiovascular risk regardless their degree of ED. The benefit of this therapy is sustained for at least two weeks after the discontinuation of therapy. Larger studies are needed in order to assess the possible clinical implications of chronic therapy with TAD. Editorial Comment: These timely data offer a variety of important points to the reader. Tadalafil can be given every other day, and can safely be given to men with increased cardiovascular risk. Tadalafil continues to improve brachial artery blood flow, here 2 weeks after tadalafil cessation. Brachial artery blood flow may be a surrogate marker for endothelial blood flow in the penis. It would be interesting to know what happens to brachial artery blood flow after as needed tadalafil use, compared to the more customary 1 to 2 doses weekly. Allen D. Seftel, M.D. Combining Programmed Intracavernous PGE1 Injections and Sildenafil on Demand to Salvage Sildenafil Nonresponders P. GUTIERREZ, P. HERNANDEZ AND M. MAS, Department of Physiology and CESEX, Faculty of Medicine, Campus CC Salud, University of La Laguna, Tenerife, Spain Int J Impot Res, 17: 354 –358, 2005 In a prospective, placebo-controlled, one group crossover design study, we tested whether adding programmed intracavernous PGE1 injections (IC-PGE1) can improve the effectiveness of sildenafil in erectile dysfunction (ED) patients unresponsive to monotherapy with this drug. In all, 40 ED patients who had experienced unsatisfactory erections with both the 50 and 100 mg sildenafil doses were treated with four bi-weekly 20 mug IC-PGE1 injections given in the clinic and provided with either placebo or 50 mg sildenafil capsules for the next 4 weeks. Thereafter, they were crossed over to the other oral treatment for an additional 4-week period. The IIEF-Erectile Function domain score (IIEF-EFS), the main outcome measure,

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was found considerably higher (P ⬍0.001) with the combined IC-PGE1-50 mg sildenafil treatment than with IC-PGE1-placebo or sildenafil alone (50 or 100 mg) in a subset of 26 subjects (65%). They thus shifted from the ‘severe’ or ‘moderate’ to the ‘mild’ grading of ED classification. Editorial Comment: These data support the combined use of oral phosphodiesterase 5 inhibitor therapy (at mid range doses) with intracavernous therapies for men who are not fully responsive to oral phosphodiesterase 5 inhibitor therapy alone. Allen D. Seftel, M.D. The Utility of Tamsulosin in the Management of Orgasm-Associated Pain: A Pilot Analysis J. BARNAS, M. PARKER, P. GUHRING AND J. P. MULHALL, Department of Urology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York Eur Urol, 47: 361–365, 2005 INTRODUCTION: Orgasmic pain is an infrequently reported but distressing problem for the patients who experience it. No consensus exists as to its etiology however bladder neck/pelvic floor spasm may play a role. This analysis was conducted to assess the effect of the alpha-blocking medication, tamsulosin on post-orgasmic pain. METHODS: In a prospective, non-placebo controlled study, patients with orgasmic pain were interviewed and administered tamsulosin 0.4 mg po qhs for at least 4 weeks. Outcome measures included libido, pain and continence and these were evaluated using the International Index of Erectile Function (IIEF), a visual analog scale (VAS) for pain and an incontinence scale respectively pre and post treatment. Patients were separated into groups based on etiology of the problem (radical prostatectomy, radiation therapy, and other) for statistical analysis. RESULTS: 98 patients were enrolled. Pain was located predominantly in the penis (72%), with other sites including testis, rectum and abdomen. Most patients (52%) experienced pain for less than 5 minutes post-orgasm. 76/98 (77%) patients reported significant improvement in pain (⬎/⫽ 2 points on pain VAS) and 12/98 (12%) noted complete resolution of their pain. The VAS for pain reflected a statistically significant decrease in pain for all groups in response to tamsulosin treatment. The entire group had a decrease of 2.7 points between pre and post-treatment phases. The IIEF libido domain increased significantly (mean of 2.4 points) for all treatment groups. CONCLUSION: Tamsulosin decreases orgasmic pain intensity in patients with orgasmic pain. These data support the hypothesis that orgasmic pain is related to bladder neck and/or pelvic floor muscle spasm. Editorial Comment: This problem is not widely seen, or perhaps better stated, it is not widely reported. Most men with orgasmic pain either have undergone radical prostatectomy, or have prostatitis or lower urinary tract symptoms. It appears to be worthwhile to offer a short course of tamsulosin for this condition. Allen D. Seftel, M.D.

MALE INFERTILITY Stress Reduction in Male Infertility Patients: A Randomized, Controlled Trial M. POOK

AND

W. KRAUSE, Department of Psychology, University of Siegen, Siegen, Germany

Fertil Steril, 83: 68 –73, 2005 OBJECTIVE: To assess the impact of preparatory information about the fertility workup on the patients’ well-being. DESIGN: Two-group, randomized controlled study. SETTING: An andrology clinic. PATIENT(S): Two hundred fifty men enrolled for fertility workup. INTERVENTION(S): A two-page leaflet with preparatory information about the fertility workup, which was mailed to half of the participants after they had made an appointment. MAIN OUTCOME MEASURE(S): Questionnaire score for infertilityrelated distress at clinic attendance, proportion of participants that still had not attended 6 months after the scheduled appointment. RESULT(S): Distress scores and the proportion of nonattendees were significantly reduced in the group receiving the leaflet. An additional analysis revealed that 55% of the receivers did not know that the andrology clinic has its own web site, which was mentioned in the leaflet several times. CONCLUSION(S): Although it is uncertain how many patients actually read a routinely sent leaflet, preparatory information in written form is beneficial, at least for a significant subgroup of men who consider undergoing fertility workup. Fertility services might reduce the number of nonattendees by sending out leaflets. Editorial Comment: Infertility presents an emotionally charged disorder for female and male patients. Often the role of the physician addressing male reproductive dysfunction is to answer