Search

Introduction Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drug. Post-SSRI sexual dysfunction (PSSD) is a condition in which patients continue to have sexual side effects after discontinuation of SSRI use. The prevalence of persistent sexual side effects after discontinuing SSRIs is unknown. The recognition and study of PSSD will increase our knowledge base of this underreported and distressing condition. Aim To provide coverage of the current literature on PSSD, update information on the pathophysiology of PSSD, and discuss potential management options. Methods Comprehensive review of literature pertaining to PSSD. Main Outcome Measures The symptoms, classification, pathophysiology, diagnostic considerations, and management of PSSD were reviewed. Results Common PSSD symptoms include genital anesthesia, pleasure-less or weak orgasm, decreased sex drive, erectile dysfunction, and premature ejaculation. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression theory, cytochrome actions, dopamine-serotonin interactions, proopiomelanocortin and melanocortin effects, serotonin neurotoxicity, downregulation of 5-hydroxytryptamine receptor 1A, and hormonal changes in the central and peripheral nervous systems. The diagnosis of PSSD is achieved by excluding all other etiologies of sexual dysfunction. Treating PSSD is challenging, and many strategies have been suggested and tried, including serotonergic antagonists and dopaminergic agonists. There is still no definitive treatment for PSSD. Low-power laser irradiation and phototherapy have shown some promising results. Conclusion PSSD is a debilitating condition that adversely affects quality of life. Further studies are warranted to investigate the prevalence, pathophysiology, and treatment of PSSD. Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A Literature Review. Sex Med Rev 2018;6:29–34.

Paige K Kuhlmann,1 Kenneth J DeLay,2 James Anaissie,2 Wayne JG Hellstrom,2 Faysal A Yafi3 1University of Missouri-Columbia School of Medicine, Columbia, MO, 2Department of Urology, Tulane University School of Medicine, New Orleans, LA, 3Department of Urology, University of California Irvine, Orange, CA, USA Abstract: The safety and efficacy of the use of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie’s disease has been confirmed over the past several years. However, identification of the ideal patient population for use of this treatment is not well established. Multiple studies have attempted to delineate various patient-specific factors that may predict response to treatment with CCH, with the intent of enhancing patient selection. To date, these include baseline curvature severity, duration of disease, disease phase at presentation, plaque calcification, baseline erectile function, plaque size, age, comorbid diabetes, previous penile trauma, responsiveness to first treatment cycle, baseline penile shortening or pain, prior treatment with intralesional injection, compliance with plaque modeling, and atypical curvature. In addition, other studies have sought to explore various aspects of treatment with CCH that may affect patient perspective of treatment. They have focused on patient-reported outcomes, female partner considerations, cost of treatment, and potential confounders of patient satisfaction. This review provides a summary and analysis of currently available literature on topics of patient selection and perspectives in regard to treatment of Peyronie’s disease with CCH. Keywords: Peyronie’s disease, collagenase Clostridium histolyticum, Peyronie’s disease questionnaire, curvature deformity, intralesional injection, erectile function

James Anaissie,Wayne JG Hellstrom Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA Abstract: Erectile dysfunction (ED) is a common and debilitating disorder seen in over 50% of men older than 70 years. Oral phosphodiesterase type 5 (PDE5) inhibitors are the mainstay of treatment for ED, but cannot be used by a significant subset of patients due to systemic side effects and drug–drug interactions. Second-line therapy may include intracavernosal therapies, but are associated with poor compliance due to their invasive nature. Alprostadil has a mechanism of action different from that of PDE5 inhibitors. Clinical trials have shown topical alprostadil cream to be effective, increasing the erectile function (EF) score of the International Index of EF by up to 13 points from baseline. It has also proven to be safe and well tolerated, with mild-to-moderate and transient treatment-related adverse events that are generally localized to the application site. Topical alprostadil cream is a safe and effective second-line therapy for ED, indicated for those who cannot tolerate, or are not satisfied with, oral PDE5 inhibitor therapy. Keywords: erectile dysfunction, topical cream, second-line treatment, alprostadil

…

Objectives. To evaluate the reliability of vardenafil efficacy and tolerability within 12 weeks in a broad population of men with erectile dysfunction (ED). Methods. In a retrospective analysis of two pivotal, Phase III, randomized, double-blind, placebo-controlled trials conducted in 107 centers, 1650 men aged 18 years or older with ED received vardenafil 5 mg, 10 mg, or 20 mg on demand for 12 to 26 weeks. Outcome measures included the first-time and subsequent overall success rate until week 12 for diary entries regarding vaginal penetration (Sexual Encounter Profile [SEP]-2), erection maintenance (SEP-3), satisfaction with erection hardness, and overall satisfaction with the sexual experience. Mean efficacy was calculated for each patient during 12 weeks and then averaged for all patients within each treatment group. Results. At baseline, the intention-to-treat population had moderate ED (International Index of Erectile Function-Erectile Function domain score of 13). For SEP-2 (penetration), the first-attempt and subsequent success rate was 44% and 74% for placebo, 71% and81% for vardenafil 5 mg, 76% and 86% for vardenafil 10 mg, and 76% and 91% for vardenafil 20 mg, respectively. For SEP-3 (maintenance), first-attempt and subsequent success rate was 25% and 56% for placebo, 51% and 76% for vardenafil 5 mg, 65% and 76% for vardenafil 10 mg, and 59% and 84% for vardenafil 20 mg, respectively. For overall satisfaction with the sexual experience, the first-attempt and subsequent success rate was 19% and 48% for placebo, 48% and 68% for vardenafil 5 mg, 57% and 72% for vardenafil 10 mg, and 56% and 79% for vardenafil 20 mg, respectively. The reliability of vardenafil was similar or slightly greater in sildenafil-naive subjects compared with prior sildenafil responders. The most common adverse events were mild-to-moderate headache, flushing, and rhinitis. Conclusions. Vardenafil provides reliable efficacy for key erectile function parameters important to patients when continuing oral treatment for ED. (C) 2004 Elsevier Inc.

Introduction. Is there any unequivocal evidence that testosterone (T) can stimulate growth and aggravate symptoms in men with locally advanced and metastatic prostate cancer (PCa)? This is not a controversial point: the answer is yes. However, this evidence does not imply that PCa is a result of T or therapy with T (TTh) of hypogonadal men. Furthermore, currently adequately powered and optimally designed long-term prostate disease data are not available to determine if there is an additional risk from normal T values in cured patients for PCa. Methods. This Controversy is introduced by an endocrinologist, the section editor (E.A.J.) with G.L.G., a fellow urologist and radiotherapist expert in basic research on PCa. Two outstanding urologists, A.M and W.J.G.H., debate clinical data and clinical guidelines, respectively. Finally, other controversial issues are discussed by another leader in the field (A.M.) and a radiation oncologist and sexologist who is actually president of the International Society for Sexuality and Cancer (L.I.). Main Outcome Measure. Expert opinion supported by the critical review of the currently available literature. Result. The answer to the main question "is the prostate a really T-dependent tissue?" is definitively yes, but T stimulates the prostatic tissue in a dose-dependent fashion only to a saturation point, achieved at low T concentrations. At these low T concentrations, stimulation is near maximal, and T supplementation above this level would not lead to significantly greater stimulation. Furthermore, there is no conclusive evidence that TTh increases the risk of PCa or even prostatic hyperplasia. There is also no evidence that TTh will convert subclinical PCa to clinically detectable PCa. However, there is a limited clinical experience of TTh after successful treatment of PCa. So far, just 48 patients have been studied in the three published articles. Conclusions. It is evident that the issue is still controversial and much more research is needed. However, the available data suggest to the expert in sexual medicine that TTh can be cautiously considered in selected hypogonadal men previously treated for curative intent of low-risk PCa and without evidence of active disease. Jannini EA, Gravina GL, Mortengaler A, Morales A, Incrocci L, and Hellstrom WJG. Is testosterone a friend or a foe of the prostate? J Sex Med 2011;8:946-955.

We sought to develop a reproducible TGF-β1 injection technique to induce urethral fibrosis in the rat urethra.A total of 32 male Sprague Dawley® rats weighing 300 to 350 gm were anesthetized with ketamine/xylazine intraperitoneally. Using a 5 mm penoscrotal incision the rat urethra was exposed. In the experimental group varying doses of TGF-β1 (5, 10 and 25 μg) were injected in each side of the urethral wall. Normal saline infiltration was used in the sham treated group. Rats were sacrificed 2 and 4 weeks following TGF-β1 injection. Urethral specimens were stained with hematoxylin and eosin, and Masson trichrome, and Western blot evaluations were performed. Normal and strictured urethral tissues from patients were collected and evaluated in the same fashion.There was no evidence of urethral wall thickening or fibrosis in the sham treated group. Varied histological evidence of fibrosis was noted in all experimental groups. There was a significant increase in collagen type I expression 2 weeks after injection of 5, 10 and 25 μg TGF-β1. Collagen type III expression was significantly increased 2 weeks after injecting 10 and 25 μg of TGF-β1, which persisted to 28 days after injection.TGF-β1 injection can successfully generate a reproducible rat model of urethral spongiofibrosis. This technique is simple, inexpensive and reproducible. Our series is a proof of concept study. Additional studies in larger animals are needed to further confirm our findings.

OBJECTIVE To examine the effect of pioglitazone on erectile function in a rat model of postprostatectomy erectile dysfunction. METHODS Twenty adult rats were divided into 4 groups: (a) sham, (b) control-bilateral cavernosal nerve crush injury (BCNI), (c) BCNI + low-dose pioglitazone (PioL), and (d) BCNI + high-dose pioglitazone (PioH). Sham and control rats were administered phosphate-buffered saline, whereas PioL and PioH rats received 0.65 and 6.5 mg/kg of pioglitazone, respectively. All treatments were administered by oral gavage for 14 days. After treatment, animals underwent surgery for endpoint cavernosal response to define hemodynamic parameters of erectile function, reported as the ratio of intracavernosal pressure to mean arterial pressure. Corporal tissue was retrieved for histologic and molecular analysis. RESULTS Animals treated with pioglitazone experienced dose-dependent improvements in the ratio of intracavernosal pressure to mean arterial pressure, with the PioH group achieving results similar to the sham group: sham, 0.774; BCNI, 0.421; PioL, 0.616; PioH, 0.758 (P = .0006). PioH animals demonstrated increased expression of endothelial nitric oxide (eNOS) and neuronal nitric oxide (nNOS), whereas both PioL and PioH animals had increased staining for anti-smooth muscle actin antibody and nonsignificant increases in cyclic guanosine monophosphate (cGMP). CONCLUSION Pioglitazone improves erectile function in rats undergoing BCNI via a nitric oxide-mediated pathway. (C) 2014 Elsevier Inc.

Objective To investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on erectile and penile vascular function in the rat. Methods The effect of chronic treatment with escitalopram (0.286 mg/kg/day) on change in intracavernosal pressure, maximum intracavernosal pressure/mean arterial pressure, and area under the intracavernosal pressure curve in response to cavernosal nerve stimulation was measured. The effect of chronic escitalopram treatment on endothelial-dependent relaxant responses was investigated in isolated mesenteric and internal pudendal resistance arteries. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and nitric oxide synthase levels were determined with enzymatic assay and Western blot, respectively. Results Chronic treatment with escitalopram resulted in a significant reduction in the erectile response to cavernosal nerve stimulation without an effect on the response to intracavernosal injection of the nitric oxide donor sodium nitroprusside. The decrease in erectile function was associated with marked increases in NADPH oxidase activity in the corpora cavernosa. Treatment with escitalopram also caused a significant reduction in the relaxant response to acetylcholine in isolated internal pudendal and mesenteric resistance arteries without altering the response to sodium nitroprusside. The decreased response to acetylcholine in the isolated vascular segments was associated with a marked increase in NADPH oxidase activity that was corrected by treatment with the NAPDH oxidase inhibitor apocynin. Conclusion The inhibitory effects of escitalopram on erectile and vascular function were not accompanied by a change in endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase expression, or endothelial nitric oxide synthase activity, suggesting that the inhibitory effect is caused by a decrease in nitric oxide bioavailability mediated by increased NADPH oxidase and reactive oxygen species production.

Introduction Androgen deprivation therapy (ADT) is commonly utilized in the management of both localized and advanced adenocarcinoma of the prostate. The use of ADT is associated with several adverse events, physical changes, and development of medical comorbidities/mortality. Aim The current article reviews known adverse events associated with ADT as well as treatment options, where available. Current recommendations and guidelines are cited for ongoing monitoring of patients receiving ADT. Methods A PubMed search of topics relating to ADT and adverse outcomes was performed, with select articles highlighted and reviewed based on level of evidence and overall contribution. Main Outcome Measures Reported outcomes of studies detailing adverse effects of ADT were reviewed and discussed. Where available, randomized trials and meta-analyses were reported. Results ADT may result in several adverse events including decreased libido, erectile dysfunction, vasomotor symptoms, cognitive, psychological and quality of life impairments, weight gain, sarcopenia, increased adiposity, gynecomastia, reduced penile/testicular size, hair changes, periodontal disease, osteoporosis, increased fracture risk, diabetes and insulin resistance, hyperlipidemia, and anemia. The definitive impact of ADT on lipid profiles, cardiovascular morbidity/mortality, and all-cause mortality is currently unknown with available data. Treatment options to reduce ADT-related adverse events include changing to an intermittent treatment schedule, biophysical therapy, counseling, and pharmacotherapy. Conclusions Patients treated with ADT are at increased risk of several adverse events and should be routinely monitored for the development of potentially significant morbidity/mortality. Where appropriate, physicians should reduce known risk factors and counsel patients as to known risks and benefits of therapy.

Phosphodiesterase-5 inhibitors (PDE5i, sildenafil, vardenafil, tadalafil and avanafil) are a first-line medical therapy for erectile dysfunction (ED). In all likelihood, PDE5i usage will increase because sildenafil (Viagra(R) and Revatio(R)) and tadalafil (Cialis(R) and Adcirca(R)) have recently been recommended as first-line therapy for patients with pulmonary hypertension (PH). PDE5i exhibit higher plasma concentrations when co-administered with cytochrome P (CYP) 3A inhibitors, which influences their side-effect profile. The higher PDE5i plasma concentrations, caused by CYP3A inhibitors, influence the severity and timing of PDE5i drug interactions and require dose adjustment. PDE5i are safe when used with most antihypertensive agents, but co-administration with nitrates or alpha-blockers can cause severe hypotension and syncope. Dose adjustment is also necessary when PDE5i are co-administered with CYP3A inducers. The combination of oral tadalafil and bosentan (endothelin receptor antagonist) reduces tadalafil levels and requires dose adjustment. Current literature reports a number of interactions between PDE5i and other agents and further studies are needed to expand our knowledge base of these interactions. This review discusses relevant PDE5i drug interactions, including those with CYP 450 inhibitors and inducers which are frequently used during the treatment of ED and PH.

Introduction Penile implant surgery continues to be an important option for men with erectile dysfunction. Advancements in technology of implants have contributed to improved survival from mechanical breakdown. Prosthesis infection remains a serious adverse event. For the last 8 years, the Titan implant (Coloplast Corporation, Minneapolis, MN, USA) has been available with an infection‐retardant polyvinylpyrrolidone coating. Aim To compare the infection rates between coated three‐piece inflatable penile prostheses (IPPs) with the previous non‐coated model. Main Outcome Measures Infection‐related revisions reported in the physician‐generated, manufacturer‐tabulated patient information forms (PIFs). Methods PIFs reported into the voluntary, post‐market registry of Coloplast Corporation from July 14, 2000 to September 30, 2011 were retrospectively reviewed. Infection‐related revisions entered into the product evaluation database for coated and non‐coated IPPs were compared. Data were analyzed using Pearson's chi‐squared test. Results The database included 36,391 PIFs related to primary IPP implantation. At 11 years of follow‐up, 4.6% (7,031) of non‐coated IPPs were removed or replaced due to infections, whereas 1.4% (29,360) of hydrophilic‐coated implants reported replacements due to device infections. The hydrophilic coating of the IPP components makes the device slippery and prevents bacterial attachment. The hydrophilic coating allows rapid absorption of antibiotics in an aqueous solution and allows these water‐soluble antibiotics to elute off the device into the implant spaces. Unfortunately, information pertaining to what agents were used in the studies patients was not tabulated. The rate of revision due to device infection was reduced 69.56% in patients with hydrophilic‐coated IPPs (P Conclusion To the best of our knowledge, this is the longest post‐marketing registry report related to IPP infections. At 8 years of follow‐up, the hydrophilic‐coated IPPs demonstrated a significant reduction in revision rates due to infection when compared with the 11‐year follow‐up of non‐coated implants. Since there was no information or uniformity of antibiotics used in the soaking solution, it is uncertain which antibiotic selection provided the best results. In vitro testing against known infectious agents may further benefit IPP patients by reducing the prosthesis infection rate. Serefoglu EC, Mandava SH, Gokce A, Chouhan JD, Wilson SK, and Hellstrom WJG. Long‐term revision rate due to infection in hydrophilic‐coated inflatable penile prostheses: 11‐year follow‐up. J Sex Med 2012;9:2182–2186.