Peyronie's Disease: An Outcomes-Based Guide to Non-Surgical and Novel Treatment Modalities.

The clinical landscape of Peyronie's disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie's disease, it can be challenging to gain a thorough understanding of this body of literature. In this clinical management review, the workup and current theories on the pathophysiology of Peyronie's disease are reviewed, and the most recent outcomes data on the currently available non-surgical treatment modalities are presented. With an accurate understanding of the current landscape of Peyronie's disease treatment, sexual health providers will be able to better evaluate and engage in evidence-based shared decision-making with their patients.

Novel Treatments of Erectile Dysfunction: Review of the Current Literature.

INTRODUCTION: Although available treatments for erectile dysfunction (ED) have expanded, there has been a concomitant shift in the treatment paradigm. Newer treatment options focus on disease modification and improving overall erectile function. OBJECTIVE: The objective of this study is to review the evidence of 3 promising novel ED treatments. METHODS: A thorough review of the literature was divided into sections corresponding to low-intensity extracorporeal shockwave therapy (Li-ESWT), stem cell therapy (SCT), and platelet-rich plasma (PRP). Search terms included "erectile dysfunction" or "ED" plus "extracorporeal shockwave therapy", "stem cell therapy" or "platelet rich plasma". International Index of Erectile Function (IIEF) scores were the primary outcome measure. Secondary outcome measures included peak systolic velocity and intracorporeal pressure. RESULTS: Li-ESWT section includes 1 randomized controlled study, 2 prospective studies, 1 animal study, and 2 meta-analyses. IIEF score improvement was 3.54 (range 1.99-6.40). Authors concluded statistically significant short-term effect and improvement in erectile function (EF) with Li-ESWT. SCT section included 4 case series and 1 open-label study. Intraperitoneal, venous, and cavernosal SCT injections improved EF in animal models. 3 studies (n = 6-8) demonstrated 83-100% and 29-50% of patients regained erection and penetration ability, respectively. 2 studies (n = 12-16) found that all patients improved IIEF scores after SCT. Literature review for PRP yielded 3 animal, 1 retrospective, and 1 prospective study. Animal studies have shown that rats sustaining crush cavernosal injuries treated with PRP significantly improved EF and preservation of cavernous nerve axons. One retrospective analysis on humans showed mean improvement by 4.14 in IIEF scores. One prospective study on humans (n = 75) demonstrated improved peak systolic velocity (P = .005) and IIEF scores (P = .046) with PRP therapy. CONCLUSIONS: This review reveals limited published evidence on current novel ED treatment options. Further research on Li-ESWT, SCT, and PRP therapy is necessary to elucidate the role of these therapies in ED treatment regimens. Raheem OA, Natale C, Dick B, et al. Novel Treatments of Erectile Dysfunction: Review of the Current Literature. Sex Med Rev 2021;9:123-132.

Application of Botulinum Neurotoxin in Male Sexual Dysfunction: Where Are We Now?

INTRODUCTION: Botulinum neurotoxin (BoNT) is a recognized therapeutic agent of modern medical care, routinely used to treat medical conditions affecting a variety of organ systems including the musculoskeletal, integumentary, and urological domains. Ongoing research is exploring BoNT's potential role as a therapeutic agent for a variety of male sexual pathologies. OBJECTIVE: To review and analyze the literature regarding BoNT as a treatment option for male sexual dysfunction. METHODS: A PubMed search was performed for English-language articles in peer-reviewed journals between 1970 and 2019 (with one article from 1897). Relevant articles referenced within these texts were also included. One article did not have an accompanied English full-text available. The following search terms were used: "Botox", "Botulinum toxin", "Botulinum toxin A", "Onabotulinum A", "Abobutlinum A", "BoNT", "BoNT-A", "Male sexual health", "Male sexual pathology", "Peyronie's disease", "Premature ejaculation", "Scrotal Pain", "Penile Retraction", "Scrotox", "Erectile Dysfunction", and "Botox in Urology". RESULTS: There is interest in the potential role of BoNT in the treatment of male sexual pathologies. We identified studies that used BoNT to treat chronic scrotal content pain, premature ejaculation, erectile dysfunction, Peyronie's disease, penile retraction, and more. However, despite preclinical/clinical data indicating some potential efficacy and safety in these settings, a lack of robust clinical trial data has resulted in no current Food and Drug Administration-approved indications for the use of BoNT in the treatment of male sexual pathology. As a result, much of the current use of BoNT by today's providers is "off-label," and ongoing clinical trials aim to further elucidate the potential role of this therapeutic agent. CONCLUSION: Current data suggest that BoNT could have a potential role as a treatment option for certain types of male sexual pathologies. However, more randomized controlled trial data regarding its long-term safety and efficacy are necessary before a widespread clinical adoption can take place. Reddy AG, Dick BP, Natale C, et al. Application of Botulinum Neurotoxin in Male Sexual Dysfunction: Where Are We Now?. J Sex Med 2021;9:320-330.

Retained Reservoirs of Inflatable Penile Prosthesis: A Systematic Review of the Literature and a Guide to Perioperative Management.

INTRODUCTION: Retained reservoirs can be a complex problem for clinicians who manage patients with inflatable penile prostheses (IPPs). Although the general safety of retained reservoirs is well documented, data on the long-term outcomes of these foreign bodies is scarce. In recent years, complications associated with retained reservoirs and the subsequent management of these cases have become more recognized. AIM: To review, analyze, and summarize the concept of retained reservoirs and their associated complications with retained reservoirs and to provide a guide for management of complicated retained reservoir patients. METHODS: We performed a systematic review of the PubMed database on retained reservoir-related complications and perioperative management. MAIN OUTCOME MEASURES: We reviewed all publications that detailed complications associated specifically with retained penile prosthesis reservoirs and analyzed perioperative strategies used by providers. Any publication outlining IPP reservoir-related complication(s) stemming from a reservoir that was part of a functioning IPP was excluded. RESULTS: Although the risk is low, serious complications can and do arise from retained reservoirs. To properly manage these patients, clinicians must have knowledge of the prosthetic history and maintain a low threshold for obtaining cross-sectional imaging. By using methodical perioperative planning, the need for reintervention in patients with complications can be reduced, and improved surgical outcomes can be achieved. CONCLUSIONS: The management of retained reservoirs and their complications can be a clinical challenge for prosthetics providers. As such, more data regarding long-term outcomes and management strategies of retained reservoirs are required to better serve this subset of patients with prostheses. Reddy AG, Tsambarlis PN, Akula KP, et al. Retained Reservoirs of Inflatable Penile Prosthesis: A Systematic Review of Literature. Sex Med Rev 2020;8:355-363.

Complex penile prosthesis reservoir extraction: a case series.

Explantation of an inflatable penile prosthesis (IPP) reservoir in the setting of acute infection can be challenging. We identified three such cases of infection and simultaneous extraction of multiple reservoirs among patients with the most recent prosthetic surgeries performed between March 2016 and November 2018. These cases were reviewed with particular emphasis on preoperative and operative management. All three patients underwent successful simultaneous explantation of all retained hardware with subsequent clinical improvement in their clinical status. Prior to surgery, none of the patients were aware of the presence of more than one reservoir. All three patients recovered well post operatively. A subset of prosthetics patients have undergone multiple implant procedures at various sites. Due to the importance of retrieving all foreign material in the setting of acute infection, the authors advocate for a low threshold to obtain cross-sectional imaging to identify the tissue plane and laterality of any retained components, with particular emphasis on creating an operative plan for reservoir retrieval.

Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury.

BACKGROUND: Previous studies have documented improvement in erectile function after bilateral cavernous nerve injury (BCNI) in rats with the use of pioglitazone. Our group determined this improvement to be mediated by the insulin-like growth factor-1 (IGF-1) pathway. AIM: To eliminate the systemic effects of pioglitazone and evaluate the local delivery of IGF-1 by polymeric microspheres after BCNI in the rat. METHODS: Male Sprague-Dawley rats aged 10-12 weeks were assigned at random to 3 groups: sham operation with phosphate buffered saline (PBS)-loaded microspheres (sham group), crush injury with PBS-loaded microspheres (crush group), and crush injury with IGF-1-loaded microspheres (IGF-1 group). Poly(lactic-co-glycolic) acid microspheres were injected underneath the major pelvic ganglion (MPG). IGF-1 was released at approximately 30 ng/mL/day per MPG per rat. OUTCOMES: Functional results were demonstrated by maximal intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP). Protein-level analysis data of IGF-1 receptor (IGF-1R), extracellular signal-regulated kinase (ERK)-1/2, and neuronal nitric oxide synthase (nNOS) were obtained using Western blot analysis and immunohistochemistry for both the cavernosal tissue and the MPG and cavernous nerve (CN). RESULTS: At 2 weeks after nerve injury, animals treated with IGF-1 demonstrated improved erectile functional recovery (ICP/MAP) at all voltages compared with BCNI (2.5V, P = .001; 5V, P < .001; 7.5V, P < .001). Western blot results revealed that up-regulation of the IGF-1R and ERK-1/2 in both the nervous and erectile tissue was associated with improved erectile function recovery. There were no significant between-group differences in nNOS protein levels in cavernosal tissue, but there was an up-regulation of nNOS in the MPG and CN. Immunohistochemistry confirmed these trends. CLINICAL TRANSLATION: Local up-regulation of the IGF-1R in the neurovascular bed at the time of nerve injury may help men preserve erectile function after pelvic surgery, such as radical prostatectomy, eliminating the need for systemic therapy. STRENGTHS & LIMITATIONS: This study demonstrates that local drug delivery to the MPG and CN can affect the CN tissue downstream, but did not investigate the potential effects of up-regulation of the growth factor receptors on prostate cancer tissue. CONCLUSION: Stimulating the IGF-1R at the level of the CN has the potential to mitigate erectile dysfunction in men after radical prostatectomy, but further research is needed to evaluate the safety of this growth factor in the setting of prostate cancer. Haney NM, Talwar S, Akula PK, et al. Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury. J Sex Med 2019;16:383-393.

Unintended Consequences: A Review of Pharmacologically-Induced Priapism.

BACKGROUND: Priapism has been linked to many commonly prescribed medications, as well as recreational drugs and toxins. Although the incidence of priapism as a result of medication is small, the increasing use of antidepressants, antipsychotics, and recreational drugs may lead to more cases of pharmacologically-induced priapism in the future. AIM: To provide a comprehensive, up-to-date review of the most common causes of pharmacologically induced priapism and discuss incidence, pathophysiology, and basic management strategies. METHODS: A review of the available literature from 1960 to 2018 was performed using PubMed with regards to pharmacologically induced priapism. MAIN OUTCOME MEASURE: We reviewed publications that outlined incidence, pathophysiology, and management strategies for various pharmacologic causes of priapism: antidepressants, antipsychotics, antihypertensives, methylphenidate, cocaine, heparin, gonadotropin-releasing hormone, propofol, spider bites, and other miscellaneous causes. RESULTS: An understanding of the pathophysiology behind common pharmacologic causes of priapism can assist in the development of better treatment strategies and prevent future episodes of priapism. By understanding the potential risks associated with the use of medications with α-blocking or sympathomimetic properties, physicians can reduce the likelihood of priapism in their patients, especially those with other medical conditions that put them at increased baseline risk. Early corporal aspiration and injection of phenylephrine reduces additional complications related to priapism. In select patients, early placement of a penile prosthesis may prevent further morbidity. CONCLUSION: By developing a greater understanding of common pharmacologic causes of priapism, physicians can promptly identify and manage symptoms, leading to decreased patient morbidity. Scherzer ND, Reddy AG, Le TV, Chernobylsky D, Hellstrom WJG. Unintended Consequences: A Review of Pharmacologically-Induced Priapism. Sex Med Rev 2019;7:283-292.

Role of Penile Prosthesis in Priapism: A Review.

Ischemic priapism is a urological emergency that has been associated with long-standing and irreversible adverse effects on erectile function. Studies have demonstrated a linear relationship between the duration of critically ischemic episodes and the subsequent development of corporal fibrosis and irreversible erectile function loss. Placement of a penile prosthesis is a well-established therapeutic option for the management of erectile dysfunction secondary to ischemic priapism, and will be the focus of this review. Review of the current literature demonstrates a growing utilization of penile prostheses in the treatment of erectile dysfunction secondary to ischemic priapism. Unfortunately, there is a paucity of randomized-controlled trials describing the use of prosthesis in ischemic priapism. As a result, there is a lack of consensus regarding the type of prosthesis (malleable vs. inflatable), timing of surgery (acute vs. delayed), and anticipated complications for each approach. Both types of prostheses yielded comparable complication rates, but the inflatable penile prosthesis have higher satisfaction rates. Acute treatment of priapism was associated with increased risk of prosthetic infection, and could potentially cause psychological trauma, whereas delayed implantation was associated with greater corporal fibrosis, loss of penile length, and increased technical difficulty of implantation. The paucity of high-level evidence fuels the ongoing discussion of optimal use and timing of penile prosthesis implantation. Current guidance is based on consensus expert opinion derived from small, retrospective studies. Until more robust data is available, a patient-centered approach and joint decision-making between the patient and his urologist is recommended.