Priapism and sickle-cell anemia: diagnosis and nonsurgical therapy

IntroductionPriapism describes a persistent erection lasting longer than 4 hours. Ischemic priapism and stuttering priapism are phenotypic manifestations of sickle‐cell disease (SCD).AimsTo define the types of priapism associated with SCD, to address pathogenesis, and to recommend best practices.SourcesLiterature review and published clinical guidelines.Summary of FindingsPriapism is a full or partial erection that persists more than 4 hours. There are three kinds of priapism: ischemic priapism (veno‐occlusive, low flow), stuttering priapism (recurrent ischemic priapism), and nonischemic priapism (arterial, high flow). Ischemic priapism is a pathologic phenotype of SCD. Ischemic priapism is a urologic emergency when untreated priapism results in corporal fibrosis and erectile dysfunction. The recommended treatment for ischemic priapism is decompression of the penis by needle aspiration and if needed, injection (or irrigation) with dilute sympathomimetic drugs. Stuttering priapism describes a pattern of recurring unwanted painful erections in men with SCD. Patients typically awaken with an erection that persists for several hours and becomes painful. The goals of managing stuttering ischemic priapism are: prevention of future episodes, preservation of erectile function, and balancing the risks vs. benefits of various treatment options. The current molecular hypothesis for stuttering priapism in SCD proposes that insufficient basal levels of phosphodiesterase type‐5 are available in the corpora to degrade cyclic guanosine monophosphate (cGMP). Nocturnal erections result from normal neuronal production and surges of cGMP. In the context of SCD stuttering priapism, these nocturnal surges in cGMP go unchecked, resulting in stuttering priapism.ConclusionsConsidering the embarrassing nature of the problem and the dire consequences to erectile function, it is important to inform patients, parents, and providers about the relationship of SCD to prolonged painful erections. Prompt diagnosis and appropriate medical management of priapism are necessary to spare patients surgical interventions and preserve erectile function. Broderick GA. Priapism and sickle‐cell anemia: Diagnosis and nonsurgical therapy. J Sex Med 2012;9:88–103.     

Erectile Dysfunction after Sickle Cell Disease–Associated Recurrent Ischemic Priapism: Profile and Risk Factors

IntroductionRisk factors associated with erectile dysfunction (ED) that results from recurrent ischemic priapism (RIP) in sickle cell disease (SCD) are incompletely defined.AimThis study aims to determine and compare ED risk factors associated with SCD and non‐SCD‐related “minor” RIP, defined as having ≥2 episodes of ischemic priapism within the past 6 months, with the majority (>75%) of episodes lasting <5 hours.MethodsWe performed a retrospective study of RIP in SCD and non‐SCD patients presenting from June 2004 to March 2014 using the International Index of Erectile Function (IIEF), IIEF‐5, and priapism‐specific questionnaires.Main Outcome MeasuresPrevalence rates and risk factor correlations for ED associated with RIP.ResultsThe study was comprised of 59 patients (40 SCD [mean age 28.2 ± 8.9 years] and 19 non‐SCD [15 idiopathic and four drug‐related etiologies] [mean age 32.6 ± 11.7 years]). Nineteen of 40 (47.5%) SCD patients vs. four of 19 (21.1%) non‐SCD patients (39% overall) had ED (IIEF <26 or IIEF‐5 <22) (P = 0.052). SCD patients had a longer mean time‐length with RIP than non‐SCD patients (P = 0.004). Thirty of 40 (75%) SCD patients vs. 10 of 19 (52.6%) non‐SCD patients (P = 0.14) had “very minor” RIP (episodes regularly lasting ≤2 hours). Twenty‐eight of 40 (70%) SCD patients vs. 14 of 19 (73.7%) non‐SCD patients had weekly or more frequent episodes (P = 1). Of all patients with very minor RIP, ED was found among 14 of 30 (46.7%) SCD patients vs. none of 10 (0%) non‐SCD patients (P = 0.008). Using logistic regression analysis, the odds ratio for developing ED was 4.7 for SCD patients, when controlling for RIP variables (95% confidence interval: 1.1–21.0).ConclusionsED is associated with RIP, occurring in nearly 40% of affected individuals overall. SCD patients are more likely to experience ED in the setting of “very minor” RIP episodes and are five times more likely to develop ED compared with non‐SCD patients. Anele UA and Burnett AL. Erectile dysfunction after sickle cell disease–associated recurrent ischemic priapism: Profile and risk factors. J Sex Med 2015;12:713–719.     

Exploring the Use of Exchange Transfusion in the Surgical Management of Priapism in Sickle Cell Disease: A Population-Based Analysis

IntroductionPriapism is a urologic emergency that may require surgical intervention in cases refractory to supportive care. Exchange transfusion (ET) has been previously used to manage sickle cell disease (SCD), including in priapism; however, its utilization in the context of surgical intervention has not been well-established.AimTo explore the utilization of ET, as well as other patient and hospital-level factors, associated with surgical intervention for SCD-induced priapismMethodsUsing the National Inpatient Sample (2010–2015), males diagnosed with SCD and priapism were stratified by need for surgical intervention. Survey-weighted regression models were used to analyze the association of ET to surgical intervention. Furthermore, negative binomial regression and generalized linear models with logarithmic transformation were used to compare ET vs surgery to length of hospital stay (LOS) and total hospital charges, respectively.Main Outcome Measures: Predictors of surgical intervention among patients with SCD-related priapismResultsA weighted total of 8,087 hospitalizations were identified, with 1,782 (22%) receiving surgical intervention for priapism, 484 undergoing ET (6.0%), and 149 (1.8%) receiving combined therapy of both ET and surgery. On multivariable regression, pre-existing Elixhauser comorbidities (e.g. ≥2 Elixhauser: OR: 2.20; P < 0.001), other forms of insurance (OR: 2.12; P < 0.001), and ET (OR: 1.99; P = 0.009) had increased odds of undergoing surgical intervention. In contrast, Black race (OR: 0.45; P < 0.001) and other co-existing SCD complications (e.g. infectious complications OR: 0.52; P < 0.001) reduced such odds. Compared to supportive care alone, patients undergoing ET (adjusted IRR: 1.42; 95% CI: 1.10–1.83; P = 0.007) or combined therapy (adjusted IRR: 1.42; 95% CI: 111–1.82; P < 0.001) had a longer LOS vs. surgery alone (adjusted IRR: 0.85; 95% CI: 0.74–0.97; P = 0.017). Patients receiving ET (adjusted Ratio: 2.39; 95% CI: 1.52–3.76; P < 0.001) or combined therapy (adjusted Ratio: 4.42; 95% CI: 1.67–11.71; P = 0.003) had higher ratio of mean hospital charges compared with surgery alone (adjusted Ratio: 1.09; 95% CI: 0.69–1.72; P = 0.710).ConclusionsNumerous factors were associated with the need for surgical intervention, including the use of ET. Those receiving ET, as well as those with combined therapy, had a longer LOS and increased total hospital charges.Ha AS, Wallace BK, Miles C, et al. Exploring the Use of Exchange Transfusion in the Surgical Management of Priapism in Sickle Cell Disease: A Population-Based Analysis. J Sex Med 2021;18:1788–1796.     

Nationwide Emergency Department Visits for Priapism in the United States

IntroductionThe epidemiology of priapism is not well characterized. A small number of studies based on inpatient data or small population samples have estimated the incidence to range from 0.34 to 1.5 cases per 100,000 males.AimTo estimate the current epidemiology and impact on resource utilization of priapism in the United States (US).Main Outcome MeasuresRate of emergency department encounters for priapism in the US.MethodsEmergency department (ED) visits for priapism were analyzed using discharge data from the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project (HCUP). Priapism encounters were identified by ICD9 code. Priapism encounters were analyzed for patient and hospital characteristics, associated diagnoses, and hospital charge. Established weighting in the sample was used to calculate nationwide estimates.ResultsA total of 8,738 ED encounters for priapism were identified between 2006 and 2009 in the NEDS. This translated to an estimated 39,964 encounters out of a total of 496,195,793 ED visits, or 8.05 per 100,000 ED visits (95% confidence interval [CI] 7.59–8.51). 21.1% of patients had a concurrent diagnosis of sickle cell disease (SCD). 72.1% of all patients were discharged home from the ED, while only 49.6% of patients with SCD were discharged home. A concurrent diagnosis of SCD was associated with an odds ratio (OR) of 3.84 (95% CI 3.65–4.05) for admission to the hospital when controlling for age, region, hospital and payer type. The mean hospital charge was $1,778 per encounter if discharged home and $41,909 per encounter if admitted. The estimated mean total annual charge for priapism was $123,860,432 with 86.8% of charges attributed to inpatient admissions.ConclusionsOur estimate of the rate of ED visits for priapism was significantly higher than prior estimates with a SCD concurrence rate lower than previously estimated. Stein DM, Flum AS, Cashy J, Zhao LC, and McVary KT. Nationwide emergency department visits for priapism in the United States. J Sex Med 2013;10:2418–2422.     

Clinical Outcomes of Periprocedural Antithrombotic Therapy in Ischemic Priapism Management

BackgroundPriapism is a urologic emergency consisting of a painful erection lasting greater than 4 hours; antithrombotic therapy (ATT) have recently been recommended as an adjunct in the treatment of ischemic priapism.AimTo determine the short- and long-term outcomes of periprocedural ATT in the management of acute ischemic priapism.MethodsA retrospective review of patients seen at the University of California, San Francisco, from 2008 to 2019 was carried out to identify those evaluated for acute priapism. Information regarding duration of priapism, etiology, treatment, periprocedural and postprocedural ATT type and dose, and follow-up data was collected.OutcomesATT use was the exposure of interest; outcome variables included priapism resolution, repeat episodes, long-term complications, and follow-up.Results70 patients with at least 1 detailed record of an acute priapism episode between 2008 and 2019 were identified. Of the 70 patients who underwent management for an acute episode of priapism, 59 (84%) received intracavernous injection of phenylephrine with or without corporal aspiration. Of the 4 patients who received ATT at the same time as intracavernous injection, none had additional priapism episodes. In the 55 patients who did not receive immediate ATT, 22 (40%) required at least 1 shunting procedure. The 9 patients who received ATT concurrently with shunting experienced less recurrence than the 13 patients who did not receive ATT (11% vs 69%, respectively P = .012). There were no significant differences in long-term erectile dysfunction (P = .627), fibrosis (P = .118), genitourinary pain (P = .474), and urinary issues (P = .158) between those who received ATT and those who did not.Clinical ImplicationsOur findings suggest that ATT has a role in preventing priapism recurrence; we observed that long-term repeat priapism episodes are less frequent in those who received periprocedural ATT compared with those who did not and that ATT may especially reduce recurrence in cases when shunting was requiredStrengths & LimitationsThis is the first study looking at the clinical outcomes of periprocedural ATT in the management of ischemic priapism. It is limited by the fact that it is a single-center study, types of ATT were heterogenous, and the exact timing of priapism management could not be measured for everyone.ConclusionIn spite of its limitations, these preliminary findings are promising and warrant further exploration of the use of ATT in the management of ischemic priapism.Ramstein JJ, Lee A, Cohen AJ, et al. Clinical Outcomes of Periprocedural Antithrombotic Therapy in Ischemic Priapism Management. J Sex Med 2020;17:2260–2266.     

Priapism in sickle-cell disease: a hematologist's perspective

IntroductionPriapism is a familiar problem to hematologists, well known for its association with sickle‐cell disease (SCD). It also occurs in a variety of other hematological illnesses, nearly all forms of congenital hemolytic anemia, including other hemoglobinopathies and red blood cell membranopathies and enzymopathies.AimProvide urologists with a comprehensive review of priapism in SCD, with an emphasis on the perspective of a practicing hematologist.MethodsMedline searches through July 2010 were conducted using the terms priapism, erectile dysfunction, and sickle cell.Main Outcome MeasuresExpert opinion was based on review of the medical literature related to this subject matter.ResultsIn men with SCD, large epidemiological studies have linked the risk of priapism to clinical markers of the severity of intravascular hemolysis. Extracellular hemoglobin and arginase released during hemolysis has been implicated in reducing nitric oxide bioavailability, although the relevance of hemolysis to vascular dysfunction has been challenged by some scientists. Consistent with the role of impairment of the nitric oxide axis, mice genetically deficient in nitric oxide production have also been shown to develop priapic activity. Provocative new data indicate that hemolysis‐linked dysregulation of adenosine signaling in the penis contributes to priapism in sickle cell mice. Serious questions have arisen regarding the efficacy of mainstays of textbook dogma for treatment of acute severe priapism, including intravenous fluids, alkalinization, and exchange transfusion, and there is increasing acceptance for early aspiration and irrigation of the corpus cavernosum.ConclusionFor patients with sickle cell with recurrent priapism, there is very limited evidence for a medical prophylaxis role for hydroxyurea, etilefrine, pseudoephedrine, leuprolide, sildenafil, and other agents. Recent publications have highlighted nitric oxide and adenosine signal transduction pathways as worthy of additional research. Research and clinical management of sickle‐cell priapism is strengthened by multidisciplinary collaboration between hematologists and urologists. Kato GJ. Priapism in sickle‐cell disease: A hematologist's perspective. J Sex Med 2012;9:70–78.     

Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation

IntroductionRecent research suggests that priapism in sickle cell disease (SCD) is due to dysregulation of penile erection homeostasis including alteration of nitric oxide synthase (NOS) and phosphodiesterase type 5 (PDE5) activities by excessive levels of reactive oxygen species (ROS) released during hemolysis. It is unknown if subacute exposure to hemolysis is sufficient or if chronic reconditioning of erectile tissues is required for perturbation of homeostatic pathways and whether PDE5 inhibitor (PDE5I) treatment can restore erectile homeostasis in the subacute setting.AimsThe aim of this study was to investigate the effects of subacute hemolysis (3‐month exposure) on priapism and NO pathway regulation.MethodsMice underwent bone marrow transplantation with either SCD (BM‐SS) or wild‐type (WT) bone marrow. BM‐SS mice were treated with sildenafil 100 mg/kg/day. We measured intracavernous pressure (ICP) measurements with or without cavernous nerve stimulation following bone marrow transplantation to assess for priapism.Main Outcome MeasuresICP and frequency of erections were assessed. Penile tissues were analyzed for NOS, protein kinase G (PKG), PDE5, and ROS activities.ResultsBM‐SS mice demonstrated a priapism phenotype. PDE5I treatment reduced the frequency of erections in BM‐SS mice (1.7 ± 1.1 vs. 5.5 ± 2.8 erections per hour, P < 0.05). Penile tissues from BM‐SS mice demonstrated decreased NOS, PKG, PDE5 and elevated ROS activities compared with that of control mice. PDE5I treatment increased NOS (11.6 ± 1.3% vs. 7.8 ± 2.3%, P < 0.05) and PDE5 (76.3 ± 9.8% vs. 52.3 ± 11.1%, P < 0.05) activities and decreased ROS activity (137.8 ± 12.1% vs. 199.1 ± 11.3%, P < 0.05) compared with non‐PDE5I treated BM‐SS mice. PKG activity was increased beyond control levels with PDE5I treatment (158.4 ± 10.3%, P < 0.05).ConclusionShort‐term hemolysis is sufficient to establish a priapism phenotype and results in loss of erectile function. PDE5I treatment ameliorates priapism, in part, because of restored NO balance with decreased ROS generation and increased PDE5 activity. Sopko NA, Matsui H, Hannan JL, Berkowitz D, Champion HC, Hsu LL, Musicki B, Burnett AL, and Bivalacqua TJ. Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation. J Sex Med 2015;12:1878–1885.     

Risk Factors for Surgical Shunting in a Large Cohort With Ischemic Priapism

BackgroundIschemic priapism is treated with a stepwise algorithm, but some patients may benefit from immediate shunt placement.AimTo identify risk factors for surgical shunt placement in a large series of patients with ischemic priapism.MethodsWe identified all patients presenting to our institution with ischemic priapism from January 2010 to December 2018. Multivariable was performed to assess risk factors for surgical shunting. Receiver operating characteristic curve analysis (Youden Index) was used to assess which cutoff time for the duration of priapism was most predictive requiring shunting.OutcomesWe assess risk factors for surgical shunting and what duration of priapism was most predictive of requiring a shunt.ResultsWe identified a total of 169 ischemic priapism encounters from 143 unique patients, of which 26 (15%) encounters resulted in a surgical shunt. Patients treated with a shunt had longer priapism durations than those without (median 36 vs 10 hours, P < .001). Independent predictors of a surgical shunt on multivariate logistic regression were the duration of priapism in hours (odds ratio: 1.05, 95% confidence interval: 1.02–1.10; P < .001) and history of prior priapism (odds ratio: 3.15, 95% confidence interval: 1.03–9.60; P = .045). Receiver operating characteristic curve analysis using priapism duration to predict the need for shunt generated an area under curve of 0.83. A duration of 24 hours correlated to a sensitivity of 0.77 and specificity of 0.90.Clinical ImplicationsThese results can be used to counsel future patients and assist in the decision-making process for providers.Strengths & LimitationsThis is one of the largest series of priapism in the literature. Most (74%) of the priapism were due to intracavernosal injections so the results may not be generalizable to populations with different priapism etiologies.ConclusionIn this study of 169 priapism encounters, we found that the priapism duration and history of prior priapism were independent predictors of surgical shunt placement. These results can aid urologists in the counseling and decision-making process of these challenging cases.Zhao H, Dallas K, Masterson J, et al. Risk Factors for Surgical Shunting in a Large Cohort With Ischemic Priapism. J Sex Med 2020;17:2472–2477.     

Priapism from Recreational Intracavernosal Injections in a High-Risk Metropolitan Community

IntroductionRecreational use of intracavernosal injections (ICIs) is a high-risk behavior that involves sharing of these agents by men without physician regulation.AimTo characterize the etiologies and outcomes of priapism at a Los Angeles metropolitan medical center to better understand patterns of usage of recreational ICIs and the public health implications of such practices.MethodsWith institutional review board approval, we retrospectively reviewed all cases of priapism presenting to the emergency room of a Los Angeles tertiary medical center from 2010 to 2018. We compared outcomes between patients who presented with priapism after recreational ICI and patients who presented with other etiologies.Main Outcome MeasureWe describe patient characteristics, etiologies, and treatments of priapism at our institution.ResultsWe identified 169 priapism encounters by 143 unique patients. Recreational ICIs accounted for 82 of the 169 priapism encounters (49%). Patients who used recreational injections were younger than those who presented with other etiologies (43.5 years vs 47.5 years; P = .048) and had delayed presentations (median, 12 hours vs 8 hours; P < .0001). There was no statistical difference across groups in the proportion of patients requiring operative intervention (14.6% of recreational ICI users vs 16.1% of all other patients; P = .23). A total of 36 out of 72 patients who used recreational ICIs (50%) were HIV+.Clinical ImplicationsOur study adds to the relatively sparse literature on priapism outcomes. We identify and describe a high-risk population that uses recreational intracavernosal injections.Strengths & LimitationsTo our knowledge, this is the largest series of priapism encounters. However, the data are retrospective from a single institution, and there is a lack of long-term follow up.ConclusionA large proportion of priapism visits at our institution were attributed to recreational use of ICIs. This is a high-risk patient population that may not be aware of the risks of recreational ICIs and the consequences of priapism. Further effort should be made to increase public and physician awareness of this harmful practice.Zhao H, Berdahl C, Bresee C, et al. Priapism from Recreational Intracavernosal Injections in a High-Risk Metropolitan Community. J Sex Med 2019;16:1650–1654.     

Adenosine Deaminase Enzyme Therapy Prevents and Reverses the Heightened Cavernosal Relaxation in Priapism

IntroductionPriapism featured with painful prolonged penile erection is dangerous and commonly seen in sickle cell disease (SCD). The preventive approaches or effective treatment options for the disorder are limited because of poor understanding of its pathogenesis. Recent studies have revealed a novel role of excess adenosine in priapism caused by heightened cavernosal relaxation, and therefore present an intriguing mechanism-based therapeutic possibility.AimThe aim of this study was to determine the therapeutic effects of adenosine deaminase (ADA) enzyme therapy to lower adenosine in priapism.MethodsBoth ADA-deficient mice and SCD transgenic (Tg) mice display priapism caused by excessive adenosine. Thus, we used these two distinct lines of mouse models of priapism as our investigative tools. Specifically, we treated both of these mice with different dosages of polyethylene glycol–modified ADA (PEG–ADA) to reduce adenosine levels in vivo. At the end points of the experiments, we evaluated the therapeutic effects of PEG–ADA treatment by measuring adenosine levels and monitoring the cavernosal relaxation.Main Outcome MeasuresAdenosine levels in penile tissues were measured by high-performance liquid chromatography, and cavernosal relaxation was quantified by electrical field stimulation (EFS)-induced corporal cavernosal strip (CCS) assays.ResultsWe found that lowering adenosine levels in penile tissues by PEG–ADA treatment from birth in ADA-deficient mice prevented the increased EFS-induced CCS relaxation associated with priapism. Intriguingly, in both ADA-deficient mice and SCD Tg mice with established priapism, we found that normalization of adenosine levels in penile tissues by PEG–ADA treatment relieved the heightened EFS-induced cavernosal relaxation in priapism.ConclusionsOur studies have identified that PEG–ADA is a novel, safe, and mechanism-based drug to prevent and correct excess adenosine-mediated increased cavernosal relaxation seen in two independent priapic animal models, and suggested its therapeutic possibility in men suffering from priapism. Wen J, Jiang X, Dai Y, Zhang Y, Tang Y, Sun H, Mi T, Kellems RE, Blackburn MR, and Xia Y. Adenosine deaminase enzyme therapy prevents and reverses the heightened cavernosal relaxation in priapism.     

Establishment of a Transgenic Sickle-Cell Mouse Model to Study the Pathophysiology of Priapism

IntroductionPriapism is a poorly understood disease process with little information on the etiology and pathophysiology of this erectile disorder. One group of patients with a high prevalence of priapism is men with sickle-cell disease.AimEstablish an in vivo transgenic sickle-cell mouse model to study the pathophysiology of sickle-cell disease-associated priapism.MethodsTransgenic sickle-cell disease mice, expressing human sickle hemoglobin, were utilized. Three groups of mice were used: (i) wild type (WT), (ii) sickle-cell heterozygotes (Hemi), and (ii) sickle-cell homozygotes (Sickle). Two age groups of each cohort of mice were utilized: young adult (4–6 months) and aged (18–22 months).Main Outcome MeasuresHistological (trichrome stain to measure ratio of collagen to smooth muscle), penile hydroxyproline content (collagen content), and transmission electron microscopic analysis of WT, Hemi, and Sickle mice penes, as well as in vivo erectile responses [change in intracavernous pressure (ICP)] to cavernous nerve stimulation (CNS), were determined. The frequency of erectile responses (erections/hour) pre- and poststimulation was also measured in each of the experimental groups.ResultsSickle mice had increased (P < 0.05) collagen to smooth muscle ratio and hydroxyproline content in the penis when compared with WT and Hemi mice penes. Transmission electron microscopy demonstrated thickened smooth muscle cell bundles, disruption of the endothelial lining of the corporal sinusoids, and increased (P < 0.05) caveolae number. Sickle mice had significantly (P < 0.05) higher ICP to CNS and increased (P < 0.05) frequency of erections pre- and post-CNS when compared with WT and Hemi mice erectile responses. Sickle mice did develop ED (change in ICP in response to CNS) with increasing age.ConclusionsThe morphometric changes of the penis and exaggerated in vivo erectile responses support the use of this transgenic sickle-cell disease animal model to study the pathophysiological mechanisms involved in sickle-cell disease-associated priapism. Bivalacqua TJ, Musicki B, Hsu LL, Gladwin MT, Burnett AL, and Champion HC. Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism. J Sex Med 2009;6:2494–2504.     

Increased Cavernosal Relaxations in Sickle Cell Mice Priapism are Associated with Alterations in the NO-cGMP Signaling Pathway

IntroductionPriapism is defined as prolonged and persistent penile erection, unassociated with sexual interest or stimulation, and is one of the many serious complications associated with sickle cell disease (SCD).AimThe aim of this study was to evaluate the role of the NO-cGMP signaling pathway in priapism in Berkeley murine model of SCD (SS).MethodsSS mice and C57BL/6 mice (control) penile tissues were removed and the erectile tissue within the corpus cavernosum (CC) was surgically dissected free. The strips were mounted in 10 mL organ baths containing Krebs solution at 37°C (95% O₂, 5% CO₂, pH 7.4), and vertically suspended between two metal hooks.Main Outcome MeasuresCumulative concentration-response curves were constructed for acetylcholine (ACh; endothelium-dependent responses), sodium nitroprusside (SNP; endothelium-independent relaxations) and BAY 41-2272 (a potent activator of NO-independent site of soluble guanylate cyclase) in CC precontracted with phenylephrine. Cavernosal responses induced by frequency-dependent electrical field stimulation (EFS) were also carried out to evaluate the nitrergic cavernosal relaxations.ResultsIn SS mice, ACh-induced cavernosal relaxations were leftward shifted by 2.6-fold (P < 0.01) that was accompanied by increases in the maximal responses (78 ± 5% and 60 ± 3% in SS and C57B6/6J mice, respectively). Similarly, SNP- and BAY 41-2272-induced CC relaxations were leftward shifted by approximately 3.3- and 2.2-fold (P < 0.01) in SS mice, respectively. A significant increase in maximal responses to SNP and BAY 41-2272 in SS mice was also observed (113 ± 6% and 124 ± 5%, respectively) compared with C57B6/6J mice (83 ± 4% and 99 ± 2%, respectively). The EFS-induced cavernosal relaxations were also significantly higher SS mice.ConclusionThese results showed that SS mice exhibit amplified corpus carvenosum relaxation response mediated by NO-cGMP signaling pathway. Intervention in this signaling pathway may be a potential therapeutic target to treat SCD priapism. Claudino MA, Franco-Penteado CF, Corat MAF, Gimenes AP, Passos LAC, Antunes E, and Costa FF. Increased cavernosal relaxations in sickle cell mice priapism are associated with alterations in the NO-cGMP signaling pathway. J Sex Med 2009;6:2187–2196.     

Anatomic and Functional Outcome Following Distal Shunt and Tunneling for Treatment İschemic Priapism: A Single-Center Experience

BackgroundIschemic priapism (IP) is a urologic emergency that requires early intervention. The main aim of IP treatment is to relieve the cavernosal pressure and provide erectile function.AimThe aim of this study was to determine the correlation between preoperative risk factors (patient’s age, duration of priapism, preoperative erectile function) and postoperative erectile dysfunction (ED).MethodsThis retrospective study consisted of 25 patients diagnosed with refractory IP between 2009–2017. The diagnosis of IP was confirmed by medical history, physical examination, and cavernosal blood gas analysis. All of the patients underwent the T-shunt procedure ± tunneling after a failed initial intervention.ResultsThe mean age at the time of the IP diagnosis was 46.84 years (range 23–77). The average follow-up time of the study population was 40.4 months (range 3–114), and the median time from the occurrence of IP to surgery was 58 hours (range 24–240). In all cases, rapid resolution of the erection was achieved with the T-shunt ± tunneling procedure. In 1 patient, priapism recurred after 12 hours. Postoperative ED was reported by 16 (84.21%) patients, with degrees of mild, mild to moderate, and severe in 6, 1, and 9 of these cases, respectively. During the follow-up, the mean International Index of Erectile Function–5 (IIEF-5) score was 12.68 (range 5–23). Only 3 (15.78%) patients achieved successful sexual intercourse without any treatment. 6 (31.5%) patients required the aid of phosphodiesterase type 5 inhibitors, and 1 (5.26%) patient required the aid of a vacuum erection device. The 9 (47.36%) patients with severe ED failed to respond to medical treatment and were considered candidates for a penile implant. According to Kendall’s tau-b correlation coefficient analysis, there was a positive correlation between the preoperative and postoperative IIEF-5 scores (P = .005), whereas the patient’s age and duration of priapism were negatively correlated with the postoperative IIEF-5 score (P = .016 and P = .046, respectively).Clinical ImplicationsTreatment options of IP should be discussed with patients in terms of both preoperative erectile function and the duration of priapism.Strengths & LimitationsThe small sample size and retrospective nature of this study were the main limitations.ConclusionsDespite high success and low complication rates of T-shunt surgery, the rate of undisturbed erectile function is only 14.6%. The patient’s age, the existence of preoperative ED, and the duration of priapism are associated with postoperative IIEF-5 scores.Ortaç M, Çevik G, Akdere H, et al. Anatomic and Functional Outcome Following Distal Shunt and Tunneling for Treatment ?schemic Priapism: A Single-Center Experience. J Sex Med 2019;16:1290–1296.     

New-onset priapism associated with ingestion of terazosin in an otherwise healthy man

IntroductionPriapism has been reported as a rare effect of the commonly used alpha 1-antagonists through direct inhibition of the sympathetic input necessary for detumescence. Although previously reported as an adverse event in a patient with spinal cord injury, to the best of our knowledge, terazosin-induced priapism in an otherwise healthy man has not been previously described.AimWe describe an otherwise healthy man with lower urinary symptoms who developed priapism after ingestion of the commonly prescribed alpha-blocker terazosin.ResultsThe priapism resolved after a combination of cavernosal aspiration and alpha-agonist administration.ConclusionPriapism is an extremely rare side effect of alpha-blocker therapy and has previously been described in association with other alpha-blockers, as well as with terazosin, in a spinal cord-injured patient. We report a case of priapism specifically associated with terazosin prescribed for lower urinary tract symptoms in an otherwise healthy man. Sadeghi-Nejad H, and Jackson I. New-onset priapism associated with ingestion of terazosin in an otherwise healthy man.     

Priapism: Pathogenesis,Epidemiology, and Management

IntroductionPriapism describes a persistent erection arising from dysfunction of mechanisms regulating penile tumescence, rigidity, and flaccidity. A correct diagnosis of priapism is a matter of urgency requiring identification of underlying hemodynamics.AimsTo define the types of priapism, address its pathogenesis and epidemiology, and develop an evidence-based guideline for effective management.MethodsSix experts from four countries developed a consensus document on priapism; this document was presented for peer review and debate in a public forum and revisions were made based on recommendations of chairpersons to the International Consultation on Sexual Medicine. This report focuses on guidelines written over the past decade and reviews the priapism literature from 2003 to 2009. Although the literature is predominantly case series, recent reports have more detailed methodology including duration of priapism, etiology of priapism, and erectile function outcomes.Main Outcome MeasuresConsensus recommendations were based on evidence-based literature, best medical practices, and bench research.ResultsBasic science supporting current concepts in the pathophysiology of priapism, and clinical research supporting the most effective treatment strategies are summarized in this review.ConclusionsPrompt diagnosis and appropriate management of priapism are necessary to spare patients ineffective interventions and maximize erectile function outcomes. Future research is needed to understand corporal smooth muscle pathology associated with genetic and acquired conditions resulting in ischemic priapism. Better understanding of molecular mechanisms involved in the pathogenesis of stuttering ischemic priapism will offer new avenues for medical intervention. Documenting erectile function outcomes based on duration of ischemic priapism, time to interventions, and types of interventions is needed to establish evidence-based guidance. In contrast, pathogenesis of nonischemic priapism is understood, and largely attributable to trauma. Better documentation of onset of high-flow priapism in relation to time of injury, and response to conservative management vs. angiogroaphic or surgical interventions is needed to establish evidence-based guidance. Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, and Shamloul R. Priapism: Pathogenesis, epidemiology and management.     

Sexual Health Outcomes Improvement in Sickle Cell Disease: A Matter of Health Policy?

IntroductionIschemic priapism is a true male sexual dysfunction, consisting of uncontrollable, prolonged, and often painful erections of the penis. A commonly observed outcome, as a result of erectile tissue damage and fibrosis in this setting, is the complete loss of natural erectile ability. Males with sickle cell disease (SCD) are commonly affected. Given the adverse health consequences of this condition coupled with its specific population extent, health policy considerations are warranted.AimThis article aimed to study circumstances surrounding priapism associated with SCD for the purpose of pushing forward health policy objectives that improve sexual health‐related outcomes.MethodsMedline searches through July 2010 were conducted using the following terms: priapism, sickle cell disease, epidemiology, public health, health economics, and health policy.Main Outcome MeasureExpert opinion was based on review of the medical literature related to this subject matter.ResultsThe literature search affirmed that SCD‐associated priapism threatens sexual health and also exerts a greatly negative impact on the physical and mental health of affected individuals. Various socioeconomic, behavioral, and cultural factors in the SCD population bearing negatively on sexual health outcomes were delineated. Deficiencies in several aspects of medical services for patients with SCD including scientific research funding support, which evoke an element of ethnic healthcare disparities, were further delineated.ConclusionsSCD‐associated priapism is a medical condition of societal health significance, which can and should be addressed through comprehensive healthcare programmatic efforts. These efforts comprise advancement of educational and clinical training programs, support of interdisciplinary healthcare delivery services, diffusion of clinical advances, enactment of guidelines for effective clinical management, and resource allocation for enabling scientific advancements. Burnett AL. Sexual health outcomes improvement in sickle cell disease: A matter of health policy? J Sex Med 2012;9:104–113.     

Standard Operating Procedures for Priapism

AimTo provide standard operating procedures for the diagnosis and management of priapism.MethodsReview of the literature.Main Outcome MeasuresReduction of priapism and preservation of erectile function.ResultsPriapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation. Priapism requires prompt evaluation and usually requires emergency management. There are two types of priapism: (i) ischemic (veno-occlusive or low flow), which is found in 95% of cases, and (ii) nonischemic (arterial or high flow). Stuttering (intermittent) priapism is a recurrent form of ischemic priapism. To initiate appropriate management, the physician must determine whether the priapism is ischemic or nonischemic. Necessary diagnostic steps are an accurate history, physical examination, and cavernous blood gas analysis and/or color duplex ultrasonography of the corpora cavernosa. Management of ischemic priapism should achieve resolution as promptly as possible. Initial treatment is therapeutic aspiration with or without irrigation of the corpora. If this fails, intracavernous injection of sympathomimetic drugs is the next step. Surgical shunts should be performed if nonsurgical treatment has failed. The initial management of nonischemic priapism should be observation. Selective arterial embolization is recommended for the management of nonischemic priapism in patients who request treatment. The goal of management for a patient with recurrent (stuttering) priapism is prevention of future episodes.ConclusionManagement of priapism has become increasingly successful as scientific understanding of the pathophysiology and molecular biology of priapism improves. The key to further success in the treatment of priapism is basic research of this uncommon but potentially devastating condition. Burnett AL and Sharlip ID. Standard operating procedures for priapism. J Sex Med **;**:**–**.     

Priapism as a Result of Chronic Myeloid Leukemia: Case Report,Pathology, and Review of the Literature

IntroductionPriapism is rare‐presenting feature in male patients with chronic myeloid leukemia (CML). Several hypotheses for pathogenesis have been described. Management has been controversial; some authors described resolution following priapism‐specific interventions, and others recommended addition of CML‐specific therapy or even CML‐specific therapy alone.AimIn this report, we describe presentation and management of a man with refractory priapism that was the first presenting manifestation of CML. We also report, for the first time, the pathology sections of the sinusoidal tissue in such cases. Literature is reviewed for similar cases and their outcome.MethodsA 21‐year‐old male patient presented with painful priapism that started 6 days earlier and failed aspiration–irrigation. CBC revealed marked leucocytosis. Oncology care diagnosed CML, and treatment with Imatinib was commenced with prior semen cryopreservation. Following remission, a penile prosthesis was implanted, assisted by optical corporotomy. Sinusoidal tissue biopsy was stained by hematoxylin/eosin (H&E) and CD34.Main Outcome MeasuresPathology sections of cavernous tissue following CML‐induced priapism.ResultsThe penile implant survived without complications. H&E examination of the sinusoidal tissue biopsy revealed leukemic infiltration associated with vascular endothelial damage. CD34 staining showed the mixed picture of leukemic infiltrates, intact vascular endothelium with lumena showing leukemic cells, alternating with destroyed vessels, and no vascular lumena and ruminants of endothelial cells.ConclusionPriapism can be the first manifestation of previously undetected CML. The pathological picture of sinusoidal tissue in such cases is presented. In the case at hand, a complete blood picture was helpful in early diagnosis of CML and early initiation of targeted chemotherapy along with the corporal irrigation/aspiration or shunt surgery. It is therefore recommended to have a CBC examined at presentation of any case of ischemic priapism of unknown etiology, early initiation of CML therapy along with aspiration/irrigation, preferably cryopreserving a semen sample before CML therapy. Shaeer OKZM, Shaeer KZM, AbdelRahman IFS, El‐Haddad MS, and Selim OM. Priapism as a result of chronic myeloid leukemia: Case report, pathology, and review of the literature. J Sex Med 2015;12:827–834.