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Current Urology Reports
Published in: Current Urology Reports 4/2012

01-08-2012 | Erectile Dysfunction (DK Montague, Section Editor)

Stuttering Priapism: Insights into Pathogenesis and Management

Authors: Belinda F. Morrison, Arthur L. Burnett

Published in: Current Urology Reports | Issue 4/2012

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Abstract

Priapism is defined as a persistent, painful erection that continues beyond, or is unrelated to, sexual stimulation. It may be categorized as either ischemic (low/absent flow) or nonischemic (high flow). Stuttering priapism is a variant of the ischemic type that is characterized by repetitive, transient, painful, self-limiting episodes of priapism. It is associated with various hematological disorders, including sickle cell disease and pharmacological treatments. The consequences of ineffective treatment of priapism are erectile dysfunction and impaired quality of life due to chronic pain and physical disfigurement. Many of the existing medical therapeutic options for treatment of stuttering priapism are nonmechanistic and associated with significant adverse effects. However, the scientific knowledge of stuttering priapism has transitioned in the past few years, from a condition that is poorly understood to one that has borne a burst of evolving molecular science. In this review, the pathophysiology of priapism is discussed, with particular emphasis on new molecular effectors and mechanisms. Novel treatment methods, as well as potential future agents, based on the emerging molecular evidence are discussed.
Literature
1.
Montague DK, Jarow J, Broderick GA, Dmochowski RR, Heaton JP, Lue TF, Nehra A, Sharlip ID. American urological association guideline on the management of priapism. J Urol. 2003;170(4 Pt 1):1318–24.PubMedCrossRef
2.
Kulmala RV, Lehtonen TA, Tammela TL. Priapism, its incidence and seasonal distribution in Finland. Scand J Urol Nephrol. 1995;29(1):93–6.PubMedCrossRef
3.
Eland IA, van der Lei J, Stricker BH, Sturkenboom MJ. Incidence of priapism in the general population. Urology. 2001;57(5):970–2.PubMedCrossRef
4.
Emond AM, Holman R, Hayes RJ, Serjeant GR. Priapism and impotence in homozygous sickle cell disease. Arch Intern Med. 1980;140(11):1434–7.PubMedCrossRef
5.
Burnett AL, Bivalacqua TJ. Priapism: new concepts in medical and surgical management. Urol Clin North Am. 2011;38(2):185–94.PubMedCrossRef
6.
Hinman F. Priapism: report of cases and a clinical study of the literature with reference to its pathogenesis and surgical treatment. Ann Surg. 1914;60(6):689–716.PubMedCrossRef
7.
Burnett AL, Bivalacqua TJ. Glucose-6-phosphate dehydrogenase deficiency: an etiology for idiopathic priapism? J Sex Med. 2008;5(1):237–40.PubMed
8.
Prabhakaran K, Jacobs BL, Smaldone MC, Franks ME. Stuttering priapism associated with hereditary spherocytosis. Can J Urol. 2007;14(5):3702–4.PubMed
9.
Dust N, Daboval T, Guerra L. Evaluation and management of priapism in a newborn: A case report and review of the literature. Paediatr Child Health. 2011;16(1):e6–8.PubMed
10.
Adeyoju AB, Olujohungbe AB, Morris J, Yardumian A, Bareford D, Akenova A, Akinyanju O, Cinkotai K, O’Reilly PH. Priapism in sickle-cell disease; incidence, risk factors and complications - an international multicentre study. BJU Int. 2002;90(9):898–902.PubMedCrossRef
11.
12.
Burnett AL. Novel nitric oxide signaling mechanisms regulate the erectile response. Int J Impot Res. 2004;16 Suppl 1:S15–9.PubMedCrossRef
13.
Trigo-Rocha F, Hsu GL, Donatucci CF, Lue TF. The role of cyclic adenosine monophosphate, cyclic guanosine monophosphate, endothelium and nonadrenergic, noncholinergic neurotransmission in canine penile erection. J Urol. 1993;149(4):872–7.PubMed
14.
Burnett AL. Phosphodiesterase 5 mechanisms and therapeutic applications. Am J Cardiol. 2005;96(12B):29M–31M.PubMedCrossRef
15.
Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 2003;83(4):1325–58.PubMed
16.
Burnett AL, Musicki B. The nitric oxide signaling pathway in the penis. Curr Pharm Des. 2005;11(31):3987–94.PubMedCrossRef
17.
Srilatha B, Adaikan PG, Li L, Moore PK. Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med. 2007;4(5):1304–11.PubMedCrossRef
18.
Liaw RL, Srilatha B, Adaikan PG. Effects of hydrogen sulfide on erectile function and its possible mechanism(s) of action. J Sex Med. 2011;8(7):1853–64.PubMedCrossRef
19.
Spycher MA, Hauri D. The ultrastructure of the erectile tissue in priapism. J Urol. 1986;135(1):142–7.PubMed
20.
Burnett AL, Allen RP, Tempany CM, Dover GJ, Brendler CB. Evaluation of erectile function in men with sickle cell disease. Urology. 1995;45(4):657–63.PubMedCrossRef
21.
Datta NS. Megalophallus in sickle cell disease. J Urol. 1977;117(5):672–3.PubMed
22.
Elahi MM, Kong YX, Matata BM. Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev. 2009;2(5):259–69.PubMedCrossRef
23.
Kanika ND, Melman A, Davies KP. Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue. Int J Impot Res. 2010;22(6):363–73.PubMedCrossRef
24.
Ul-Hasan M, El-Sakka AI, Lee C, Yen TS, Dahiya R, Lue TF. Expression of TGF-beta-1 mRNA and ultrastructural alterations in pharmacologically induced prolonged penile erection in a canine model. J Urol. 1998;160(6 Pt 1):2263–6.PubMed
25.
Muneer A, Cellek S, Dogan A, Kell PD, Ralph DJ, Minhas S. Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model. Int J Impot Res. 2005;17(1):10–8.PubMedCrossRef
26.
Filippi S, Marini M, Vannelli GB, Crescioli C, Granchi S, Vignozzi L, Luconi M, Ferruzzi P, Morelli A, Forti G, et al. Effects of hypoxia on endothelin-1 sensitivity in the corpus cavernosum. Mol Hum Reprod. 2003;9(12):765–74.PubMedCrossRef
27.
Broderick GA, Gordon D, Hypolite J, Levin RM. Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism. J Urol. 1994;151(1):259–62.PubMed
28.
Burnett AL, Chang AG, Crone JK, Huang PL, Sezen SE. Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase. J Androl. 2002;23(1):92–7.PubMed
29.
Champion HC, Bivalacqua TJ, Takimoto E, Kass DA, Burnett AL. Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci U S A. 2005;102(5):1661–6.PubMedCrossRef
30.
Bivalacqua TJ, Musicki B, Hsu LL, Gladwin MT, Burnett AL, Champion HC. Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism. J Sex Med. 2009;6(9):2494–504.PubMedCrossRef
31.
Bivalacqua TJ, Liu T, Musicki B, Champion HC, Burnett AL. Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis. Eur Urol. 2007;51(6):1732–40.PubMedCrossRef
32.
Musicki B, Champion HC, Hsu LL, Bivalacqua TJ, Burnett AL. Post-translational inactivation of endothelial nitric oxide synthase in the transgenic sickle cell mouse penis. J Sex Med. 2011;8(2):419–26.PubMedCrossRef
33.
Wood KC, Hsu LL, Gladwin MT. Sickle cell disease vasculopathy: a state of nitric oxide resistance. Free Radic Biol Med. 2008;44(8):1506–28.PubMedCrossRef
34.
Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, Lewis RL, Mills TM, Hellstrom WJ, Kadowitz PJ. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S A. 2004;101(24):9121–6.PubMedCrossRef
35.
Bivalacqua TJ, Ross AE, Strong TD, Gebska MA, Musicki B, Champion HC, Burnett AL: Attenuated RhoA/Rho-kinase signaling in penis of transgenic sickle cell mice. Urology 2010, 76(2):510 e517-512.
36.
Phatarpekar PV, Wen J, Xia Y. Role of adenosine signaling in penile erection and erectile disorders. J Sex Med. 2010;7(11):3553–64.PubMedCrossRef
37.
Tostes RC, Giachini FR, Carneiro FS, Leite R, Inscho EW, Webb RC. Determination of adenosine effects and adenosine receptors in murine corpus cavernosum. J Pharmacol Exp Ther. 2007;322(2):678–85.PubMedCrossRef
38.
Mi T, Abbasi S, Zhang H, Uray K, Chunn JL, Xia LW, Molina JG, Weisbrodt NW, Kellems RE, Blackburn MR, et al. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Invest. 2008;118(4):1491–501.PubMedCrossRef
39.
• Wen J, Jiang X, Dai Y, Zhang Y, Tang Y, Sun H, Mi T, Kellems RE, Blackburn MR, Xia Y. Adenosine deaminase enzyme therapy prevents and reverses the heightened cavernosal relaxation in priapism. J Sex Med. 2010;7(9):3011–22. This article provides the first evidence that reducing adenosine levels may prevent priapism.PubMedCrossRef
40.
Wen J, Jiang X, Dai Y, Zhang Y, Tang Y, Sun H, Mi T, Phatarpekar PV, Kellems RE, Blackburn MR, et al. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling. FASEB J. 2010;24(3):740–9.PubMedCrossRef
41.
Tong Y, Tar M, Monrose V, DiSanto M, Melman A, Davies KP. hSMR3A as a marker for patients with erectile dysfunction. J Urol. 2007;178(1):338–43.PubMedCrossRef
42.
Wisner A, Dufour E, Messaoudi M, Nejdi A, Marcel A, Ungeheuer MN, Rougeot C. Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc Natl Acad Sci U S A. 2006;103(47):17979–84.PubMedCrossRef
43.
Kanika ND, Tar M, Tong Y, Kuppam DS, Melman A, Davies KP. The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway. Am J Physiol Cell Physiol. 2009;297(4):C916–27.PubMedCrossRef
44.
Shamloul R. The potential role of the heme oxygenase/carbon monoxide system in male sexual dysfunctions. J Sex Med. 2009;6(2):324–33.PubMedCrossRef
45.
Motterlini R, Hidalgo A, Sammut I, Shah KA, Mohammed S, Srai K, Green CJ. A precursor of the nitric oxide donor SIN-1 modulates the stress protein heme oxygenase-1 in rat liver. Biochem Biophys Res Commun. 1996;225(1):167–72.PubMedCrossRef
46.
Jin YC, Gam SC, Jung JH, Hyun JS, Chang KC. Expression and activity of heme oxygenase-1 in artificially induced low-flow priapism in rat penile tissues. J Sex Med. 2008;5(8):1876–82.PubMedCrossRef
47.
Traish AM, Guay AT. Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med. 2006;3(3):382–404. discussion 404-387.PubMedCrossRef
48.
Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med. 2005;2(6):759–70.PubMedCrossRef
49.
Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, Orlando C, Vannelli GB, Aversa A, Natali A, et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology. 2004;145(5):2253–63.PubMedCrossRef
50.
Meusburger SM, Keast JR. Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult pelvic ganglion cells in vitro. Neuroscience. 2001;108(2):331–40.PubMedCrossRef
51.
Serjeant GR, de Ceulaer K, Maude GH. Stilboestrol and stuttering priapism in homozygous sickle-cell disease. Lancet. 1985;2(8467):1274–6.PubMedCrossRef
52.
53.
Steinberg J, Eyre RC. Management of recurrent priapism with epinephrine self-injection and gonadotropin-releasing hormone analogue. J Urol. 1995;153(1):152–3.PubMedCrossRef
54.
Abern MR, Levine LA. Ketoconazole and prednisone to prevent recurrent ischemic priapism. J Urol. 2009;182(4):1401–6.PubMedCrossRef
55.
Rachid-Filho D, Cavalcanti AG, Favorito LA, Costa WS, Sampaio FJ. Treatment of recurrent priapism in sickle cell anemia with finasteride: a new approach. Urology. 2009;74(5):1054–7.PubMedCrossRef
56.
• Olujohungbe AB, Adeyoju A, Yardumian A, Akinyanju O, Morris J, Westerdale N, Akenova Y, Kehinde MO, Anie K, Howard J, et al. A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial--the priapism in sickle cell study. J Androl. 2011;32(4):375–82. This was the largest randomized trial on the prevention of priapism.PubMedCrossRef
57.
Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Long-term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism. Urology. 2006;67(5):1043–8.PubMedCrossRef
58.
Musicki B, Champion HC, Becker RE, Liu T, Kramer MF, Burnett AL. Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation. Mol Pharmacol. 2005;68(1):226–32.PubMed
59.
Bialecki ES, Bridges KR. Sildenafil relieves priapism in patients with sickle cell disease. Am J Med. 2002;113(3):252.PubMedCrossRef
60.
Tzortzis V, Mitrakas L, Gravas S, Mamoulakis C, Meissner A, Kyriakou D, Melekos MD. Oral phosphodiesterase type 5 inhibitors alleviate recurrent priapism complicating thalassemia intermedia: a case report. J Sex Med. 2009;6(7):2068–71.PubMedCrossRef
61.
•• Pierorazio PM, Bivalacqua TJ, Burnett AL. Daily phosphodiesterase type 5 inhibitor therapy as rescue for recurrent ischemic priapism after failed androgen ablation. J Androl. 2011;32(4):371–4. The first case report to demonstrate that a eugonadal, as opposed to a hypogonadal mileu (traditionally achieved by androgen ablation) may reverse molecular abnormalities in stuttering priapism.PubMedCrossRef
62.
Saad ST, Lajolo C, Gilli S, Marques Junior JF, Lima CS, Costa FF, Arruda VR. Follow-up of sickle cell disease patients with priapism treated by hydroxyurea. Am J Hematol. 2004;77(1):45–9.PubMedCrossRef
63.
Siegel JF, Rich MA, Brock WA. Association of sickle cell disease, priapism, exchange transfusion and neurological events: ASPEN syndrome. J Urol. 1993;150(5 Pt 1):1480–2.PubMed
Metadata
Title
Stuttering Priapism: Insights into Pathogenesis and Management
Authors
Belinda F. Morrison
Arthur L. Burnett
Publication date
01-08-2012
Publisher
Current Science Inc.
Published in
Current Urology Reports / Issue 4/2012
Print ISSN: 1527-2737
Electronic ISSN: 1534-6285
DOI
https://doi.org/10.1007/s11934-012-0258-9

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