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Hydroxyurea therapy for priapism prevention and erectile function recovery in sickle cell disease: a case report and review of the literature


Prolonged ischemic priapism in patients with sickling hemoglobinopathies is a urologic emergency requiring immediate intervention to avoid irreversible anoxic penile injury, corporal fibrosis, and erectile dysfunction. Therapeutic options, however, are limited and often ineffective. Here, we report recovery of erectile function with hydroxyurea therapy in an adolescent with hemoglobin SS following a prolonged episode of priapism and subsequent severe erectile dysfunction. This case suggests a potential role of hydroxyurea in reversing end organ damage in patients with hemoglobin SS and also supports basic science work indicating involvement of the NO-dependent pathway in the pathogenesis of sickle cell disease-associated priapism.

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  1. 1.

    Montague DK, Jarow J, Broderick GA, Dmochowski RR, Heaton JP, Lue TF, Nehra A, Sharlip ID, Members of the Erectile Dysfunction Guideline Update P, American Urological A (2003) American Urological Association guideline on the management of priapism. J Urol 170(4 Pt 1):1318–1324. doi:10.1097/01.ju.0000087608.07371.ca

  2. 2.

    Bivalacqua TJ, Musicki B, Kutlu O, Burnett AL (2012) New insights into the pathophysiology of sickle cell disease-associated priapism. J Sex Med 9(1):79–87. doi:10.1111/j.1743-6109.2011.02288.x

  3. 3.

    Champion HC, Bivalacqua TJ, Takimoto E, Kass DA, Burnett AL (2005) Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci USA 102(5):1661–1666. doi:10.1073/pnas.0407183102

  4. 4.

    Montorsi F, Adaikan G, Becher E, Giuliano F, Khoury S, Lue TF, Sharlip I, Althof SE, Andersson KE, Brock G, Broderick G, Burnett A, Buvat J, Dean J, Donatucci C, Eardley I, Fugl-Meyer KS, Goldstein I, Hackett G, Hatzichristou D, Hellstrom W, Incrocci L, Jackson G, Kadioglu A, Levine L, Lewis RW, Maggi M, McCabe M, McMahon CG, Montague D, Montorsi P, Mulhall J, Pfaus J, Porst H, Ralph D, Rosen R, Rowland D, Sadeghi-Nejad H, Shabsigh R, Stief C, Vardi Y, Wallen K, Wasserman M (2010) Summary of the recommendations on sexual dysfunctions in men. J Sex Med 7(11):3572–3588. doi:10.1111/j.1743-6109.2010.02062.x

  5. 5.

    Zacharakis E, Raheem AA, Freeman A, Skolarikos A, Garaffa G, Christopher AN, Muneer A, Ralph DJ (2014) The efficacy of the T-shunt procedure and intracavernous tunneling (snake maneuver) for refractory ischemic priapism. J Urol 191(1):164–168. doi:10.1016/j.juro.2013.07.034

  6. 6.

    Al Jam’a AH, Al Dabbous IA (1998) Hydroxyurea in the treatment of sickle cell associated priapism. J Urol 159(5):1642. doi:10.1097/00005392-199805000-00065

  7. 7.

    Saad ST, Lajolo C, Gilli S, Marques Junior JF, Lima CS, Costa FF, Arruda VR (2004) Follow-up of sickle cell disease patients with priapism treated by hydroxyurea. Am J Hematol 77(1):45–49. doi:10.1002/ajh.20142

  8. 8.

    Gladwin MT, Shelhamer JH, Ognibene FP, Pease-Fye ME, Nichols JS, Link B, Patel DB, Jankowski MA, Pannell LK, Schechter AN, Rodgers GP (2002) Nitric oxide donor properties of hydroxyurea in patients with sickle cell disease. Br J Haematol 116(2):436–444

  9. 9.

    Cokic VP, Beleslin-Cokic BB, Tomic M, Stojilkovic SS, Noguchi CT, Schechter AN (2006) Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells. Blood 108(1):184–191. doi:10.1182/blood-2005-11-4454

  10. 10.

    Lagoda G, Sezen SF, Hurt KJ, Cabrini MR, Mohanty DK, Burnett AL (2014) Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism. FASEB J 28(1):76–84. doi:10.1096/fj.13-228817

  11. 11.

    Akinsheye I, Klings ES (2010) Sickle cell anemia and vascular dysfunction: the nitric oxide connection. J Cell Physiol 224(3):620–625. doi:10.1002/jcp.22195

  12. 12.

    Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO 3rd, Schechter AN, Gladwin MT (2002) Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 8(12):1383–1389. doi:10.1038/nm799

  13. 13.

    Ware RE (2010) How I use hydroxyurea to treat young patients with sickle cell anemia. Blood 115(26):5300–5311. doi:10.1182/blood-2009-04-146852

  14. 14.

    Rockey DC, Chung JJ (1996) Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J Clin Invest 98(6):1381–1388. doi:10.1172/JCI118925

  15. 15.

    Shi-Wen X, Chen Y, Denton CP, Eastwood M, Renzoni EA, Bou-Gharios G, Pearson JD, Dashwood M, du Bois RM, Black CM, Leask A, Abraham DJ (2004) Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol Biol Cell 15(6):2707–2719. doi:10.1091/mbc.E03-12-0902

  16. 16.

    Hatzipantelis ES, Pana ZD, Gombakis N, Taparkou A, Tzimouli V, Kleta D, Zafeiriou DJ, Garipidou V, Kanakoudi F, Athanassiou M (2013) Endothelial activation and inflammation biomarkers in children and adolescents with sickle cell disease. Int J Hematol 98(2):158–163. doi:10.1007/s12185-013-1392-y

  17. 17.

    Rybicki AC, Benjamin LJ (1998) Increased levels of endothelin-1 in plasma of sickle cell anemia patients. Blood 92(7):2594–2596

  18. 18.

    Brun M, Bourdoulous S, Couraud PO, Elion J, Krishnamoorthy R, Lapoumeroulie C (2003) Hydroxyurea downregulates endothelin-1 gene expression and upregulates ICAM-1 gene expression in cultured human endothelial cells. Pharmacogenomics J 3(4):215–226. doi:10.1038/sj.tpj.6500176

  19. 19.

    Lapoumeroulie C, Benkerrou M, Odievre MH, Ducrocq R, Brun M, Elion J (2005) Decreased plasma endothelin-1 levels in children with sickle cell disease treated with hydroxyurea. Haematologica 90(3):401–403

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Author information

Correspondence to Arthur L. Burnett.

Additional information

Uzoma A. Anele and A. Kyle Mack have contributed equally to this work.

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Anele, U.A., Kyle Mack, A., Resar, L.M.S. et al. Hydroxyurea therapy for priapism prevention and erectile function recovery in sickle cell disease: a case report and review of the literature. Int Urol Nephrol 46, 1733–1736 (2014). https://doi.org/10.1007/s11255-014-0737-7

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  • Priapism
  • Impotence
  • Hydroxyurea
  • Sickle cell anemia