Stuttering priapism in patients with sickle cell anemia: efficacy and safety of a pharmacologic prevention with sildenafil

Maurizio Carrino1, Luigi Pucci1, Gaetano Battaglia1, Riccardo Giannella1, Francesco Chiancone1, Paolo Fedelini1
  • 1 A.O.R.N. A. Cardarelli (Napoli)

Objective

Stuttering priapism is a recurrent form of ischemic priapism in which unwanted painful erections occur repeatedly with intervening periods of detumescence1. This historical term identifies a patient whose pattern of recurrent ischemic priapism encourages the clinician to seek options for prevention of future episodes. The aim of our study is to evaluate the use of a long-term, continuos phosphodiesterase type 5 (PDE5) inhibitor therapeutic regimen in controlling recurrent ischemic priapism. The main outcome measure was reduction in frequency or duration of priapism episodes.

Materials and Methods

From January 2011 to January 2013, 15 patients with sickle cell disease-associated “stuttering” priapism were enrolled in our study (11 patients were followed by the Department of Hematology for a sickle cell anemia and 4 patients reached our emergency department). The average age was 26 years (age 19-37 years). For each patient, standard history and physical examination were performed. Laboratory testing was also conducted to screen for psychoactive drugs and urine toxicology to evaluate for the involvement of legal or illegal drugs know to precipitate priapism. All the patients had undergone cavernous blood gas testing from penile aspirates, to determine the classification of the presentation (ischemic or nonischemic). They were counseled and consented to the “off-label” use of PDE5 inhibitor sildenafil citrate2. We asked for drugs to our hospital pharmacy. The duration of clinical follow-up extended through 1 year.

Results

We confirmed that all patients had a sickle cell disease-associated priapism. Patients received sildenafil citrate at a 50-mg daily at the same hour in the morning. The treatment was successful in eleven patients, with an important decrease of priapism episodes after about 2 weeks of starting treatment and no patients reached our emergency department. All patient had no more priapism episodes after long-term therapy (from two to seven month with an average of three months of starting treatment). Each patient developed some priapism episodes after discontinuing the use of sildenafil citrate, believing that their priapism disorders had been resolved. Now all patients continue their PDE5 inhibitor therapy. Two patients had no reduction of frequency and duration of priapism episodes. One of these last two patients underwent a Winter’s shunt procedure to resolve one priapism episode. Two patients interrupted therapy because of chest pain but therapy did not cause any serious adverse effects. Erectile function improved in nine patients and was unchanged in four patients.

Discussions

In this report we have evaluated a new treatment option for recurrent ischemic priapism. Recurrent priapism is a manifestation of defective PDE5 regulatory function in the penis, resulting from altered endothelial nitric oxide/cGMP signaling in this organ3. Sickle cell anemia patients are known to have chronically lower levels of NO than non sickle cell anemia patients and the cyclic nucleotide is produced in low steady-state amounts. This situation thereby down regulates the set point of PDE5 function (secondary to altered cGMP-dependent feedback control mechanism). In this context, when nitric oxide in neuronally dischargerd in sexual stimulation or during sleep-related erectile activity, cGMP production surges in a manner that leads to excessive erectile tissue relaxation because of basally insufficient functional PDE5 to degrade the cyclic nucleotide. The use of a PDE5 inhibitor in a long term, causes a heightened, basal amount of cGMP in the penis, which then progressively reestablishes normal PDE5 expression and activity. We suggest that patients use sildenafil citrate in the morning time after awakening under conditions of complete penile flaccidity while restricting sexual stimulation until only many hours later, in order to metabolize medication without risk of a priapism episode when unrestricted sexual activity or nighttime sleep would occur.

Conclusion

Our finding supports the feasibility of using PDE5 inhibitor sildenafil citrate in a clinical management program for patients with ischemic priapism in order to avoid the development of major complications from priapism recurrences. The use of this therapy is also supported by scientific principles. Moreover our patients preserved their sexual function and this therapy improved their quality of life. The only limitation of this therapy is its costs. Further investigations in the form of controlled clinical trials involved a bigger number of patient are necessary to confirm the utility of this treatment and the safeness also concerning an unclear increased risk of vasoocclusive pain crisis related to sildenafil citrate4.

References

1-Drogo K. Montague et. all., Aua guideline on the management of priapism (2003)
2- Burnett al et all., Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. j sex med. 2006 nov;3(6):1077-84.
3-Champion hc et all., Phosphodiesterase-5a dysregulation in penile erectile tissue is a mechanism of priapism. proc natl acad sci u s a. 2005 feb 1;102(5):1661-6
4-Lane a. et all., Potential risks of chronic sildenafil use for priapism in sickle cell disease. j sex med. 2011 nov;8(11):3193-5

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