Priapism is responsive to PDE5 inhibitor therapy

August 1, 2006

Atlanta-Phosphodiesterase-5 inhibitor therapy, which is commonly used to treat erectile dysfunction, may have a paradoxical benefit as a treatment for priapism in patients with sickle cell anemia, according to research presented at the AUA annual meeting here and at the American Society of Andrology annual meeting in Chicago.

"We have been using PDE-5 inhibitors to treat priapism, which sounds completely bizarre and counterintuitive," said lead study author Arthur L. Burnett, II, MD, professor of urology at the James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore.

"I had seven patients to talk about at the ASA meeting, although I probably have managed a good 10 or so by now. These include patients with sickle-cell-disease-associated priapism and those with no recognizable etiology for the problem," he said, noting that six of those seven patients responded to PDE-5 inhibitor treatment.

"This is very important in certain populations, such as sickle cell patients. If you have an erection that goes up for more than an hour, it is painful; you can lose sensation and tissue function," Dr. Burnett said.

He noted that he is currently studying the relationship between priapism and sickle cell anemia and expects results in about a year.

Durable results

The current study was conducted with seven patients between the ages of 22 and 37 years. Four had sickle cell-associated priapism, while the rest had idiopathic priapism. Medically refractory episodes of priapism between 8 months and 15 years had been reported, and, in some cases, episodes had progressed to daily frequency and had lasted as long as 5 hours.

Patients were given sildenafil citrate (Viagra), 25 mg daily in the morning under condition of complete penile flaccidity. They were then converted to the longer-acting PDE-5 inhibitor tadalafil (Cialis), 5 mg in the morning, 3 times per week.

After 2 to 3 weeks of continual treatment, six patients experienced significant alleviation of recurrent priapism ranging from less-frequent or shorter episodes to complete resolution after treatment. Three patients temporarily required injections of intracorporeal phenylephrine (Prometh) on an as-needed basis. Treatment has been well tolerated over a 3-to 24-month period, and all seven men have retained erectile ability sufficient for sexual intercourse.

Dr. Burnett said his group's research establishes that PDE-5 is "changeable, and depending on how the penile tissue sees a lot of PDE-5 inhibitors, it creates a feedback mechanism in the penis, causing the body to upregulate PDE-5. So this protective factor for normal erections is restored to a normal range," he said.

During arousal, nitric oxide is liberated from nerve endings and from the endothelium in the flesh of the penis. The whole cascade initiated by nitric oxide is itself controlled by PDE-5. Related research indicates why some men who have erectile dysfunction fail to respond to PDE-5 inhibitors.

"Some men don't respond to PDE-5 inhibitors because their hormones are out of whack. If they actually get the hormone, in the form of androgen replacement therapy, it allows them to respond better," Dr. Burnett said.

PDE-5 inhibitors can be effective in treating priapism because PDE-5 inhibits erections. Thus, an agent that increases the amount of PDE-5 in the penis might effectively treat men who get many prolonged or uncontrollable erections (unlike agents that reduce the level of PDE-5, allowing erections to occur).