Erectile Dysfunction Drugs: No Effect on Prostate Cancer Risk

Pam Harrison

August 05, 2016

The phosphodiesterase type 5 inhibitors (PDE-5is) used to treat erectile dysfunction (ED) do not significantly affect prostate cancer risk in any subgroup of men or any grade of disease, according to a secondary analysis of the Reduction of Dutasteride of Prostate Cancer Events (REDUCE) trial.

"There were some safety concerns prior to us doing this analysis, and there was also some rationale behind the idea that the PDE-5 inhibitors might have some benefit," Stephen J. Freedland, MD, from the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, told Medscape Medical News.

 
Taking these drugs is probably not doing significant harm in terms of prostate cancer risk Dr Stephen J. Freedland
 

"And while this is not a definitive study, findings do give us some level of comfort that taking these drugs is probably not doing significant harm in terms of prostate cancer risk," Dr Freedland added.

The study was published online August 1 in The Journal of Urology.

The authors comment that PDE-5is were first introduced in 1998 and quickly gained widespread popularity because of efficacy and minimal side effects. Given the high frequency of PDE-5i use in older men (ie, those at greatest risk for prostate cancer), several groups have previously examined the relationship between PDE-5i use and prostate cancer, with conflicting results, they add. These include two studies with diametrically opposite results reported recently by Medscape Medical News.

New Analysis of REDUCE Data

REDUCE was a double-blind, multicenter trial in which men aged 50 to 75 years were randomly assigned to receive 0.5 mg/d dutasteride (Avodart, GlaxoSmithKline) or placebo for 4 years.

To meet enrollment criteria, at baseline, men had a prostate-specific antigen level ranging from 2.5 to 10.0 ng/mL if they were 50 to 60 years of age and 3.0 to 10.0 ng/mL if they were older than age 60 years.

Participants also had to have a negative result on a 6- to 12-core prostate biopsy within 6 months of study enrollment.

The main study results, as previously reported by Medscape Medical News, showed that men taking dutasteride had a 23% lower risk for prostate cancer during a treatment interval of 4 years compared with men receiving placebo. However, when these data were submitted to the Food and Drug Administration, dutasteride was not approved for chemoprevention of prostate cancer.

For the current analysis, lead author Juzar Jamnagerwalla, MD, a urology resident at the Cedars-Sinai Medical Center, and colleagues looked at data from 6501 men — 5.6% of whom were using a PDE-5i at baseline — and found that PDE-5i use was not associated with the diagnosis of prostate cancer during the 4-year study interval (odds ratio, 0.90).

Prostate cancer was diagnosed in 19.5% of PDE-5i users compared with 22.7% of nonusers, a difference that was not statistically significant.

Use of a PDE-5i was also not related to the development of low-grade or high-grade disease on univariable or multivariable analysis, Dr Jamnagerwalla added.

Findings were unchanged when the analysis was directed at high-grade disease, defined as a Gleason score or 7 or greater or a Gleason score of 8 or greater, he noted.

PDE-5i use was associated with a lower detection rate of prostate cancer, Dr Jamnagerwalla pointed out, but this did not reach statistical significance on univariable or multivariable analysis at an odds ratio of 0.83 and 0.90, respectively.

North American Cohort

Because PDE-5i use was significantly higher among men from North America than other geographic areas included in the trial, Dr Jamnagerwalla and colleagues compared clinically relevant outcomes among PDE-5i users and nonusers in a subgroup analysis involving only North American men.

Among men using a PDE-5i, the overall risk for prostate cancer during the 4-year study was 33% lower than that in men not using an erectile dysfunction (ED) drug, but this difference again did not reach statistical significance, as Dr Jamnagerwalla pointed out.

Stratified by disease grade, the use of an ED drug resulted in a 58% and 22% lower risk for high-grade and low-grade prostate cancer, respectively, during the 4-year interval compared with no use of a PDE-5i.

Despite a suggestion of an inverse association in the subgroup of North American men, this did not reach statistical significance on univariable or multivariable analysis, the researchers note.

Asked whether a 58% difference in the risk for high-grade prostate cancer between PDE-5i users and nonusers wasn't at least clinically meaningful, Dr Freedland agreed that these differences would be highly clinically meaningful if in fact they were real findings.

"However, the fact that they were not statistically significant gives you pause that this difference may be a chance finding," he said.

"Our best guess is that PDE-5 inhibitors may reduce high-grade prostate cancer risk by 58%, but we're really not confident that they provide any benefit whatsoever," Dr Freedland added.

Dr Jamnagerwalla noted that future studies involving larger groups of men are warranted to firmly rule out an association between PDE-5i use and prostate cancer risk during a longer-term follow-up.

The study was supported by GlaxoSmithKline and the National Institutes of Health. The authors have disclosed no relevant financial relationships.

J Urol. Published online August, 2016. Abstract

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