Erectile Dysfunction Drugs Again Cleared of Melanoma Risk

Pam Harrison

May 22, 2017

Yet another analysis of published data does not support a causal link between the use of drugs to treat erectile dysfunction (ED) and melanoma risk, suggesting that any association between their use and heightened skin cancer risk is likely lifestyle-related.

It has been postulated that because phosphodiesterase type 5 (PDE5) is downregulated in BRAF mutations commonly seen in melanoma, inhibition of PDE5 by PDE5 inhibitors might increase melanoma risk.

But the new study reconfirms that this is not the case.

"Overall, Viagra (sildenafil, Pfizer Inc) and other PDE inhibitors are safe medications as long as men are not taking nitrates, which carry a risk of reducing blood pressure," lead author Stacy Loeb, MD, assistant professor, NYU Langone Medical Center in New York City, said in a statement.

"Physicians and patients should not be concerned about taking these medications on account of worry about melanoma," she added.

The new data come from a meta-analysis that was published online May 19 in the Journal of the National Cancer Institute.

A literature search identified three case-control studies and two cohort studies involving a total of 866,049 men, among whom 41,874 were diagnosed with melanoma.

Among users of ED drugs, the risk for melanoma was increased by 11%, at a relative risk (RR) of 1.11, compared to those who did not use PDE5 inhibitors, Dr Loeb and colleagues report.

However, the association between ED drug use and increased melanoma risk was only statistically significant, at an RR of 1.15, among men who had the least exposure to these drugs; it was not statistically significant among men who used the drugs the most, at an RR of 1.09, the investigators note.

As Dr Loeb pointed out in a previous report on ED drug use and melanoma risk, "if it was a causal relationship...we would have expected that the men who filled the most prescriptions would have the highest risk, and that was not the case at all."

Moreover, there was a 16% increased risk for basal cell carcinoma among users of ED drugs vs nonusers, at an RR of 1.16 — which was similar to that seen for melanoma risk among users of ED drugs, Dr Loeb pointed out.

If ED drugs really did increase the risk for melanoma, there should not be any association with basal cell carcinoma, she noted.

However, in both the previous report and the current meta-analysis, there was an increased risk for basal cell cancer among users of ED drugs, obviating the proposition that upregulation of PDE5 by PDE5 inhibition upregulates BRAF mutations involved in melanoma, thus increasing melanoma risk in users of ED drugs.

It is widely accepted that the risk for basal cell carcinoma is directly related to sun exposure.

Dr Loeb and colleagues also reasoned that if ED drugs cause melanoma, they could expect to see more aggressive disease among users of ED drugs than among nonusers, but again, this was not the case.

In fact, in their meta-analysis, they found that persons who used PDE5 inhibitors frequently were at lower risk for stage II to IV melanoma, at an RR of 0.67, than nonusers, although the risk for early-stage melanoma was higher, at an RR of 1.45, among men with the greatest exposure to ED drugs compared to nonusers.

Sildenafil and Melanoma

In 2014, it was reported that the risk for invasive melanoma was almost twice as high among users of sildenafil compared to nonusers.

This report prompted the US Food and Drug Administration to place sildenafil and other ED drugs on its watch list of medications with possible safety issues in 2016.

It was this action that prompted Dr Loeb and colleagues to undertake the current meta-analysis to search for a causal link between PDE5 inhibitors and melanoma risk.

"Both PDE5 inhibitor use and skin cancer are strongly associated with socioeconomic status, raising statistically significant potential for confounding by lifestyle factors," Dr Loeb and colleagues conclude.

"The lack of dose-response, biological gradient and specificity suggest against a causal relationship [between PDE5 inhibitor use and melanoma risk]," they add.

The study authors attribute the risk to "detection bias," whereby the group of patients likely to take medicines for ED also happens to be more health conscious, more likely to see a physician, and so more likely to be diagnosed with melanoma than other men of similar age.

"Physicians should still screen for melanoma risk, but they do not need to add the use of Viagra and similar drugs to the list of screening criteria specifically," Dr Loeb said in a statement. "In general, men should continue to be careful about the risk of any kind of skin cancer from excessive sun exposure and use sun protection."

The research was supported by grants from the Swedish Cancer Society, the Louis Fell Charitable Lead Trust, and the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center.

J Natl Cancer Inst. Published online May 19, 2017. Abstract

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