London, UK—Reduced expression of phosphodiesterase type 5 (PDE5) has been linked to increased growth of melanoma cells in vitro, leading to the possibility of a long-term increase in melanoma risk in men taking PDE5 inhibitors for erectile dysfunction.
Previous research projects examining the issue have come to conflicting conclusions, according to a study published recently in the journal PLOS Medicine. It found that men who took sildenafil, tadalafil, and vardenafil had only a very slight increase in risk of malignant melanoma compared to a control group and that could be explained by greater sun exposure.
An earlier study using U.S. data found nearly double the risk of developing malignant melanoma in PDE5 inhibitor users, but a later Swedish study was unable to replicate the results.
For the most recent investigation comparing 145,104 men prescribed a PDE5 inhibitor with 560,933 controls in the Clinical Research Practice Datalink, researchers from the London School of Hygiene & Tropical Medicine observed a slight increase in risk of cutaneous melanoma, adjusted hazard ratio 1.14, as well as similarly heightened risk of basal cell carcinoma and solar keratosis, which are known to be related to sun exposure. No increase was observed in risk of colorectal carcinoma, which is unrelated to sun exposure.
Because the group of men prescribed a PDE5 inhibitor experienced a higher risk of solar keratosis in the period before receiving their first prescription, study authors surmise that they had higher rates of sun exposure on average than the control group. They caution, however, that, without individual-level data on sun exposure, they could not directly control for that in the primary analysis.
“This large matched cohort study using data from UK primary care strongly suggests that the previously reported association between PDE5 inhibitors and malignant melanoma is not causal,” the researchers conclude. “Consistent with recent data from Sweden, we found weak evidence of a small increased risk of melanoma among PDE5 inhibitor users in our primary analysis; however, greater exposure did not appear to be associated with higher risk, the association was not specific to melanoma and was also observed for other sun-exposure-related conditions, and there was strong evidence that exposed patients were more likely to have had high sun or UV exposure, even before their first PDE5 inhibitor prescription.”
“All of our observations pointed towards the small apparent increase in risk of melanoma in men prescribed PDE5 inhibitors being explained by greater sun exposure, rather than a side-effect of the drugs themselves,” added senior author Krishnan Bhaskaran, PhD, MSc.
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