Researchers from the London School of Hygiene & Tropical Medicine 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, which appeared to be explained by greater exposure to the sun.
The three drugs are known to inhibit the enzyme phosphodiesterase type 5 (PDE5), and reduced expression of this enzyme has been linked to increased growth of melanoma cells in vitro. Epidemiological studies are therefore important to examine the possibility of a long-term increase in melanoma risk in men taking these PDE5 inhibitors for erectile dysfunction.
Previous studies on a possible increase in melanoma risk in men prescribed one of the drugs have come to conflicting conclusions, and consequently Anthony Matthews and colleagues carried out a large study in UK men, using anonymized data from the Clinical Research Practice Datalink.
This study involved a comparison of 145,104 men prescribed a PDE5 inhibitor with 560,933 controls. The researchers observed a slight increase in risk of cutaneous melanoma (adjusted hazard ratio 1.14, 95% CI 1.01-1.29, p=0.04). However, similar increases in risk of basal cell carcinoma and solar keratosis, which are known to be related to sun exposure, were observed, while there was no increase in risk of colorectal carcinoma, which is unrelated to sun exposure.
In addition, the group of men prescribed a PDE5 inhibitor experienced a higher risk of solar keratosis even in the period before receiving their first prescription, suggesting that they had higher rates of sun exposure on average than the control group.
Krishnan Bhaskaran, the study's senior author, said "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."
The study also illustrates the value of large-scale studies using clinical information gathered in primary care.
KB is funded by a Wellcome Trust/Royal Society Sir Henry Dale fellowship (107731/Z/15/Z) and undertook part of this work under a previous National Institute for Health Research postdoctoral fellowship (PDF-2011-04-007). LS is funded by a Senior Wellcome Fellowship in Clinical Science. SML is funded by a National Institute for Health Research Clinician Scientist fellowship. IJD is funded by a Medical Research Council Methodology Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
IJD has consulted for and holds stock in GlaxoSmithKline. All other authors have declared that no competing interests exist.
Article: Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink, Matthews A, Langan SM, Douglas IJ, Smeeth L, Bhaskaran K, PLoS Medicine, doi:10.1371/journal.pmed.1002037, published 14 June 2016.