Use of phosphodiesterase-5 inhibitors and the incidence of melanoma

1Introduction

Phosphodiesterase-5 inhibitor (PDE-5i) therapy is an established standard care for patients with erectile dysfunction (ED). More than 20 million men were treated with Sildenafil in the first 6 years after the drug was introduced into the market in 1998 [1] . In 2002, the National Health and Nutrition Examination Survey (NHANES) reported the overall prevalence of ED in men over the age of 20 was 18.4% [2] . Meanwhile, in 2011, the Global Online Sexual Survey (GOSS) found that 23.7% of surveyed men in the US were consistently using PDE-5i [3] . Even when considering its additional off-label uses, such as pulmonary hypertension (pHTN) and congestive heart failure (CHF), the number of patients with ED using PDE-5i has increased drastically since being introduced [4] . Additionally, more than one-third of men who undergo radical prostatectomy (RP) for prostate cancer (PCa) experience ED, and PDE-5i therapy is used as a safe and effective treatment in these patients [56] .

The incidence of melanoma and its associated mortality has been increasing for the past 2 decades, with the majority of new diagnoses being made among males over the age of 50 [7] . In 2021, the new cases in males is estimated to be 62,260 compared to 29,000 in 2001 [78] . The association of PDE-5i and melanoma was first suggested based on the observation that in melanoma cells, oncogenic BRAF induces invasion through downregulation of phosphodiesterase-5A (PDE5A), the same biochemical pathway through which PDE-5i drugs act [9] . Given the proposed association between PDE-5i and melanoma, along with the rise in PDE-5i use, one might expect a shift in melanoma diagnoses since the introduction of PDE-5i. We thus looked at the SEER database to see if the incidence of melanoma changed among the patient population after the introduction of PDE-5i.