Viagra Linked to Skin Cancer

Strangely enough, PDE5 inhibitor use is linked to melanoma

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The body works in mysterious ways. For example, who would ever predict that Viagra use may somehow be linked to malignant melanoma, a dangerous type of skin cancer. After all, erection and sunburn—the main risk factor for melanoma—make unlikely bedfellows. Although we're randomized-controlled-trials-away from establishing any causal link, there is some evidence out there that Viagra is in fact associated or linked to malignant melanoma.

Malignant melanoma is the fifth most common cancer among men and the sixth most common cancer among women. If caught early, five-year survival rates for malignant melanoma top 90 percent with surgery being curative. Once cancer has spread to lymph nodes, bone and organs like the brain, lungs, and liver, however, it's more deadly with only 10 to 15 percent of patients surviving 5 years after being diagnosed with stage IV (highest-stage) melanoma.

Based on shared biochemical pathways, researchers postulate that PDE5 inhibitors like Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) may increase melanoma invasiveness. Specifically, PDE5 inhibitors may increase cytosolic calcium via cyclic guanosine monophosphate (cGMP) and thus increase the ability for melanoma cancer cells to invade and spread throughout the body. To date, small studies have supported an association between PDE5 inhibitors and melanoma.

Intent on proving this association in a more powerful way, researchers mined 2006 to 2012 Swedish medical registries and matched 4065 cases of melanoma with 20,325 controls (people without melanoma). They found that 11 percent of men with melanoma had filled prescriptions for PDE5 inhibitors like Viagra versus 8 percent of controls who had filled prescriptions for PDE5 inhibitors.

A closer look at this study yielded the following insights:

  • Men who were taking only PDE5 inhibitors were more likely to have melanoma than men taking multiple medications. These men who took only PDE5 inhibitors were on average younger, richer, healthier and more educated.
  • The type of PDE5 inhibitor (short-acting versus long-acting) made no difference with respect to associated melanoma. Originally, researchers hypothesized that longer-acting PDE5 inhibitors like Cialis would result in increased association on account of longer half-life and exposure.
  • In addition to an increased association with malignant melanoma, use of PDE5 inhibitors was also associated with basal cell carcinoma. Once again, this finding defied researcher expectations because, unlike melanoma and PDE5 inhibitors, basal cell carcinoma and PDE5 inhibitors share no known common pathways.
  • PDE5 inhibitors were associated with stage 0 and stage 1 melanoma, or cancers which haven't spread to distant lymph nodes and organs. Because PDE5 inhibitors are postulated to increase invasiveness of melanoma, researchers had originally hypothesized that higher-stage melanoma would be associated with PDE5 inhibitor use.

    Although these Swedish researchers proved a moderate but significant association between melanoma and PDE5 inhibitor use in a large sample size, their findings question the postulated mechanism by which PDE5 inhibitors could increase the associated risk of melanoma. Moreover, as conceded by the researchers, lifestyle choices like sun exposure were not controlled for in this study. Increased melanoma among richer, more educated and healthier men could be because these men spend more time participating in outdoor leisure, vacation, and sport.

    While researching this article, I ran across a Google advertisement inviting people with melanoma to take legal action against Viagra or whomever else. Such alarmist advertising reflects an adulteration of evidence-based medicine. We are far from determining any causal link between melanoma and drugs like Viagra. 

    Additionally, it's questionable whether dermatologists or other physicians should act on this association just yet. At present, the association between malignant melanoma and PDE5-inhibitor use may encourage physicians who prescribe Viagra in men with a history of sunburn to be on the lookout for melanoma and perform thorough skin exams and stress sunscreen use.

    Sources

    Kim KB, Davies MA, Rapini RP, Hwu P, Bedikian AY. Chapter 39. Malignant Melanoma. In: Kantarjian HM, Wolff RA, Koller CA. eds. The MD Anderson Manual of Medical Oncology, 2e. New York, NY: McGraw-Hill; 2011.

    Article titled "Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma" by SS Loeb published in JAMA in 2015.

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