New Research Knocks Down Melanoma-Viagra Theory

For the last year or so, Viagra users have had a bit of a dark cloud hanging over their heads in the form of a study showing that use of the little blue pill is associated with an increased risk of melanoma, the deadliest form of skin cancer.

Hopefully, they will be able to breathe a little easier in the future, thanks to research led by New York urologist Stacy Loeb, M.D.. While Dr. Loeb’s study also detected a link between Viagra and a higher incidence of melanoma, it traces that increased risk not to the medication itself but instead to the lifestyle typical of most Viagra users.

It’s the Viagra Lifestyle

The study led by Dr. Loeb observes that men who use the little blue pill to overcome their erection problems typically tend to be of a higher than average socioeconomic status. And as befits men who have the wherewithal to vacation where they please,  they are more likely to spend vacation and leisure time in sunnier climes, thus increasing their exposure to the sun and the threat of skin cancer.

Thus, according to the findings of Dr. Loeb and her team, it is probably not the medication that increases a Viagra user’s risk of developing melanoma but rather his lifestyle. Knowing this, Viagra users who still want to spend time in the sun but reduce their risk of skin cancer can take increased measures to protect themselves from the harmful rays of the sun.

This finding is more in line with recent studies that show sildenafil citrate, the active ingredient in Viagra, may actually be helpful in treating cancer when used in combination with other cancer-fighting drugs.

Earlier Study Stirred Fears

The study that first stirred up fears of a causal link between Viagra and melanoma was published in the June 2014 issue of “JAMA Internal Medicine.” Conducted by a team of dermatologists and epidemiologists, this earlier study theorized that temporarily lowering levels of the phosphodiesterase-5 enzyme — Viagra’s primary mechanism of action — somehow increased the invasiveness of melanoma cells.

Although the researchers suggested that this could be the reason for the increased incidence of melanoma among Viagra users, it cautioned that more studies would have to be conducted to definitively prove such a cause-and-effect relationship. While Dr. Loeb’s study adds to the body of knowledge about whatever relationship might exist between Viagra use and the incidence of melanoma, it appears to reach conclusions contrary to those of the earlier study.

Dr. Loeb’s study focused on Swedish male subjects, including 4,065 men who had been diagnosed with melanoma. For each of the melanoma patients, Dr. Loeb’s team randomly selected five Swedish men with the same birth year as controls. In all, researchers looked at the prescription drug habits and lifestyle choices of 4,065 men with melanoma and 20,325 control subjects, or a total of 24,390 study participants.

Findings of Loeb Study

Dr. Loeb’s study, published in a June 2015 issue of “Journal of the American Medical Association,” found that 435 men with melanoma,  or 11 percent of those diagnosed with this form of skin cancer, had filled prescriptions for PDE5 inhibitors. Such drugs, taken to temporarily regain erectile function, include not only Viagra but also other drugs such as Cialis and Levitra, all of which have a similar mechanism of action.

Among the 20,325 control subjects, the Loeb research team found that 1,713, or roughly 8 percent of those men, had purchased PDE5 inhibitors. In multivariable analysis, researchers detected an increased risk of melanoma among the men taking the impotence drugs, especially among those who had filled only a single prescription.

Melanoma Risk Increased

Statistically, the increased risk after filling a single prescription for a PDE5 inhibitor was 4 percent among men diagnosed with melanoma and 3 percent in control subjects. Among both melanoma patients and control subjects, the increased risk after filling multiple prescriptions was determined to be of little statistical significance.

Researchers also detected an increased risk for basal cell carcinoma, another form of skin cancer, among men using PDE5 inhibitors. Risk increased 9 percent among men in the melanoma group and 8 percent among control subjects.

However, researchers also found that men taking PDE5 inhibitors generally had a higher educational level and annual income, both of which are factors that have been found to be linked to increased melanoma risk.

Is the Association Causal?

In the conclusion to the study led by Dr. Loeb, researchers acknowledge that the use of PDE5 inhibitors was associated with a modest but “statistically significant” increase in risk for developing melanoma. “However, the pattern of association (e.g., the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.”

While the Loeb study’s findings don’t totally clear Viagra and the other impotence drugs of any involvement in increasing melanoma risk, they raise some serious questions about the conclusions of the earlier study that caused such alarm.

As previously noted, these findings seem to be more in line with a flurry of recent research studies that have found Viagra and some of the other PDE5 inhibitors may have a role in fighting a variety of cancers.

Sildenafil as a Cancer Fighter

Among the studies purporting to show a cancer-fighting role for PDE5 inhibitors, one conducted at Virginia Commonwealth University found that the impotence drugs had a synergistic effect when combined with anti-tumor medications already in use. The VCU study revealed that sildenafil combined with an anti-cancer drug known as OSU-03012 was more effective in killing brain cancer cells than OSU-03012 alone.

Paul Dent, Ph.D., lead author of the VCU study, explained that sildenafil and OSU-03012 together have been shown to be very effective at destabilizing a chaperone protein known as GRP78. Chaperone proteins are also sometimes known as heat shock proteins, which help to protect cancer cells from medicine’s efforts to kill them.

In the case of the OSU-03012 combination with sildenafil, Dent explains that reducing GRP78 expression and reducing chaperone function in general ¨kills brain cancer cells, including stem cell selected variants.”

Earlier Study with Doxorubicin

Previous research conducted at VCU demonstrated that sildenafil helped to increase the efficacy of the chemotherapeutic agent doxorubicin against prostate cancer when the two were combined in laboratory and animal studies. The combination not only proved more effective in killing prostate cancer cells than doxorubicin alone, but when used together the heart-damaging effects of doxorubicin also seemed to be significantly reduced.

Additional evidence of sildenafil’s ability to help fight cancer came from research conducted at Johns Hopkins Kimmel Cancer Center. Findings from that study were published in the November 2006 issue of “The Journal of Experimental Medicine.” Researchers found that sildenafil used by itself helped to unmask cancer cells so that the immune system could more readily identify and attack them. They based their findings on animal tests in which laboratory mice were implanted with breast and colon tumors. Tumors were reduced two- and threefold in animals treated with sildenafil, compared with mice that received no treatment at all.

Don Amerman is a freelance author who writes extensively about a wide array of nutrition and health-related topics.