Men with high levels of testosterone have an increased risk of developing a potentially deadly skin cancer, researchers have found.
According to Cancer Research UK, which funded the study, one in 36 UK males and one in 47 UK females will be diagnosed with melanoma skin cancer in their lifetime. It said 86% of melanoma cases were preventable, typically caused by use of sunbeds or staying out in the sun, but other factors played a role in who is most at risk, including age and genetics.
Testosterone levels may also be a factor, at least in men. “There has been indirect evidence for testosterone and melanoma before, but this is the first time we have been able to look directly at the hormones in the blood,” said Dr Eleanor Watts, the first author of the research from the University of Oxford. “Although we have seen associations of prostate, breast and endometrial cancer [with testosterone] before, this is the first time we have seen an association with risk of melanoma in men.”
Writing in the International Journal of Cancer, Watts and colleagues report that they studied data relating to levels of testosterone in blood samples collected by the UK Biobank from 182,600 men and 122,100 postmenopausal women aged 40 to 69.
All participants were free from cancer for at least two years after the samples were taken, and were not taking hormone-related medication at the start of the study.
The researchers looked both the total level of testosterone in the blood samples, as well as levels that were freely circulating – in other words testosterone that was not bound to proteins. They then used national registries and NHS records to explore whether participants went on to develop or die from cancer.
The results show that by 2015-16, after being followed for an average of seven years, 9,519 men and 5,632 postmenopausal women – 5.2% and 4.6% of participants respectively – had been diagnosed with a malignant cancer. Cases of skin cancer that were not melanoma were not included.
The team then took into account a host of factors including ethnicity, body mass index, smoking, alcohol consumption and physical activity to explore whether there was a correlation between the levels of testosterone and particular cancers.
The results show that for men, higher levels of testosterone, whether freely or in total, were associated with a greater risk of developing malignant melanoma. Indeed, each 50 pmol/L increase in free testosterone was found to raise the chance of developing this cancer by 35%. According to Watts, 90% of men included in the study had free testosterone concentrations of between 130 pmol/L and 310 pmol/L.
Among other findings, higher levels of freely circulating testosterone were associated with a greater risk of prostate cancer in men, while in post-menopausal women, higher levels of testosterone, whether freely circulating or in total, were associated with a greater chance of endometrial and breast cancer.
But there are limitations. “It is really hard to say for sure that it is testosterone that is having these effects rather than another biomarker linked to it,” said Watts, adding that further research was needed.
Hashim Ahmed, a professor of urology at Imperial College London, said: “This large study showing a possible link of testosterone to skin cancer adds an insight into another cancer that could be prevented or treated using hormones. We already treated treat prostate cancer using anti-testosterone medication and there is some evidence that prostate cancer could be prevented with anti-testosterone medication, and I look forward to seeing whether similar approaches might be useful for melanoma.”
Dr Samra Turajlic, a consultant oncologist at the Royal Marsden and a group leader at the Francis Crick Institute, cautioned that the study did not prove high testosterone levels cause melanoma.
“Whether testosterone levels are linked to behavioural patterns with respect to sun exposure, including occupational exposure, or whether testosterone in some way changes the risk of melanomas developing following sun exposure is not answered by this study,” she said. “For everyone, irrespective of their gender, the main way to reduce the risk of skin cancer including melanoma is avoiding and reducing harmful sun exposure.”