Hydrochlorothiazide and the risk of non-melanoma skin cancer: a critical review

Several recent large studies, most of which were performed in Denmark, have revealed a link between hydrochlorothiazide use and the risk of non-melanoma skin cancer. Photosensitizing properties of hydrochlorothiazide, inherent in many antihypertensive drugs, are considered a key pathophysiological mechanism underlying this association. The results of these studies prompted an update to the recommendations of the European Medical Agency for the safety of hydrochlorothiazide. However, to date there have been no convincing evidence of causality of this association. The accumulation of data on usage of hydrochlorothiazide, the most widely used diuretic worldwide, made the discussion of this association possible despite the low prevalence of skin cancer. At the same time, the retrospective design of these studies should be considered, as well as limited sample and lack of adjustment for important confounders. Therefore, the results obtained in these studies must be interpreted with extreme caution to prevent the decrease in hypertension control due to reduced compliance with treatment, unjustified withdrawal or replacement of hydrochlorothiazide, including its fixed combinations, with other thiazide or thiazide-like diuretics, which also have photosensitizing action.