Introduction: Hydrochlorothiazide (HCT) has been suggested to induce photosensitivity, thereby increasing the incidence of skin cancers. After a pharmacovigilance alert, HCT was frequently withdrawn or substituted by other diuretics. The aim of this study was to compare the association of exposure to HCT with cancer risk versus alternative diuretics.

Methods: A retrospective cohort study was conducted based on data from the AOK PLUS, a large German statutory health insurance fund. Patients with HCT treatment were propensity score matched (PSM) to patients using non-HCT diuretics. Incidence of cancer of any kind and, specifically, skin cancer was assessed in both groups. Time to incident cancer diagnosis was evaluated and compared between the groups.

Results: A total of 199,708 patients were included in the final analysis (n=76,855 in the HCT-group; n=122,853 in the non-HCT-diuretics group). After PSM, 122,554 patients remained in the sample (n=61,277 for both groups, of which >96% had hypertension, mean age 73 years, 61% female). HCT treatment was associated with a lower incidence of cancer of any kind, compared with non-HCT diuretics (Incidence rate ratio (IRR) per 100 patient years 0.84 95% Confidence interval (CI): 0.82-0.87). HCT treatment was associated with a small albeit significantly higher IRR of skin cancer (1.14 95% CI: 1.06-1.24) with significant variances over time. Although numerically higher, the difference accounts to only 0.05 more skin cancer diagnoses in 100 patient years.

Conclusions: HCT treatment compared to alternative diuretics was associated with a lower all-cancer risk and was not associated with a meaningful increase in skin cancer risk in a large German population. Nevertheless, advice for skin protection is warranted in all patients taking thiazide or thiazide-like diuretics.