Relationship of the extended use of hydrochlorothiazide with melanoma: a literature review




Melanoma; Hydrochlorothiazide; Association; Risk.


Recent studies show a strong relationship between the use of hydrochlorathiazide (diuretic and antihypertensive drug) and the risk of developing melanoma due to its photosensitizing feature on the skin. The aim of this paper is to show the association between the use of hydrochlorathiazide and the increased risk of melanoma onset. The methodology was a bibliographic survey with articles published from 2016 to 2019 in the electronic databases of scientific reliability PubMed, Medline, Science Direct and journals specialized in the subject. Four pertinent studies were found on the subject, which identified that hydrochlorothiazide is classified as a carcinogenic drug by the International Agency for Research on Cancer. As exposure to ultraviolet light increases skin cell damage, long-term concomitant administration of hydrochlorothiazide leads to an increased likelihood of skin malignancy, including the development of melanoma. A meta-analysis was performed involving melanoma patients in Denmark. The total study population was 19,273 cases and 192,730 controls; Among these, 413 cases (2.1%) and 3,406 controls (1.8%) were classified as users of high cumulative doses of hydrochlorothiazide (≥ 50,000 mg), resulting in an adjusted odds ratio (OR) of 1.22 for melanoma. Therefore, it is suggested that the use of hydrochlorothiazide is associated with the onset of melanoma. More large studies, mainly national, are needed to confirm the findings. Therefore, the indication that hydrochlorothiazide use increases the risk of melanoma may have clinical relevance related to drug choice, particularly for patients with melanoma risk factors.


Archier, E., Devaux, S., & Castela, E. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. 2012; 26(Suppl 3), 22-31.

Cognetta, A. B., Wolfe, A. M., & Heinrichs, E. Hydrochlorothiazide Use and Skin Cancer: A Mohs Surgeon's Con- cern. Dermatol Surg. 2016; 42(9):1107-1109.

De vries, E., Trakatelli, M., & Kalabalikis, D. Known and potential new risk factors for skin cancer in European populations: a multicentre case-control study. Br J Dermatol. 2012; 167(Suppl 2),1-13.

Friedman, G. D., Asgari, M. M., & Warton, E. M. Antihypertensive drugs and lip cancer in non-His- panic whites. Arch Intern Med. 2012; 172(16):1246-1251.

Gandini, S., Palli, D., Spadola, G., & Bendinelli, B.. Antihypertensive drugs and skin cancer risk: a review of the literature and meta- analysis. Crit Rev Oncol Hematol. 2018; 122:1-9.

Gomez-Bernal, S., Alvarez-Perez, A., & Rodriguez-Pazos, L. Photosensitivity due to thiazides. Actas Dermosifiliogr. 2014; 105(4):359-366.

Gu, Q., Burt, V. L., Dillon, C. F., & Yoon, S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: The National Health and Nutrition Examination Survey, 2001 to 2010. Circulation. 2012; 126(17):2105-2114.

Guy, G. P., Machlin, S. R., Ekwueme, D. U. Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011. Am J Prev Med. 2015; 48(2):183-187.

Hartling, L., Hamm, M., Milne, A., et al. Validity and Inter-Rater Reliability Testing of Quality Assessment Instruments. Rockville (MD), 2012.

James, P. A., Oparil, S., Carter, B. L., et al. Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311(5),507-520.

Kunisada, M., Masaki, T., Ono, R. Hydrochlorothiazide enhances UVA-induced DNA damage. Photochem Photo- biol. 2013; 89(3), 649-654.

Mills, K. T., Bundy, J. D., & Kelly, T. N. Global disparities of hyper- tension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation.2016; 134(6),441-450.

Nardone, B., Majewski, S., & Ashley, S. Association of melanoma and nonmelanoma skin cancer with antihypertensive drugs: A report from the Research on Adverse Drug events And Reports project. J am acad dermatol. Maio, 2016.

Nardone, B., Majewski, S., Kim, A. S., et al. Melanoma and non-melanoma skin cancer associated with angioten- sin-converting-enzyme inhibitors, angiotensin-receptor blockers and thiazides: a matched cohort study. Drug Saf. 2017; 40(3), 249-255.

Pedersen, E. Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study. J Am Acad Dermatol. 2018. 80(2).

Pereira, A. S., et al. (2018). Metodologia da pesquisa científica. [e-book]. Santa Maria. Ed. UAB/NTE/UFSM. Recuperado de 824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1.

Pottegard, A., Hallas, J., & Olesen, M. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med. 2017; 282(4), 322-331.

Pottegård, A., Pedersen, S. A., Johannesdottir Schmidt, S. A. J., et al. Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma. JAMA Internal Medicine. Agosto, 2018. 178(8).

Rogers, H. W., Weinstock, M. A., Feldman, S. R., & Coldiron, B. M. Incidence estimate of nonmelanoma skin cancer (Keratinocyte Carcinomas) in the U.S. population, 2012. JAMA Dermatol. 2015; 151(10), 1081-1086.

Schmidt, S. A., Schmidt, M., Mehnert, F., Lemeshow, S., et al. Use of antihypertensive drugs and risk of skin cancer. J Eur Acad Dermatol Venereol. 2015; 29(8), 1545- 1554.

Shin, D., Lee, E. S., Kim, J., Guerra, L., Naik, D., et al. Association Between the Use of Thiazide Diuretics and the Risk of Skin Cancers: A Meta-Analysis of Observational Studies. J Clin Med Res. 2019; 11(4), 247–255. doi:10.14740/jocmr3744

Sica, D. A. Diuretic therapy in cardiovascular disease. In: Black HR, Elliott WJ, eds. Hypertension: A companion to Braunwald's Heart Disease. (2a ed.), Philadelphia: Saun- ders, 2012. 169-170.

Stern, R. S. Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol. 2010; 146(3), 279-282.

Stern, R. S., Study, P. F. U. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Derma- tol. 2012; 66(4), 553-562.

Zuba, E. B, Koronowska S, Osmola-Mankowska A. Drug-induced photosensitivity. Acta Dermatovenerol Croat. 2016; 24(1),55-64.



How to Cite

Chaves Calabria, A., Spaniol, C., Társis Araujo Carvalho, G., & Limas de Souza, L. (2020). Relationship of the extended use of hydrochlorothiazide with melanoma: a literature review. Research, Society and Development, 9(9), e958998175.



Health Sciences