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Exogenous hormones -- namely oral contraceptives and hormonal replacement therapy (HRT) -- may increase the risk of keratinocyte carcinoma (KC) in females, a recent review and meta-analysis has found.

A total of 5,293 patients with KC and 106,424 controls were included in the analysis. The meta-analysis indicated that oral contraceptives and HRT were associated with an increased risk of squamous cell carcinoma (OR/RR 1.25, 95% CI 1.10-1.43, P=0.080) and also of basal cell carcinoma (OR/RR 1.16, 95% CI 1.09-1.25, P=0.188).

The analysis, which appears in , was conducted by a team of researchers based at the Chengdu Second People's Hospital Department of Dermatology in Sichuan, China. The following study excerpts have been edited for length and clarity.

What catalyzed the initial need for this investigation?

According to epidemiological data, KC incidence rates have been increasing globally even as mortality rates are stable or declining. The role of exogenous hormone exposure as a potential risk factor for KC has been controversial.

Several previous studies have investigated the potential association between KC and hormone exposure, although results were conflicting. Researchers sought to further investigate a possible connection between the use of exogenous sex hormones and the risk of KC in women.

What were the key findings?

Use of exogenous sex hormones may increase the risk of KC among females. The analysis revealed that oral contraceptives were associated with elevated risk of squamous cell carcinoma, while users of HRT were prone to basal cell carcinoma.

What are some potential underlying reasons for these associations?

The potential impact of sex hormones in the development of KC may be supported by some epidemiological and laboratory studies. Estrogen receptors on the surface of keratinocytes can be activated to induce cell proliferation, changing the capacity of DNA to repair itself. It has also been reported that oxidants indirectly induce DNA damage, resulting in genomic and gene mutations.

Furthermore, the photosensitivity reaction induced by oral contraceptives may play a potential role in KC progression. Cumulative estrogen exposure may result in phototoxic reactions (in a dose-dependent manner) that damage skin cell membranes or DNA after they absorb ultraviolet radiation into the skin.

What is the bottom-line message for dermatologists?

Sex hormones may act as a potential risk factor for KC. Given the wide use of oral contraceptives globally, the authors note that their findings should be verified by more powerful evidence, but its impact on the risk of KC cannot be ignored.