We read with great interest the study by Johannesdottir and coworkers,1 who report that a high-intensity and long-term use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with a decreased risk of squamous cell carcinoma. Their observation is highly intriguing in the light of the reported higher frequency of keratinocyte skin cancer (ie, actinic keratoses and squamous cell carcinoma) among men compared with women.2 To date, the sex-related different frequency of keratinocyte skin cancer has been solely attributed to a higher occupational sun exposure of men compared with women.3
The study by Johannesdottir et al1 provides the first evidence for an alternative explanation, which could be linked to the chronic use of painkillers and menstrual cycle–related symptoms. It has been estimated that as many as 2.5 million women each year are affected by menstrual disorders such as primary dysmenorrhea, which often cause excessive pain shortly before or during the menstruation.4 The use of NSAIDs have been shown to effectively reduce the pain and represents first-line treatment.4
Given that approximately 25% of women5 will presumably use NSAIDs on a monthly basis for several years, if not decades, the observation made Johannesdottir et al1 supports the hypothesis that NSAIDs may represent a currently unrecognized factor associated with a lower incidence of keratinocyte skin cancer in women compared with men. Although the authors did not investigate such correlation, their data strongly emphasize the need to look closer at the potential role of NSAIDs in the prevention of keratinocyte skin cancer in the future.