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Am Fam Physician. 2008;78(4):512

Background: Retrospective studies have noted an unexpected association between melanoma and a history of endometriosis; however, prospective data are lacking. Because female hormonal factors have been theorized to play a role in the development of melanoma, gynecologic diseases such as endometriosis, ovarian cysts, benign breast diseases, fibromas, and uterine polyps could be associated with cutaneous malignancy. Kvaskoff and colleagues analyzed the occurrence of melanoma in women with endometriosis and other benign gynecologic diseases.

The Study: The authors collected data from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale, a large-scale prospective cohort study in France of women 40 to 65 years of age. Participants completed a baseline questionnaire upon enrollment in the study. Every two years, participants completed follow-up questionnaires regarding medical issues, such as benign gynecologic disease and cancer. Participants were excluded from the analysis if they had a baseline history of cancer other than basal cell carcinoma or if they had never menstruated.

For this study, the diagnosis of a benign gynecologic disease (e.g., endometriosis, ovarian cysts, uterine fibromas or polyps) or breast disease (e.g., fibroadenoma, fibrocystic disease) must have been confirmed or treated via a specific diagnostic procedure, such as laparoscopy, biopsy, or radiologic or ultrasonic imaging. Baseline factors were also analyzed in relation to health outcomes. These factors included skin complexion, hair color, skin sensitivity to sun exposure, and number of nevi and freckles.

Results: A total of 363 primary melanoma cases were identified among the 91,965 women over a median follow- up time of 12 years. The relative risk (RR) of developing melanoma was significantly increased among the 5,949 women who had previously been diagnosed with endometriosis (RR = 1.62; 95% confidence interval [CI], 1.15 to 2.29), as well as among women with a history of uterine fibroma (RR = 1.33; CI, 1.06 to 1.67). No significant association was found between a history of ovarian cysts, uterine polyps, breast adenoma or fibroadenoma, or breast fibrocystic disease and the development of melanoma. Although women with melanoma were more likely to have certain phototype factors (e.g., fair skin; increased sensitivity to sun exposure; large number of nevi or freckles; blonde, red, or chestnut hair color), adjusting for these factors did not significantly affect the results. The use of exogenous hormones (e.g., oral contraceptives, progestagens, postmenopausal hormone therapy) also did not significantly affect results.

Conclusion: A history of endometriosis was associated with a significantly increased risk of developing melanoma. This may encourage physicians to play a role in melanoma prevention by alerting patients with endometriosis to their susceptibility. Additionally, this is the first study to report a positive association between uterine fibroma and melanoma development. Further investigation of this finding is warranted.

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