PORTLAND, ORE. – Long-term exposure to commonly used estrogen-based contraceptives was not associated with malignant melanoma in a single-center retrospective study of more than 77,000 women.
This null result belied decades-old studies performed when contraceptives contained much higher doses of estrogen, Kelly A. Mueller of Northwestern University, Chicago, said in a poster presented at the annual meeting of the Society for Investigative Dermatology. Current microdosing of ethinyl estradiol (EE) “is not associated with subsequent diagnosis of melanoma in our population, and is not inconsistent with the full prescribing information for commonly prescribed contraceptives containing EE,” she said. The study also shows how large retrospective analyses of long-term follow-up data can inform pharmacovigilance for rare, serious medical events.Dennis P. West, PhD, professor of dermatology at Northwestern. However, older studies repeatedly linked malignant melanoma with exogenous estrogen exposure, and rates of this cancer are higher in young women, compared with men, before dropping along with estrogen levels after menopause. Currently, the prescribing information for oral, skin patch, and vaginal ring estrogen-based contraceptives lists hormone-sensitive tumors as a possible concern, but does not specify melanoma.
To help clarify whether current microdosing (10-40 mcg/day) of EE can increase melanoma risk, the researchers compared 2,425 women prescribed oral, vaginal ring, or skin patch EE contraceptives for at least 12 months with 74,868 unexposed women. For both groups, initial clinical encounters occurred between 2001 and 2011, women were followed for at least 5 years, and none had a baseline history of melanoma or exogenous estrogen exposure. The data source was the Northwestern Medicine Enterprise Data Warehouse, which integrates electronic medical records from more than 4 million patients in the urban Midwest.
When first seen, patients tended to be in their late 20s and ranged in age between 18 and 40 years. Excluding cutaneous malignant melanomas diagnosed within 12 months of initial contraceptive prescription left three cases in the exposed group and 194 cases in the unexposed group, which translated to statistically similar rates of melanoma (0.1% and 0.3%, respectively; P = 0.3). The three cases in the exposed group were diagnosed between 37 and 92 months after initial prescription of EE contraceptives, but “the limited sample size for the outcome of interest did not allow for further analyses,” she reported. Nevertheless, the findings suggest no link between long-term microdosing of EE exposure and cutaneous melanoma, Ms. Mueller added.
The National Institutes of Health helps support the Northwestern Enterprise Data Warehouse. Ms. Mueller and her associates had no relevant financial conflicts of interest.