Postmenopausal hormone use and cutaneous melanoma risk: A French prospective cohort study

Abstract

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between menopausal hormone therapy (MHT) use and melanoma risk; however, previous findings were conflicting. We sought to explore the associations between MHT use and melanoma risk in a prospective cohort of women in France, where a particularly wide variety of MHT formulations are available. E3N is a prospective cohort of 98,995 French women aged 40–65 years in 1990. MHT use was assessed through biennial self‐administered questionnaires. We used Cox proportional hazards regression models adjusted for age and skin cancer risk factors. Over 1990–2008, 444 melanoma cases were ascertained among 75,523 postmenopausal women. Ever use of MHT was associated with a higher melanoma risk (hazard ratio (HR) = 1.35, 95% confidence intervals (CI) = 1.07–1.71). The association was strongest among past users (HR = 1.55, CI = 1.17–2.07, homogeneity for past vs. recent use: p = 0.11), and users of MHT containing norpregnane derivatives (HR = 1.59, CI = 1.11–2.27), although with no heterogeneity across types of MHT (p = 0.13). Among MHT users, the association was similar across durations of use. However, a higher risk was observed when treatment onset occurred shortly after menopause (<6 months: HR = 1.55, CI = 1.16–2.07 vs. ≥2 years). Associations between MHT use and melanoma risk were similar after adjustment for UV exposure, although MHT users were more likely to report sunscreen use than nonusers. Our data do not support a strong association between MHT use and melanoma risk. Further investigation is needed to explore potential effect modification by UV exposure on this relationship.

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

“…We found positive associations with unopposed estradiol and unopposed estrogens administrated by cream. This is consistent with the results from the analyses of national data in France, Norway and Sweden, showing a positive association with unopposed estrogens overall (mainly estradiol) . In contrast, previous U.S. studies reported no association with unopposed estrogens, but it should be noted that the main type of estrogens prescribed in the United States is conjugated equine estrogens (CEE), while the main type prescribed in European countries is estradiol, as reflected from the distribution in our population (except for Germany and the United Kingdom for which about half of opposed estrogens were CEE).…”

“…MHTs containing promegestone were also positively associated with melanoma risk in our study, consistent with the findings from the French E3N cohort . In sensitivity analyses, MHTs containing norethindrone acetate also became positively associated with melanoma risk.…”

“…In our main analyses, we found a modest positive association between MHT use and melanoma risk, which contrasts with the existing meta‐analysis and two recent U.S. studies, but is consistent with three recent European cohort studies reporting positive associations . In addition, associations became stronger and statistically significant in our sensitivity analyses.…”

“…Although we used hours of recreational physical activity in summer as a proxy for time spent outdoors, the EPIC cohort did not evaluate behavioral sun exposure and there is high potential for residual confounding. It has indeed been suggested that exogenous hormone users are more prone to intentional UV exposure, with associations found between sunscreen use, sunburns, tanning bed use and melanoma risk . Another limitation is the single baseline assessment of exogenous hormone exposure from self‐reports, which does not take into account variability in use over time and might procure recall bias, especially in case of past exogenous hormone use.…”

Exogenous hormone use and cutaneous melanoma risk in women: The European prospective investigation into cancer and nutrition

“…The use of OCs and MHT has been associated with a higher risk of several cancers, including in the EPIC cohort (breast (18)(19)(20), cervical (21), and endometrial cancer (22,23), and meningioma (24)), and estrogen-only and combined estrogen-progestin hormonal therapy has been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer (IARC) (15,25). With regards to melanoma, while several studies reported a higher melanoma risk associated with exogenous hormone use (26)(27)(28)(29)(30)(31), findings are inconsistent to date. A meta-analysis concluded to no association between exogenous hormone use and melanoma risk (14); however, previous studies were heterogeneous, and few were based on a prospective design.…”