Late age of natural menopause and use of menopausal hormone therapy were associated with significantly increased risk of basal cell carcinoma (BCC), according to results of a large, nationwide cohort study.
Women who experienced menopause at age 55 years or later, compared with age 50-54 years, had higher BCC risk (hazard ratio, 1.50; 95% confidence interval, 1.04-2.17; P for trend = .017). Among all women, those who had used menopausal hormone therapy had a higher risk (HR, 1.16; 95% confidence interval, 1.03-1.30) (J Clin Oncol. 2015 Nov 2. doi: 10.1200/JCO.2015.62.0625).
©Kelly Nelson/National Cancer Institute
The findings are consistent with the hypothesis that exposure to endogenous and exogenous estrogens is photocarcinogenic, according to Dr. Elizabeth Cahoon, research fellow in the Radiation Epidemiology Branch of the National Cancer Institute, Bethesda, Md., and colleagues. Women with the highest observed BCC risk were those who experienced natural menopause and used menopausal hormone therapy for 10 or more years (HR, 1.97; 95% CI, 1.35-2.87; P for trend less than .001).
“In contrast to surgical menopause, which is associated with an immediate and dramatic drop in estrogen levels, women undergoing natural menopause may be exposed to a nontrivial amount of total and unopposed estrogen during the menopausal transition,” they wrote. “In this group, the combination of endogenous and exogenous estrogens may have increased the cumulative estrogen exposure (and, thus, the cumulative phototoxic effects).
The prospective study included 46,100 female, white participants of the US Radiologic Technologists Study, an occupational cohort composed of radiologic technologists. All participants were cancer free at baseline, and 4% had an incident BCC during the approximately 10-year follow-up.
Results showed no association between oral contraceptives and BCC, which may be due a to lower susceptibility in young adults to photosensitizing medications or to the lower doses typical of oral contraceptives. The ethinyl estradiol level in oral contraceptives typically ranges from 20 to 50 mcg, compared with a typical equine estrogen dose in menopausal therapy of 625 mcg.
Most reproductive factors evaluated, including age at menarche, number of live births, and age at first birth, showed no association with BCC.
Dr. Cahoon and coauthors reported having no disclosures.