Hormone replacement therapy and cancer risks in perimenopausal women: A retrospective cohort study using a Japanese claims database

Abstract Aim Hormone replacement therapy (HRT) relieves menopausal syndromes but concerns regarding certain cancer risks remain. This study aimed to investigate cancer risks in perimenopausal women using HRT. Methods Using a health care database in Japan, we compared breast cancer and other cancer risks in perimenopausal women who started HRT between January 2011 and October 2021 at age 45–54 years with that of women who did not use HRT. Women in the control group were selected by 1:4 exact matching on birth year, and followed from the same index time as their counterparts. Results Data from 12 207 women in the exposure group and 48 828 age‐matched women in the control group were analyzed. The median HRT duration was 16.1 (interquartile range, 9.9–28.0) months. Breast cancer risk was lower in the HRT group (adjusted hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.54–0.82). When stratified by age, breast cancer risk was lower in the HRT group who started HRT at age 45–49 years (adjusted HR, 0.54; 95% CI, 0.40–0.72). Estrogen‐major HRT accounted for approximately one‐third of HRT and uterine corpus cancer risk was increased in estrogen‐major HRT (adjusted HR, 2.44; 95% CI, 1.56–3.81). Conclusions Breast cancer risk in women starting HRT between 45 and 49 years is lower than that in the average population; this finding might be susceptible to unmeasured factors such as early menopause among HRT recipients. Unopposed estrogen therapy accounts for considerable proportion of HRT in Japan and it increases uterine corpus cancer.