Estrogen metabolites in premenopausal women living in China, Mongolia, and the United Kingdom

Breast cancer incidence is lower in women living in Asia than women living in North America and Northern Europe. However, large differences exist within Asia, for example, Mongolia’s breast cancer rate is even lower than China’s. Endogenous estrogens in Asian populations have been hypothesized to explain the disparity because of their strong positive correlations with breast cancer, though few studies have compared estrogen metabolites (EM) within Asia or between Asia and higher breast cancer risk countries.

We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 EM (non-parent estrogens) formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in premenopausal women living in Ulaanbaatar, Mongolia (n = 282), Shanghai, China (n = 121), and the United Kingdom (n = 125). We performed analysis of variance (ANOVA) using a generalized linear model procedure to assess differences in hormone concentrations between British and Asian (Chinese and Mongolian), and Chinese and Mongolian. Exponentiated least square means were used to calculate percent differences. We compared differences in overall means adjusted for age, body mass index, and parity by country during the follicular, peri-ovulatory, and luteal phases.

Total, parent, and non-parent estrogen concentrations were generally higher in British than Asian women, while the non-parent to parent ratio was lower. While parent estrogens appeared higher in Chinese compared with Mongolian women, differences did not reach statistical significance except for peri-ovulatory estrone; total estrogen metabolites in the 2-, 4-, and 16-pathways were higher in Mongolian than Chinese women. The non-parent to parent ratio was highest in Mongolian women followed by Chinese women, with British women having the lowest ratio.

Total urinary estrogens, both parent and their metabolites, were higher in British compared with Asian women. Our data showing the ratio of non-parent to parent estrogens, possibility reflecting greater estrogen metabolism, in women living in Mongolia, with one of the lowest breast cancer rates globally, than in women living in China, and in Chinese compared with British women, are consistent with their relative breast cancer risks and suggestive of a potentially protective metabolic profile.