Association of Adiposity Phenotypes With 27-Hydroxycholesterol and Sex Hormones: The Multiethnic Cohort Study

Abstract

Abstract Context The distribution of body fat has been linked to circulating levels of lipids and sex steroid hormones. The cholesterol metabolite and endogenous selective estrogen receptor modulator, 27-hydroxychlolesterol (27HC), may be influenced by adiposity phenotypes, particularly among females. No study has examined the relationships of 27HC with adiposity phenotypes. Objective To investigate the associations of 27HC and steroid hormones with detailed adiposity phenotypes among a multiethnic population of postmenopausal women. Methods A cross-sectional study was conducted among 912 postmenopausal women from the Multiethnic Cohort Adiposity Phenotype study. Multivariable linear regression examined the associations of circulating levels of 27HC, steroid hormones, and sex hormone–binding globulin (SHBG) with detailed adiposity phenotypes, adjusting for demographics, lifestyle factors, diabetes status, and use of lipid-lowering drugs. Subgroup analyses were conducted across race and ethnicity. Results Total fat mass (P trend = .003), subcutaneous adipose tissue (SAT) (P trend = .006), and superficial subcutaneous adipose tissue (P trend = 4.41 × 10−4) were inversely associated with circulating 27HC levels. In contrast, visceral adipose tissue (VAT) (P trend = .003) and liver fat (P trend = .005) were positively associated with 27HC levels. All adiposity phenotypes were associated with higher levels of free estradiol and testosterone and lower levels of SHBG. Generally, similar patterns of associations were observed across race and ethnicity. Conclusion Adiposity phenotypes, such as SAT, VAT, and liver fat, were differentially associated with circulating 27HC, while consistent directions of associations were seen for circulating hormones among postmenopausal women. Future studies are warranted to further understand the biology and relationships of 27HC and adiposity-related diseases.