Association of Endogenous Sex Hormones with Adipokines and Ghrelin in Postmenopausal Women

Context: Sex hormones, adipokines, and ghrelin have been implicated in central control of appetite, energy homeostasis, maintenance of fat mass, and inflammation. Women tend to gain weight after menopause and adipose tissue is a major source of sex steroid postmenopause. Understanding the dynamics of these analytes are of particular importance in postmenopausal women, who are at greater risk for cardiometabolic diseases. Objectives: This study sought to evaluate the associations of adipokines and ghrelin with sex hormone concentrations in postmenopausal women. Design: We conducted a cross-sectional analysis of baseline clinical trial data. Setting: The parent trial was conducted at a university clinical research facility. Participants: Baseline data from 634 postmenopausal women participating in the Early vs Late Intervention Trial with Estradiol (ELITE). Participants had no history of chronic illness in the past 5 years and were not taking exogenous hormone therapy. Main Outcome Measures: Serum levels of estrone (E1), total estradiol (E2), free estradiol (FE2), free testosterone (FT), total testosterone (T), and sex hormone-binding globulin (SHBG). Results: Adjusted for age, race, time since menopause, and body mass index (BMI), leptin concentrations were significantly positively associated with E1, E2, FE2, and FT and inversely associated with SHBG levels. Only the associations of adiponectin with FE2 (inverse) and SHBG(positive) remained significant after controlling for BMI. The inverse associations of adiponectin with E1, E2, and FT were substantially mediated by BMI. Associations of ghrelin with E1, E2, FE2, and SHBG were not independent of BMI. Waist-to-hip circumference ratio was not a mediator in any of the associations. Conclusions: In postmenopausal women, leptin and adiponectin concentrations are substantially correlated with sex hormone and SHBG concentrations regardless of obesity status.