Effects of 17β‐oestradiol plus different doses of drospirenone on adipose tissue, adiponectin and atherogenic metabolites in postmenopausal women

Abstract. Objective. To investigate how variation in the dose of the progestogen influence the impact of 17 β ‐oestradiol plus drospirenone (DRSP) treatment on adipose tissue and its secretor function with direct implications for atherogenic metabolites. Design. Randomized, double‐blind, placebo‐controlled trial. Setting. Primary care, single study site. Subjects. A total of 240 healthy postmenopausal women 53–65 years old, 178 completer. Intervention. Daily treatment with 1 mg 17 β ‐oestradiol plus 1, 2, or 3 mg DRSP, or placebo for 2 years. Main outcome measures. Absolute changes in central (CFM) and peripheral fat mass (PFM; dual‐energy X‐ray absorptiometry, DEXA), adipokines [interleukin (IL)‐6 and adiponectin], atherogenic metabolites [triglycerides, high‐density lipoprotein cholesterol (HDL‐C), glucose] and blood pressure. Results. Oestradiol plus 1 mg DRSP evoked significant decreases in CFM and the CFM/PFM ratio from baseline. These benefits virtually decreased with increasing dose of DRSP confounded by dose‐dependent increases in CFM and PFM in smokers ( P ‐value for trends <0.001), in whom the increases in bioavailable oestradiol were half of that in nonsmokers ( P < 0.001). Treatment with 3 mg DRSP induced decreases in serum adiponectin by month 6 ( P < 0.05), which persisted in nonsmokers only and led to significant increases in glucose and triglycerides and decreases in HDL‐C ( P < 0.05). Adiponectin in smokers normalized by the end of the study parallel with the increases in body fat mass. Conclusions. Interactions of the sex steroids with adipose tissue and its secretor function are important determinants of the overall impact of hormone therapy on cardiovascular risk. A DRSP dose up to 2 mg does not seem to exert adverse effects when combined with 1 mg 17 β ‐oestradiol.