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J Intern Med. 2005 Dec;258(6):544-53.

Effects of 17beta-oestradiol plus different doses of drospirenone on adipose tissue, adiponectin and atherogenic metabolites in postmenopausal women.

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1
Center for Clinical and Basic Research, Ballerup, Denmark. lbt@ccbr.dk

Abstract

OBJECTIVE:

To investigate how variation in the dose of the progestogen influence the impact of 17beta-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 17beta-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 17beta-oestradiol.

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