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


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Primary care, single study site.


METHODS
A total of 240 healthy postmenopausal women 53-65 years old, 178 completer.


METHODS
Daily treatment with 1 mg 17beta-oestradiol plus 1, 2, or 3 mg DRSP, or placebo for 2 years.


METHODS
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.
Tankó
L B
LB
Center for Clinical and Basic Research, Ballerup, Denmark. lbt@ccbr.dk
Christiansen
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C
D015502:Absorptiometry, Photon / Q000379:methods; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects; D000368:Aged; D000736:Androstenes / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D017698:Postmenopause / Q000502:physiology*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D000736:Androstenes; D008076:Cholesterol, HDL; D015850:Interleukin-6; D000451:Mineralocorticoid Receptor Antagonists; D014280:Triglycerides; D004958:Estradiol; C035144:drospirenone