Circulating levels of atherogenesis-associated adipocytokines and apoptotic markers are differentially influenced by hormone therapy, tibolone and raloxifene in healthy postmenopausal women.
OBJECTIVE
Estrogen agonist compounds may exert cardioprotective activity by modulating adipocytokine concentration and apoptosis. The objective of this study was to evaluate the effects of hormone therapy, tibolone and raloxifene on the serum adipocytokines resistin and adiponectin as well as on circulating markers of receptor-mediated apoptosis. Design Randomized, open-label, intervention study in the Menopause Clinic of a University Hospital.


METHODS
One hundred healthy postmenopausal women were randomized to the following groups: conjugated equine estrogens 0.625 mg (CEE) (n = 16); 17 beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (E(2)/NETA) (n = 15); tibolone 2.5 mg (n = 18); raloxifene HCl 60 mg (n = 20); and no treatment (n = 19). Eighty-eight women completed the 3-month study period. Main outcome measures were levels of serum adiponectin, resistin, soluble Fas and Fas ligand.


RESULTS
Levels of serum adiponectin decreased significantly in the tibolone group (baseline: 10 556.7 +/- 4213.5 ng/ml; 3 months: 7856.3 +/- 3450.7 ng/ml; p = 0.0001) and increased in the CEE group (baseline: 9268.1 +/- 5158 ng/ml; 3 months: 11 302.6 +/- 4980.9 ng/ml; p = 0.01). Serum resistin values increased only in the tibolone group (baseline: 2.81 +/- 0.89 ng/ml; 3 months: 3.55 +/- 1.31 ng/ml; p = 0.04), while the level of Fas ligand decreased significantly in the E2/NETA (baseline: 70.4 +/- 21.9 pg/ml; 3 months: 62.1 +/- 18.6 pg/ml; p = 0.02) and tibolone group (baseline: 68.2 +/- 25.7 pg/ml; 3 months: 59.2 +/- 21.7 pg/ml; p = 0.01).


CONCLUSIONS
Of the regimens investigated, only unopposed estrogens may exert an atheroprotective effect through the increase of adiponectin and a resultant favorable lipid and anti-inflammatory profile.
Christodoulakos
G E
GE
2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens.
Lambrinoudaki
I V
IV
Creatsa
M G
MG
Economou
E V
EV
Siasou
Z
Z
Panoulis
C P
CP
Kalligerou
I
I
Papadias
C
C
D054392:Adipokines / Q000097:blood; D052242:Adiponectin / Q000097:blood*; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000097:blood / Q000517:prevention & control*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D006115:Greece; D006801:Humans; D008055:Lipids / Q000097:blood*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008875:Middle Aged; D009652:Norpregnenes / Q000494:pharmacology; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D052243:Resistin / Q000097:blood*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D019014:fas Receptor / Q000097:blood
D054392:Adipokines; D052242:Adiponectin; D004966:Estrogens, Conjugated (USP); C491901:FAS protein, human; D053222:Fas Ligand Protein; D008055:Lipids; D009652:Norpregnenes; D052243:Resistin; D020845:Selective Estrogen Receptor Modulators; D019014:fas Receptor; D020849:Raloxifene Hydrochloride; D017258:Medroxyprogesterone Acetate; C027385:tibolone