Circulating leptin and ghrelin are differentially influenced by estrogen/progestin therapy and raloxifene.
BACKGROUND
Leptin and ghrelin are increasingly being recognized as cardiotropic hormones, promoting or inhibiting the atherosclerotic process, respectively. Apoptosis may be one pathway through which the actions of these hormones are mediated. Sex hormones are reported to influence the secretion and action of ghrelin and leptin.


OBJECTIVE
To evaluate (1) the association of circulating ghrelin and leptin with selected markers of receptor-mediated apoptosis and (2) the effect of estrogen monotherapy, low dose estrogen-progestin therapy, tibolone and raloxifene on serum ghrelin and leptin in healthy postmenopausal women.


METHODS
Eighty eight postmenopausal women aged 44-62 years were randomly allocated to daily (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5 mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum markers of apoptosis sFas, Fas-ligand (Fas-L) and caspase-1 were measured at baseline. Serum leptin and ghrelin were measured at baseline and at 3 months.


RESULTS
Body Mass Index (BMI) and estradiol levels correlated positively, while FSH correlated negatively with serum leptin (BMI: r=0.646, p=0.005, estradiol: r=0.432, p=0.001, FSH: r=-0.401, p=0.002). Insulin levels associated positively with circulating leptin (r=0.394, p=0.011) and negatively with circulating ghrelin (r=-0.401, p=0.009). Serum leptin decreased significantly in E2/NETA group (baseline: 2.882+/-0.76 ng/ml, 3 months: 2.687+/-0.66 ng/ml, p=0.043), while it increased significantly in the raloxifene group (baseline: 2.671+/-0.54 ng/ml, 3 months: 2.839+/-0.47 ng/ml). Ghrelin levels decreased significantly only in the raloxifene group (baseline: 1634+/-592 pg/ml, 3 months: 1408+/-534 pg/ml).


CONCLUSIONS
Apoptosis may be a pathway through which leptin exerts a pro-atherogenic effect. Low dose HT may act cardioprotectively by decreasing leptin levels in healthy recently menopaused women.
Lambrinoudaki
Irene V
IV
2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, 27 Themistokleous Street, Dionysos, Athens, Greece. ilambrinoudaki@hotmail.com
Christodoulakos
George E
GE
Economou
Emmanuel V
EV
Vlachou
Sofia A
SA
Panoulis
Constantinos P
CP
Alexandrou
Andreas P
AP
Kouskouni
Evangelia E
EE
Creatsas
George C
GC
D000328:Adult; D015992:Body Mass Index; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D054439:Ghrelin / Q000097:blood*; D020249:Hormone Replacement Therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
D003280:Contraceptives, Oral, Synthetic; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D053222:Fas Ligand Protein; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D009652:Norpregnenes; D012738:Sex Hormone-Binding Globulin; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone