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) 17 beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (E-2/NETA), (3) tibolone 2.5 mg, (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 +/- 10.66 ng/ml, p = 0.043), while it increased sig,nificantly 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). Conclusion: Apoptosis may be a pathway through which leptin exerts a pro-atherogenic effect. Low dose HT may act carioprotectively by decreasing letpin levels in healthy recently menopaused women. (c) 2007 Elsevier Ireland Ltd. All rights reserved.