Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal women.

OBJECTIVES: To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. METHODS: A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. RESULTS: Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. CONCLUSIONS: Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis.

The effect of hormone therapy and tibolone on serum CD40L and ADAM-8 in healthy post-menopausal women.

BACKGROUND/AIM: The role of neutrophils and platelets in atherothrombotic disease is well established. The aim of our study was to investigate the effect of HT and tibolone on the soluble markers of neutrophil and platelet activation, "a disentigrin and metalloproteinase domain" (ADAM-8) and CD40 ligand (CD40L) respectively, in healthy post-menopausal women. SUBJECTS AND METHODS: One hundred and six healthy post-menopausal women were randomly allocated to: estradiol plus drospirenone (E2/DSP), E2 hemihydrate 1 mg plus norethisterone acetate (E2/NETA) 0.5 mg, and tibolone 2.5 mg. Serum ADAM-8 and CD40L were measured at baseline and at 6 months. RESULTS: Baseline values of ADAM-8 and CD40L were similar between groups. No significant correlation was revealed between ADAM-8 or CD40L and parameters related to cardiovascular risk factors in each group. No significant changes were observed between baseline values and values at 6 months (E2/DSP group: ADAM-8: 267.4±71.3 pg/ml vs 270.7±42.8 pg/ml, p=0.86, CD40L: 6.43±3.13 vs 6.79±2.70 ng/ml, p=0.67), (E2/NETA group: ADAM-8: 308.3±64.3 vs 294.7±57.7 pg/ml, p=0.40, CD40L: 9.68±2.81 vs 8.59±5.13 ng/ml, p=0.51), (tibolone group: ADAM-8: 307.5±87.5 vs 289±48.1 pg/ml, p=0.48, CD40L: 9.46±4.30 vs 9.26±4.60 ng/ml, p=0.99). CONCLUSIONS: Our study has not revealed an association between estrogen plus progestin treatment or tibolone on serum ADAM-8 and CD40L levels in healthy post-menopausal women. Larger prospective studies are needed to further investigate the effect of low-dose HT or tibolone on serum markers of neutrophil and platelet activation.