Effects of either Tibolone or Continuous Combined Transdermal Estradiol with Medroxyprogesterone Acetate on Coagulatory Factors and Lipoprotein(a) in Menopause

Abstract

Background/Aim: The aim of this prospective controlled study was to compare the effects of two therapies for menopause on factor VII (FVII) and hemostatic variables. Methods: Postmenopausal women were assigned to receive one of the following treatments: transdermal estradiol (TTS E2; 50 μg) combined in a continuous sequential regimen with oral medroxyprogesterone acetate (MPA; 10 mg/day for 12 days) (group A; n = 20), tibolone (2.5 mg/day) (group B; n = 21) or placebo (group C; n = 19). Sixty women completed the 1-year treatment and underwent follow-up examinations after 3, 6 and 12 months. Results: TTS E2/MPA induced various changes in procoagulatory factors. At 12 months, fibrinogen, activated FVII (FVIIa) and coagulative FVII (FVIIc) had increased by 10.7, 12.9 and 3.7%, respectively. Among the fibrinolytic factors, plasminogen and α2-antiplasmin increased by 11.3 and 7.2%, respectively. Lipoprotein(a) [Lp(a)] and antithrombin III (ATIII) did not show any significant variation. Tibolone induced some changes toward a more homogeneous antithrombotic profile. Fibrinogen, FVIIa and FVIIc decreased significantly by 7.5, 8.1 and 21.3%, respectively. Plasminogen increased (by 11.8%) and Lp(a) decreased (by 28.4%). ATIII was unchanged with tibolone therapy. Conclusion: Our results show that tibolone induces a significant reduction in FVIIc and Lp(a) and a greater enhancement of factors promoting fibrinolysis than the TTS E2/MPA regimen.

Lipoprotein (a): impact by ethnicity and environmental and medical conditions

“…In a recent doubleblind placebocontrolled trial among postmenopausal women, treatment with letrozole, an oral nonsteroidal aromatase inhibitor, resulted in more than a doubling of mean Lp(a) levels (112). Treatment with tibo lone, a synthetic steroid drug, at a dose of 2.5 mg/day for a year in postmenopausal women significantly decreased Lp(a) concentration by 28% (113).…”

Lipoprotein(a) and apolipoprotein(a) in polycystic ovary syndrome

“…Lp(a) levels are under a strong genetic regulation and are not affected by changes in lifestyle and physical characteristics, as well as currently available lipid‐lowering drugs. However, sex hormones constitute an important exception and studies have shown menopause‐related changes in Lp(a) concentration and Lp(a)‐lowering effect by testosterone administration and Lp(a)‐increasing effect by orchidectomy in men, or hormone‐replacement therapy in women . In view of this, a better understanding of the role of Lp(a) in PCOS has attracted attention.…”

“…shown menopause-related changes in Lp(a) concentration and Lp(a)-lowering effect by testosterone administration and Lp(a)increasing effect by orchidectomy in men, 25,26 or hormone-replacement therapy in women. 14,[27][28][29][30][31][32] In view of this, a better understanding of the role of Lp(a) in PCOS has attracted attention. One study in Turkish women reported a higher mean Lp(a) level in PCOS women compared to healthy controls (25Á2 mg/dl vs 16Á7 mg/dl, respectively).…”

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options

“…In general, tibolone seems to induce a greater reduction in Lp(a) in comparison with HRT when transdermal oestrogen (50 μg/d) is used and similar or greater reduction when oral oestrogen is used (0.625 mg/d of CEE or 2 mg of 17β‐estradiol) . The exact mechanisms for tibolone‐induced reductions in Lp(a) have not been clarified.…”