Effects of tibolone and combined 17β-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women:: a randomized trial

BACKGROUND: Serum C-reactive protein (CRP) is an independent risk factor for the development of cardiovascular diseases in healthy post-menopausal women. Oral unopposed and progestin-combined 17beta-estradiol (E-2) increase serum CRP in post-menopausal women. The aim of this study was to compare the effects of tibolone, a steroid with estrogenic, androgenic or progestogenic properties, with a combination of E-2 and norethisterone acetate (E-2 + NETA) on serum CRP levels in healthy post-menopausal women. METHODS: A total of 139 post-menopausal women (mean age: 55 years, range 44-48) was randomly assigned to receive tibolone 1.25 mg(day (n = 52), tibolone 2.5 mg/day (n = 39) or E-2 2 mg/day plus NETA 1 mg(day (n = 48) for 2 years. Serum CRP was measured at baseline and at 6, 12 and 24 months. RESULTS: Both doses of tibolone and E-2 + NETA increased serum CRP by a similar extent as soon as 6 months with a sustained effect over the 24 month treatment period. For example, after 6 months of treatment, serum CRP increased by a median of +106% (P < 0.001), +89% (P < 0.05) and + 139% (P < 0.001) for tibolone 1.275 mg(day, tibolone 2.5 mg/day and E2 + NETA respectively. CONCLUSIONS: Tibolone and E-2 + NETA significantly increase serum CRP levels in healthy post-menopausal women to a comparable extent. Relationships between induced elevated CRP levels with tibolone and E-2 + NETA and cardiovascular events require further studies.