Objective: To investigate short-term and long-term effects of combined hormone replacement therapy (HRT) on C-reactive protein (CRP) and fibrinogen plasma concentrations in healthy postmenopausal women.

Methods: In this cross-sectional study 241 healthy postmenopausal women were enrolled. A total of 81 women were receiving the following treatments for 3 months; transdermal 17beta-estradiol (17beta-E2) + medroxyprogesterone acetate (MPA) (n = 21), oral 17beta-E2 + norethisterone acetate (NETA) (n = 27), and conjugated equine estrogens (CEE) + MPA (n = 33). The same combined therapies were implemented in another 58 women for 12 months; transdermal 17beta-E2 + MPA (n = 10), oral 17beta-E2 + NETA (n = 16), and CEE + MPA (n = 32). Control group included 102 healthy postmenopausal women not receiving HRT. The effect of the type and the duration of HRT regimens on plasma levels of CRP, fibrinogen and lipids were investigated.

Results: Median CRP concentrations were significantly higher in women receiving oral 17beta-E2 + NETA (P = 0.037) and CEE + MPA (P = 0.0001) for 3 months than in women taking the same types of HRT for 12 months and of those were not on HRT. Median CRP levels were similar in women taking transdermal 17beta-E2 + MPA for 3 and 12 months, compared with controls. Fibrinogen levels were not different between nonusers and any group of HRT users.

Conclusions: These elevated levels of CRP, which appears very recently as a crucial marker for cardiovascular disease, may be responsible for the early increased cardiovascular risk after starting oral combined HRT. But this increased risk in the early period seems to decrease with long-term use. Transdermal 17beta-E2 + MPA had insignificant effect on CRP both in short-term or in long-term use.