Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women

Objective: To study the short-term effect of unopposed oestradiol (E-2,) an d sequentially combined hormone replacement therapy (E-2 + P) on C-reactive protein (CRP) in healthy postmenopausal women. Design: Prospective, random ised, placebo-controlled 12-week study. Sixty healthy, normotensive, non-hy sterectomised postmenopausal women received either placebo (N = 16) or dail y 2 mg micronised oestradiol, either unopposed (N = 16, E-2 group) or seque ntially combined with a progestagen on 14 days of each cycle (N = 28, E-2,P group). Data were collected at baseline and at 4 and 12 weeks. Results: C RP levels increased significantly during the 12 weeks in the E-2 and the E- 2+P groups compared to placebo. No differences were found between the E-2? group and the E-2+P group [E-2 and E-2+P group together (N = 44) versus pla cebo: P = 0.01; E-2 versus E-2+P: P = 0.75]. To give a quantitative estimat e of the increase, the median change calculated from baseline in both treat ment groups together was +87% (P = 0.02) at 4 weeks, and +114% (P = 0.08) a t 12 weeks, as compared to the placebo group. Conclusion: In healthy postme nopausal women, short-term treatment with E-2 or E(2)tP was associated with a rapid rise in CRP concentrations. These observations raise the possibili ty that the increased risk of cardiovascular events is related to an initia l increase in CRP levels after starting hormone replacement therapy.