Hormone replacement therapy: estrogen and progestin effects on plasma C-reactive protein concentrations

Our purpose was to assess the effect of hormone replacement therapy (HRT) on C-reactive protein blood concentrations with special reference to the progestin component.

Changes from baseline and between groups in blood concentrations of C-reactive protein were determined during 12-month periods in 6 groups of postmenopausal women. Group A (the reference group) received no HRT; group B received 2 mg of estradiol valerate (E2V) daily combined with 1 mg of cyproterone acetate (CPA) for 10 days (28/10 days); group C received 2 mg of E2V plus 1 mg of CPA sequentially (21/10 days); group D received a combination of 2 mg of E2V and 1 mg of norethindrone acetate continuously; group E received 2 mg of E2V in combination with local delivery of levonorgestrel (20 microg/24 h); and group F received a long-cycle regimen consisting of 2 mg of E2V (84/91 days) plus 20 mg of medroxyprogesterone (14/91 days).

No significant variation in CRP levels was observed in the reference group. HRT resulted in a significant increase in CRP concentrations in the women receiving the continuous combination of E2V plus norethindrone acetate and the continuous regimen of E2V plus local delivery of levonorgestrel. Cyclic or continuous intake of E2V plus CPA did not change CRP levels significantly. During the long-cycle regimen, the concentrations of CRP showed a significant variance over time. The concentrations increased during the estrogen phase but were modulated by the progestin intake throughout the study period.

HRT can increase CRP levels in healthy women, and both the estrogen and the progestin component are of importance for the change. Whether the increase in CRP levels only reflects a changed steady-state metabolism is unknown. However, the clinical significance should be viewed from the perspective of changes in other inflammatory risk markers of importance for the evolution of cardiovascular disease.