Effects of intranasal 17beta-estradiol administration on serum bioactive interleukin-6 and C-reactive protein levels in healthy postmenopausal women.

OBJECTIVE: Oral estrogen increases the levels of C-reactive protein (CRP), which is an independent risk factor for coronary heart disease in healthy individuals. The aim of our study was to investigate the effects of intranasal 17beta-estradiol (E2) on serum CRP and its most potent stimulant, interleukin-6 in healthy postmenopausal women.

DESIGN: Thirty-six healthy postmenopausal women (45-54 y) were enrolled. According to their individual preferences, they were assigned to intranasal (n = 10), transdermal (n = 14), or oral (n = 12) continuous E2 treatment with a sequential progestin (10-14 d in a 28-d cycle). Blood samples were drawn at baseline and after 3, 6, and 12 months during the estrogen-only phase to adjust for the progestin effect.

RESULTS: In women taking intranasal or transdermal E2, there were no significant changes in median serum CRP levels during the 12-month treatment period. In women taking oral E2 preparations, serum median CRP levels were significantly higher compared to baseline after 6 and 12 months of the therapy (P < 0.05). Conversely, serum median bioactive interleukin-6 levels were significantly lower after 6 and 12 months in women taking E2 intranasally or orally and after 12 months in women taking E2 transdermally (P < 0.05).

CONCLUSIONS: The results of our study show that intranasal, similarly to transdermal, E2 administration does not increase serum CRP levels in postmenopausal women. They also support the hypothesis that CRP increase during oral estrogen treatment is not mediated by the enhancement of interleukin-6 production by the immune cells but is rather caused by the hepatic first-pass metabolism effect.