Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment.
The effects of two third-generation monophasic combined oral contraceptives (COC) and a postmenopausal hormone replacement therapy (HRT) consisting of 2 mg 17 beta-oestradiol on the plasma level of the acute-phase indicator C-reactive protein (CRP) and other acute-phase reactants were analysed. Two studies were conducted: (1) a randomised, open-label study with two different oral contraceptive preparations with an equal dose of ethinylestradiol (30 micrograms) and a different progestogen, either 75 micrograms gestodene (GSD-EE) or 150 micrograms desogestrel (DSG-EE); blood samples of 39 young women were analysed before and after 3, 6, 12 treatment cycles; (2) a randomised, blinded placebo-controlled study with 2 mg 17 beta-oestradiol in postmenopausal women with non-insulin-dependent diabetes mellitus without signs of cardiac involvement; blood samples of 38 women were analysed before and after 6 weeks of treatment. The plasma concentration of CRP increased strongly during oral contraceptive use for both preparations; the increase persisted over 12 cycles. The already elevated CRP in postmenopausal diabetic women showed a moderate increase after 6 weeks of treatment with 17 beta-oestradiol. CRP increases during oral contraceptive use were associated with changes in some other acute-phase proteins (fibrinogen, ceruloplasmin, von Willebrand factor [vWF]) originating from the liver and vessel wall, but not in others (interleukin-6 [IL-6], serum amyloid A [SAA]). The results demonstrate an increase in a specific set of acute-phase reactants caused by oestrogen-containing preparations. It is proposed that the pro-inflammatory effect of oestrogens should be checked for a relationship with the increased risk of thromboembolism for both oral contraceptive and HRT.
Kluft
C
C
Gaubius Laboratory, TNO-PG, Vascular and Connective Tissue Research, Zernikedreef 9, P.O. Box 2215, 2333 CK Leiden, The Netherlands. C.Kluft@pg.tno.nl
Leuven
J A Gevers
JA
Helmerhorst
F M
FM
Krans
H M J
HM
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D003276:Contraceptives, Oral / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced*; D008875:Middle Aged; D018709:Statistics, Nonparametric
D003276:Contraceptives, Oral; D004967:Estrogens; D002097:C-Reactive Protein