Use of Combined Oral Contraceptives Alters Metabolic Determinants and Genetic Regulation of C-reactive Protein. The Cardiovascular Risk in Young Finns Study

Background: Use of combined oral contraceptives (COCs) is known to increase concentrations of C-reactive protein (CRP), an important predictor of cardiovascular disease. The inflammatory nature of the disease is well acknowledged. The aim of this study was to find out whether the metabolic, lifestyle and genetic determinants of CRP differ between women who use COCs and those who do not use any hormonal contraceptives (non-users).

Material And Methods: A total of 1,257 women (24-39 years) participated in the ongoing Cardiovascular Risk in Young Finns Study, a population based cross-sectional follow-up study. Use of hormonal contraceptives was determined by questionnaire. Plasma CRP and other cardiovascular risk factors were measured; five CRP gene polymorphisms were genotyped (-717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A) and CRP haplotypes were constructed.

Results: Multivariate regression analysis revealed that BMI and leptin were the main determinants of CRP in non-users, whereas in COC users the main determinants were BMI, leptin and triglycerides. The median CRP and triglyceride values were significantly higher in COC users than in non-users. The correlations between triglyceride and CRP were tested separately in different COC users in accordance with progestagen content and dosage, the analysis revealing significant association only in women using a high dosage of progestagen or cyproterone. The haplotypes of CRP gene had no significant association with CRP concentration in COC users, while independent effects on CRP were found in non-users.

Conclusion: Our study suggests that use of COCs alters the metabolic determinants and genetic regulation of CRP.