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Effects of Third-Generation Oral Contraceptives on High-Sensitivity C-reactive Protein and Homocysteine in Young Women

From the ¹Department of Biomedical Sciences and Technologies, School of Medicine, University of Udine, Udine, Italy; ²Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, Pennsylvania; ³Department of Experimental and Clinical Pathology and Medicine, School of Medicine, University of Udine, Udine, Italy; and ⁴Obstetric and Gynecologic Unit, Department of Reproductive and Development Sciences, IRCCS Burlo Garofolo Hospital, School of Medicine, University of Trieste, Trieste, Italy.

OBJECTIVE: To evaluate the effect of third-generation oral contraceptives on high-sensitivity C-reactive protein (CRP), homocysteine, and lipids levels in a population of young, fertile, nonobese women.

METHODS: Blood markers were evaluated in 277 healthy white women (mean age 23 years and mean body-mass index 21 kg/m²). Seventy-seven oral contraceptive users were compared with 200 non–oral contraceptive users. Progressive cutoffs of high-sensitivity CRP and homocysteine levels were examined.

RESULTS: Levels of high-sensitivity CRP posing a high risk of cardiovascular disease (3.0 to less than 10.0 mg/L) were found in 27.3% of oral contraceptive users and in 8.5% of non–oral contraceptive users (odds ratio 4.04; 95% confidence interval [CI] 1.99–8.18). Levels of high-sensitivity CRP at intermediate risk (1.0 to less than 3.0 mg/L) were found in 32.5% of oral contraceptive users and in 11.0% of non–oral contraceptive users (odds ratio 3.89; 95% CI 2.03–7.46). Notably, non–oral contraceptive users were 8.65 (95% CI 4.39–17.1) times as likely to demonstrate a protective level of high-sensitivity CRP (less than 0.5 mg/L) compared with oral contraceptive users. Oral contraceptive use increased serum triglycerides (P<.001) and total cholesterol P=.001); however, high-density lipoprotein, not low-density lipoprotein, contributed to this increase. A decreased ratio of low-density lipoprotein to high-density lipoprotein cholesterol was observed in oral contraceptive users compared with nonusers (P=.016). Oral contraceptive use did not affect homocysteine levels.

CONCLUSION: Third-generation oral contraceptive use increases low-grade inflammatory status measured by high-sensitivity CRP concentrations. Alteration of inflammatory status in oral contraceptive users could affect the risk of venous thromboembolism, cardiovascular disease, and other oral contraceptive-associated adverse conditions in young women.

LEVEL OF EVIDENCE: II

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