Abstract 3537: Oral Contraceptives Cause Major C-reactive Protein Rises in the Female General Population
Purpose: High-sensitive C-reactive protein (hs-CRP) is a marker of inflammation, identifying subjects at increased cardiovascular risk. Hormonal therapy with estrogen (E) alone or combined with progestins (P) are among the most used drugs worldwide. Recent reports link hormone replacement therapy (HRT) to hs-CRP elevation, thrombosis and adverse outcome. Oral contraception (OC) is a drug therapy using 10 to 100 fold higher estrogen levels than HRT, yet its effects on inflammation at the population level are less documented.
Methods: The Asklepios study is a blinded sample of 2524 M/F volunteers (median age 45.9 y), representative of the Belgian population between 35–55 years, free from overt cardiovascular disease. The subjects were extensively screened (chemistry, questionnaires, cardiac, vascular echography). hs-CRP was assayed by particle-enhanced immuno-turbidimetry on fasting subjects, free from clinical inflammation.
Results: Of 1301 women, 803 (NoH; 62.6%) were taking neither OC/HRT, 352 women (OC; 27.4%) were taking OC and 128 (HRT; 10.0%) were taking HRT. Crude hs-CRP levels were (in mg/l; median [IQR]): NoH 1.0 [0.5–2.1]; HRT 1.3 [0.7–2.6] and OC 3.5 [1.5–5.9]. After multivariate adjustment for: age, season, smoking, blood pressure, cholesterol, body size, diabetes, physical activity, fruit, vegetable and alcohol intake, educational level and drug therapy (lipid-lowering, antihypertensive, aspirin), the hs-CRP levels were (adjusted geometric mean [95% CI]): NoH 1.0 [0.9 –1.1]; HRT 1.2 [1.1–1.5] and OC 3.3 [3.0 –3.6]; (OC vs NoH: p<0.001; HRT vs NoH: p<0.05). Effects on other inflammatory markers (interleukin-6, ox-LDL cholesterol) were far less pronounced.
Conclusions: Contraceptive therapy is a major cause of hs-CRP rise. The magnitude of CRP-rise (3-fold) far exceeds other population-prevalent non-infectious stimuli and is much larger than the hs-CRP rise for HRT (+20%). More than 50% of apparently healthy women taking OC have hs-CRP levels >3 mg/l, considered to indicate “high-risk”. Future research should take into account this effect when reporting CRP data in women, aim to qualify its biological significance and assess the potential of hs-CRP as a tool to select those women at high thrombotic risk under hormonal therapy.