Effect of Hormonal Contraceptives on Circulating Biomarkers of Inflammation, Chemotaxis, Angiogenesis, and Vascular Stress

Hormonal contraceptive (HC) use is known to be associated with elevated CRP levels. However, evidence on the effect of HC on several circulating inflammatory biomarkers in healthy humans is limited. The aim of this study was to examine the association between hormonal contraceptives and circulating biomarker levels and differential cell counts. A cross-sectional observational study design with biomarker measurements from 4,160 healthy females was used, coupled with registered HC prescriptions. We compared 752 high and low dose combined oral contraceptive (COC) users, 77 progestin-only pill users, 417 levonorgestrel intrauterine device users, 65 hormonal therapy users, and 1,523 post-menopausal women with a control group of 1,326 women below 50 years. Repeated differential cell counts from a different dataset of 16,231 females were analyzed for the effects of HC. Data were analyzed using various regression models. COC use was associated with higher vascular marker levels but lower chemokine levels. We found no association with progestin-only use. The association with differential cell counts was limited for most HC types. This study emphasizes the widespread impact of HC on the immune and vascular systems and how the impact may differ between HC types. The biomarker associations found could be targets for elucidation in functional studies.