Estradiol Valerate In Coc Has More Favorable Inflammatory Profile Than Synthetic Ethinyl Estradiol: A Randomized Trial

Context: Combined oral contraceptives (COCs) alter inflammatory status and lipid metabolism. Whether different estrogens have different effects is poorly understood.Objective: We compared the effects of COCs containing ethinyl estradiol (EE) or estradiol valerate (EV) and dienogest (DNG) with those containing DNG only on inflammation and lipid metabolism.Design: Randomized, controlled, open-label clinical trial.Setting: Two-center study in Helsinki and Oulu University Hospitals.Participants: Fifty-nine healthy, young, nonsmoking women with regular menstrual cycles. Age, body mass index, and waist-to-hip ratio were comparable in all study groups at the beginning. Fifty-six women completed the study (EV + DNG, n = 20; EE + DNG, n = 19; DNG only, n = 17).Interventions: Nine-week continuous use of COCs containing either EV + DNG or EE + DNG, or DNG only as control.Main Outcome Measures: Parameters of chronic inflammation (high-sensitivity C-reactive protein [hs-CRP], and pentraxin 3 [PTX-3]) and lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol).Results: Serum hs-CRP increased after 9-week use of EE + DNG (mean change +/- standard deviation 1.10 t 2.11 mg/L) compared with EV + DNG (-0.06 t 0.97 mg/L, P = 0.001) or DNG only (0.13 +/- 0.68 mg/L, P= 0.021). Also, PTX-3 increased in the EE + DNG group compared with EV + DNG and DNG-only groups (P = 0.017 and P = 0.003, respectively). In the EE + DNG group, HDL and triglycerides increased compared with other groups (HDL: EE + DNG 0.20 +/- 0.24 mmol/L vs EV + DNG 0.02 +/- 0.20 mmol/L [P = 0.002] vs DNG 0.02 +/- 0.18 mmol/L [P = 0.002]; triglycerides: EE + DNG 0.45 +/- 0.21 mmol/L vs EV + DNG 0.18 +/- 0.36 mmol/L [P= 0.003] vs DNG 0.06 +/- 0.18 mmol/L [P < 0.001]).Conclusions: EV + DNG and DNG only had a neutral effect on inflammation and lipids, while EE + DNG increased both hs-CRP and PTX-3 levels as well as triglycerides and HDL.