Estradiol Valerate Vs. Ethinylestradiol In Combined Oral Contraceptives : Effects On The Pituitary-Ovarian Axis

Context There are limited studies comparing the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. Objective To compare estradiol valerate (EV)+dienogest (DNG), EE+DNG, and DNG alone (an active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, Anti-Mullerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the Free Androgen Index (FAI). Design Spin-off study from a randomized trial. Setting Outpatient setting at Helsinki and Oulu University Hospitals, Finland. Participants 59 healthy, 18-35-year-old ovulatory women were enrolled. Three women discontinued. The groups were comparable as regards age and body mass index. Interventions EV 2mg+DNG 2-3mg (n=20), EE 0.03mg+DNG 2mg (n=20) and DNG 2mg (n=19) were used continuously for nine weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Main Outcome Measures EV+DNG suppressed FSH by -27% (-51:-3) (median [95%CI]) vs. EE+DNG, -64% (-78: -51), P=0.04, but AMH levels decreased similarly by -9% (-18: -0.1) vs. -13% (-28:0.2), P=0.38, respectively. EV+DNG increased SHBG levels by 56% (30:82) and EE+DNG by 385% (313:423), PPeer reviewe

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.Peer reviewe

Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids: A randomized trial

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Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids: A randomized trial

Objectives: Ethinylestradiol (EE)-based combined oral contraceptives (COC) affect adrenal function by altering steroid and corticosteroid-binding globulin (CBG) synthesis that may contribute to adverse effects related to these drugs. The effects of COCs containing natural estrogens remain unclear. We compared the effects of COCs containing estradiol valerate (EV) and EE on cortisol and other adrenal steroid hormones. Study design: A spin-off study of a randomized, open-label trial. Fifty-nine healthy women were allocated to groups that engaged in the continuous use of EV+dienogest (DNG), EE+DNG, or DNG only for 9 weeks. We measured changes in adrenal steroids, CBG, and the free cortisol index (FCI). Results: Treatment with EE+DNG increased total cortisol (mean increment 668 nmol/L, p < 0.001) and cortisone (10 nmol/L, p= 0.001) levels, whereas the change from the baseline was insignificant for the EV+DNG and DNG-only groups. Dehydroepiandrosterone sulfate decreased by 24% in the EE+DNG group but remained unchanged in the EV+DNG and DNG-only groups. Aldosterone and 17-hydroxyprogesterone levels did not differ between the groups. All preparations increased CBG, but the increase in the EE+DNG group (median increment 42 µg/mL, p < 0.001) was 9- and 49-fold higher than that in the EV+DNG and DNG-only groups, respectively. The FCI remained unchanged in all study groups, indicating that cortisol and CBG mainly increased in parallel, although some individuals demonstrated larger alterations in the cortisol–CBG balance. Conclusion: In COCs, EV had a milder effect on circulating CBG and adrenal steroid levels than EE; however, further research is necessary to determine the long-term effects.publishedVersio