Estradiol Valerate in COC Has More Favorable Inflammatory Profile Than Synthetic Ethinyl Estradiol: A Randomized Trial

Abstract

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 ± 2.11 mg/L) compared with EV + DNG (−0.06 ± 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. Trial Registration ClinicalTrials.gov NCT02352090

A Clinical Study of the Effect of Estradiol Valerate on Sleep Disorders, Negative Emotions, and Quality of Life in Perimenopausal Women

“…In this study, we used estradiol valerate to treat patients. Estradiol valerate is an estrogen derivative, and its combined use with progesterone can supplement estrogen deficiency, maintain estrogen levels in the body, avoid the occurrence of neuropsychiatric symptoms, and relieve clinical symptoms such as sleep disorders and neurasthenia [17,18]. In perimenopausal women, the level of hormones secreted by the ovaries changes significantly, causing uneven texture and reduced thickness of the endometrium [19].…”

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

“…This study is a spin-off from a researcher-initiated randomized open-label trial conducted at the Helsinki and Oulu University Hospitals, Finland, between April 2015 and January 2018. The detailed study protocol has been described previously [17,20], and it was approved by the independent Ethics Committee of Helsinki University Central Hospital. The study was registered in the Clinical Trials database (NCT02352090; https://clinicaltrials.gov/) and the EU Clinical trials register (2014-001243-20; https://www.clinicaltrialsregister.eu).…”

“…EE is a highly potent estrogen with an up-to-600-fold effect on hepatic protein synthesis compared to estradiol (E2) [11]. EEcontaining COCs also affect cortisol-related inflammatory cascades, glucose metabolism, and blood coagulation [12][13][14][15][16][17]. To avoid these unfavorable effects from EE, COCs containing natural estrogens, such as E2 (and its valerate, EV) and estetrol (E4), have been developed.…”

A Comprehensive Update on the Chylomicronemia Syndrome

“…Oral estrogen administration increases triglyceride levels 10% to 50% (76). Importantly the effect varies by dose and type of estrogen preparation, is generally smaller with estrogen/ progestin combinations (77) and not observed with transdermal estrogen. The increase in triglyceride level is thought to be due to VLDL overproduction resulting from activation of the estrogen receptor (78).…”