Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Kangasniemi MH
PROVIDER: S-EPMC9825269 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial.
Kangasniemi M H MH Arffman R K RK Joenväärä S S Haverinen A A Luiro K K Tohmola T T Renkonen R R Heikinheimo O O Tapanainen J S JS Piltonen T T TT
Human reproduction (Oxford, England) 20230101 1
<h4>Study question</h4>Does an estradiol-based combined oral contraceptive (COC) have a milder effect on the serum proteome than an ethinylestradiol (EE)-based COC or dienogest (DNG) only?<h4>Summary answer</h4>The changes in serum proteome were multifold after the use of a synthetic EE-based COC compared to natural estrogen COC or progestin-only preparation.<h4>What is known already</h4>EE-based COCs widely affect metabolism, inflammation, hepatic protein synthesis and blood coagulation. Studie ...[more]
Similar Datasets
Project description:Ethinylestradiol (EE)-based combined oral contraceptives (COC) have multiple beneficial effects besides contraception, but they also cause certain unfavorable health outcomes. They interfere, for example, with metabolism, inflammation, hepatic protein synthesis, and blood coagulation. COCs containing natural estrogens have recently been developed, yet little is known about their non-contraceptive effects compared to conventional EE-based COCs. The aim of the study was to analyze the serum proteome during three different treatments: EE+dienogest (DNG), estradiol valerate (EV)+DNG, and DNG only.
2022-11-25 | PXD033618 | Pride
Project description:Ethinylestradiol (EE)-based combined oral contraceptives (COC) have multiple beneficial effects besides contraception, but they also cause certain unfavorable health outcomes. They interfere, for example, with metabolism, inflammation, hepatic protein synthesis, and blood coagulation. COCs containing natural estrogens have recently been developed, yet little is known about their non-contraceptive effects compared to conventional EE-based COCs. The aim of the study was to analyze the serum proteome during three different treatments: EE+dienogest (DNG), estradiol valerate (EV)+DNG, and DNG only.
2022-11-25 | PXD033617 | Pride
Project description:IntroductionContraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin.Material and methodsWe enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover).Clinical trial registrationNCT02352090.ResultsLag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers.ConclusionsBoth in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.
| S-EPMC9812067 | biostudies-literature
Project description:A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance.The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel.Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3?mg, 5 days estradiol valerate 2?mg/dienogest 2?mg, 17 days estradiol valerate 2?mg/dienogest 3?mg, 2 days estradiol valerate 1?mg, 2 days placebo) or ethinylestradiol 0.03?mg/levonorgestrel 0.15?mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1?+?2 and D-dimer from baseline to cycle three.Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1?+?2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel.The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.
| S-EPMC3585947 | biostudies-other
Project description:Natural estrogens such as estradiol (E(2)) or its valerate ester (E(2)V) offer an alternative to ethinyl estradiol (EE). E(2)-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E(2)V-containing preparations have been approved to date for contraceptive use: E(2)V/cyproterone acetate (CPA) (Femilar(®); only approved in Finland and only in women >40 years or women aged 35-40 years in whom a COC containing EE is not appropriate) and E(2)V/dienogest (DNG; Qlaira(®)/Natazia(®)). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E(2)V/DNG.
| S-EPMC3399636 | biostudies-literature
Project description:Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate.Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18-38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 ?g ethinyl E2/150 ?g levonorgestrel) for 12-16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5-12 days, until the day before starting stimulation.Pretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, -2.0% [95% CI -21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups.This is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield-due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization-could more easily be demonstrated.ClinicalTrials.gov http://NCT01501448.
| S-EPMC3849807 | biostudies-literature
Project description:BackgroundTo investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women.MethodsIn this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study.ResultsA total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG.ConclusionEV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population.Clinical trials registryClinicalTrials.gov identifier: NCT01638910.
| S-EPMC5995293 | biostudies-literature
Project description:Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24-11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44-2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.
| S-EPMC7790405 | biostudies-literature
Project description:BackgroundOral contraceptives are still associated with high discontinuation rates, despite their efficacy. There is a wide choice of oral contraceptives available, and the aim of this study was to assess continuation rates, bleeding profile acceptability, and the satisfaction of women in the first year of using a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) versus a progestogen-only pill (POP) in a real-life setting after discontinuing an ethinylestradiol-containing pill.Methods and resultsIn this prospective, noninterventional, observational study, 3,152 patients were included for the efficacy analyses (n=2,558 women in the E2V/DNG group and n=592 in the POP group (two patients fulfilled the criteria of the efficacy population, but the used product was not known). Women had been taking an ethinylestradiol-containing pill ≥3 months before deciding to switch to the E2V/DNG pill or a POP. Overall, 19.8% (n=506) of E2V/DNG users and 25.8% (n=153) of POP users discontinued their prescribed pill. The median time to discontinuation was 157.0 days and 127.5 days, respectively. Time to discontinuation due to bleeding (P<0.0001) or other reasons (P=0.022) was significantly longer in the E2V/DNG group versus the POP group. The E2V/DNG pill was also associated with shorter (48.7% vs 44.1%), lighter (54% vs 46.1%), and less painful bleeding (91.1% vs 73.7%) and greater user satisfaction (80.7% vs 64.6%) than POP use, within 3-5 months after switch.ConclusionThe E2V/DNG pill was associated with higher rates of continuation, bleeding profile acceptability, and user satisfaction than POP use and may be an alternative option for women who are dissatisfied with their current pill.
| S-EPMC5029837 | biostudies-literature
Project description:ObjectiveTo determine the relative bioavailability of ethinyl estradiol (EE) and gestodene (GSD) after application of a novel transdermal contraceptive patch vs. a standard combined oral contraceptive (COC) pill (study 1), and to evaluate the pharmacokinetics (PK) of EE after application of the EE/GSD patch compared with an EE/norelgestromin (NGMN) patch (study 2).MaterialsParticipants were healthy, nonobese women aged 18 - 45 years (study 1) or 18 - 35 years (study 2). Compositions of study treatments were as follows: 0.55 mg EE/2.1 mg GSD (EE/GSD patch); 0.02 mg EE/0.075 mg GSD (standard COC); 0.6 mg EE/6 mg NGMN (EE/NGMN patch).MethodsIn study 1, which consisted of 3 treatment periods (each followed by 7 patch- or pill-free days), treatments were administered in one of two randomized orders: either P-M-E (EE/GSD patch (P) every 7 days for 28 days → COC (M) once-daily for 21 days → two 7-day patch-wearing periods followed by one 10-day patch-wearing phase (E)), or the same treatments administered in sequence M-P-E. For study 2, participants received either the EE/GSD patch or EE/NGMN patch for seven treatment cycles (one patch per week for 3 weeks followed by a 7-day patch-free interval).ResultsIn study 1, average daily exposure to EE was similar for treatments P and M; the mean daily area under the concentration-time curve (AUC) ratio of treatment P vs. treatment M for EE was 1.06 (90% confidence interval (CI): 0.964 - 1.16), indicating average daily delivery similar to oral administration of 0.019 - 0.023 mg EE. For unbound GSD, average daily exposure was lower for treatment P vs. treatment M. The mean AUC ratio of treatment P vs. treatment M for unbound GSD was 0.820 (90% CI: 0.760 - 0.885), indicating average daily delivery from the patch of 0.057 - 0.066 mg GSD. Prolonged patch wearing did not result in a distinct decline in GSD and EE serum concentrations. In study 2, AUC at steady state (AUC0-168,ss), average steady-state serum concentration, and maximum steady-state serum concentration for EE was 2.0 - 2.7-fold higher for the EE/NGMN patch vs. the EE/GSD patch. The EE/GSD patch was well tolerated in both studies.ConclusionsBased on the 90% CI of the AUC ratio of oral treatment vs. patch application for unbound GSD and EE, the daily doses of GSD and EE released from the EE/GSD patch over the 7-day application period provided the same systemic exposure as those recorded after daily oral administration of a COC containing 0.02 mg EE and 0.06 mg GSD. The EE/GSD patch showed reduced EE exposure compared with the EE/NGMN patch. Together with its good tolerability, these properties support the EE/GSD patch as an effective and well-tolerated alternative to available transdermal and oral contraceptives.
| S-EPMC4285808 | biostudies-literature