Estradiol valerate 2mg / Norgestrel 500microgram tablets

Breakthrough bleeding (BTB) is a common side effect of hormonal contraception and is thought to impact adherence to combined oral contraceptives (COCs) but respective dose-response relationships are not yet fully understood. Therefore, the objective of this model-based meta-analysis (MBMA) was to establish dose-response for COCs containing different progestin/EE combinations using BTB as the pharmacodynamic endpoint. Data from 25 studies containing BTB information of 4 progestins (desogestrel, drospirenone, gestodene, and levonorgestrel) in combination with ethinyl estradiol (EE) at various dose levels was used for this analysis. The results of our MBMA show that BTB is significantly increased upon initiation of COC use but subsides over time. The time needed for BTB to return to baseline depends on the EE dose and differs marginally between progestins during the initial months of use at the same EE dose. BTB typically returns to baseline within 3 months at the highest (30 μg) dose, whereas it can take significantly longer to reestablish a regular bleeding pattern at lower EE doses (15 and 20 μg), irrespective of the progestin used. The dose-response relationships established for BTB across different progestin/EE combinations can now be used to support the selection of optimal COC dosing/treatment regimens and serve as the scientific basis for evaluating the impact of clinically relevant factors, including drug-drug interactions and demographics, on BTB.

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BackgroundThe long-term use of contraceptive methods that contain estrogens, progestogens or combinations of the above among women aged 15 to 49 years is extensive. Both estrogens and progestogens affect bone metabolism.ObjectiveTo systematically investigate and appraise the quality of the available evidence from animal studies regarding the impact of exogenous administration of female sex hormones on the rate of orthodontic tooth movement and root resorption.Search methodsSearch without restriction in seven databases (including grey literature) and hand searching were performed until May 2021.Selection criteriaWe looked for controlled animal studies investigating the effect from exogenous administration of formulations containing female sex hormones on the rate of orthodontic tooth movement and root resorption.Data collection and analysisAfter study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. The quality of available evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation.ResultsThree studies were identified, all being at unclear risk of bias. Overall, administration of progesterone and the combinations of estradiol with norgestrel and desogestrel were shown to significantly decrease the rate of orthodontic tooth movement when given for longer periods (>3 weeks). Inconsistent information was detected for shorter periods of consumption. Estradiol, with desogestrel use, resulted in less root resorption. The quality of the available evidence was considered to be low.ConclusionsExogenous administration of female sex hormones may decelerate in the long term the rate of tooth movement and decrease orthodontically induced root resorption in animals. Until more information becomes available, an orthodontist should be able to identify a patient consuming such substances and understand the potential clinical implications and adverse effects that may arise.RegistrationPROSPERO: CRD42017078208; https://clinicaltrials.gov/.

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Delayed-start contraception may reduce the risk of unintended pregnancy; however, data on newer formulations, such as estetrol (E4)-containing pills are limited. Therefore, this study aimed to evaluate the effectiveness of delayed start combined oral contraceptives (COCs) containing 15 mg E4 and 3 mg drospirenone (E4/DRSP). In this randomized, single-blind, non-inferiority trial, 36 healthy women aged 18-45 years with regular menstrual cycles were assigned to receive either E4/DRSP or 20 µg ethinyl estradiol/75 µg gestodene (EE/GS), starting treatment between cycle day 7 and 9. The primary outcome was ovulation inhibition, assessed using the modified Hoogland score. The secondary outcomes included cervical mucus changes and adverse effects. Baseline characteristics did not differ significantly between the groups. The mean age and menstrual cycle length were 38.75 ± 5.8 years and 28.67 ± 1.96 days, respectively. More than half (55.56%) of the participants began COC use on day 9, with 50% of them showing active follicular development at baseline (Hoogland score of 4). Ovulation was inhibited in 61.11% of participants in both groups (adjusted relative risks: 0.95, 95% confidence interval [CI]: 0.56-1.59, p = 0.841, and absolute risk difference: -0.03, 95% CI: -0.39 to 0.33). Approximately half of the participants who ovulated showed ovarian activity that was not associated with theoretical pregnancy risk. Cervical mucus profiles and adverse events, including unscheduled bleeding, did not differ significantly between the groups. Initiating E4/DRSP on cycle day 7-9 appears comparable to that of EE/GS for ovulation inhibition; however, high ovulation rates limit the confirmation of non-inferiority.Clinical trial registration: ClinicalTrials.gov Registration on April 25, 2024 (ID: NCT06396221; https://clinicaltrials.gov/study/NCT06396221 ).

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ObjectiveThis study employed population pharmacokinetic (popPK) models to predict levonorgestrel (LNG) and ethinyl estradiol (EE) exposure after dosing with the transdermal contraceptive TWIRLA® (LNG/EE TDS) as a 12-week extended regimen in a healthy female population.MethodsPopPK models were developed using data from a previously published phase 1, open-label, randomized clinical trial, ATI-CL14 (NCT01243580), in 36 healthy individuals. Models used cycle 2 data from 18 individuals who received the LNG/EE TDS, delivering LNG 120 μg/day and EE 30 μg/day, followed by a 1-week TDS-free period. Noncompartmental PK analyses were performed on simulated concentration-time profiles of 12 consecutive weeks of LNG/EE TDS use.ResultsThe simulated concentration-time profiles and PK parameters for the simulated extended regimen indicated that predicted LNG and EE exposures at week 12 were similar to week 3 (predicted geometric mean EE area under the concentration-time curve from time 0 to 168 h [AUC0-168] on week 3 was 0.2% lower than week 12 and LNG AUC0-168 on week 3 was 0.9% lower than week 12), suggesting both were at steady state by week 3. Therefore, no notable accumulation beyond that at week 3 is predicted for LNG and EE following a 12-week extended regimen. The results are supported by the accumulation ratios based on maximum concentration and the area under the curve being similar at weeks 3 and 12 for LNG and EE.ConclusionThese results indicate that a 12-week extended LNG/EE regimen would provide similar systemic hormonal exposure as that seen by week 3 in a standard 28-day regimen, without further hormonal accumulation. The data support the safe use of a non-daily, low-dose hormonal contraceptive in an extended regimen but should be confirmed in a clinical PK study.

Abstract licence: CC BY