Ethinylestradiol 30microgram / Drospirenone 3mg tablets

BackgroundVenous thromboembolism (VTE) poses a significant global health challenge, notably exacerbated by the use of combined oral contraceptives (COCs). Evidence mainly focuses on the type of progestogen used in COCs to establish the increased risk of VTE with less data assessed on the type of estrogen used. This meta-analysis aims to assess the risk of VTE associated with COCs containing synthetic estrogens like ethinylestradiol (EE) versus natural estrogens like estradiol (E2).MethodsA systematic review and meta-analysis was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were performed in December 2023 in MEDLINE and EMBASE to identify clinical studies comparing the VTE risk between COCs containing synthetic versus natural estrogens. Studies were selected through rigorous screening, and data extraction followed standardized protocols, with statistical analyses employing a random effects model.ResultsThe search yielded five relevant studies, involving over 560,000 women/time, demonstrating a significant 33% reduction in VTE risk among users of natural estrogen-based COCs compared to synthetic estrogen-based COCs (OR 0.67, 95% CI 0.51-0.87). Stratification analyses using adjusted hazard ratios (HR) of the main observationnal studies showed a 49% reduced VTE risk of E2-based pills compared to EE in association with levonorgestrel.Discussion and conclusionDespite the longstanding use of EE-based COCs, emerging evidence supports a lower thrombotic risk associated with natural estrogens. This meta-analysis substantiates the lower VTE risk associated with natural estrogen-based COCs compared to synthetic alternatives, advocating for a re-evaluation of contraceptive guidelines to prioritize patient safety and reduce thrombotic risks.

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IntroductionIn the WHO eligibility criteria, there is agreement that hypertensive women taking Oral Contraceptive Hormonal Combined (OCHC) may be at increased risk of cardiovascular disease. The risk-to-benefit ratio hinges on the severity of the condition. While a mild increase in blood pressure is a common occurrence in consumers of OCHC, the potential for developing high blood pressure exists during oral contraceptive use. Consequently, there is a possibility of increased cardiovascular risk, with limited available data on this issue.ObjectiveTo evaluate the potential effects of OCHC on blood pressure through a systematic review with statistical analysis of existing randomized controlled trials.MethodThis systematic review with statistical comparison adheres to the recommendations outlined in the PRISMA (Principal Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The analysis strategy involves comparing the mean difference in blood pressure change according to the type of treatment, in addition to the calculation of clinically relevant outcomes (CRO).ResultsOur findings suggest a clinically relevant outcome related to the increase in blood pressure in users of ethinyl estradiol combined with gestodene in a cyclic regimen over 6 months. Conversely, a decrease in blood pressure was observed among users of ethinyl estradiol combined with chlormadinone over 24 months of usage.ConclusionWhile our study found minor variations in blood pressure across varying forms of oral contraceptives, these differences are not significant enough to warrant specific clinical recommendations. However, the results suggest that individuals with hypertension should exercise caution with ethinyl estradiol, particularly when administered cyclically alongside gestodene, due to the potential risk of increased blood pressure. Additionally, the use of oral contraceptives containing ethinyl estradiol paired with chlormadinone acetate or ethinyl estradiol combined with drospirenone may be more suitable for individuals at a high risk of developing hypertension.

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Heavy menstrual bleeding (HMB) is a common gynecological condition among women of reproductive age that significantly affects quality of life and often leads to iron deficiency anemia. Hormonal treatments are usually prescribed in combination to include combined oral contraceptives (COCs) and progestin-only pills (POPs) in treating HMB. This systematic review aims to compare the effectiveness and safety of COCs and POPs in the management of HMB in terms of menstrual blood loss, hemoglobin levels, side effects, and patient satisfaction. The literature search was conducted on PubMed, Scopus, Web of Science, and Google Scholar and covered articles published between 2000 and 2025. Blood loss reduction, hemoglobin levels, side effects, and patient satisfaction data were extracted, and a narrative review was conducted. The review included 10 studies. Both POPs and COCs had a great impact on minimizing menstrual blood loss and enhancing hemoglobin index. There were no mean differences in the two treatments concerning the improvement of hemoglobin, with a mean change of 2.75-2.71 g/dL in both treatment groups (p = 0.84). The heterogeneity within the companies made the calculation of confidence intervals impossible, and the comparison was done regarding the differences in mean only. COCs were linked with an increased incidence of nausea, headaches, and weight gain, whereas POPs were found to have more desirable side effects. Drospirenone (POP) showed reduced unscheduled bleeding days and patient satisfaction with the medication compared to other POPs. Risk of bias was moderate to low across studies, with some concerns regarding randomization and blinding in certain trials. Further research with larger sample sizes, longer follow-up periods, and head-to-head comparisons between COCs and POPs is needed to confirm these findings and evaluate the long-term impact of these treatments.

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IntroductionCombined oral contraceptive pills (COCs) are a common contraceptive method among women of reproductive age. Ethinylestradiol (EE) is a frequently used estrogen component in COCs. However, EE may increase the risk of cardiovascular complications by affecting coagulation, fibrinolysis, and blood pressure. Lowering the dose of EE to minimize the risk has been linked to disadvantageous bleeding patterns. The natural estrogen estetrol (E4) has been introduced as an alternative component to EE. E4 has been suggested to have beneficial effects on targeted tissue with a limited impact on the liver and coagulation, compared to EE-containing COCs, and thus, offers a potential for improving the safety of future COCs. This systematic review examines the safety and efficacy of COCs containing E4 compared to traditional COCs.Material and methodsA systematic search was conducted in Embase and PubMed databases. Studies investigating the effects of COCs containing E4 in a study population of healthy women of reproductive age were included. All clinical outcomes related to contraceptive efficacy, bleeding patterns, mood and sexual health, endocrine and liver metabolism parameters, and markers for cardiovascular health were evaluated. Literature reviews, meta-analyses, and in vivo and animal studies were excluded. Retrieval and assessment of articles were performed in Covidence software following PRISMA guidelines and Cochrane risk of bias assessment tools.ResultsFourteen studies were included in the review. Results indicate that E4-containing COCs offer a high contraceptive reliability, predictable menstrual cycles, and favorable bleeding patterns. E4-containing COCs effectively suppressed ovulation while allowing for rapid return of ovulation after discontinuation. Furthermore, E4-containing COCs present milder effects on coagulation factors and a more neutral impact on thrombin generation, suggesting a reduced risk for venous thromboembolisms.ConclusionsE4-containing COCs could potentially be a safer and more effective alternative to contraceptive use. The findings should be interpreted with caution, as study limitations such as design and confounder bias, small study populations, and short follow-up times characterize the studies included in this review. Further, industry sponsorship bias cannot be ruled out. Further independent research is needed to confirm long-term safety and applicability of E4-containing COCs across diverse populations.

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IntroductionAlthough several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown.MethodsWe identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA).ResultsWe identified 10 articles on eight RCTs and included seven drugs (six LEPs and one progestin, i.e., dienogest) and placebo in the analysis. Meta-analysis showed improvements in total dysmenorrhea score and VAS for almost all drugs compared with placebo. In NMA, VAS in secondary dysmenorrhea improved more with dienogest than with norethisterone/ethinylestradiol (mean difference - 25.84 [95% CrI - 44.46 to - 7.15]). In the comparison of administration regimens, VAS improved more with progestin-continuous than LEP-cyclic and the surface under the cumulative ranking (SUCRA) of LEP-extended and progestin-continuous appeared to be higher than that of LEP-cyclic.ConclusionsWe confirmed that LEPs and dienogest are effective for primary and secondary dysmenorrhea and suggest that continuous regimens may be more effective than cyclic regimens in improving outcomes.

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