Ethinylestradiol 30microgram / Norethisterone acetate 1.5mg tablets

The widespread presence of estrogens in aquatic environments represents a One Health concern, as it simultaneously threatens environmental integrity, wildlife health, and human well-being. These compounds, widely used in human and veterinary medicine, are excreted in partially or unmetabolized forms and persist in the environment due to the inefficiency of conventional water treatment systems in removing them. This systematic review provides a global overview of the occurrence of estrogens in water resources. We synthesized data on study characteristics, estrogen compounds detected, their concentrations, types of water bodies, and geographic locations. In total, 39 estrogens, including natural, synthetic, and metabolite forms, were reported at concentrations ranging from 0.002 to 10,380,000.0 ng/L across 40 water body types in 59 countries on all continents. The most frequently detected compounds were estrone, estradiol, and ethinylestradiol. Estrogens were predominantly identified in wastewater treatment plant effluents, rivers, lakes, surface waters, and even drinking water sources. These findings underscore the estrogen contamination and its potential to disrupt endocrine functions across species, posing serious implications for ecosystems. Within the One Health framework, this review highlights the urgent need for integrated strategies to improve water quality monitoring, develop advanced treatment technologies, and update regulatory standards to address the multifaceted risks posed by estrogenic contaminants.

Abstract licence: CC BY

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.

Abstract licence: CC BY-NC-ND

BackgroundEndometrial hyperplasia (EH) is a hyperplastic endometrial lesion with irregular gland size, increased glands, and increased glandular interstitial ratio. During follow-up, some EH progressed further to endometrial cancer. It is crucial to provide timely treatment for EH and improve the overall prognosis of EH patients.MethodsWe searched the PubMed, ClinicalTrials.gov., and Embase databases for studies published from their inception to March 31, 2023. The methodological quality of each study was evaluated in accordance with the Cochrane Collaboration's tool for assessing the risk of bias. The RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis statistical analysis; and the relative risk and 95% confidence interval along with the mean difference and 95% confidence interval, were used as evaluation indexes.ResultsWe included 21 randomized controlled trials involving a total of 2276 women with EH, 6 studies were of high quality, and 15 were of moderate quality. The blinding of subjects and intervention providers was identified as the main source of potential bias. Six interventions were addressed in the network meta-analysis: medroxyprogesterone acetate (MPA), plus metformin, norethisterone (NET), levonorgestrel-releasing intrauterine system (LNG-IUD), megestrol acetate, and other drugs. In the direct meta-analysis, we found the probability of endometrial complete regression (CR) in the LNG-IUD group to be significantly higher than those in the NET. In the network meta-analysis, we found the probability of CR in the NET group to be significantly lower than those in the MPA and plus metformin groups, the probability of CR in the LNG-IUD group to be significantly higher than those in the NET, the probability of CR in the other drugs group to be significantly higher than those in the LNG-IUD. The NET group had the lowest incidences of endometrial complete regression, plus metformin could have a better outcome.ConclusionAccording to the 21 randomized controlled trials included in this study, MPA is the most effective for EH endometrial outcome when applied as a single agent, while the combination of metformin can achieve a more significant effect.

Abstract licence: CC BY-NC

AimThis systematic review aimed to assess the efficacy and safety of Drospirenone and Ethinylestradiol Tablets (II) in the treatment of dysmenorrhea.MethodsElectronic databases, namely PubMed, Embase, Cochrane Controlled Register of Trials (CENTRAL), Scopus, Science, CBM, CNKI, Wanfang, and VIP, were searched before September 2022. Randomized controlled trials (RCTs), non-randomized controlled trials, cohort studies, case-control studies, and single-arm studies were included. Furthermore, the Cochrane Risk of Bias Tool for Systematic Reviews version 1 was used for the risk of bias assessment on RCTs. The Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used for risk of bias assessment on non-randomized studies. The risk ratio (RR) was calculated for dichotomous data. Mean difference (MD) or standardized MD (SMD) were used as the effect size for continuous data.ResultsA total of 11 studies involving 2,251 participants with dysmenorrhea were included. When Drospirenone and Ethinylestradiol Tablets (II) conventional 24/4-day regimen was compared with placebo, the total efficiency rate (defined as pain symptom disappearing or being relieved) in Drospirenone and Ethinylestradiol Tablets (II) 24/4-day regimen group was higher than in placebo group (RR = 5.55, 95%CI: 2.48-12.39, P P > 0.05).ConclusionDrospirenone and Ethinylestradiol Tablets (II) could improve symptoms of dysmenorrhea and decrease other related pain symptoms. More high-quality evidence is needed to confirm the advantages.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271605], identifier [CRD42021271605].

Abstract licence: CC BY

BackgroundEndometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Recurrence of symptoms following an operation is common. Although hormonal treatment can reduce this risk, there is uncertainty about the best option.ObjectivesTo evaluate the clinical and cost-effectiveness of long-acting progestogen therapy compared with the combined oral contraceptive pill in preventing recurrence of endometriosis-related pain and quality of life.DesignA multicentre, open, randomised trial with parallel economic evaluation. The final design was informed by a pilot study, qualitative exploration of women's lived experience of endometriosis and a pretrial economic model.SettingThirty-four United Kingdom hospitals.ParticipantsWomen of reproductive age undergoing conservative surgery for endometriosis.InterventionsLong-acting progestogen reversible contraceptive (either 150 mg depot medroxyprogesterone acetate or 52 mg levonorgestrel-releasing intrauterine system) or combined oral contraceptive pill (30 µg ethinylestradiol, 150 µg levonorgestrel).Main outcome measuresThe primary outcome was the pain domain of the Endometriosis Health Profile-30 questionnaire at 36 months post randomisation. The economic evaluation estimated the cost per quality-adjusted life-years gained.ResultsFour hundred and five women were randomised to receive either long-acting reversible contraceptive (N = 205) or combined oral contraceptive pill (N = 200). Pain scores improved in both groups (24 and 23 points on average) compared with preoperative values but there was no difference between the two (adjusted mean difference: -0.8, 95% confidence interval -5.7 to 4.2; p = 0.76). The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the combined oral contraceptive group (73 vs. 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). The mean adjusted quality-adjusted life-year difference between two arms was 0.043 (95% confidence interval -0.069 to 0.152) in favour of the combined oral contraceptive pill, although this cost an additional £533 (95% confidence interval 52 to 983) per woman.LimitationsLimitations include the absence of a no-treatment group and the fact that many women changed treatments over the 3 years of follow-up. Use of telephone follow-up to collect primary outcome data in those who failed to return questionnaires resulted in missing data for secondary outcomes. The COVID pandemic may have affected rates of further surgical treatment.ConclusionsAt 36 months, women allocated to either intervention had comparable levels of pain, with both groups showing around a 40% improvement from presurgical levels. Although the combined oral contraceptive was cost-effective at a threshold of £20,000 per quality-adjusted life-year, the difference between the two was marginal and lower rates of repeat surgery might make long-acting reversible contraceptives preferable to some women.Future workFuture research needs to focus on evaluating newer hormonal preparations, a more holistic approach to symptom suppression and identification of biomarkers to diagnose endometriosis and its recurrence.Trial registrationThis trial is registered as ISRCTN97865475. https://doi.org/10.1186/ISRCTN97865475.FundingThis award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/114/01) and is published in full in Health Technology Assessment; Vol. 28, No. 55. See the NIHR Funding and Awards website for further award information. The NIHR recognises that people have diverse gender identities, and in this report, the word 'woman' is used to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary.

Abstract licence: CC BY

Background Abnormal uterine bleeding (AUB) impacts women’s health and quality of life globally. Pharmacological management has prioritized hormonal agents such as norethisterone acetate; however, selective estrogen receptor modulators such as ormeloxifene have emerged as potential alternatives. Hence, this study aimed to assess and compare the effectiveness and safety of ormeloxifene and norethisterone acetate in women with AUB. Methodology This parallel, open-label, randomized controlled trial conducted at a tertiary center in central India included 60 women aged 21-47 years with AUB. Thirty participants each were assigned to ormeloxifene (60 mg twice weekly for 12 weeks, followed by once weekly for 12 weeks) or norethisterone acetate (5 mg twice daily for 21 days per cycle for six cycles). Primary endpoints included changes in pictorial blood loss assessment chart (PBAC) scores, hemoglobin concentration, and endometrial thickness (ET). Safety and the need for a hysterectomy were also assessed. Results Both groups were demographically comparable. The mean reduction in PBAC score at six months favored the ormeloxifene arm (-124.63 ± 14.65 vs. -103.73 ± 18.33, p < 0.001). The mean hemoglobin increase was significantly greater with ormeloxifene (2.26 ± 0.43 g/dL vs. 1.91 ± 0.66 g/dL, p = 0.019). ET reduction at six months was also superior in the ormeloxifene group (-8.90 ± 3.74 mm versus -6.20 ± 2.66 mm, p = 0.002). Side effects were infrequent and well-controlled, and surgical intervention was rarely required. Conclusions Ormeloxifene demonstrates superior efficacy in reducing menstrual blood loss, improving anemia, and suppressing endometrial proliferation in women with AUB compared to norethisterone acetate, with an acceptable safety profile.

Abstract licence: CC BY