Estradiol 4mg / Norethisterone 1mg tablets

ObjectiveDespite the fact that some evidence suggests that the administration of 17β-estradiol plus norethisterone acetate influences glucose and insulin metabolism in women, these findings are still contradictory. Thus, we aimed to examine the impact of the co-administration of 17β-estradiol and norethisterone acetate on glycated haemoglobin (HbA1c), fasting glucose, insulin and C-peptide concentrations in females by means of a systematic review and meta-analysis of randomized controlled trials (RCTs).MethodsWe searched four databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) using specific keywords and word combinations. The random-effects model (DerSimonian and Laird model) was employed to compute the weighted mean difference (WMD) and 95% confidence intervals (CIs) for the variations from baseline of HbA1c, fasting glucose, insulin, and C-peptide concentrations.ResultsIn total, 14 RCTs were entered into the quantitative synthesis. The combined administration of 17β-estradiol and norethisterone acetate decreased HbA1c (WMD: -0.65%, 95% CI: -1.15 to -0.15; P=0.011), fasting glucose (WMD: -11.05 mg/dL, 95% CI: -16.6 to -5.5; P<0.001) and insulin (WMD: -1.35 mIU/L, 95% CI: -2.20 to -0.50; P=0.001) levels. C-peptide concentrations’ declined only in females diagnosed with overweight/obesity or diabetes.ConclusionEvidence to date points out that the administration of 17β-estradiol and norethisterone acetate has a positive impact on glucose metabolism in women by reducing fasting glucose, HbA1c, and insulin values. Future studies need to confirm the potential benefits of this drug combination in the prevention and/or management of cardiometabolic disorders.

Abstract licence: CC BY 4.0

Pharmaceutical residues are increasingly detected in aquatic environments and are recognized as contaminants of emerging concern. This systematic literature review compiled and evaluated published concentrations of pharmaceutical residues in bottled water, tap water, and surface water in Portugal, applying risk quotient (RQ) and screening-level risk quotient (RQ_screen) approaches to evaluate potential human health risks and prioritize contaminants. Assessment based on the compiled literature data across age groups showed bottled and tap water posed low risk, while surface water presented the highest concern, with compounds spanning the full risk spectrum. Key contributors to potential human health risk included hormones (17-alpha-ethinylestradiol, 17-beta-estradiol, estrone), ramipril, betamethasone, citalopram, and amoxicillin. RQ_screen highlighted compounds relevant for ongoing monitoring even in treated waters, such as carbamazepine, diclofenac, salicylic acid, warfarin, fluoxetine, and erythromycin, due to their persistence and toxicological significance. Both RQ and RQ_screen indicated higher risk values for infants and children, reflecting lower body weight and higher water intake per unit mass, underscoring the need for age-specific evaluations. The RQ_screen method proved useful for contaminant prioritization, identifying substances relevant for monitoring despite low concentrations. Overall, this systematic review highlights pharmaceutical residues as an emerging public and environmental health concern in Portugal and emphasizes the importance of targeted monitoring and risk-based management within a One Health framework.

Abstract licence: CC BY

Abstract Background Relugolix, an oral GnRH receptor antagonist, is effective in treating uterine myomas and endometriosis. However, concerns persist regarding the venous thromboembolism (VTE) risk associated with its combination with oral estradiol (E2) and norethisterone acetate (NETA). Objective This expert opinion evaluates the thrombotic risk of relugolix combined therapy (relugolix-CT) based on pharmacological data, clinical trials, and regulatory assessments. Methods A review of pivotal trials (LIBERTY 1, LIBERTY 2, SPIRIT 1, SPIRIT 2), regulatory reports (European Medicines Agency, Food and Drug Administration), and real-world safety data was conducted, focusing on hemostatic effects and VTE risk. Results Relugolix monotherapy reduces estrogen levels, leading to minor decreases in coagulation factors. While E2 and NETA mitigate hypoestrogenic effects, concerns about their prothrombotic potential remain. However, clinical trials and postmarketing surveillance have not shown a significant increase in VTE risk. A meta-analysis suggests that E2-based regimens have a lower thrombotic risk than ethinylestradiol-based therapies. Conclusion The VTE risk of relugolix-CT appears lower than that of traditional combined oral contraceptives. Nonetheless, patient selection is essential, particularly for those with thrombotic risk factors. Continued real-world surveillance is crucial to refining its safety profile in clinical practice.

Abstract licence: CC BY-NC-ND 4.0