Estradiol 30micrograms/24hours / Norethisterone 95micrograms/24hours transdermal patches

Objective: Despite 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). Methods: We 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. Results: In 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. Conclusion: Evidence 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

Background and aimMenopausal hormone therapy (MHT) remains a pivotal approach in managing menopausal symptoms; however, its effects on inflammation and cardiovascular risk markers are still under debate. In particular, the combination of medroxyprogesterone acetate (MPA) and conjugated equine estrogens (CEE) has shown variable impacts on inflammatory biomarkers. This systematic review and meta-analysis aimed to synthesize evidence from randomized controlled trials (RCTs) assessing the effects of oral MPA combined with CEE (MPA/CEE) on systemic inflammation in postmenopausal women.MethodsThirteen RCTs (comprising 16 arms) reporting data on inflammatory markers, including C-reactive protein (CRP), fibrinogen, homocysteine, and interleukin-6 (IL-6), were included, with a total sample size of 2,278 participants. A random-effects model was used to calculate pooled weighted mean differences (WMDs) with 95% confidence intervals. Subgroup and sensitivity analyses were performed to explore heterogeneity, and publication bias was assessed using Egger's test and trim-and-fill methods.ResultsMPA/CEE treatment was associated with a significant decrease in CRP levels (WMD = -0.173 mg/dL; 95% CI: -0.25 to -0.10; P ConclusionWhile MPA/CEE therapy significantly reduces CRP and fibrinogen, key inflammatory and cardiovascular risk markers, these findings suggest a notable protective effect of oral MPA/CEE on inflammation, highlighting the need for individualized therapeutic strategies based on patient risk profiles.

Abstract licence: CC BY

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health.

Abstract licence: CC BY

BackgroundTo date, no meta-analysis has reported on the role of transdermal estrogens combined with Medroxyprogesterone Acetate (MPA) in relation to cardiovascular disease (CVD) risk factors in postmenopausal women. To fill this knowledge gap, a meta-analysis of randomized controlled trials (RCTs) was conducted to assess the effects of transdermal estrogens and MPA on CVD risk factors in postmenopausal women.MethodsA systematic literature search was conducted in major databases including PubMed/Medline, Web of Science, SCOPUS, and Embase, from inception to 12 February 2025. The combination of Medical Subject Headings (MeSH) and non-MeSH keywords was used.ResultsA total of 14 trials were included in the meta-analysis. The combined eligible trials found that transdermal estrogens combined with MPA significantly decreased total cholesterol (TC) (WMD: -13.37 mg/dL, 95% CI: -21.54 to -5.21, p = 0.001), low density lipoprotein cholesterol (LDL-C) (WMD: -12.17 mg/dL, 95% CI: -23.26 to -1.08, p = 0.031), and apolipoprotein B (ApoB) (WMD: -7.26 mg/dL, 95% CI: -11.48 to -3.03, p = 0.001) compared to the control. No statistically significant associations were observed between transdermal estrogens combined with MPA on triglyceride (TG), high density lipoprotein cholesterol (HDL-C), lipoprotein(a) (Lp(a)), and apolipoprotein A1 (ApoAI).ConclusionBased on the results of the current meta-analysis, transdermal estrogens combined with oral MPA administration had a beneficial effect on certain CVD risk factors in postmenopausal women, as evidenced by the significant reductions in TC, LDL-C, and ApoB.

Abstract licence: CC BY-NC-ND

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