Estradiol 1mg / Norethisterone acetate 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

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

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

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

BackgroundElagolix, an approved oral treatment for endometriosis-associated pain, has been associated with hypoestrogenic effects when used as monotherapy. Hormonal add-back therapy has the potential to mitigate these effects.ObjectiveTo evaluate efficacy, tolerability, and bone density outcomes of elagolix 200 mg twice daily with 1 mg estradiol/0.5 mg norethindrone acetate (add-back) therapy once daily compared with placebo in premenopausal women with moderate-to-severe endometriosis-associated pain.Study designThis ongoing, 48-month, phase 3 study consists of a 12-month double-blind period, with randomization 4:1:2 to elagolix 200 mg twice daily with add-back therapy, elagolix 200 mg twice daily monotherapy for 6 months followed by elagolix with add-back therapy, or placebo. The coprimary endpoints were proportion of patients with clinical improvement (termed "responders") in dysmenorrhea and nonmenstrual pelvic pain at month 6. We report 12-month results on efficacy of elagolix with add-back therapy vs placebo in reducing dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and fatigue. Tolerability assessments include adverse events and change from baseline in bone mineral density.ResultsA total of 679 patients were randomized to elagolix with add-back therapy (n=389), elagolix monotherapy (n=97), or placebo (n=193). Compared with patients randomized to placebo, a significantly greater proportion of patients randomized to elagolix with add-back therapy responded with clinical improvement in dysmenorrhea (62.8% vs 23.7%; P≤.001) and nonmenstrual pelvic pain (51.3% vs 36.8%; P≤.001) at 6 months. Compared with placebo, elagolix with add-back therapy produced significantly greater improvement from baseline in 7 hierarchically ranked secondary endpoints including dysmenorrhea (months 12, 6, 3), nonmenstrual pelvic pain (months 12, 6, 3), and fatigue (months 6) (all PConclusionCompared with placebo, elagolix with add-back therapy resulted in significant, clinically meaningful improvement in dysmenorrhea, nonmenstrual pelvic pain, and fatigue at 6 months that continued until month 12 for both dysmenorrhea and nonmenstrual pelvic pain. Elagolix with add-back therapy was generally well tolerated. Loss of bone mineral density at 12 months was greater in patients who received elagolix with add-back therapy than those who received placebo. However, the change in bone mineral density with elagolix plus add-back therapy was <1% and was attenuated compared with bone loss observed with elagolix monotherapy.

Abstract licence: CC BY-NC-ND