The effect of 17?-estradiol plus norethisterone acetate on blood pressure and inflammation markers: A meta-analysis of randomized controlled trials

Objective: Several randomized controlled trials (RCTs) have explored the impact of 17 beta-estradiol plus nor-ethisterone acetate administration on blood pressure and inflammation markers, however, their findings have often been contradictory. Thus, we conducted a systematic review and meta-analysis of RCTs to assess the effects of this drug combination on systolic blood pressure (SBP), diastolic blood pressure (DBP) and C-reactive protein (CRP) concentrations. Methods: The Cochrane Library, PubMed/Medline, Scopus, and Google Scholar were searched to identify relevant published RCTs. The pooled mean change and standard deviation (SD) of the outcomes were calculated using the STATA software (version 14) for Statistical Computing. Results: A total of 18 publications were included in the current meta-analysis. In total, there were 12 RCT arms on SBP, 12 RCT arms on DBP, and 6 RCT arms on CRP levels. The administration of 17 beta-estradiol plus nor-ethisterone acetate intake increased SBP (WMD: 3.48 mmHg, 95% CI: 0.73, 6.23, P = 0.013), particularly in subjects aged >= 60 years (WMD: 5.89 mmHg, 95% CI: 1.71, 10.07, P = 0.006) or with a body mass index (BMI) < 30 kg/m2 (WMD: 6.55 mmHg, 95% CI: 2.64, 10.46, P = 0.012), as well as in the RCTs which lasted >= 6 months (WMD: 6.47 mmHg, 95% CI: 3.03, 9.90, P < 0.001),when 17 beta-estradiol dosages were >= 2 mg/day (WMD: 4.12 mmHg, 95% CI: 1.03, 7.22, P = 0.009; I2 = 99%, P < 0.001) and in RCTs conducted on healthy postmenopausal women (WMD: 4.22 mmHg, 95% CI: 0.43, 8.01, P = 0.02; I2 = 94%, P < 0.001). DBP decreased following this drug combination in the RCTs which lasted < 6 months (WMD:-1.42 mmHg, 95% CI:-2.27,-0.57, P = 0.001). CRP concentrations increased following the use of this drug combination (WMD: 1.01 mg/L, 95% CI: 0.62, 1.41, P < 0.001), especially in participants aged < 60 years (WMD: 1.22 mg/L, 95% CI: 0.77, 1.68, P < 0.001) or with a BMI < 30 kg/m2 (WMD: 0.97 mg/L, 95% CI: 0.67, 1.27, P < 0.001), as well as in RCTs with a duration of >= 6 months (WMD: 1.15 mg/L, 95% CI: 0.57, 1.73, P < 0.001), when 17 beta-estradiol dosages were >= 2 mg/day (WMD: 0.97 mg/L, 95% CI: 0.67, 1.27, P < 0.001; I2 = 55%, P = 0.107) and in RCTs conducted on healthy post-menopausal women (WMD: 1.22 mg/L, 95% CI: 0.77, 1.68, P < 0.001; I2 = 90%, P < 0.001). Conclusion: The administration of 17 beta-estradiol plus norethisterone acetate increases SBP and CRP concentrations and, when prescribed for less than 6 months, decreases DBP. However, despite being statistically significant, the impact of this drug combination on SBP and DBP is not clinically relevant as the variation in blood pressure values was low.

Automated summary

A systematic review and meta-analysis examined the effects of 17 beta-estradiol plus nor-ethisterone acetate administration on blood pressure and inflammation markers. The results showed that this drug combination increased systolic blood pressure and C-reactive protein concentrations, while decreasing diastolic blood pressure. However, the clinical relevance of these effects was low.