Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: A systematic review and meta-analyses of randomized clinical trials

Abstract

Context: Hormone therapy (HT), the most efficient treatment for menopausal symptoms, might have deleterious cardiovascular (CV) effects. Objective: This study aimed to evaluate the effects of low-dose estrogen HT on CV risk factors vs conventional-dose HT and placebo in postmenopausal women with no established CV disease. Data Sources: MEDLINE, Cochrane Central, and EMBASE were searched for trials published in 1990-2013; a hand search of reference lists of selected articles was performed; and ClinicalTrials.gov was searched for unpublished trials. Study Selection: Within randomized controlled trials of healthy postmenopausal women comparing low-dose HT to placebo or conventional-dose HT, 11 418 studies were initially identified. Data Extraction: Data were independently extracted by two investigators. Disagreements were resolved by a third author. Data Synthesis: Twenty-eight trials (3360 patients) were included. Low-dose HT vs placebo or conventional-dose HT did not effect weight, body mass index (BMI), blood pressure, C-reactive protein, or high-density lipoprotein cholesterol (HDL-C). Low-dose HT was associated with lower levels of total cholesterol (-12.16 mg/dL, 95% confidence interval [CI], -17.41--6.92) and low-density lipoprotein cholesterol (LDL-C) (-12.16 mg/dL; 95% CI, -16.55--7.77) vs placebo. Compared with conventional-dose HT, low-dose HT was associated with higher total cholesterol (5.05 mg/dL; 95% CI, 0.88-9.21) and LDL-C (4.49 mg/dL; 95% CI, 0.59-8.39). Low-dose HT was not associated with differences in triglycerides vs placebo. Oral, low-dose HT was associated with lower triglycerides vs conventional-dose HT (-14.09 mg/dL; 95% CI, -24.2--3.93). Conclusion: In this population of apparently healthy postmenopausal women, the effect of low-dose HT did not differ from that of placebo or conventional-dose HT regarding weight, BMI, blood pressure, CRP, or HDL-C. In contrast, low-dose HT was associated with better lipid profile vs placebo, and induced higher total and LDL-C and lower triglycerides vs conventional-dose HT.