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

Hormone therapy (HT), the most efficient treatment for menopausal symptoms, might have deleterious cardiovascular (CV) effects. 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. 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1990-2013; a hand search of reference lists of selected articles was performed; and ClinicalTrials.gov was searched for unpublished trials. 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 were independently extracted by two investigators. Disagreements were resolved by a third author. 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). 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.