One hundred and seven RCTs (n=33,315) were included in the review. The mean sample size was 311 patients and the mean drop-out rate was approximately 9.2% in the intervention group and 7.2% in the control group.
The authors reported that funnel plots showed no evidence of bias, but data were not presented in the review. There were some discrepancies between the numbers reported in the text and those in the tables; numbers from the text have been used in this abstract.
Abdominal obesity (9 studies): HRT was reported to be more beneficial in non-diabetic women compared with controls, increasing lean body mass (WMD 3.3%, 95% CI: 0.02, 6.6). Pooled results for 5 studies showed reduced waist circumference in the intervention group (WMD -0.8%, 95% CI: -1.2, -0.4, p<0.05), and 4 studies showed reductions in abdominal fat (WMD -6.8%, 95% CI: -11.8, -1.9).
Insulin resistance and diabetes (18 studies): insulin resistance (homeostasis model assessment, HOMA-IR) was significantly reduced in non-diabetic women receiving HRT compared with controls (WMD 12.9%, 95% CI: 8.6, 17.1, p<0.05). Significant differences were reported for fasting glucose and fasting insulin, also favouring HRT (respectively: WMD 2.5%, 95% CI: 1.5, 3.5; WMD 9.3%, 95% CI: 4.9, 13.7). The RR for developing diabetes mellitus indicated a 30% reduction in new-onset diabetes in those receiving HRT (RR 0.7, 95% CI: 0.6, 0.9). Subgroup analyses by agent type showed no significant differences in HOMA-IR. HRT reduced HOMA-IR, fasting glucose and fasting insulin in women with diabetes compared with controls (respectively: WMD 35.8, 95% CI: 19.8, 51.7; WMD 11.5, 95% CI: 5.1, 18.0; WMD 20.2%, 95% CI: 4.2, 36.3). A greater reduction in HOMA-IR was observed for women with diabetes compared with non-diabetics (p=0.07).
Lipids and lipoproteins (61 studies): HRT increased high-density lipoprotein (HDL) cholesterol and decreased low-density lipoprotein (LDL) cholesterol, LDL/HDL ratio (WMD -15.7%, 95% CI: -18.0, -13.5, p<0.05) and lipoprotein(a) (WMD -25%, 95% CI: -32.9, -17.1, p<0.05) compared with controls. Subgroup analyses indicated greater reductions in the LDL/HDL ratio using oral agents compared with transdermal agents (p=0.004), and conjugated oestrogens compared with oral esterified oestrogens (p<0.0001). A significant dose-dependent effect for conjugated oestrogens was reported for LDL/HDL ratio (p=0.0001). Fifty-four studies reported no significant effect of HRT on triglycerides. Subgroup analyses indicated increased levels of triglycerides with oral agents (WMD 6.0%, 95% CI: 4.3, 7.6, p<0.05).
Mean blood-pressure: HRT significantly reduced blood-pressure (WMD -1.7%, 95% CI: -2.9, -0.5, p<0.05). Subgroup analyses indicated a significant reduction using conjugated oestrogens only.
Inflammatory components (15 studies): HRT significantly increased C-reactive protein, thus favouring controls (WMD 37%, 95% CI: 17.4, 61.3, p<0.05). However, significant differences were reported between the intervention and control groups for E-selectin reduction, in favour of HRT (WMD -17.3%, 95% CI: -22.4, -12.1, p<0.05). Subgroup analyses did not significantly alter these results. Subgroup analyses for C-reactive protein indicated a significant increase using oral agents (WMD 47.0%, 95% CI: 29.0, 67.0, p<0.05). Single oestrogens showed greater increases in C-reactive protein compared with combined treatment, and there was a significant dose-dependent effect (p=0.0006).
Thrombotic components (40 studies): HRT significantly reduced fibrinogen (24 studies; WMD - 5.5%, 95% CI: -7.8, -3.2, p<0.05) and plasminogen activator inhibitor-1 (16 studies; WMD -25.1%, 95% CI: -33.6, -15.5) . Subgroup analyses did not significantly alter the results for fibrinogen, but indicated a significant reduction in plasminogen activator inhibitor-1 using oral agents (WMD -27.0%, 95% CI: -38.0, -22.0). There were no significant differences for protein C or protein S by treatment type. Subgroup analyses indicated a significant reduction in protein S using oral agents (WMD 8.6%, 95% CI: -13.1, -4.1, p<0.05).
Sensitivity analyses did not significantly alter the results. Interactions between subgroups were reported in the review and analyses of other outcomes were discussed.
Significant heterogeneity was reported for LDL/HDL ratio, triglycerides, blood-pressure, C-reactive protein, protein S and plasminogen activator inhibitor-1.