A cochrane review included 22 studies involving 43 637 women. Nearly 70% of the data was derived from 2 studies (HERS 1998; WHI 1998). Oestrogen-only hormone therapy (HT) increased the risk of venous thromboembolism, stroke and gallbladder disease but reduced the risk of breast cancer and clinical fracture and did not increase the risk of coronary events at any follow-up time (table . Combined HT in women over 65 years of age increased risk of cardiovascular disease, stroke, venous thromboembolism, and breast cancer, and decreased incidence of fracture. (table . Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women.
| Outcome: Follow-up: mean 7.1 years | Relative effect (95% CI) | Assumed risk - Placebo | Corresponding risk - Oestrogen-only hormone therapy (95% CI) | No. of participants (studies) Quality of evidence |
|---|---|---|---|---|
| Coronary events (MI or cardiac death) | RR 0.94 (0.78 to 1.13) | 41 per 1000 | 38 per 1000 (32 to 46) | 10 739 (1) Moderate |
| Stroke | RR 1.33 (1.06 to 1.67) | 24 per 1000 | 32 per 1000 (25 to 40) | 10 739 (1) Moderate |
| Venous thromboembolism (DVT or PE) | RR 1.32 (1.00 to 1.74) | 16 per 1000 | 21 per 1000 (16 to 28) | 10 739 (1) Moderate |
| Breast cancer | RR 0.79 (0.61 to 1.01) | 25 per 1000 | 20 per 1000 (15 to 25) | 10 739 (1) Moderate |
| Gallbladder disease | RR 1.78 (1.42 to 2.24) | 27 per 1000 | 47 per 1000 (38 to 60) | 8 376 (1) Moderate |
| All clinical fractures | RR 0.73 (0.65 to 0.80) | 141 per 1000 | 103 per 1000 (92 to 113) | 10 739 (1) Moderate |
| Outcome | Relative effect (95% CI) | Assumed risk - Placebo | Corresponding risk - Combined continuous hormone therapy (95% CI) | No. of participants (studies) Quality of evidence |
|---|---|---|---|---|
| Coronary events (MI or cardiac death) Follow-up: mean/median 1 year | RR 1.89 (1.15 to 3.10) | 2 per 1000 | 4 per 1000 (3 to 7) | 20 993 (2) Moderate |
| Stroke Follow-up: mean 3 years | RR 1.46 (1.02 to 2.09) | 6 per 1000 | 8 per 1000 (6 to 12) | 17 585 (2) Moderate |
| Venous thromboembolism (DVT or PE) Follow-up: mean/median 1 year | RR 4.28 (2.49 to 7.34) | 2 per 1000 | 7 per 1000 (4 to 11) | 20 993 (2) Moderate |
| Breast cancer Follow-up: median 5.6 years | RR 1.27 (1.03 to 1.56) | 19 per 1000 | 24 per 1000 (20 to 30) | 16 608 (1) Moderate |
| Death from lung cancer Follow-up: median 8 years | RR 1.74 (1.18 to 2.55) | 5 per 1,000 | 9 per 1000 (6 to 13) | 16 608 (1) Moderate |
| All clinical fractures Follow-up: mean 5.6 years | RR 0.78 (0.71 to 0.86) | 111 per 1000 | 87 per 1000 (79 to 96) | 16 608 (1) Moderate |
The Women's Health Initiative (WHI) conducted in 40 US clinical centers enrolled 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy . Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Estimated hazard ratios (HRs) (95% CIs) for CEE vs placebo for the major clinical outcomes were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22).
Comment: The quality of evidence is downgraded by indirectness (conjugated equine estrogen used in the intervention).