Hormone replacement therapy is recommended as second-line drug for prevention and treatment of osteoporosis in women with menopausal symptoms and who do not have contraindications, and other treatments for osteoporosis can´t be used.
The recommendation is strong because of large effect size on patient-important outcomes: hot flushes and night sweats may deteriorate sleep and working ability and strongly decrease quality of life and treatment is also beneficial for fracture prevention.
A Cochrane review [Abstract] 1 included 22 studies with a total of 43 637 women. Most participants were postmenopausal American women with at least some degree of co-morbidity, and the mean participant age in most studies was over 60 years. All the statistically significant results were derived from the two biggest trials, i.e., HERS (n=2 763) and WHI (n=16 608). These trials evaluated oral conjugated equine oestrogen 0.625 mg, with or without continuous methoxyprogesterone (MPA 2.5 mg).
In relatively healthy women, combined continuous hormone therapy (HT) significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5.6 years) and gallbladder disease (after 5.6 years), and death from lung cancer (after 5.6 years). Long-term oestrogen-only HT also significantly increased the risk of venous thrombo-embolism, stroke and gallbladder disease, but did not significantly increase the risk of breast cancer. Women taking HT had a significantly decreased incidence of fractures with long term use (after 5.6 years of combined HT (RR 0.78, 95% CI 0.71 to 0.86; 1 trial, n=16,608). Risk of fracture was the only outcome for which there was strong evidence of clinical benefit from HT. There was no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thromboembolism.
No trials focussed specifically on younger women. However, one trial analysed subgroups of 2 839 relatively healthy 50 to 59 year-old women taking combined continuous HT and 1 637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low.
In WHI-study 2the 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).
In the HER-study 3, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the HRT group and 176 women in the placebo group had MI or CHD death (RR 0.99; 95% CI 0.80-1.22). More CHD events occurred in the HRT group than in the placebo group in year 1 and fewer in years 4 and 5.
A meta-analysis 4 included 28 RCTs with a total of 33 426 participants and 2 516 fractures cases. The overall relative risk of HRT was 0.74 (95% CI 0.69 to 0.80) for total fractures, 0.72 (95% CI 0.53 to 0.98) for hip fractures, and 0.63 (95% CI 0.44 to 0.91) for vertebral fractures. Estradiol led to greater decrease in the risk of total fractures compared with CEE (P 0.01). No increase in the incidence of total cancer events but an increase in the incidence of thrombus was found to be associated with HRT.
The following decision support rules contain links to this evidence summary:
Primary/Secondary Keywords