The US WHI clinical trials were designed to assess the effects of major disease incidence rates of hormone replacement therapy (HRT) in post-menopausal women. It was a 2 parallel randomised, double blind, placebo-controlled clinical trials to determine whether conjugated equine estrogen (CEE) alone (for women with hysterectomy) or in combination with progestin (medroxyprogesterone acetate [MPA]) would reduce cardiovascular events in mostly healthy post-menopausal women (aged 50 – 79 years).
The combination HRT trial (JAMA, 2002; 288, 321-333) was stopped early (July 2002) based on reasons that the health risks that exceeded health benefits after a mean of 5.2 years of follow-up while the CEE trial continued. HSA published the findings of the combination HRT trial in an earlier issue of ADR news (2002, Vol.4 No.2) and issued a public advisory which included a recommendation advising physicians not to use HRT for prevention of coronary heart disease (CHD).
The CEE alone arm was recently terminated prematurely after an average follow-up period of 6.8 years. The study was initially scheduled to end between October 2004 and March 2005 (JAMA, 2004; 291: 1701-1712).
 |
Trials Results
The findings of the CEE alone trial reveal the following: the use of CEE alone increases the risk of stroke (hazard ratio = 1.39 and 95% confidence interval = 1.10 – 1.77), decreases the risk of total fracture (0.70; 0.63 – 0.79) and does not affect the incidence of total cardiovascular disease (1.12; 1.01 – 1.24) and breast cancer (0.77; 0.59 – 1.01).
Table 1: Summary of the incidence of events with HRTs in both arms of the WHI trials
Study findings | Change in number of events per 10,000 women-years | |
Combined HRT vs placebo (baseline rate-events per 10,000 women-years) | CEE alone vs placebo (baseline rate-events per 10,000 women-years) | |
Cardiovascular events | ||
(i) Stroke | 8 extra (21) | 12 extra (32) |
(ii) Coronary heart disease | 7 extra (30) | No difference (54) |
(Iii) Venous thromboembolism | 18 extra (16) | 7 extra (21) |
Cancer | ||
(i) Breast | 8 extra (30) | No difference (33) |
(ii) Colorectal | 6 fewer (16) | No difference (16) |
Fracture | ||
(i) Hip | 5 fewer (15) | 6 fewer (17) |
(ii) All fractures | 47 fewer (199) | 56 fewer (195) |
|
Recommendations
The termination of the CEE alone arm has brought a closure to the WHI trials. HSA's advisory on combined HRT issued to healthcare professionals on 3 October 2002 still stands:
a) HRTs do not protect postmenopausal women against cardiovascular events hence HRTs should not be initiated or continued for the purpose of reducing risk or prevention of CHD.
b) For the treatment of menopausal symptoms, HRTs are beneficial in the short term. The lowest effective dose and the shortest duration of treatment should be used.
c) The potential harm may outweigh the potential benefits for women who are using HRTs solely for the long-term prevention of osteoporosis. They should be made aware of other non-HRT therapies for both treatment and prevention of osteoporosis.
d) Women on HRT should have their therapy and health reviewed regularly.
|
Reference
|
