WHI CEE PM Hyst

Question 1

Aims

Answer 1

To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in US

Question 2

Study Design

Answer 2

Randomised, double-blind, placebo controlled disease prevention trial

Question 3

Participants

Answer 3

• 40 US clinical centres beginning in 1993
• 10,739 postmenopausal women, aged 50-79 years, with prior hysterectomy (23% of minority race/ethnicity)

Question 4

Inclusion Criteria

Answer 4

Women 50-79 years at initial screening, had undergone hysterectomy, and likely to reside in area for 3 years

Question 5

Exclusion Criteria

Answer 5

• Competing risks: any medical condition likely to be associated with a predicted survival <3 years
• Safety: prior breast cancer, other prior cancer within last 10 years except nonmelanoma skin cancer
• Adherence & retention concerns: alcoholism, dementia, transportation problems
• Clinical judgment of participant’s health care practitioner to continue HRT in symptomatic or osteoporotic women

Question 6

Intervention

Answer 6

Randomly assigned to receive either 0.625mg/d of conjugated equine estrogen (CEE) or placebo

Question 7

Primary end-points

Answer 7

• CHD incidence (nonfatal myocardial infarction or CHD death)
• Invasive breast cancer incidence

Question 8

Secondary end-points

Answer 8

A global index of risks and benefits, including the primary outcomes plus stroke, PE, colorectal cancer, hip fracture, death from other causes

Question 9

Summary of results

Answer 9

• In Feb 2004, after reviewing data through 30/11/03, NIH decided to end the intervention phase of trial early
• Estimated hazard ratios for CEE vs placebo
  
  • Decreased risk: Hip fracture 0.61 (sig), CHD 0.91, Breast cancer 0.77
  • Increased risk: Stroke 1.39 (sig), PE 1.34, Colorectal cancer 1.08
• Total CHD 1.12, total cancer 0.93, total fractures 0.70, total mortality 1.04
• Absolute excess risk of 12 additional strokes per 10,000 person-years
• Absolute risk reduction of 6 fewer hip fractures per 10,000 person-years
• Estimated excess risk for all monitored events in global index was nonsignificant 2 events per 10,000 person-years

Question 10

Limitations

Answer 10

• Only oral preparation -> results do not apply to other formations, doses or routes of administration
• High rates of discontinuation
  
  • Lack of adherence -> diluted CEE effects, both +ve and –ve
• Lower than anticipated event rates for some outcomes
• Trial was stopped early therefore strong associations for breast cancer cannot be shown

Question 11

Conclusion

Answer 11

• Use of CEE increases risk of stroke, decreases risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years
• Possible reduction in breast cancer risk requires further investigation
• Burden of incidence disease events were equivalent in CEE and placebo groups (à no overall benefit)
• Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women