Principal WHI Risks and benefits of Estrogen + Progestin in Healthy Post-menopausal Women

Question 1

Principal WHI Risks and benefits of Estrogen + Progestin in Healthy Post-menopausal Women
- study design, N

Answer 1

JAMA 2002
RCT

N = 16,608
40 centres
Duration 5.2yrs

Aim: assess major health risks and benefits of most commonly used combined HRT in US in women with intact uterus

Mean age 63yo
50-79yo Post menopausal with intact uterus - randomised to:
- CEE 0.625mg + MPA 2.5mg (n=8506)
- Placebo (n=8102)

Exclude: comorbid condition less then 3 yr survival, adherence, prev breast ca or other ca

Question 2

Primary Outcome: WHI Risks and benefits of Estrogen + Progestin in Healthy Post-menopausal Women

Answer 2

Primary Outcome
Coronary heart disease
– Increased in combined group 37 vs 30/10 000 person years. Mostly non-fatal MI. No difference in CVD deaths or PCI interventions. Overall risk was low. Difference between groups developed soon after randomization. This difference was largely accounted for by women with a past history of CHD at time of randomization.

Invasive breast cancer – Increased risk of breast cancer with cHRT 38 vs 30/10 000 person years. Cumulative hazards comparable in the 2 groups for the first 4 years and then diverge. Higher risk in those on previous HRT

Question 3

Secondary Outcome: Principal WHI Risks and benefits of Estrogen + Progestin in Healthy Post-menopausal Women

Answer 3

• Stroke [RR 1.41 – 8 more/10,000]
• PE [RR 2.13 – 18 more/10,000]
• Lung CA [no diff]
• Endometrial CA [RR 0.83 – no diff]

Hip fracture – Lower in the cHRT group 10 vs 15/10 000 person years
Other cardiovascular disease – 2x increased risk of VTE in the cHRT group (34 vs 16/10 000py), increased risk of stroke in the cHRT group 29 vs 21/10 000py.
Endometrial cancer – no difference
Colorectal cancer – Reduced in the cHRT group 10 vs 16/10 000 person years – beneficial effect appears after 3 years of use.
Other cancers – not effected
Other fractures – significantly reduced in the cHRT group

Question 4

Principal WHI Risks and benefits of Estrogen + Progestin in Healthy Post-menopausal Women

Answer 4

Early stopping of the trial risk> benefit – Evidence for harm due to breast cancer, and possibly some increase in CHD, stroke and PE outweighed any benefits and therefore trial stopped prematurely. Average of 5.2year follow-up (rather than anticipated 8.5yr F/U)
High rates of drop out occurred – 42% test group and 38% controls

Limitations:
7.7% had pre-existing CHD
some previously on HRT
Wide age range, Average age at enrolment was 63, and 21% were >70yo (therapeutic window hypothesis)
Only tested one type of cHRT
High rates of discontinuation
Lack of data re long term treatment effects
Showed small increase in stroke and VTE regardless of history