Download - DISCLAIMER

www.menopausetoday.comWomen’s Health Initiative - Summary of results

DISCLAIMER

• Menopausetoday gives the following presentation for your information and to promote discussion.

• We welcome your comments

• We advise you if you have concerns to consult your doctor or local health department for further information.


Dr Beverley Lawton Dr Jill Shepherd 18/7/2002 comment on WHI study

• The following is a presentation covering the results of the recent WHI study. This is designed primarily for a medical audience

• Please feel free to send comments to [email protected] and discussion will be reported under book exerpt

Women’s Health Initiative - Summary of results

National Institutes of Health (NIH)

Women’s Health Initiative (WHI)

The Results

JAMA, July 17, 2002 - Vol 288, No.3


WHI Study Design

Two study arms:

1. Combined HRT vs Placebo TerminatedConjugated equine oestrogens (0.625mg) + medroxyprogesterone acetate (2.5mg) vs placebo

2. Oestrogen vs Placebo Ongoing Conjugated equine oestrogens (0.625mg) vs placebo


Combined HRT vs Placebo Study Design

• n=16,608 women with an intact uterus

• Age range= 50-79yrs (Average age = 63 yrs)

Recruited from 40 US centres between 1993-1998

Follow-up of 5.2 years (8.5 years planned)


Main FindingsRELATIVE AND ABSOLUTE RISK OR BENEFIT SEEN IN OESTROGEN

PLUS PROGESTOGEN ARM OF WHI(n =16,608, placebo and study drug)

Health Event Relative Riskvs. Placebo

Groupat 5.2 Years

(Nominal 95% CI)

IncreasedAbsolute Risk

per 10,000Women/Year

IncreasedAbsoluteBenefit

per 10,000Women/Year

Heart AttacksStrokesBreast CancerThromboembolic EventsColorectal CancerHip Fractures

1.29 (1.02-1.63)1.41 (1.07-1.85)1.26 (1.00-1.59)2.11 (1.58-2.82)0.63 (0.43-0.92)0.66 (0.45-0.98)

788

1865

Adapted from JAMA 2002; 288: 321-


Composite Outcomes for E+P

Outcome Hazard Ratio (95% CI)

Total Cardiovascular Disease 1.22 (1.09-1.36)

Total Cancer 1.03 (0.90-1.17)

Combined Fractures 0.76 (0.69-0.85)

Total Mortality 0.98 (0.82-1.18)

Global Index 1.15 (1.03-1.28)

No difference in mortality and no overall increase in cancers


Main Findings: the Risks

Per 10,000 women after 5 years there was an increased risk of:

• Breast Cancer (from 30 to 38 cases)

• Coronary Heart Disease (from 30 to 37 cases)

• Stroke (from 21 to 29 cases)


Main Findings: the Benefits

Per 10,000 women after 5 years there were reductions in:

• Colorectal Cancer (from 16 to 10 cases)

• Hip Fracture (from 15 to 10 cases)


Absolute Excess RisksAbsolute excess risks per 10,000 person years

attributable to oestrogen+progestin were:

• 7 more CHD events

• 8 more strokes

• 8 more PEs

• 8 more invasive breast cancers

The absolute excess risk of events included in the global index was 19 per 10,000 person years


Absolute Risk Reductions

Absolute risk reductions per 10,000 person years attributable to oestrogen+progestin were:

• 6 fewer colorectal cancers

• 5 fewer hip factures


DSMB recommendation

• Study terminated because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect

• The global index statistic supported risks exceeding benefits


Study Conclusions

• Overall the health risks exceeded benefits from use of combined estrogen+progestin among healthy postmenopausal US women

• Results indicate that this regimen should not be initiated or continued for the primary prevention of CHD


Discussion points

• Significant study

• Breast cancer “strong trend” as rates not statistically significant

• Study stopped on breast Ca, and global trend not CHD events

• Trial could not distinguish the effects of oestrogen from progestin


Discussion points

• Older women – average age 63 years

• Not taking HRT for symptoms

• Large dropout rate – 42 % HRT group and 38% of placebo

• What is the significance of Progestin?

• Oestrogen arm had NO increased breast cancer rate and is continuing


• The risk to an individual is small for example the increased risk for a women for 1 year for breast cancer is less than 1tenth of a per cent.

• Oestrogen alone appears to be safer as this arm is continuing.


Other issues not covered

• Quality of life

• Vaginal Health

• Cognition

• Gallbladder


Benefits of HRT


Established Benefits

• Eliminates hot flushes, night sweats, dry vagina, and palpitations.

• Reduces osteoporotic bone fracture (?P)

• Reduces colorectal cancer (?P)


Possible Benefits

• May increase mood and feeling of well-being –quality of life

• May reduce risk of Alzheimer’s disease

• May reduce arthritis

• May maintain dental health


Contraindications for HRT

• Active hepatitis- acute

• Previous DVT (?)

• MI in the last 6 months

• Undiagnosed vaginal bleeding


RISKS of HRT


Established Risks

• HRT increases the risk of VTE (?P)

• HRT increases the risk of non-fatal stroke (?P)

• HRT increases the rate of non-fatal MI (?P).


Established Risks 2

• Estrogen increases the risk of endometrial cancer when it is taken without a progestin.

• HRT increases the incidence of gallbladder disease in some women


Possible Risks

• There may be an increased risk of breast cancer after taking HRT for five years or more (?P)


What to say to patients

• The risk to individual women is small and includes a small risk in DVT, stroke, CHD.

• No increased breast cancer risk in first 4 years of use (?P)

• Safe and effective for symptoms

• Effective for osteoporosis; but other medications longterm

Download - DISCLAIMER

Top Related