This document summarizes a study that analyzed the association between postmenopausal hormone therapy and cardiovascular disease using data from the Nurses' Health Study. Over 70,000 postmenopausal nurses were followed through questionnaires for up to 20 years. The study found that current hormone therapy was associated with a decreased risk of major coronary events but a modest increase in stroke risk at higher doses. Previous publications from this study had endorsed hormone therapy for cardiovascular disease prevention but this study's conclusions were more cautious given other research linking hormone therapy to increased breast cancer risk.

1. Example - estrogen and CHD
• Analysis of the association between
postmenopausal hormonal therapy and nonfatal
myocardial infarction and cardiovascular disease
• Concurrent, prospective cohort design
• Grodstein et al. 2000

2. Example - estrogen and CHD
• Analysis of the Nurses’ Health Study data
– Enrolled 121,964 female nurses aged 30-55 in 1976
– Follow-up questionnaires biennially through 1996

3. Example - estrogen and CHD
• Postmenopausal status established based on
questionnaire responses
– Natural menopause
– Hysterectomy with bilateral oophorectomy
– Hysterectomy without bilateral oophorectomy but of
an age by which natural menopause would have
occurred

4. Example - estrogen and CHD
• 70,533 postmenopausal women were eligible for
some portion of the study period
• Excluded nurses with stroke, MI, angina,
coronary revascularization or cancer on 1976
questionnaire, and excluded from further follow-
up if reported on subsequent questionnaire
– Diseases that may have caused alteration of hormone
use

5. Example - estrogen and CHD
• Questionnaire assessed use and duration of use
of postmenopausal hormones at all follow-ups
– Type of hormone
– Does of oral conjugated estrogen

6. Example - estrogen and CHD
• Outcomes
– Nonfatal MI and fatal coronary heart disease
– Fatal and nonfatal stroke
– Reported nonfatal MI and stroke were verified with
medical record review (blinded)

7. Example - estrogen and CHD
• Outcomes
– Fatal coronary disease and stroke
• Most deaths reported by next of kin or postal service
• Searched National Death Index for deaths for all non-
respondents at each interview
• Confirmed cause of deaths by medical record review or
autopsy records
• Record reviews conducted by physicians with no knowledge
of exposures (blinded)

8. Example - estrogen and CHD
• Outcomes were quantified with incidence density
– Person-months allocated according to 1976 exposure
variables and updated every 2 years
• Counted in a given exposure category from return date of a
given questionnaire (e.g., 1976) to date of death, non-fatal MI
or return of next questionnaire (e.g., 1978)
– Follow-up ended for an individual at the first diagnosis
of cardiovascular disease, death, or June 1 1996,
whichever came first

9. Example - estrogen and CHD
• 953 incident nonfatal MIs
• 305 coronary deaths
• 767 strokes
• 119 deaths due to stroke
• 808,825 person-years of follow-up

10. Example - estrogen and CHD

11. Example - estrogen and CHD
• Rate of major coronary events substantially
decreased among current users of hormone
therapy
• Earlier publications from NHS had endorsed
hormone therapy as preventive for CHD
• Conclusions of this publication more circumspect

12. Example - estrogen and CHD
• Noted potential adverse outcomes of HRT
• Observed a modest increase in risk of stroke for
higher hormone doses
• Previous research has established increased risk of
breast cancer related to hormone therapy
• Conclude that alternatives for reducing CHD risk
should be considered (e.g., physical activity,
healthy diet)
• Why did they change their tune?

13. Example - estrogen and CHD
• This paper was published after an initial press
release from the Women’s Health Initiative (WHI)
trial that found early increases in CHD risks
associated with hormone therapy

14. Example - estrogen and CHD
• Notes on the methods in this example
– Large cohort allowing examination of a range of
exposures (no distinct exposed and unexposed
cohorts)
– Questionnaire used for exposure assessment
– Combined questionnaire and medical record review
for non-fatal MI and stroke determination
– Vital records for CHD and stroke death determination
– Homogeneous population, familiar with research
– Extensive control for confounding