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

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

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

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

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

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)

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)

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

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

Example - estrogen and CHD

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

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?

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

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