National Heart, Lung, and Blood Institute
Because many of the diseases and conditions that fall within the NHLBI mandate
(e.g., coronary disease, hypertension, congestive heart failure, chronic obstructive
pulmonary disease) primarily affect older people, many postmenopausal women
are being studied in the Institute's clinical research programs. This document
focuses specifically on NHLBI-supported research in women that is related to
reproductive hormonal status or to changes in health risks that occur as women
pass through menopause.
Women's Health Initiative
The Women's Health Initiative (WHI) is a complex multicenter project examining
strategies for the prevention and control of the most common causes of death,
disability, and impaired quality of life among postmenopausal women, including
cardiovascular disease, breast and colorectal cancers, and osteoporotic fractures.
Initiated in 1991 with planned completion in 2007, the WHI is conducted as a
consortium effort led by the NHLBI in cooperation with the Office of Research
on Women's Health, the National Cancer Institute, and the National Institute
of Arthritis and Musculoskeletal Diseases. Recruitment was completed in 1998.
Over 68,000 women of diverse racial, ethnic, geographic, and socioeconomic background
are participating in three overlapping randomized controlled Clinical Trials
(CT), and an additional 93,676 women are enrolled in a parallel Observational
Study (OS). A third component, the Community Prevention Study, focused on community-based
prevention strategies to enhance adoption of healthful behaviors and was conducted
by the Centers for Disease Control and Prevention.
The CT component is designed to evaluate the effect of:
1) Low-fat eating pattern in preventing breast and colorectal cancers
(N = 48,836)
2) Postmenopausal hormone therapy in preventing coronary heart disease
and other cardiovascular diseases, with breast cancer as a possible adverse
outcome (N=27,347). The estrogen-plus-progestin component of the hormone trial
was stopped on July 9, 2002, because WHI researchers found that the risks of
long-term estrogen-plus-progestin therapy outweigh its protective benefits.
(See publications for related papers.) The estrogen-only component of the hormone
3) Calcium and vitamin D supplementation in preventing osteoporotic
fractures (N = 36,282)
Women may participate in one, two, or all three trials. Overall benefit-versus-risk
assessment is a central focus in each of the three CT components.
The OS is identifying predictors of disease by: 1) examining the associations
of known or putative risk factors (including biomarkers) to disease status at
baseline and during follow-up; 2) seeking to find new risk factors using the
stored biological samples and data as a resource; and 3) examining the effects
of change in known or putative risk factors on disease outcome.
A detailed description of the WHI is available in Controlled Clinical Trials
1998;19:61 - 109.
Representative NHLBI Research Projects
|Epidemiology of Cardiovascular Risk Factors in Women
|A long-term investigation of the evolution
of cardiovascular risk factors and subclinical cardiovascular disease from
premenopause through menopause.
||Caffeine Influences on Exercise and Psychological Stress
|An evaluation of the effects of caffeine
intake on blood pressure and cortisol secretion, under conditions of mental
and exercise stress, with an emphasis on variations in response as women
|Positron Tomography in Ischemic Heart Disease
|A study of coronary vasomotor function that,
in postmenopausal women, will explore protective effects of estrogens against
coronary atherosclerosis and examine whether these effects are negated or
modified by progestins, as well as whether adequate protection requires
addition of statins and antioxidants.
||Risk Factors for Cardiovascular Disease in Women
||Brigham & Women's
|Continued follow-up of the Nurses Health
Study cohort, first recruited in 1976, to evaluate hypotheses regarding
dietary and hormonal risk factors for coronary heart disease and ischemic
and hemorrhagic stroke.
|Cardiovascular Benefits of Soy Phytoestrogens
||Wake Forest U.
|A group of studies focused on the potential
cardiovascular benefits of soy photoestrogen supplementation/treatment.
|CVD Risk & Health in Postmenopausal Phytoestrogen
||Kritz - Silverstein
||U. Cal., San Diego
|A study to determine the acceptability and
benefits of use of a dietary supplement of phytoestrogen (genistein) versus
placebo on heart disease risk factors, bone density, and psychosocial outcomes
in postmenopausal women.
|Mutations, Hormone Therapy Venous and Thromboembolism
|An assessment of the interaction between
HRT and prothrombotic mutations as it affects the incidence of venous thromboembolism.
|Thrombotic, Inflammatory, & Gene Markers of CVD in
||Brigham & Women's Hospital
|A substudy of the WHI observational study
exploring inherited and environmental determinants of coronary thrombosis.
|SCOR in Ischemic Heart Disease: Cardiac Estrogen Receptors
||New Engl. Med. Ctr.
|An investigation of the hypothesis that
the genetics, expression, and function of cardiovascular estrogen receptors
and estrogen-regulated target genes mediate protection against ischemic
diseases and their sequelae, including vascular dysfunction, post-myocardial
infarction remodeling, and arrhythmias.
|Longitudinal Study of the Menopause and Fat Patterning
||Rush Presbyterian- St. Luke's Med. Ctr.
|A study of the natural history of the accumulation
of intra-abdominal fat as women progress through menopause.
||Estrogen, Cytokines and Heart Failure in Women
|A clinical research study to determine the
effects of estrogen therapy on postmenopausal women with congestive heart
||Prevalence & Progression of
|A determination of the extent to which diminishing
ovarian function affects vascular function and accelerates the development
of atherosclerosis in the coronary arteries, aorta, and carotid arteries.
Recent Representative Publications
- Manson JE et al. Estrogen plus progestin and the risk of coronary heart
disease. N Engl J Med 2003 Aug 7;349(6):523-34.
- Hodis HN et al. Hormone therapy and the progression of coronary-artery atherosclerosis
in postmenopausal women. N Engl J Med 2003 Aug 7;349(6):535-45.
- Chlebowski RT et al. Influence of estrogen plus progestin on breast cancer
and mammography in healthy postmenopausal women: the Women's Health Initiative
Randomized Trial. JAMA 2003 Jun 25;289(24):3243-53.
- Shumaker SA et al. Estrogen plus progestin and the incidence of dementia
and mild cognitive impairment in postmenopausal women: the Women's Health
Initiative Memory Study: a randomized controlled trial. JAMA 2003 May 28;289(20):2651-62.
- Rapp SR et al. Effect of estrogen plus progestin on global cognitive function
in postmenopausal women: the Women's Health Initiative Memory Study: a randomized
controlled trial. JAMA 2003 May 28;289(20):2663-72.
- Wassertheil-Smoller S et al. Effect of estrogen plus progestin on stroke
in postmenopausal women: the Women's Health Initiative: a randomized trial.
JAMA 2003 May 28;289(20):2673-84.
- Waters DD et al. Effects of hormone replacement therapy and antioxidant
vitamin supplements on coronary atherosclerosis in postmenopausal women: a
randomized controlled trial. JAMA 2002 Nov 20;288(19):2432-40.
- Dwyer KM et al. Carotid wall thickness and years since bilateral oophorectomy:
the Los Angeles Atherosclerosis Study. Am J Epidemiol 2002 Sep 1;56(5):438-44.
- Pradhan AD et al. Inflammatory biomarkers, hormone replacement therapy,
and incident coronary heart disease: prospective analysis from the Women's
Health Initiative Observational Study. JAMA 2002 Aug 28;288(8):980-7.
- Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy
postmenopausal women: principal results from the Women's Health Initiative
Randomized Controlled Trial. JAMA 2002 Jul 17;288(3):321-33.
- Greendale GA et al. Bone mass response to discontinuation of long-term hormone
replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions
(PEPI) Safety Follow-up Study. Arch Intern Med 2002 Mar 25;162(6):665-72.
- Zhang Y et al. The effect of estrogen use on levels of glucose and insulin
and the risk of type 2 diabetes in American Indian postmenopausal women: the
Strong Heart Study. Diabetes Care 2002 Mar;25(3):500-4.
- Sutton-Tyrrell K et al. Subclinical atherosclerosis in multiple vascular
beds: an index of atherosclerotic burden evaluated in postmenopausal women.
Atherosclerosis 2002 Feb;160(2):407-16.
- Fang Z et al. Estrogen depletion induces NaCl-sensitive hypertension in
female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol
The Postmenopausal Hormone Therapy Fact Sheet
explains research findings, issues related to long- and short-term hormone use,
risk factors for heart disease, and alternatives to hormone therapy.
- The Heart Truth
a national awareness campaign, targets women ages 40 to 60 and encourages
them to take their heart health seriously, talk to their doctors about it,
and take steps to reduce their risk.