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Menopause-Related Research

National Heart, Lung, and Blood Institute

August 2003

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.

Clinical Trials

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 trial continues.

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.

Observational Study

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


Project No.

Title Investigator Institution
R01 HL28266
Epidemiology of Cardiovascular Risk Factors in Women Kuller U. Pittsburgh
A long-term investigation of the evolution of cardiovascular risk factors and subclinical cardiovascular disease from premenopause through menopause.
R01 HL32050 Caffeine Influences on Exercise and Psychological Stress Lovallo U. Oklahoma
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 enter menopause.
R01 HL33177
Positron Tomography in Ischemic Heart Disease Schelbert UCLA
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.
R01 HL34594 Risk Factors for Cardiovascular Disease in Women Manson 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.
P01 HL45666
Cardiovascular Benefits of Soy Phytoestrogens Clarkson Wake Forest U.
A group of studies focused on the potential cardiovascular benefits of soy photoestrogen supplementation/treatment.
R0l HL57790
CVD Risk & Health in Postmenopausal Phytoestrogen Users 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.
R01 HL60739
Mutations, Hormone Therapy Venous and Thromboembolism Psaty U. Washington
An assessment of the interaction between HRT and prothrombotic mutations as it affects the incidence of venous thromboembolism.
R01 HL63293
Thrombotic, Inflammatory, & Gene Markers of CVD in Women Ridker Brigham & Women's Hospital
A substudy of the WHI observational study exploring inherited and environmental determinants of coronary thrombosis.
P50 HL63494
SCOR in Ischemic Heart Disease: Cardiac Estrogen Receptors & MI Mendelson 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.
R01 HL67128
Longitudinal Study of the Menopause and Fat Patterning Powell 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.
R01 HL68939 Estrogen, Cytokines and Heart Failure in Women Reis University of
A clinical research study to determine the effects of estrogen therapy on postmenopausal women with congestive heart failure.
Multiproject Prevalence & Progression of
Subclinical Atherosclerosis
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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. Fang Z et al. Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 2001 Dec;281(6):R1934-9.


Public Education

  • 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.
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