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
Hospital |
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
Pittsburgh |
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
- 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 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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