Hardening of the arteries (atherosclerosis) and heart disease are much more common in men
than in women. However, as women grow older, especially after menopause the incidence of
atherosclerosis and heart disease increases. These findings suggest that estrogen may be
protective and help in preventing heart disease.
Studies of large groups of post-menopausal women suggest that hormone replacement therapy
(therapy that includes estrogen) reduces the risk of heart disease. Estrogen causes
favorable changes in particles that carry cholesterol in the blood stream and improves
function of blood vessels. Estrogen may also stimulate the immune system's ability to fight
off infections that may lead to or contribute to atherosclerosis.
Researchers believe two specific infectious agents (Chlamydia pneumoniae and human
cytomegalovirus) may cause damage to the lining of blood vessels resulting in inflammation
and the development of atherosclerosis.
The purpose of this study is to determine if estrogen treatment can change how the immune
system responds to chronic infections, by Chlamydia pneumoniae and human cytomegalovirus, in
The incidence of atherosclerotic cardiovascular disease in women does not approach rates
seen in men until approximately a decade following menopause, suggesting that estrogen is
vasculoprotective. Infectious pathogens such a Chlamydia pneumoniae (C. pneumoniae) and
human cytomegalovirus (hCMV) have been implicated in the pathogenesis of atherosclerosis.
Experimental studies in cultured lymphocytes and animals suggest that estrogen stimulates
cell-mediated immune responsiveness, observations that are potentially relevant to the
eradication of intracellular pathogens including C. pneumoniae and hCMV. The purpose of
this study is to determine whether estrogen therapy augments cell-mediated immune
responsiveness in estrogen-deficient postmenopausal women who have serologic evidence of
chronic infection with C. pneumoniae and/or hCMV. A comparison will be made between
seropositive and seronegative women. We propose that estrogen therapy will stimulate a more
efficient cell-mediated response to these chronically persistent infectious intracellular
pathogens, resulting in eradication of these organisms that are of potential importance in
Must be a postmenopausal woman 65 years of age or younger.
Time since last date of menses should be at least 12 months, with plasma estradiol less
than 50 pg/ml and FSH greater than 50 pg/ml.
Women must be without clinical evidence of CAD as determined by history, cardiovascular
physical examination, and EKG.
Must not have used hormone replacement therapy within past 6 months.
Must not have used dietary supplements and any medication (over-the-counter or prescribed)
within 1 month. Acetaminophen use is allowed.
Must not have a history of alcoholism or binge-drinking.
Must not have diabetes mellitus or known abnormal glucose intolerance test.
Must not have a history of stroke, angina or myocardial infarction.
Must not have a history of deep venous thrombosis/pulmonary embolism.
Must not have a history of cancer (except for treated squamous cell and basal cell
Must not have evidence of liver disease (liver function enzymes greater than twice the
upper limit of normal).
Must not have impaired renal function (creatinine greater than 1.6 mg/dl).
Must not have a diagnosis of an autoimmune disease (e.g., systemic lupus erythematosus,
rheumatoid arthritis, thyroiditis, Raynaud's Disease).
Must not have a history of intermittent vaginal bleeding.
Must not have serum triglycerides greater than 400 mg/dL.