Estrogen Deficiency and Cardiovascular Disease in Premenopausal Women
Estrogen Deficiency and Cardiovascular Disease in Premenopausal Women
For unexplained reasons, young premenopausal women with heart disease have twice the rate of
 death compared to men of the same age. Animal experiments have shown that stress can reduce
 ovary function in females monkeys due to reductions in brain hormones. This stress and
 reduced brain hormone levels lead to low estrogen levels and can cause menstrual cycles to
 become irregular, leading to reductions in fertility. These monkeys are also more likely to
 develop heart disease. In order, to better understand this relationship the investigators
 would like to study estrogen levels in premenopausal women with heart disease.

 Premenopausal women who have recently undergone a study of their coronary (heart) arteries
 will have their blood hormone levels measured over one menstrual cycle. The investigators
 will correlate the blood hormone levels with coronary angiography results and with other
 markers of heart disease, such as a test that uses noninvasive, painless ultrasound waves to
 study the thickness of the arteries in the neck (carotid arteries). In addition blood
 cholesterol levels, blood sugar levels and other blood tests have been shown to correlate
 with heart disease will be measured.

 Another aim of the study is to evaluate a potential link between environmental stress and
 hormone levels. Each patient will be given multiple questionnaires to evaluate stress,
 anxiety and depression and the investigators will be measuring the stress hormone (cortisol)
 levels in saliva for additional information.

 The results of the study will further explore a possible link between low estrogen levels and
 heart disease in young premenopausal women and help pave the way for larger research studies
 to define better ways of preventing heart disease in these women.
Specific Aims

 1. To document that estrogen deficiency of hypothalamic (central brain) origin is a stable
 trait, when measured over one menstrual cycle or an approximate thirty days apart in
 premenopausal women undergoing angiography for coronary ischemia.

 2. To document a relationship between estrogen deficiency, other reproductive hormones and
 environmental stress in premenopausal women.

 3. To measure prevalence of angiographic coronary artery disease among premenopausal women
 and correlate it with noninvasive markers of coronary artery disease and the genetic
 relationship of estrogen in cardiovascular disease through genotyping and analysis of
 genes related to estrogen metabolism and pathways.

 We are recruiting female patients who have undergone coronary angiography and are under the
 age of 55. After subject has signed the informed consent, we will screen her by testing her
 blood for two hormones to see if subject is premenopausal. If she is, she will be enrolled in
 the study and scheduled to return for a baseline visit on day 12-18 of the following
 menstrual cycle or 22-30 days later.

 During the baseline visit we will measure height, weight, blood pressure, heart rate and
 waist-hip ratio. Subject will have to be fasting and we will draw blood for cholesterol,
 glucose and insulin levels and levels of various hormones, including but not limited to
 estrogen. Subject's saliva will be collected to test for cortisol levels. If subject agrees,
 a tablespoon of your blood will also be collected for genetic testing. Subject will be asked
 to fill out a separate consent form. Participation in the study does not mandate
 participation in genetic testing. Subject also will be given multiple questionnaires
 including questions regarding medical history, family history, medication use, stress,
 anxiety, and depression. They should be filled out within 48 hours of the blood draw to
 correlate findings. Neck arteries will be examined by ultrasound waves to measure the
 thickness of the arteries. This test can be performed on your second of third visit.

 The final exit visit will be timed 26-33 days from your baseline visit. It will include all
 the tests that subjects underwent during their baseline visit except for the ultrasound,
 which will only be done once.

 In summary, subjects will make three to four visits, the total study duration will be three
 to four months.

 We will evaluate your hormone levels and other blood markers with respect to your coronary
 angiogram and thickness of the neck arteries. We will also assess whether your hormone levels
 are related to stress, anxiety and depression. And finally, we will measure the variability
 in your hormone levels over the testing period.
Inclusion Criteria:

 -  Premenopausal by WISE criteria

 -  English speaking (for the purposes of complete psychosocial assessment)

 -  Able to give informed consent

 -  Clinically-indicated coronary angiography within the last 24 months prior to
 enrollment with no interim change in symptoms, hospitalization, or events.

 -  Non-English speaking patients will be consented but will not undergo psychosocial
 assessment as part of the study.

 Exclusion Criteria:

 -  Pregnant or intention of becoming pregnant during study period.

 -  Current hormonal therapy (oral contraceptives, hormone replacement therapy, designer
 estrogens or phytoestrogens)

 -  History of bilateral salpingoophorectomy