Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| IRB#0505140 | Other Identifier | University of Pittsburgh |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Parke-Davis | INDUSTRY |
| University of Pittsburgh | OTHER |
| University of Florida | OTHER |
| Allegheny University |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The goal of the main trial was to evaluate the effect of low dose hormone replacement therapy with 1 mg norethindrone/10mcg ethinyl estradiol in postmenopausal women with a history of chest discomfort, myocardial ischemia and no obstructive CAD. For the purposes of this study as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; glucose, insulin and HOMA core lab analyses; exercise stress test/Holter monitor core lab analyses; brachial artery reactivity test core lab analyses; full study data analyses for manuscript preparation and the writing and submission and publication of manuscript.
The main trial duration: December 1999 - May 2003.
The ancillary data analysis project duration: April 2006 - March 2010.
See Brief Summary above.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hormone replacement therapy | Active Comparator | Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE) |
|
| Placebo | Placebo Comparator | 1mg placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 1/10 NA/EE | Drug | Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Inducible Myocardial Ischemia | Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia. | Baseline |
| Endothelial Dysfunction (FMD) | Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of endothelial dysfunction. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100]. | Baseline |
| Endothelial Dysfunction (FMD) | Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100]. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Physical Functional Disability - Functional Capacity (METs) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on. |
Not provided
Inclusion Criteria
Postmenopausal WISE and nonWISE study participants
Normal/minimally diseased coronary arteries (<50% luminal diameter stenosis in all epicardial coronary arteries) within 36 months of ancillary study entry and no intercurrent MI, PTCA, CABG
Any one (or multiple) of the following criteria suggestive of myocardial ischemia within 36 months of ancillary study entry:
No contraindications to 12 weeks of FemHRT or hormone replacement therapy
Normal mammogram and pelvic exam (including PAP smear for those with an intact uterus) within 12 months of study entry
Documented normal liver function testing (SGOT) within 3 months of study entry.
Exclusion Criteria
Women with elevated diastolic (> or = 90 mm Hg) or systolic (> or = 140 mm Hg) blood pressure, LDL-cholesterol (> or = 160 mg/dl), fasting blood sugar (> or = 130 mg/dl) and women who smoke cigarettes will be told their risk factor levels and referred for evaluation and treatment by their private physician.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| C. Noel Bairey Merz, MD | Cedars-Sinai Medical Center | Study Chair |
| Carl Pepine, MD | University of Florida | Principal Investigator |
| Steve Reis, MD | University of Pittsburgh | Principal Investigator |
| Nathaniel Reichek, MD | Allegheny University of the Health Sciences | Principal Investigator |
| William Rogers, MD | University of Alabama at Birmingham | Principal Investigator |
| Vijay Misra, MD | University of Alabama at Birmingham | Principal Investigator |
| Robert B Weiss, MD | Johns Hopkins University | Principal Investigator |
| Sheryl Kelsey, PhD | University of Pittsburgh | Principal Investigator |
| George Sopko, MD | National Institute of Health (WISE Project Officer) | Study Director |
| James Symons, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Women's Heart Center, 8631 W. 3rd St, Suite 740 | Los Angeles | California | 90048 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12075053 | Background | Panza JA. Myocardial ischemia and the pains of the heart. N Engl J Med. 2002 Jun 20;346(25):1934-5. doi: 10.1056/NEJMp020047. No abstract available. | |
| 9396408 | Background | Cannon RO 3rd. Does coronary endothelial dysfunction cause myocardial ischemia in the absence of obstructive coronary artery disease? Circulation. 1997 Nov 18;96(10):3251-4. No abstract available. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Hormone Replacement Therapy | Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE). |
| FG001 | Placebo | 1 mg placebo. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Hormone Replacement Therapy | Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE). |
| BG001 | Placebo | 1 mg placebo. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Inducible Myocardial Ischemia | Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia. | Among the 35 women, 28 baseline and 26 exit MRS results were technically adequate for spectral analyses with rest, handgrip exercise, and recovery spectra. A total of 24 women (13 drug, 11 placebo) had both baseline and exit P31's. | Posted | Mean | Standard Deviation | percent changed in PCR/ATP ratio | Baseline |
|
12 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hormone Replacement Therapy | Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for angina and a stroke | Cardiac disorders | Non-systematic Assessment | Hospitalization for angina an a stroke |
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| C. Noel Bairey Merz | Cedars-Sinai Medical Center | 310-423-9680 | Noel.BaireyMerz@cshs.org |
Not provided
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
Not provided
Not provided
| UNKNOWN |
| University of Alabama at Birmingham | OTHER |
| Johns Hopkins University | OTHER |
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | 1 mg placebo |
|
| Inducible Myocardial Ischemia | Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia. | 12 weeks |
| Baseline |
| Quality of Life - Menopause Symptoms | Quality of life assessed by menopausal symptoms and psychological questionnaires | Baseline |
| Quality of Life - Menopause Symptoms | Quality of life assessed by menopausal symptoms and psychological questionnaires | 12 weeks |
| Quality of Life - Health Survey | Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | Baseline |
| Quality of Life - Health Survey | Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | 12 weeks |
| Physical Functional Disability - Functional Capacity (METs) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on. | Exit at 12 weeks |
| Physical Functional Disability - Functional Capacity (Metabolism Equivalents) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. | Baseline |
| Physical Functional Disability - Functional Capacity (Metabolism Equivalents) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. | Exit (12 weeks) |
| Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point). | Baseline |
| Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point). | Exit (12 weeks) |
| Parke-Davis |
| Study Director |
| Connie McLaughlin, PharmD | Parke-Davis | Study Director |
| 2331772 | Background | Williams JK, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation. 1990 May;81(5):1680-7. doi: 10.1161/01.cir.81.5.1680. |
| 8044971 | Background | Williams JK, Shively CA, Clarkson TB. Determinants of coronary artery reactivity in premenopausal female cynomolgus monkeys with diet-induced atherosclerosis. Circulation. 1994 Aug;90(2):983-7. doi: 10.1161/01.cir.90.2.983. |
| 8205663 | Background | Gilligan DM, Quyyumi AA, Cannon RO 3rd. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994 Jun;89(6):2545-51. doi: 10.1161/01.cir.89.6.2545. |
| 8281693 | Background | Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, Brinker JA. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation. 1994 Jan;89(1):52-60. doi: 10.1161/01.cir.89.1.52. |
| 10334408 | Background | Merz CN, Kelsey SF, Pepine CJ, Reichek N, Reis SE, Rogers WJ, Sharaf BL, Sopko G. The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999 May;33(6):1453-61. doi: 10.1016/s0735-1097(99)00082-0. |
| 11305981 | Background | Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, Sopko G, Kelsey SF, Holubkov R, Olson M, Miele NJ, Williams DO, Merz CN; WISE Study Group. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol. 2001 Apr 15;87(8):937-41; A3. doi: 10.1016/s0002-9149(01)01424-2. |
| Background | The manual of laboratory operations 1. Lipid and lipoprotein analysis. Bethesda: Lipid Research Clinics Program. National Institutes of Health. DHEW Publication No. 75-628; 1974. |
| 7488894 | Background | Barrett-Connor E, Goodman-Gruen D. Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women. BMJ. 1995 Nov 4;311(7014):1193-6. doi: 10.1136/bmj.311.7014.1193. |
| 1985442 | Background | Helmer DC, Ragland DR, Syme SL. Hostility and coronary artery disease. Am J Epidemiol. 1991 Jan 15;133(2):112-22. doi: 10.1093/oxfordjournals.aje.a115850. |
| Background | Naughton MJ, Shumaker SA, Anderson RT, et al. Psychological aspects of health-related quality of life measurement: tests and scales. Philadelphia: Lippincott-Raven Publishers; 1996. |
| 13538604 | Background | MANDLER G, MANDLER JM, UVILLER ET. Autonomic feedback: the perception of autonomic activity. J Abnorm Psychol. 1958 May;56(3):367-73. doi: 10.1037/h0048083. No abstract available. |
| Background | Ware JE, Kosinski M, Gandek B. SF-36 Health Survey. Manual and interpretation guide. Lincoln: Quality Metric Inc.; 1993. |
| 1593914 | Background | Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83. |
| 8844630 | Background | Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas. 1996 Jul;24(3):161-75. doi: 10.1016/s0378-5122(96)82006-8. |
| 8101254 | Background | Rosano GM, Sarrel PM, Poole-Wilson PA, Collins P. Beneficial effect of oestrogen on exercise-induced myocardial ischaemia in women with coronary artery disease. Lancet. 1993 Jul 17;342(8864):133-6. doi: 10.1016/0140-6736(93)91343-k. |
| 12919775 | Background | Olson MB, Kelsey SF, Matthews K, Shaw LJ, Sharaf BL, Pohost GM, Cornell CE, McGorray SP, Vido D, Bairey Merz CN. Symptoms, myocardial ischaemia and quality of life in women: results from the NHLBI-sponsored WISE Study. Eur Heart J. 2003 Aug;24(16):1506-14. doi: 10.1016/s0195-668x(03)00279-3. |
| 8792180 | Background | Albertsson PA, Emanuelsson H, Milsom I. Beneficial effect of treatment with transdermal estradiol-17-beta on exercise-induced angina and ST segment depression in syndrome X. Int J Cardiol. 1996 Apr 19;54(1):13-20. doi: 10.1016/0167-5273(96)02560-0. |
| 11449079 | Background | Adamson DL, Webb CM, Collins P. Esterified estrogens combined with methyltestosterone improve emotional well-being in postmenopausal women with chest pain and normal coronary angiograms. Menopause. 2001 Jul-Aug;8(4):233-8. doi: 10.1097/00042192-200107000-00003. |
| 8917264 | Background | Rosano GM, Peters NS, Lefroy D, Lindsay DC, Sarrel PM, Collins P, Poole-Wilson PA. 17-beta-Estradiol therapy lessens angina in postmenopausal women with syndrome X. J Am Coll Cardiol. 1996 Nov 15;28(6):1500-5. doi: 10.1016/s0735-1097(96)00348-8. |
| 9743505 | Background | Gerhard M, Walsh BW, Tawakol A, Haley EA, Creager SJ, Seely EW, Ganz P, Creager MA. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation. 1998 Sep 22;98(12):1158-63. doi: 10.1161/01.cir.98.12.1158. |
| 10362210 | Background | Herrington DM, Werbel BL, Riley WA, Pusser BE, Morgan TM. Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease. J Am Coll Cardiol. 1999 Jun;33(7):2030-7. doi: 10.1016/s0735-1097(99)00128-x. |
| 9918521 | Background | Koh KK, Cardillo C, Bui MN, Hathaway L, Csako G, Waclawiw MA, Panza JA, Cannon RO 3rd. Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation. 1999 Jan 26;99(3):354-60. doi: 10.1161/01.cir.99.3.354. |
| 10954759 | Background | Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, Furberg CD, Kowalchuk GJ, Stuckey TD, Rogers WJ, Givens DH, Waters D. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000 Aug 24;343(8):522-9. doi: 10.1056/NEJM200008243430801. |
| 9718051 | Background | Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998 Aug 19;280(7):605-13. doi: 10.1001/jama.280.7.605. |
| 12435256 | Background | Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. 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. doi: 10.1001/jama.288.19.2432. |
| 15006823 | Background | Lobo RA. Evaluation of cardiovascular event rates with hormone therapy in healthy, early postmenopausal women: results from 2 large clinical trials. Arch Intern Med. 2004 Mar 8;164(5):482-4. doi: 10.1001/archinte.164.5.482. No abstract available. |
| 17405972 | Background | Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, Ko M, LaCroix AZ, Margolis KL, Stefanick ML. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007 Apr 4;297(13):1465-77. doi: 10.1001/jama.297.13.1465. |
| 11815423 | Background | Campisi R, Nathan L, Pampaloni MH, Schoder H, Sayre JW, Chaudhuri G, Schelbert HR. Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration. Circulation. 2002 Jan 29;105(4):425-30. doi: 10.1161/hc0402.102860. |
| 15197152 | Background | Johnson BD, Shaw LJ, Buchthal SD, Bairey Merz CN, Kim HW, Scott KN, Doyle M, Olson MB, Pepine CJ, den Hollander J, Sharaf B, Rogers WJ, Mankad S, Forder JR, Kelsey SF, Pohost GM; National Institutes of Health-National Heart, Lung, and Blood Institute. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation. 2004 Jun 22;109(24):2993-9. doi: 10.1161/01.CIR.0000130642.79868.B2. Epub 2004 Jun 14. |
| 10727587 | Background | Buchthal SD, den Hollander JA, Merz CN, Rogers WJ, Pepine CJ, Reichek N, Sharaf BL, Reis S, Kelsey SF, Pohost GM. Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med. 2000 Mar 23;342(12):829-35. doi: 10.1056/NEJM200003233421201. |
| 12163423 | Background | Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA, Nour KR, Quyyumi AA. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 2002 Aug 6;106(6):653-8. doi: 10.1161/01.cir.0000025404.78001.d8. |
| 7884081 | Background | Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol. 1995 Mar 15;25(4):807-14. doi: 10.1016/0735-1097(94)00507-M. |
| 3512658 | Background | Kemp HG, Kronmal RA, Vlietstra RE, Frye RL. Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. J Am Coll Cardiol. 1986 Mar;7(3):479-83. doi: 10.1016/s0735-1097(86)80456-9. |
| 7897110 | Background | Lichtlen PR, Bargheer K, Wenzlaff P. Long-term prognosis of patients with anginalike chest pain and normal coronary angiographic findings. J Am Coll Cardiol. 1995 Apr;25(5):1013-8. doi: 10.1016/0735-1097(94)00519-v. |
| 16923752 | Background | Shaw LJ, Merz CN, Pepine CJ, Reis SE, Bittner V, Kip KE, Kelsey SF, Olson M, Johnson BD, Mankad S, Sharaf BL, Rogers WJ, Pohost GM, Sopko G; Women's Ischemia Syndrome Evaluation (WISE) Investigators. The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation. Circulation. 2006 Aug 29;114(9):894-904. doi: 10.1161/CIRCULATIONAHA.105.609990. Epub 2006 Aug 21. |
| 16720691 | Background | Johnson BD, Shaw LJ, Pepine CJ, Reis SE, Kelsey SF, Sopko G, Rogers WJ, Mankad S, Sharaf BL, Bittner V, Bairey Merz CN. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J. 2006 Jun;27(12):1408-15. doi: 10.1093/eurheartj/ehl040. Epub 2006 May 23. |
| 14970106 | Background | von Mering GO, Arant CB, Wessel TR, McGorray SP, Bairey Merz CN, Sharaf BL, Smith KM, Olson MB, Johnson BD, Sopko G, Handberg E, Pepine CJ, Kerensky RA; National Heart, Lung, and Blood Institute. Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation. 2004 Feb 17;109(6):722-5. doi: 10.1161/01.CIR.0000115525.92645.16. |
| 10513787 | Background | Lanza GA, Colonna G, Pasceri V, Maseri A. Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol. 1999 Oct 1;84(7):854-6, A8. doi: 10.1016/s0002-9149(99)00450-6. |
| 9626172 | Background | Lerman A, Burnett JC Jr, Higano ST, McKinley LJ, Holmes DR Jr. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation. 1998 Jun 2;97(21):2123-8. doi: 10.1161/01.cir.97.21.2123. |
| 8159194 | Background | Cannon RO 3rd, Quyyumi AA, Mincemoyer R, Stine AM, Gracely RH, Smith WB, Geraci MF, Black BC, Uhde TW, Waclawiw MA, et al. Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med. 1994 May 19;330(20):1411-7. doi: 10.1056/NEJM199405193302003. |
| 11079667 | Background | Eriksson BE, Tyni-Lenne R, Svedenhag J, Hallin R, Jensen-Urstad K, Jensen-Urstad M, Bergman K, Selven C. Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X. J Am Coll Cardiol. 2000 Nov 1;36(5):1619-25. doi: 10.1016/s0735-1097(00)00931-1. |
| 12117397 | Result | Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. 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. doi: 10.1001/jama.288.3.321. |
| 20569710 | Derived | Merz CN, Olson MB, McClure C, Yang YC, Symons J, Sopko G, Kelsey SF, Handberg E, Johnson BD, Cooper-DeHoff RM, Sharaf B, Rogers WJ, Pepine CJ. A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE). Am Heart J. 2010 Jun;159(6):987.e1-7. doi: 10.1016/j.ahj.2010.03.024. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Education | Number | participants |
|
| Current HT use prior to entry | Number | participants |
|
| History of Hypertension | Number | participants |
|
| History of Diabetes | Number | participants |
|
| History of Dyslipidemia | Number | participants |
|
| Current Smoking | Number | participants |
|
| Total Cholesterol | Mean | Standard Deviation | mg/dl |
|
| HDL-Cholesterol | Mean | Standard Deviation | mg/dl |
|
| LDL-Cholesterol | Mean | Standard Deviation | mg/dl |
|
| Triglycerides | Mean | Standard Deviation | mg/dl |
|
| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Pulse | Mean | Standard Deviation | beats per minute |
|
| Fasting Blood Sugar | Mean | Standard Deviation | mg/dl |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Waist circumference | Mean | Standard Deviation | cm. |
|
Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE).
| OG001 | Placebo | 1 mg placebo. |
|
|
|
| Secondary | Physical Functional Disability - Functional Capacity (METs) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on. | Exercise stress testing at baseline by treatment | Posted | Mean | Standard Deviation | metabolism equivalents | Baseline |
|
|
|
|
| Primary | Endothelial Dysfunction (FMD) | Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of endothelial dysfunction. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100]. | Brachial artery reactivity testing at baseline by treatment | Posted | Mean | Standard Deviation | percentage of pre-stimulus diameter | Baseline |
|
|
|
|
| Secondary | Quality of Life - Menopause Symptoms | Quality of life assessed by menopausal symptoms and psychological questionnaires | Menopause Symptoms at baseline by treatment | Posted | Number | percent of participants | Baseline |
|
|
|
| Primary | Endothelial Dysfunction (FMD) | Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100]. | Brachial artery reactivity testing at study exit by treatment | Posted | Mean | Standard Deviation | percentage of pre-stimulus diameter | 12 weeks |
|
|
|
|
| Secondary | Quality of Life - Menopause Symptoms | Quality of life assessed by menopausal symptoms and psychological questionnaires | Menopause Symptoms at exit by treatment | Posted | Number | percent of participants | 12 weeks |
|
|
|
| Secondary | Quality of Life - Health Survey | Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | SF-36 scale at baseline by treatment | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Quality of Life - Health Survey | Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | SF-36 scale at exit by treatment | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
| Primary | Inducible Myocardial Ischemia | Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (∆) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia. | Among the 35 women, 28 baseline and 26 exit MRS results were technically adequate for spectral analyses with rest, handgrip exercise, and recovery spectra. A total of 24 women (13 drug, 11 placebo) had both baseline and exit P31's. | Posted | Mean | Standard Deviation | percent change in PCR/ATP ratio | 12 weeks |
|
|
|
|
| Secondary | Physical Functional Disability - Functional Capacity (METs) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on. | Exercise stress testing at exit (12 weeks) by treatment | Posted | Mean | Standard Deviation | metabolism equivalents | Exit at 12 weeks |
|
|
|
|
| Secondary | Physical Functional Disability - Functional Capacity (Metabolism Equivalents) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. | Exercise stress testing at baseline by treatment | Posted | Mean | Standard Deviation | metabolism equivalents | Baseline |
|
|
|
|
| Secondary | Physical Functional Disability - Functional Capacity (Metabolism Equivalents) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. | Exercise stress testing at exit (12 weeks) by treatment | Posted | Mean | Standard Deviation | metabolism equivalents | Exit (12 weeks) |
|
|
|
|
| Secondary | Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point). | Exercise stress testing at baseline by treatment | Posted | Mean | Standard Deviation | mm | Baseline |
|
|
|
|
| Secondary | Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression) | Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point). | Exercise stress testing at exit (12 weeks) by treatment | Posted | Mean | Standard Deviation | mm | Exit (12 weeks) |
|
|
|
|
| 2 |
| 18 |
| 0 |
| 18 |
| EG001 | Placebo | 1 mg placebo. | 0 | 19 | 0 | 19 |
|
| Hospitalizaton for biliary colic | Hepatobiliary disorders | Non-systematic Assessment | Hospitalizaton for biliary colic |
|
Not provided
Not provided
| Change in sexual desire |
|
| Vaginal dryness |
|
| Avoiding intimacy |
|
| Change in sexual desire |
|
| Vaginal dryness |
|
| Avoiding intimacy |
|
| Role-emotional |
|
| Bodily pain |
|
| General health |
|
| Mental health |
|
| Vitality |
|
| Social functioning |
|
| Role-emotional |
|
| Bodily pain |
|
| General health |
|
| Mental health |
|
| Vitality |
|
| Social functioning |
|