Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000466
Status:
COMPLETED
Last Update Posted:
2016-05-13
First Post:
1999-10-27
Brief Title:
Postmenopausal EstrogenProgestin Interventions PEPI
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2005-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To assess the effects of various postmenopausal estrogen replacement therapies on selected cardiovascular risk factors including high density lipoprotein cholesterol systolic blood pressure fibrinogen and insulin and on osteoporosis risk factors Conducted in collaboration with the National Institute of Child Health and Human Development the National Institute of Arthritis and Musculoskeletal and Skin Diseases The National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Aging The extended follow-up is for 3 years focusing on endometrium and breast evaluation
Detailed Description:
BACKGROUND
The life expectancy of American women is 78 years More than one-third of those years are postmenopausal during which time the risk of coronary heart disease is increased The current United States estimate of more than 40 million women over the age of 50 indicates a large segment of the population at increased risk for coronary heart disease Heart disease accounts for a third of all deaths in 50-69 year old women In 1978 for example approximately 66000 of the 210000 deaths in women 50-69 were attributed to heart disease
Premenopausal women have a lower rate of ischemic heart disease compared to men of similar age Surgically induced or natural early menopause increases the risk of ischemic heart disease These facts have focused interest on estrogens as possible mediators of the beneficial effects and pointed to the need for further study of their relationship to atherosclerosis risk factors
Estimates from the Lipid Research Clinics Program indicate estrogen use in approximately one third of postmenopausal women Analysis of Lipid Research Clinics data confirmed that administration of estrogens results in lower plasma low density lipoprotein levels and elevated plasma high density lipoprotein levels Thus the ratio of high density lipoproteinlow density lipoprotein levels is substantially increased Given the inverse relationship between high density lipoprotein levels and coronary heart disease risk this effect of estrogens on the plasma lipoproteins could be expected to further reduce coronary heart disease risk in women
Although the bulk of currently available evidence suggests benefit some controversy concerning the effects of postmenopausal estrogens on morbidity and mortality from coronary heart disease persists Analysis of the Lipid Research Clinics Follow-up Study population indicated a potentially profound beneficial effect of postmenopausal estrogen use Mortality from all causes decreased considerably in postmenopausal estrogen users and the effect was most pronounced in hysterectomized and oophorectomized women Similar results have been observed for cardiovascular deaths These benefits appeared to be mediated by the higher high density lipoprotein levels associated with postmenopausal estrogen use Framingham data are the primary sources reporting possible detrimental effects of postmenopausal estrogen use on cardiovascular morbidity mortality from all cause and cardiovascular disease was not reported to vary by use
NHLBI convened a Trans-NIH Estrogen Working Group to make recommendations to NHLBI on the feasibility of undertaking a clinical trial of the effects of postmenopausal estrogen use on cardiovascular disease mortality The Working Group identified a number of important research questions which needed to be answered to elucidate the effects of postmenopausal estrogen use on risk factors for cardiovascular disease and osteoporosis This initiative was the result of the Working Groups deliberations and recommendations
DESIGN NARRATIVE
There were seven clinical centers and a coordinating center in this randomized double-blind clinical trial The women were allocated to one of five treatment arms placebo conjugated equine estrogen CEE 0625 milligrams per day conjugated equine estrogen 0625 milligrams per day plus cyclic medroxyprogesterone acetate MPA 10 milligrams per day for 12 days per month CEE 0625 milligrams per day plus consecutive MPA 25 milligrams per day CEE 0625 milligrams per day plus cyclic micronized progesterone MP 200 milligrams per day for 12 days a month The four primary endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease and included high density lipoprotein cholesterol HDL-C systolic blood pressure serum insulin and fibrinogen Recruitment began in October 1989 and ended in February 1991 Baseline data collected included blood pressure resting heart rate weight waisthip ratios and endometrial biopsy Laboratory evaluations included lipid panel high density lipoprotein cholesterol insulin and glucose bone density fibrinogen and in three clinics additional hemostasis factors renin substrate plasma renin activity aldosterone and oral post-heparin lipase activity All women underwent an endometrial aspiration biopsy at baseline and annually thereafter Additional biopsy specimens were obtained if there was noncyclic endometrial bleeding All women also had baseline and annual mammograms Other data were collected on quality of life exercise diet alcohol use and smoking Participants were followed at three six and twelve months post-randomization and at six month intervals thereafter for three years Post-trial analyses of existing data sets were funded for three years by the cooperative agreement mechanism beginning August 1 1994 A three-year safety follow-up funded through the contract mechanism began in 1994 It included three annual visits at which endometrial biopsies mammograms and some limited health information were obtained
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
The life expectancy of American women is 78 years More than one-third of those years are postmenopausal during which time the risk of coronary heart disease is increased The current United States estimate of more than 40 million women over the age of 50 indicates a large segment of the population at increased risk for coronary heart disease Heart disease accounts for a third of all deaths in 50-69 year old women In 1978 for example approximately 66000 of the 210000 deaths in women 50-69 were attributed to heart disease
Premenopausal women have a lower rate of ischemic heart disease compared to men of similar age Surgically induced or natural early menopause increases the risk of ischemic heart disease These facts have focused interest on estrogens as possible mediators of the beneficial effects and pointed to the need for further study of their relationship to atherosclerosis risk factors
Estimates from the Lipid Research Clinics Program indicate estrogen use in approximately one third of postmenopausal women Analysis of Lipid Research Clinics data confirmed that administration of estrogens results in lower plasma low density lipoprotein levels and elevated plasma high density lipoprotein levels Thus the ratio of high density lipoproteinlow density lipoprotein levels is substantially increased Given the inverse relationship between high density lipoprotein levels and coronary heart disease risk this effect of estrogens on the plasma lipoproteins could be expected to further reduce coronary heart disease risk in women
Although the bulk of currently available evidence suggests benefit some controversy concerning the effects of postmenopausal estrogens on morbidity and mortality from coronary heart disease persists Analysis of the Lipid Research Clinics Follow-up Study population indicated a potentially profound beneficial effect of postmenopausal estrogen use Mortality from all causes decreased considerably in postmenopausal estrogen users and the effect was most pronounced in hysterectomized and oophorectomized women Similar results have been observed for cardiovascular deaths These benefits appeared to be mediated by the higher high density lipoprotein levels associated with postmenopausal estrogen use Framingham data are the primary sources reporting possible detrimental effects of postmenopausal estrogen use on cardiovascular morbidity mortality from all cause and cardiovascular disease was not reported to vary by use
NHLBI convened a Trans-NIH Estrogen Working Group to make recommendations to NHLBI on the feasibility of undertaking a clinical trial of the effects of postmenopausal estrogen use on cardiovascular disease mortality The Working Group identified a number of important research questions which needed to be answered to elucidate the effects of postmenopausal estrogen use on risk factors for cardiovascular disease and osteoporosis This initiative was the result of the Working Groups deliberations and recommendations
DESIGN NARRATIVE
There were seven clinical centers and a coordinating center in this randomized double-blind clinical trial The women were allocated to one of five treatment arms placebo conjugated equine estrogen CEE 0625 milligrams per day conjugated equine estrogen 0625 milligrams per day plus cyclic medroxyprogesterone acetate MPA 10 milligrams per day for 12 days per month CEE 0625 milligrams per day plus consecutive MPA 25 milligrams per day CEE 0625 milligrams per day plus cyclic micronized progesterone MP 200 milligrams per day for 12 days a month The four primary endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease and included high density lipoprotein cholesterol HDL-C systolic blood pressure serum insulin and fibrinogen Recruitment began in October 1989 and ended in February 1991 Baseline data collected included blood pressure resting heart rate weight waisthip ratios and endometrial biopsy Laboratory evaluations included lipid panel high density lipoprotein cholesterol insulin and glucose bone density fibrinogen and in three clinics additional hemostasis factors renin substrate plasma renin activity aldosterone and oral post-heparin lipase activity All women underwent an endometrial aspiration biopsy at baseline and annually thereafter Additional biopsy specimens were obtained if there was noncyclic endometrial bleeding All women also had baseline and annual mammograms Other data were collected on quality of life exercise diet alcohol use and smoking Participants were followed at three six and twelve months post-randomization and at six month intervals thereafter for three years Post-trial analyses of existing data sets were funded for three years by the cooperative agreement mechanism beginning August 1 1994 A three-year safety follow-up funded through the contract mechanism began in 1994 It included three annual visits at which endometrial biopsies mammograms and some limited health information were obtained
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U01HL040232 | NIH | None | httpsreporternihgovquickSearchU01HL040232 |