Postmenopausal Estrogen/Progestin Interventions (PEPI)

NCT00000466 | Completed Phase 3

• 2 other identifiers: 55U01HL040232
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Bone Diseases; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Heart Diseases; Hypercholesterolemia; Hypertension; Myocardial Ischemia; Osteoporosis; Thrombosis; Postmenopause

Interventions

estrogens, conjugated DRUG

medroxyprogesterone DRUG

progesterone DRUG

estrogen replacement therapy DRUG

Eligibility Criteria

• Age: 45 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

Postmenopausal women, ages 45 to 64. One third of the subjects had had a hysterectomy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• National Institute on Aging (NIA): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Related Publications (36)

• Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA. 1996 Nov 6;276(17):1389-96.

  PMID: 8892713 BACKGROUND

• Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1995 Jan 18;273(3):199-208.

  PMID: 7807658 BACKGROUND

• Healy B. PEPI in perspective. Good answers spawn pressing questions. JAMA. 1995 Jan 18;273(3):240-1. doi: 10.1001/jama.273.3.240. No abstract available.

  PMID: 7807665 BACKGROUND

• National Heart , Lung and Blood Institute. Hormone replacement therapy and heart disease: The PEPI trial. DHHS. NIH Publication No.95-3277. August 1995

  BACKGROUND

• Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1996 Feb 7;275(5):370-5. doi: 10.1001/jama.1996.03530290040035.

  PMID: 8569016 BACKGROUND

• Bush TL, Espeland MA, Mebane-Sims I. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. Introduction. Control Clin Trials. 1995 Aug;16(4 Suppl):1S-2S. doi: 10.1016/0197-2456(94)00119-n. No abstract available.

  PMID: 7587216 BACKGROUND

• Espeland MA, Bush TL, Mebane-Sims I, Stefanick ML, Johnson S, Sherwin R, Waclawiw M. Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions. Control Clin Trials. 1995 Aug;16(4 Suppl):3S-19S. doi: 10.1016/0197-2456(95)91154-3.

  PMID: 7587218 BACKGROUND

• Johnson S, Mebane-Sims I, Hogan PE, Stoy DB. Recruitment of postmenopausal women in the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions. Control Clin Trials. 1995 Aug;16(4 Suppl):20S-35S. doi: 10.1016/0197-2456(94)00111-f. No abstract available.

  PMID: 7587217 BACKGROUND

• Wood PD, Kessler G, Lippel K, Stefanick ML, Wasilauskas CH, Wells HB. Physical and laboratory measurements in the PEPI Trial Postmenopausal Estrogen/Progestin Interventions. Control Clin Trials. 1995 Aug;16(4 Suppl):36S-53S. doi: 10.1016/0197-2456(95)96882-c. No abstract available.

  PMID: 7587219 BACKGROUND

• Miller VT, Byington RL, Espeland MA, Langer R, Marcus R, Shumaker S, Stern MP. Baseline characteristics of the PEPI participants. Postmenopausal Estrogen/Progestin Interventions. Control Clin Trials. 1995 Aug;16(4 Suppl):54S-65S. doi: 10.1016/0197-2456(94)00113-h. No abstract available.

  PMID: 7587220 BACKGROUND

• Stefanick ML, Legault C, Tracy RP, Howard G, Kessler CM, Lucas DL, Bush TL. Distribution and correlates of plasma fibrinogen in middle-aged women. Initial findings of the Postmenopausal Estrogen/Progestin Interventions (PEPI) study. Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2085-93. doi: 10.1161/01.atv.15.12.2085.

  PMID: 7489228 BACKGROUND

• Marcus R, Greendale G, Blunt BA, Bush TL, Sherman S, Sherwin R, Wahner H, Wells B. Correlates of bone mineral density in the postmenopausal estrogen/progestin interventions trial. J Bone Miner Res. 1994 Sep;9(9):1467-76. doi: 10.1002/jbmr.5650090920.

  PMID: 7817832 BACKGROUND

• Greendale GA, Bodin-Dunn L, Ingles S, Haile R, Barrett-Connor E. Leisure, home, and occupational physical activity and cardiovascular risk factors in postmenopausal women. The Postmenopausal Estrogens/Progestins Intervention (PEPI) Study. Arch Intern Med. 1996 Feb 26;156(4):418-24.

  PMID: 8607727 BACKGROUND

• Barrett-Connor E, Schrott HG, Greendale G, Kritz-Silverstein D, Espeland MA, Stern MP, Bush T, Perlman JA. Factors associated with glucose and insulin levels in healthy postmenopausal women. Diabetes Care. 1996 Apr;19(4):333-40. doi: 10.2337/diacare.19.4.333.

  PMID: 8729156 BACKGROUND

• Greendale GA, James MK, Espeland MA, Barrett-Connor E. Can we measure prior postmenopausal estrogen/progestin use? The Postmenopausal Estrogen/Progestin Interventions Trial. The PEPI Investigators. Am J Epidemiol. 1997 Nov 1;146(9):763-70. doi: 10.1093/oxfordjournals.aje.a009352.

  PMID: 9366624 BACKGROUND

• Langer RD, Pierce JJ, O'Hanlan KA, Johnson SR, Espeland MA, Trabal JF, Barnabei VM, Merino MJ, Scully RE. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Interventions Trial. N Engl J Med. 1997 Dec 18;337(25):1792-8. doi: 10.1056/NEJM199712183372502.

  PMID: 9400035 BACKGROUND

• Barrett-Connor E, Slone S, Greendale G, Kritz-Silverstein D, Espeland M, Johnson SR, Waclawiw M, Fineberg SE. The Postmenopausal Estrogen/Progestin Interventions Study: primary outcomes in adherent women. Maturitas. 1997 Jul;27(3):261-74. doi: 10.1016/s0378-5122(97)00041-8.

  PMID: 9288699 BACKGROUND

• Smith EM, Johnson SR, Figuerres EJ, Mendoza M, Fedderson D, Haugen TH, Turek LP. The frequency of human papillomavirus detection in postmenopausal women on hormone replacement therapy. Gynecol Oncol. 1997 Jun;65(3):441-6. doi: 10.1006/gyno.1997.4703.

  PMID: 9190973 BACKGROUND

• Espeland MA, Stefanick ML, Kritz-Silverstein D, Fineberg SE, Waclawiw MA, James MK, Greendale GA. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators. J Clin Endocrinol Metab. 1997 May;82(5):1549-56. doi: 10.1210/jcem.82.5.3925.

  PMID: 9141548 BACKGROUND

• Espeland MA, Marcovina SM, Miller V, Wood PD, Wasilauskas C, Sherwin R, Schrott H, Bush TL. Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Circulation. 1998 Mar 17;97(10):979-86. doi: 10.1161/01.cir.97.10.979.

  PMID: 9529266 BACKGROUND

• Legault C, Espeland MA, Wasilauskas CH, Bush TL, Trabal J, Judd HL, Johnson SR, Greendale GA. Agreement in assessing endometrial pathology: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. J Womens Health. 1998 May;7(4):435-42. doi: 10.1089/jwh.1998.7.435.

  PMID: 9611701 BACKGROUND

• Greendale GA, Reboussin BA, Sie A, Singh HR, Olson LK, Gatewood O, Bassett LW, Wasilauskas C, Bush T, Barrett-Connor E. Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Postmenopausal Estrogen/Progestin Interventions (PEPI) Investigators. Ann Intern Med. 1999 Feb 16;130(4 Pt 1):262-9. doi: 10.7326/0003-4819-130-4_part_1-199902160-00003.

  PMID: 10068383 BACKGROUND

• Espeland MA, Hogan PE, Fineberg SE, Howard G, Schrott H, Waclawiw MA, Bush TL. Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Diabetes Care. 1998 Oct;21(10):1589-95. doi: 10.2337/diacare.21.10.1589.

  PMID: 9773716 BACKGROUND

• Hall SL, Greendale GA. The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int. 1998 Sep;63(3):183-9. doi: 10.1007/s002239900512.

  PMID: 9701620 BACKGROUND

• Greendale GA, Reboussin BA, Hogan P, Barnabei VM, Shumaker S, Johnson S, Barrett-Connor E. Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial. Obstet Gynecol. 1998 Dec;92(6):982-8. doi: 10.1016/s0029-7844(98)00305-6.

  PMID: 9840563 BACKGROUND

• Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, Sakkinen PA, Tracy RP. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation. 1999 Aug 17;100(7):717-22. doi: 10.1161/01.cir.100.7.717.

  PMID: 10449693 BACKGROUND

• Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C, Kelaghan J. The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Bone Miner Res. 1999 Sep;14(9):1583-95. doi: 10.1359/jbmr.1999.14.9.1583.

  PMID: 10469288 BACKGROUND

• Whiteman MK, Cui Y, Flaws JA, Espeland M, Bush TL. Low fibrinogen level: A predisposing factor for venous thromboembolic events with hormone replacement therapy. Am J Hematol. 1999 Aug;61(4):271-3. doi: 10.1002/(sici)1096-8652(199908)61:43.0.co;2-0.

  PMID: 10440916 BACKGROUND

• Barnabei VM, Phillips TM, Hsia J. Plasma homocysteine in women taking hormone replacement therapy: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. J Womens Health Gend Based Med. 1999 Nov;8(9):1167-72. doi: 10.1089/jwh.1.1999.8.1167.

  PMID: 10595329 BACKGROUND

• Legault C, Stefanick ML, Miller VT, Marcovina SM, Schrott HG. Effect of hormone replacement therapy on the validity of the Friedewald equation in postmenopausal women: the postmenopausal estrogen/progestins interventions (PEPI) trial. J Clin Epidemiol. 1999 Dec;52(12):1187-95. doi: 10.1016/s0895-4356(99)00107-9.

  PMID: 10580781 BACKGROUND

• Greendale GA, Espeland M, Slone S, Marcus R, Barrett-Connor E; PEPI Safety Follow-Up Study (PSFS) Investigators. 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. doi: 10.1001/archinte.162.6.665.

  PMID: 11911720 BACKGROUND

• Simon JA, Symons JP. Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial. Obstet Gynecol. 2003 May;101(5 Pt 1):1020; author reply 1020-1. doi: 10.1016/s0029-7844(03)00113-3. No abstract available.

  PMID: 12738166 BACKGROUND

• Lindenfeld EA, Langer RD. Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial. Obstet Gynecol. 2002 Nov;100(5 Pt 1):853-63. doi: 10.1016/s0029-7844(02)02245-7.

  PMID: 12423841 BACKGROUND

• Hu P, Greendale GA, Palla SL, Reboussin BA, Herrington DM, Barrett-Connor E, Reuben DB. The effects of hormone therapy on the markers of inflammation and endothelial function and plasma matrix metalloproteinase-9 level in postmenopausal women: the postmenopausal estrogen progestin intervention (PEPI) trial. Atherosclerosis. 2006 Apr;185(2):347-52. doi: 10.1016/j.atherosclerosis.2005.06.011. Epub 2005 Jul 14.

  PMID: 16023653 BACKGROUND

• Abrams FR. The Postmenopausal Estrogen/Progestin Interventions Trial. JAMA. 1995 Dec 6;274(21):1675; author reply 1676. doi: 10.1001/jama.274.21.1675b. No abstract available.

  PMID: 7474268 BACKGROUND

• Garg A. The Postmenopausal Estrogen/Progestin Interventions Trial. JAMA. 1995 Dec 6;274(21):1675-6. doi: 10.1001/jama.1995.03530210029022. No abstract available.

  PMID: 7474269 BACKGROUND

MeSH Terms

Conditions

Bone Diseases; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Heart Diseases; Hypercholesterolemia; Hypertension; Myocardial Ischemia; Osteoporosis; Thrombosis

Interventions

Estrogens, Conjugated (USP); Medroxyprogesterone; Progesterone; Estrogen Replacement Therapy

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Bone Diseases, Metabolic; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hydroxyprogesterones; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Progesterone Congeners; Hormone Replacement Therapy; Drug Therapy; Therapeutics

Study Officials

• Mark Espeland

  Bowman Gray School of Medicine

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 27, 1999
• First Posted: October 28, 1999
• Study Start: September 1, 1987
• Study Completion: October 1, 2000
• Last Updated: May 13, 2016

Record last verified: 2005-07