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Tables for:
Mortality Associated with Hormone Replacement Therapy in Younger and Older Women

[J Gen Intern Med 19(7):791-804, 2004. © 2004 Blackwell Publishing]


Table 1. Characteristics of Included Studies


Study (Reference #)Design, DurationInclusion and Exclusion CriteriaParticipants (n) in HRT PlaceboDropout Rate in HRT Placebo, %Mean Age in HRT PlaceboActive Comparison InterventionOutcomesComments
Angerer, 200020Double blind, 1 yearInclusion: Postmenopausal women aged 40 to 70 years with more than 1 mm intima media thickness in at least one segment of the carotid arteries2152859.0Estradiol 1 mg/day plus gestodone 0.25 mg/day vs placeboCarotid artery dispensability 
Exclusion: Myocardial infarction within 6 months, angina or any contraindication to hormone use662959.5
Arrenbrecht, 200221Double blind, 2 yearsInclusion: Healthy postmenopausal women with hysterectomy1082450.5sTransdermal estradiol 50 or 100 mcg/day vs placeboBone mineral density, bone turnover 
Exclusion: Medication that affects bone metabolism, smoking, or osteoporosis53combinedcombined
Binder, 200122Double blind, 9 monthsInclusion: Postmenopausal women over the age of 75 years412282.0CEE 0.625 mg/day plus MPA 5 mg/day vs placeboLipid profiles 
Exclusion: Recent hormone use, breast, or gynecological malignancy, current treatment for thromboembolism, cardiovascular disease, or unstable thyroid disease229.183.0
Cherry, 200223Double blind, 2 yearsInclusion: Women aged 50 to 69 with recent myocardial infarction51357.362.3Estradiol valerate, 2 mg/day vs placeboReinfarction, cardiac death, all-cause mortality 
Exclusion: Recent use of hormones or vaginal bleeding, gynecological malignancy, liver or renal disease, history of venous thromboembolism50436.562.9
Gallagher, 200124Double blind, 3 yearsInclusion: Elderly postmenopausal women12116.572.0CEE 0.625 mg/day plus MPA 2.5 mg/day vs placeboBone mineral densityCalcitriol with and without hormones were also studied
Exclusion: Severe chronic illness or medications that affect bone metabolism1238.971.0
Giske, 200225Double blind, 2 yearsInclusion: Healthy postmenopausal women with hysterectomy12311.449.1Estradiol 0.5 mg, 1 mg or 2 mg/day vs placeboBone mineral density 
Exclusion: Medications that affect bone metabolism4330.249.6
Guidozzi, 199926Open label, 4 yearsInclusion: Postmenopausal women with ovarian cancer62451CEE 0.625 mg/day plus MPA 2.5 mg/day vs placeboDisease-free survival and overall survival 
Exclusion: Previous hormone replacement or ovarian malignancy of low malignant potential68combinedcombined
Hall, 199427Open label, 2 yearsInclusion: Postmenopausal women with rheumatoid arthritis1003755.8Transdermal estradiol 50 mcg/day vs placeboBone mineral density 
Exclusion: Contraindications to hormone replacement, breast or gynecological malignancy, or thromboembolism1001656.1
Hall, 199828Single blind, 1 yearInclusion: Postmenopausal women with coronary heart disease402058.6Transdermal estradiol 50 mcg/day and MPA 5 mg/day vs placeboAngina 
Exclusion: None listed203061.3
Herrington, 200029Double blind, 3.2 yearsInclusion: Postmenopausal women with coronary disease2042065.9CEE 0.625 mg/ day plus MPA 2.5 mg/day vs placeboAngiographic changes and lipid profiles 
Exclusion: Breast or gynecological malignancy, planned coronary artery surgery, thromboembolism, symptomatic gallstones, renal or liver dysfunction, uncontrolled diabetes, hypertension, or hypertryiglyceridemia105combined65.6
Hodis, 200130Double blind, 2 yearsInclusion: Postmenopausal women at least 45 years old with elevated cholesterol11125.260.9Estradiol 1 mg/day vs placeboChange in intimal thickness 
Exclusion: Breast or gynecological malignancy, recent or long- term hormone use, severe hot flushes, severe hypertension, or severe illness11125.262.1
Hulley, 200231Double blind, 4.1 yearsInclusion: Postmenopausal women under the age of 80 years with coronary heart disease138011.567CEE 0.625 mg/day plus MPA 2.5 mg/day vs placeboCoronary heart disease events or deaths 
Exclusion: Thromboembolism, breast or gynecological malignancy, recent hormone use and serious disease138311.267
Komulainen, 199932Open label, 5 yearsInclusion: Early postmenopausal women1155.252.9Estradiol 2 mg/day plus cyproterone acetate 1 mg/day vs placeboBone mineral densityVitamin D with or without hormones was also studied
Exclusion: Breast or gynecological malignancy, thromboembolism, or medication-resistant hypertension1155.252.6
Kyllonen, 199833Double blind, 2 yearsInclusion: Healthy early postmenopausal women age 49 to 55 years522252.6Estradiol 2 mg/day plus MPA 10 mg/day for 10 days vs placeboLumbar spine mobility and low-back symptoms 
Exclusion: None listed26combinedcombined
Lindsay, 197634Double blind, 5 yearsInclusion: Postmenopausal women with oophorectomy636.344 to 50Mestranol 28.4 mg/day vs placeboBone mineral content 
Exclusion: Prior estrogen use575.3 
MacDonald, 199435Double blind, 1 yearInclusion: Postmenopausal women with rheumatoid arthritis4022.553Transdermal estradiol 50 mcg/day with or without norethisterone 1 mg/day for 10 days vs placeboBone mineral density and rheumatoid arthritis disease activity 
Exclusion: Significant menopausal symptoms2240.955
Mijatovic, 199836Double blind, 2 yearsInclusion: Healthy postmenopausal women with hysterectomy13555.7CEE 0.625 mg/day vs placeboHomocysteine levelsRaloxifine also studied
Exclusion: Hepatic, renal, endocrinologic, gastrointestinal, or cardiovascular disease or breast or gynecological malignancies136.754.9
Mosekilde, 200237Open label, 5 yearsInclusion: Postmenopausal women5029.649.5Estradiol 2 mg/day plus norethisterone 1 mg/day for 10 days vs placeboBone mineral density 
Exclusion: Metabolic bone disease, recent estrogen or corticosteroid use, steroids, malignancy, chronic disease, or alcohol abuse5049.150.0
Mulnard, 200038Double blind, 1 yearInclusion: Postmenopausal women with hysterectomies and mild to moderate Alzheimer's disease8119.875.6CEE 0.615 or 1.25 mg/day vs placeboGlobal measures of cognition, mood, motor function, and activities of daily living 
Exclusion: Recent myocardial infarction, thromboembolism, hypercoagulable state, hyperlipidemia, or use of antipsychotics, anticonvulsants, anticoagulants, beta-blockers, narcotics, methyldopa, clonidine, or cognitive-enhancing or anti-Parkinson medications3917.974.1
Nachtigall, 197939Double blind, 10 yearsInclusion: Postmenopausal women hospitalized for chronic diseases843.655.3CEE 2.5 mg/day plus MPA 2.5 mg/day vs placeboClinical outcomes such as medical illness or death 
Exclusion: Hypertension, hysterectomy, coronary heart disease, or previous hormone use848.354.9
Os, 200040Open label, 1 yearInclusion: Postmenopausal women with documented coronary artery disease60 10.263Transdermal estradiol 50 mcg/day plus MPA 5 mg/day for 14 days vs placeboLipid profiles 
Exclusion: Previous hormone use, previous myocardial infarction or coronary artery bypass surgery, thromboembolism, breast or gynecological malignancy, alcoholism, or psychiatric disorder5815.366
PEPI trial Writing Group, 199541Double blind, 3 yearsInclusion: Healthy postmenopausal women7011656.1CEE 0.625 mg/day plus MPA 2.5 mg/ day or MPA 10 mg/day for 10 days or micronized progesterone 200 mg/day for 12 days vs placeboLipid profiles, fibrinogen, blood pressure, and insulin 
Exclusion: Severe menopausal symptoms, unstable thyroid disease, serious illness, or contraindications to hormone use17432.8combined
Perez-Jaraiz, 199642Open-label, 1 yearInclusion: Early postmenopausal with rapid bone loss26 5.848Transdermal estradiol transdermal 50 mcg/day plus MPA 10 mg for 12 days vs calcium supplementationBone mineral densityCalcitonin also studied
Exclusion: None listed525.850
Ravn, 199943Open label, 4 yearsInclusion: Healthy early postmenopausal women age 49 to 55 years11025.255CEE 0.625 mg/day plus MPA 5 mg/day or estradiol 1 to 2 mg/day plus noresisterone 1 mg/day on days 13 to 22 vs placeboBone mineral density and bone turnoverAlendronate also studied
Exclusion: Hormone use10926.755
Raz, 199344Double blind, 8 monthsInclusion: Postmenopausal women with 3 or more confirmed urinary tract infections during previous year502864.7Intravaginal estradiol cream 0.5 mg/day vs placebo vaginal creamIncidence of urinary tract infections, and vaginal pH and cultures 
Exclusion: Thromboembolism disorders, liver disease, estrogen-dependent tumors, anatomical lesions in urogenital area, indwelling urinary catheter, long-term use of antimicrobial agents, or oral estrogen therapy4320.965.4
Recker, 199945Double blind, 3.5 yearsInclusion: Healthy women over the age of 65 years with low bone mass6428.173.2CEE 0.3 mg/day with MPA 2.5 mg/day vs placeboBone mineral density, serum total alkaline phosphatase and osteocalcin levels, and urinary creatinine and hydoxyproline 
Exclusion: Previous hip fracture, use of estrogen, calcitonin, or corticosteroids in the past 6 months, any use of bisphosphonates or fluoride, endometrial thickness more than 6 mm, breast cancer, and smoking6418.874.0
Viscoli, 200146Double Blind, 2.8 yearsInclusion: Postmenopausal women with recent stroke, cerebrovascular disease33734.472Estradiol 1 mg/day vs placeboDeath and stroke incidence 
Exclusion: Coexisting condition that limits life expectancy, breast or gynecological malignancy, thromboembolism while on estrogen therapy, or neurological or psychiatric disease32724.271
Waters, 200247Double blind, 2.8 yearsInclusion: Postmenopausal women with coronary stenosis documented on angiogram10821.365CEE 0.625 mg/day with medroxyproge sterone acetate 2.5 mg/day vs placeboAnnualized mean change in minimum lumen diameter on angiogram, myocardial infarction, deathAntioxidant vitamins also studied
Exclusion: Hormone use in previous 3 months, concurrent use of vitamin C or E, gynecological or breast cancer, uncontrolled diabetes or hypertension, myocardial infarction with 1 month, renal insufficiency, gallstones, congestive heart failure, hemorrhagic stroke, thromboembolism, or untreated osteoporosis10336.266
Watts, 200048Double Blind, 2 yearsInclusion: Early postmenopausal women3031051.8CEE 0.3, 0.625 or 1.25 mg/day vs placeboBone mineral density 
Exclusion: Recent hormone use, osteoporosis, smoking, or medications that affect mineral metabolism103combined51.3
Women's Health Initiative Writing Group, 200249Double Blind, 5.2 yearsInclusion: Postmenopausal women aged 50 to 79 years85066.363.2CEE 0.625 mg/day plus MPA 2.5 mg/day vs placeboCoronary heart disease events, breast cancer, and a global index for risks and benefits 
Exclusion: Serious illness, cancer, anemia, alcohol abuse, or dementia81026.163.3

HRT, hormone replacement therapy.


Table 2. Odds Ratio for Total, Cardiovascular, Cancer, and Other Mortality in Younger and Older Women Associated with Hormone Replacement Therapy


  HRT DeathsNControl DeathsNOR (95% CI)
All agesTotal death51814,14750112,5610.98 (0.87 to 1.18)
CV death215 187 1.10 (0.90 to 1.34)
Cancer death184 171 1.03 (0.23 to 1.29)
Other death91 126 0.67 (0.51 to 0.88)*
Mean age, y < 60Total death532,576681,5650.61 (0.39 to 0.95)*
CV death3 3 0.68 (0.22 to 2.15)
Cancer death45 54 0.69 (0.59 to 1.08)
Other death5 12 0.44 (0.17 to 1.13)
Mean age, y > 60Total death46511,57143310,9961.03 (0.90 to 1.18)
CV death212 184 1.11 (0.91 to 1.36)
Cancer death137 123 1.07 (0.84 to 1.37)
Other death86 116 0.68 (0.56 to 0.91)*

* Statistical significance.
OR, odds ratio; CV, cardiovascular; HRT, hormone replacement therapy.