Evidence
The research behind menopausal hormone therapy
Beeler Wellness
Landmark Menopausal Hormone Therapy Studies
Hormone optimization at Beeler Wellness in Evansville, IN is grounded in published, peer-reviewed research. The randomized clinical trials below evaluate estradiol-based menopausal hormone therapy, including bioidentical 17β-estradiol and micronized progesterone, and what they show about cardiovascular outcomes, symptom relief, cognitive health, and safety. We share them so you can read the science for yourself and bring informed questions to your visit.
The six studies in the first section are the ones we consider most relevant to the therapies we offer. The studies that follow add important context, including trials where hormone therapy did not help, which is part of why timing and individual health history matter so much.
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Core Studies
ELITE Trial · New England Journal of Medicine, 2016
Estradiol Started Early After Menopause and Atherosclerosis Progression
The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blind, placebo-controlled trial built to test the “timing hypothesis.” Women received oral 17β-estradiol 1 mg/day; those with a uterus also received micronized progesterone vaginal gel cyclically.
Among women less than six years past menopause, estradiol slowed progression of carotid intima-media thickness compared with placebo. That effect was not seen in women 10 or more years beyond menopause, which is why when therapy begins matters.
Read the study: PubMed | Free full text | NEJM
EPAT Trial · Annals of Internal Medicine, 2001
17β-Estradiol and Prevention of Atherosclerosis Progression
The Estrogen in the Prevention of Atherosclerosis Trial (EPAT) was a randomized, double-blind, placebo-controlled trial of 222 postmenopausal women without established cardiovascular disease. Participants received micronized 17β-estradiol 1 mg/day or placebo for two years.
Overall carotid atherosclerosis progression was slower in the estradiol group. Notably, the intervention was micronized 17β-estradiol specifically, rather than conjugated equine estrogen.
KEEPS · Annals of Internal Medicine, 2014
Transdermal Estradiol and Micronized Progesterone in Recently Menopausal Women
The Kronos Early Estrogen Prevention Study (KEEPS) was a four-year randomized, double-blind, placebo-controlled trial in healthy women within three years of their final menstrual period. One treatment arm used transdermal 17β-estradiol 50 mcg/day plus oral micronized progesterone 200 mg/day for 12 days each month, an entirely bioidentical regimen.
Neither hormone regimen significantly reduced progression of carotid thickness or coronary artery calcium compared with placebo during the treatment period, but both substantially improved menopausal symptoms and provided important randomized safety data in healthy, recently menopausal women.
Read the study: PubMed | ClinicalTrials.gov | DOI
KEEPS Symptom Study · Menopause
Estradiol + Micronized Progesterone for Hot Flashes, Sleep and Menopausal Symptoms
This KEEPS analysis looked at what clients tend to care about most: day-to-day symptoms rather than only cardiovascular biomarkers.
Women receiving transdermal 17β-estradiol plus micronized progesterone experienced significant improvement in menopausal symptoms over the study period compared with placebo, including hot flashes and sleep.
Read the study: Free full text | DOI
REPLENISH Trial · Phase 3 RCT, 2019
Bioidentical Estradiol + Progesterone for Menopausal Hot Flashes
REPLENISH was a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial of roughly 1,800 menopausal women studying combinations of 17β-estradiol and natural progesterone in a single oral capsule.
The higher-dose combinations significantly reduced moderate-to-severe vasomotor symptoms, and the trial also evaluated endometrial safety at the studied doses. The FDA-approved 1 mg estradiol / 100 mg progesterone formulation that came out of this research is Bijuva.
Read the study: PubMed | Journal article | DOI
KEEPS-Cog & ELITE-Cog · PLOS Medicine, 2015 & Neurology, 2016
Estradiol + Micronized Progesterone and Cognitive Health in Early Menopause
KEEPS-Cog was a randomized, placebo-controlled substudy of nearly 700 recently menopausal women; the bioidentical arm received transdermal 17β-estradiol plus oral micronized progesterone. Over about four years, treatment neither significantly improved nor worsened cognition compared with placebo.
ELITE-Cog used the same estradiol regimen as the parent ELITE trial and compared women starting within six years of menopause with women 10 or more years beyond it. It did not show the hypothesized cognitive benefit from early initiation, but it provides rigorous randomized data using estradiol rather than conjugated estrogens in women starting therapy close to menopause.
Read the study: KEEPS-Cog PubMed | KEEPS-Cog full text | ELITE-Cog full text
Context Matters
Additional Studies
KEEPS · JAMA Internal Medicine, 2017
Transdermal Estradiol and Sexual Function After Menopause
This randomized KEEPS analysis looked specifically at sexual function. Women receiving transdermal 17β-estradiol plus micronized progesterone had improvement in certain measures of sexual function compared with placebo.
Read the study: PubMed | Free full text
REPLENISH Analysis · Menopause, 2020
Breast Effects of Estradiol + Micronized Progesterone
A randomized controlled analysis from REPLENISH comparing oral 17β-estradiol plus progesterone with placebo, focused on breast-related effects, a common question for clients considering therapy.
This study was not designed or powered to establish long-term breast cancer risk; it reports breast effects during the trial only.
Read the study: Free full text
REPLENISH Analysis · Menopause, 2019
Metabolic and Cardiovascular Effects of Estradiol + Progesterone
A secondary analysis of the REPLENISH trial examining metabolic and cardiovascular measures in menopausal women with vasomotor symptoms who received the combined oral 17β-estradiol and progesterone capsule.
Read the study: PubMed
DOPS · BMJ, 2012
Hormone Therapy Started Early After Menopause
The Danish Osteoporosis Prevention Study evaluated hormone therapy begun in healthy women relatively soon after menopause. During long-term follow-up, women assigned to hormone therapy had fewer events in the combined endpoint of death, myocardial infarction, or heart failure, without a statistically significant increase in cancer, venous thromboembolism, or stroke reported in the trial.
Read the study: PubMed | Free full text
WEST Trial · New England Journal of Medicine, 2001
Estradiol After Previous Stroke: Why Client Selection Matters
The Women’s Estrogen for Stroke Trial randomized 664 postmenopausal women with a recent ischemic stroke or TIA to oral 17β-estradiol or placebo. It did not show that estradiol prevented recurrent stroke or death. This was an older, high-risk population with established vascular disease, and it reinforces why age, timing, and baseline cardiovascular health drive treatment decisions.
WELL-HART · New England Journal of Medicine, 2003
Hormone Therapy and Established Coronary Atherosclerosis
WELL-HART examined whether oral estradiol, with or without a progestogen, could slow progression of coronary artery disease in postmenopausal women who already had coronary atherosclerosis. Hormone therapy did not significantly slow progression of established coronary lesions during the study.
Research & Education Disclaimer: The studies on this page are shared for educational purposes and to help clients better understand the scientific literature surrounding menopausal hormone therapy. Individual studies differ in the hormones used, route of administration, dose, participant age, time since menopause, underlying health conditions, and outcomes measured. These studies should not be interpreted as proving that hormone therapy is appropriate or risk-free for every person. Treatment decisions should be individualized after consultation with a qualified healthcare professional.