MenopausePhase 4NCT00154180
Kronos Early Estrogen Prevention Study (KEEPS)
A Phase 4 study testing Conjugated equine estrogens 0.45 mg/day, Transdermal estradiol, 50 mcg/day and Micronized progesterone, 200 mg/day x 12 d/month in people with Menopause and Arteriosclerosis, run by Kronos Longevity Research Institute at 9 sites in United States.
Trial summary
The study will examine the effects of estrogen and progesterone on the development of atherosclerosis in menopausal women when hormone treatment is initiated within 3 years of the menopausal transition. Read more about this study
- Who is it for?
- Ages 42 to 58 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause, Arteriosclerosis
- What is being tested?
- Conjugated equine estrogens 0.45 mg/day, Transdermal estradiol, 50 mcg/day and Micronized progesterone, 200 mg/day x 12 d/month
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 728 participants
- Where
- 9 sitesUnited States
- Study dates
- Sep 2005to Jul 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 42 to 58 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- menses absent for at least 6 months and no more than 36 months
- good general health
- plasma FSH level greater than or equal to 35 mIU/ml
- estradiol levels < 40 pg/ml
- normal mammogram within 1 year of randomization
Who cannot join
- use of hormone replacement or supplement within 3 months of randomization
- endometrial thickness >5 mm by vaginal ultrasound
- in utero exposure to diethylstilbestrol (DES)
- current smoking > 10 cigarettes/day
- obesity-body mass index > 35
- history of clinical cardiovascular disease
Show all 18Show fewer
- history of cerebrovascular disease
- history of thromboembolic disease
- coronary calcium score ≥ 50 units
- dyslipidemia-LDL cholesterol >190 mg/dl
- hypertriglyceridemia-triglycerides >400 mg/dl
- lipid lowering medication (statin, fibrate,or > 500 mg/day of niacin)
- nut allergy (Prometrium includes peanut oil)
- uncontrolled hypertension-systolic BP >150 and/or diastolic BP > 95
- hysterectomy
- history of, or prevalent, chronic diseases including any cancer (other than basal cell skin cancers), renal failure, cirrhosis, diabetes mellitus, and endocrinopathies other than adequately treated thyroid disease
- known HIV infection and/or medications for HIV infection
- results of any safety laboratory test chemistries, (TSH, CBC, U/A) more than 20% abnormal
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Yale University Medical Center
New Haven, Connecticut, 06519
Columbia Presbyterian Hospital
New York, New York, 10032
Kronos Longevity Research Institute
Phoenix, Arizona, 85016-3452
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84108
University of California, San Francisco
San Francisco, California, 94115
University of Washington/VA Puget Sound, HCS
Seattle/Tacoma, Washington, 98493
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women
The study will examine the effects of estrogen and progesterone on the development of atherosclerosis in menopausal women when hormone treatment is initiated within 3 years of the menopausal transition.
Read the detailed description
The KEEPS is designed to explore the hypothesis that early initiation of hormone therapy, in women who are at the inception of their menopause, will decrease the rate of accumulation of atherosclerotic plaque, indicating a likely delay in the onset of clinical cardiovascular disease. The study is designed as a multicenter, 4 year randomized clinical trial. It will evaluate the effectiveness of of 0.45 mg/day of oral conjugated equine estrogens or 50 mcg/day of transdermal estradiol via skin patch changed weekly (each in combination with cyclic oral, micronized progesterone, 200 mg daily for 12 days per month), versus placebo in preventing progression of carotid intimal medial thickness by sonogram and the accrual of coronary calcium in women aged 42-58 who are within 36 months of their final menstrual period at initiation of treatment. A number of secondary endpoints including biochemical and genetic risk factors for cardiovascular and thrombotic disease, and effects on cognition will also be studied. The study will enroll a total of 720 women in 2005-6, with an anticipated completion of the trial in 2010.
- Conditions
- Menopause, Arteriosclerosis
- Being tested
- Conjugated equine estrogens 0.45 mg/day, Transdermal estradiol, 50 mcg/day, Micronized progesterone, 200 mg/day x 12 d/month, CEE , progesterone, estradiol patch or placebo for each, CEE, progesterone, transdermal patch or the placebo
- Keywords
- Perimenopause, Coronary Disease, Estrogen Replacement Therapy, Hormone Replacement Therapy
- Medical subject headings
- Arteriosclerosis, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conjugated equine estrogens 0.45 mg/dayDrug
Also called Premarin or placebo
Pill, 1 pill taken daily each month for the study duration
Transdermal estradiol, 50 mcg/dayDrug
Also called Climara 50 mcg/day or placebo
Patch; 1 patch is applied to the skin weekly. Patch site is rotated on a weekly basis.
Micronized progesterone, 200 mg/day x 12 d/monthDrug
Also called Prometrium or placebo
capsule, 1 capsule taken daily for the first 12 days of each month for the study duration
CEE , progesterone, estradiol patch or placebo for eachDrug
Also called Premarin, Prometrium, Climara Patch
CEE 0.45mg 1 PO QD Progesterone 200 mg 1 PO HS first 12 days of the month estradiol patch use 1 per week
CEE, progesterone, transdermal patch or the placeboDrug
Also called Premarin, Prometrium, Climara
CEE 0.45 mg 1 PO QD or placebo equivalent Prometrium 200 mg 1 PO qHS for first 12 dasy of each month or placebo equivalent transdermal patch 0.05 mg use 1 patch per week or placebo equivalent
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | CEE 0.45 mg w/ Prometrium 200 mg patch 0.05 mg w/ Prometrium 200 mg Receives: Drug: Conjugated equine estrogens 0.45 mg/day; Drug: Transdermal estradiol, 50 mcg/day; Drug: Micronized progesterone, 200 mg/day x 12 d/month; Drug: CEE, progesterone, transdermal patch or the placebo |
| Arm 2 | Placebo comparator | Placebo patch, placebo CEE, placebo Prometrium Receives: Drug: CEE , progesterone, estradiol patch or placebo for each; Drug: CEE, progesterone, transdermal patch or the placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of change of carotid intimal medial thickness by ultrasound
Measured: Measured at screening, 12, 24, 36, and 48 months
Secondary outcomes (7)
Change in coronary calcium score by X-ray tomography
Measured: Meassured at screening and at 48 months
Plasma lipid profiles
Measured: Samples taken at screening , 12, 36, and 48 months
Blood clotting factors
Measured: Samples taken at screening, 12, 36 and 48 months
Serum inflammatory factors
Measured: Samples taken at screening, 12, 36 and 48 months
Hormone levels
Measured: Samples taken at screening, 12, 36 and 48 months
Cognitive and Affective scores on standard psychometric tests
Measured: Testing is conducted at Baseline, 18, 36 and 48 months
Quality of life
Measured: Measured at Baseline, 18, 36 and 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionMay 2012 (estimated)
- Study completionJul 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 728 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kronos Longevity Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Albert Einstein College of Medicine, Brigham and Women's Hospital, Columbia University, Mayo Clinic, University of California, San Francisco, University of Utah, University of Washington, Yale University
- Investigators
- S Mitchell Harman, MD, PhD, Study director, Kronos Longevity Research InstituteFrederick Naftolin, MD, PhD, Study director, Kronos Longevity Research InstituteMichael Mendelsohn, MD, Principal investigator, Tufts Medical CenterHoward Hodis, MD, Principal investigator, University of Southern CaliforniaMatthew Budoff, MD, Principal investigator, University of California, Los AngelesSanjay Asthana, MD, Principal investigator, University of Wisconsin, MadisonDennis M Black, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00154180
- Sponsor's protocol ID
- KLRI-04-1
- Other IDs
- WIRB Protocol #20040792
- Status last verified
- Sep 2009
- First submitted
- 7 Sep 2005
- Last updated
- 14 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Harman SM, Naftolin F, Brinton EA, Judelson DR. Is the estrogen controversy over? Deconstructing the Women's Health Initiative study: a critical evaluation of the evidence. Ann N Y Acad Sci. 2005 Jun;1052:43-56. doi: 10.1196/annals.1347.004.
PubMed 16024750Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N. KEEPS: The Kronos Early Estrogen Prevention Study. Climacteric. 2005 Mar;8(1):3-12. doi: 10.1080/13697130500042417.
PubMed 15804727Harman SM, Brinton EA, Clarkson T, Heward CB, Hecht HS, Karas RH, Judelson DR, Naftolin F. Is the WHI relevant to HRT started in the perimenopause? Endocrine. 2004 Aug;24(3):195-202. doi: 10.1385/ENDO:24:3:195.
PubMed 15542885Kantarci K, Kara F, Tosakulwong N, Fought AJ, Schwarz CG, Senjem ML, Kendall-Thomas J, Min P, Lowe VJ, Jack CR, Kapoor E, Fields JA, Bailey KR, James TT, Faubion L, Lobo RA, Manson JE, Pal L, Hammers DB, Brinton EA, Malek-Ahmadi M, Cedars MI, Naftolin FN, Santoro N, Miller VM, Harman SM, Dowling NM, Gleason CE. Long-term amyloid PET and MRI outcomes in a menopausal hormone therapy trial. Alzheimers Dement. 2026 Feb;22(2):e71067. doi: 10.1002/alz.71067.
PubMed 41618732Kara F, Tosakulwong N, Lesnick TG, Fought AJ, Kendell-Thomas J, Kapoor E, Faubion LL, Schwarz CG, Senjem ML, Fields JA, Min PH, Lowe VJ, Jack CR Jr, Bailey KR, James TT, Lobo RA, Manson JE, Pal L, Hammers DB, Malek-Ahmadi M, Cedars MI, Naftolin FN, Santoro N, Miller VM, Harman SM, Dowling NM, Gleason CE, Kantarci K. Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy. Menopause. 2025 Jan 1;32(1):12-22. doi: 10.1097/GME.0000000000002481.
PubMed 39729067Kling JM, Dowling NM, Bimonte-Nelson H, Gleason CE, Kantarci K, Stonnington CM, Harman SM, Naftolin F, Pal L, Cedars M, Manson JE, James TT, Brinton EA, Miller VM. Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy. Maturitas. 2023 Jan;167:113-122. doi: 10.1016/j.maturitas.2022.10.002. Epub 2022 Oct 27.
PubMed 36395695Kling JM, Miller VM, Tosakulwong N, Lesnick T, Kantarci K. Associations of pituitary-ovarian hormones and white matter hyperintensities in recently menopausal women using hormone therapy. Menopause. 2020 Aug;27(8):872-878. doi: 10.1097/GME.0000000000001557.
PubMed 32520900El Khoudary SR, Venugopal V, Manson JE, Brooks MM, Santoro N, Black DM, Harman M, Naftolin F, Hodis HN, Brinton EA, Miller VM, Taylor HS, Budoff MJ. Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial. Menopause. 2020 Mar;27(3):255-262. doi: 10.1097/GME.0000000000001472.
PubMed 32015261El Khoudary SR, Zhao Q, Venugopal V, Manson JE, Brooks MM, Santoro N, Black DM, Harman SM, Cedars MI, Hopkins PN, Kearns AE, Miller VM, Taylor HS, Budoff MJ. Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial. J Am Heart Assoc. 2019 Aug 6;8(15):e012763. doi: 10.1161/JAHA.119.012763. Epub 2019 Aug 1.
PubMed 31652073Jayawardena E, Li D, Nakanishi R, Dey D, Dailing C, Qureshi A, Dickens B, Hathiramani N, Kim M, Flores F, Kearns AE, Lui LY, Black D, Budoff MJ. Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study. J Cardiovasc Comput Tomogr. 2020 Jan-Feb;14(1):55-59. doi: 10.1016/j.jcct.2019.05.004. Epub 2019 May 4.
PubMed 31078511Taylor HS, Tal A, Pal L, Li F, Black DM, Brinton EA, Budoff MJ, Cedars MI, Du W, Hodis HN, Lobo RA, Manson JE, Merriam GR, Miller VM, Naftolin F, Neal-Perry G, Santoro NF, Harman SM. Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med. 2017 Oct 1;177(10):1471-1479. doi: 10.1001/jamainternmed.2017.3877.
PubMed 28846767Cintron D, Beckman JP, Bailey KR, Lahr BD, Jayachandran M, Miller VM. Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy. Maturitas. 2017 May;99:59-65. doi: 10.1016/j.maturitas.2017.01.016. Epub 2017 Feb 17.
PubMed 28364870Owen CM, Pal L, Mumford SL, Freeman R, Isaac B, McDonald L, Santoro N, Taylor HS, Wolff EF. Effects of hormones on skin wrinkles and rigidity vary by race/ethnicity: four-year follow-up from the ancillary skin study of the Kronos Early Estrogen Prevention Study. Fertil Steril. 2016 Oct;106(5):1170-1175.e3. doi: 10.1016/j.fertnstert.2016.06.023. Epub 2016 Jul 5.
PubMed 27393520Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, Brinton EA, Cedars MI, Lobo RA, Merriam GR, Neal-Perry G, Santoro NF, Taylor HS, Black DM, Budoff MJ, Hodis HN, Naftolin F, Harman SM, Asthana S. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015 Jun 2;12(6):e1001833; discussion e1001833. doi: 10.1371/journal.pmed.1001833. eCollection 2015 Jun.
PubMed 26035291Harman SM, Black DM, Naftolin F, Brinton EA, Budoff MJ, Cedars MI, Hopkins PN, Lobo RA, Manson JE, Merriam GR, Miller VM, Neal-Perry G, Santoro N, Taylor HS, Vittinghoff E, Yan M, Hodis HN. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014 Aug 19;161(4):249-60. doi: 10.7326/M14-0353.
PubMed 25069991
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women
- ClinicalTrials.gov ID
- NCT00154180
- Acronym / sponsor ID
- KLRI-04-1
- Conditions
- Menopause, Arteriosclerosis
- Keywords
- Perimenopause, Coronary Disease, Estrogen Replacement Therapy, Hormone Replacement Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 728 participants (estimated)
- Lead sponsor
- Kronos Longevity Research InstituteUniversity, hospital or other
- Collaborators
- Albert Einstein College of Medicine, Brigham and Women's Hospital, Columbia University, Mayo Clinic, University of California, San Francisco, University of Utah, University of Washington, Yale University
- Study start
- Sep 2005
- Primary completion
- May 2012 (estimated)
- Study completion
- Jul 2012 (estimated)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will examine the effects of estrogen and progesterone on the development of atherosclerosis in menopausal women when hormone treatment is initiated within 3 years of the menopausal transition.
Detailed description
The KEEPS is designed to explore the hypothesis that early initiation of hormone therapy, in women who are at the inception of their menopause, will decrease the rate of accumulation of atherosclerotic plaque, indicating a likely delay in the onset of clinical cardiovascular disease. The study is designed as a multicenter, 4 year randomized clinical trial. It will evaluate the effectiveness of of 0.45 mg/day of oral conjugated equine estrogens or 50 mcg/day of transdermal estradiol via skin patch changed weekly (each in combination with cyclic oral, micronized progesterone, 200 mg daily for 12 days per month), versus placebo in preventing progression of carotid intimal medial thickness by sonogram and the accrual of coronary calcium in women aged 42-58 who are within 36 months of their final menstrual period at initiation of treatment. A number of secondary endpoints including biochemical and genetic risk factors for cardiovascular and thrombotic disease, and effects on cognition will also be studied. The study will enroll a total of 720 women in 2005-6, with an anticipated completion of the trial in 2010.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: Conjugated equine estrogens 0.45 mg/day, Drug: Transdermal estradiol, 50 mcg/day, Drug: Micronized progesterone, 200 mg/day x 12 d/month, Drug: CEE, progesterone, transdermal patch or the placeboCEE 0.45 mg w/ Prometrium 200 mg patch 0.05 mg w/ Prometrium 200 mg |
| Arm 2 | Placebo comparator | Drug: CEE , progesterone, estradiol patch or placebo for each, Drug: CEE, progesterone, transdermal patch or the placeboPlacebo patch, placebo CEE, placebo Prometrium |
Who may qualify
- Ages
- 42 to 58 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- menses absent for at least 6 months and no more than 36 months
- good general health
- plasma FSH level greater than or equal to 35 mIU/ml
- estradiol levels < 40 pg/ml
- normal mammogram within 1 year of randomization
Key exclusion criteria (18 listed)
- use of hormone replacement or supplement within 3 months of randomization
- endometrial thickness >5 mm by vaginal ultrasound
- in utero exposure to diethylstilbestrol (DES)
- current smoking > 10 cigarettes/day
- obesity-body mass index > 35
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conjugated equine estrogens 0.45 mg/dayAlso: Premarin or placeboPill, 1 pill taken daily each month for the study duration | Drug | Arm 1 |
| Transdermal estradiol, 50 mcg/dayAlso: Climara 50 mcg/day or placeboPatch; 1 patch is applied to the skin weekly. Patch site is rotated on a weekly basis. | Drug | Arm 1 |
| Micronized progesterone, 200 mg/day x 12 d/monthAlso: Prometrium or placebocapsule, 1 capsule taken daily for the first 12 days of each month for the study duration | Drug | Arm 1 |
| CEE , progesterone, estradiol patch or placebo for eachAlso: Premarin, Prometrium, Climara PatchCEE 0.45mg 1 PO QD Progesterone 200 mg 1 PO HS first 12 days of the month estradiol patch use 1 per week | Drug | Arm 2 |
| CEE, progesterone, transdermal patch or the placeboAlso: Premarin, Prometrium, ClimaraCEE 0.45 mg 1 PO QD or placebo equivalent Prometrium 200 mg 1 PO qHS for first 12 dasy of each month or placebo equivalent transdermal patch 0.05 mg use 1 patch per week or placebo equivalent | Drug | Arm 1, Arm 2 |
Primary outcome
Rate of change of carotid intimal medial thickness by ultrasound
Time frame: Measured at screening, 12, 24, 36, and 48 months
7 secondary outcomes
Change in coronary calcium score by X-ray tomography
Time frame: Meassured at screening and at 48 months
Plasma lipid profiles
Time frame: Samples taken at screening , 12, 36, and 48 months
Blood clotting factors
Time frame: Samples taken at screening, 12, 36 and 48 months
Serum inflammatory factors
Time frame: Samples taken at screening, 12, 36 and 48 months
Hormone levels
Time frame: Samples taken at screening, 12, 36 and 48 months
Cognitive and Affective scores on standard psychometric tests
Time frame: Testing is conducted at Baseline, 18, 36 and 48 months
Quality of life
Time frame: Measured at Baseline, 18, 36 and 48 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2009.
- Background: PubMed 16024750Harman SM, Naftolin F, Brinton EA, Judelson DR. Is the estrogen controversy over? Deconstructing the Women's Health Initiative study: a critical evaluation of the evidence. Ann N Y Acad Sci. 2005 Jun;1052:43-56. doi: 10.1196/annals.1347.004.
- Background: PubMed 15804727Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N. KEEPS: The Kronos Early Estrogen Prevention Study. Climacteric. 2005 Mar;8(1):3-12. doi: 10.1080/13697130500042417.
- Background: PubMed 15542885Harman SM, Brinton EA, Clarkson T, Heward CB, Hecht HS, Karas RH, Judelson DR, Naftolin F. Is the WHI relevant to HRT started in the perimenopause? Endocrine. 2004 Aug;24(3):195-202. doi: 10.1385/ENDO:24:3:195.
- Derived from this study: PubMed 41618732Kantarci K, Kara F, Tosakulwong N, Fought AJ, Schwarz CG, Senjem ML, Kendall-Thomas J, Min P, Lowe VJ, Jack CR, Kapoor E, Fields JA, Bailey KR, James TT, Faubion L, Lobo RA, Manson JE, Pal L, Hammers DB, Brinton EA, Malek-Ahmadi M, Cedars MI, Naftolin FN, Santoro N, Miller VM, Harman SM, Dowling NM, Gleason CE. Long-term amyloid PET and MRI outcomes in a menopausal hormone therapy trial. Alzheimers Dement. 2026 Feb;22(2):e71067. doi: 10.1002/alz.71067.
- Derived from this study: PubMed 39729067Kara F, Tosakulwong N, Lesnick TG, Fought AJ, Kendell-Thomas J, Kapoor E, Faubion LL, Schwarz CG, Senjem ML, Fields JA, Min PH, Lowe VJ, Jack CR Jr, Bailey KR, James TT, Lobo RA, Manson JE, Pal L, Hammers DB, Malek-Ahmadi M, Cedars MI, Naftolin FN, Santoro N, Miller VM, Harman SM, Dowling NM, Gleason CE, Kantarci K. Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy. Menopause. 2025 Jan 1;32(1):12-22. doi: 10.1097/GME.0000000000002481.
- Derived from this study: PubMed 36395695Kling JM, Dowling NM, Bimonte-Nelson H, Gleason CE, Kantarci K, Stonnington CM, Harman SM, Naftolin F, Pal L, Cedars M, Manson JE, James TT, Brinton EA, Miller VM. Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy. Maturitas. 2023 Jan;167:113-122. doi: 10.1016/j.maturitas.2022.10.002. Epub 2022 Oct 27.
- Derived from this study: PubMed 32520900Kling JM, Miller VM, Tosakulwong N, Lesnick T, Kantarci K. Associations of pituitary-ovarian hormones and white matter hyperintensities in recently menopausal women using hormone therapy. Menopause. 2020 Aug;27(8):872-878. doi: 10.1097/GME.0000000000001557.
- Derived from this study: PubMed 32015261El Khoudary SR, Venugopal V, Manson JE, Brooks MM, Santoro N, Black DM, Harman M, Naftolin F, Hodis HN, Brinton EA, Miller VM, Taylor HS, Budoff MJ. Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial. Menopause. 2020 Mar;27(3):255-262. doi: 10.1097/GME.0000000000001472.
- Derived from this study: PubMed 31652073El Khoudary SR, Zhao Q, Venugopal V, Manson JE, Brooks MM, Santoro N, Black DM, Harman SM, Cedars MI, Hopkins PN, Kearns AE, Miller VM, Taylor HS, Budoff MJ. Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial. J Am Heart Assoc. 2019 Aug 6;8(15):e012763. doi: 10.1161/JAHA.119.012763. Epub 2019 Aug 1.
- Derived from this study: PubMed 31078511Jayawardena E, Li D, Nakanishi R, Dey D, Dailing C, Qureshi A, Dickens B, Hathiramani N, Kim M, Flores F, Kearns AE, Lui LY, Black D, Budoff MJ. Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study. J Cardiovasc Comput Tomogr. 2020 Jan-Feb;14(1):55-59. doi: 10.1016/j.jcct.2019.05.004. Epub 2019 May 4.
- Derived from this study: PubMed 28846767Taylor HS, Tal A, Pal L, Li F, Black DM, Brinton EA, Budoff MJ, Cedars MI, Du W, Hodis HN, Lobo RA, Manson JE, Merriam GR, Miller VM, Naftolin F, Neal-Perry G, Santoro NF, Harman SM. Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med. 2017 Oct 1;177(10):1471-1479. doi: 10.1001/jamainternmed.2017.3877.
- Derived from this study: PubMed 28364870Cintron D, Beckman JP, Bailey KR, Lahr BD, Jayachandran M, Miller VM. Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy. Maturitas. 2017 May;99:59-65. doi: 10.1016/j.maturitas.2017.01.016. Epub 2017 Feb 17.
- Information on hormone treatment and KEEPS rationaleLink provided by the sponsor.
- Information on sponsoring institutionLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
S Mitchell Harman, MD, PhD study director
Kronos Longevity Research Institute
Frederick Naftolin, MD, PhD study director
Kronos Longevity Research Institute
Michael Mendelsohn, MD principal investigator
Tufts Medical Center
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Conjugated equine estrogens 0.45 mg/day, Transdermal estradiol, 50 mcg/day and Micronized progesterone, 200 mg/day x 12 d/month in people with Menopause and Arteriosclerosis, run by Kronos Longevity Research Institute at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of change of carotid intimal medial thickness by ultrasound (time frame: Measured at screening, 12, 24, 36, and 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00154180, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2009.