Publications

Abstracts & Manuscripts

Below are abstracts and manuscripts about the Kronos Early Estrogen Prevention Study (KEEPS). Click on the links (PDF or HTML format) to view the full abstract or manuscript.

KEEPS Abstracts
KEEPS Manuscripts
KEEPS Ancillary Abstracts
KEEPS Ancillary Manuscripts

KEEPS Abstracts

  • Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)
    The Women's Health Initiative (WHI) hormone trials did not confirm data from observational studies showing that menopausal hormone therapy reduced the risk of coronary heart disease. Two variables that differed between WHI and observational studies were the chronological age and proximity to menopause at which women initiated therapy. KEEPS compared baseline characteristics of KEEPS participants to those in the WHI.
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  • Atherosclerosis and Menopausal Symptoms: Baseline Characteristics of Recently Menopausal Women Screened for the Kronos Early Estrogen Prevention Study
    The cardiac effects of estrogen may depend on menopausal status. Declining estrogen levels lead to menopausal symptoms that can be ameliorated by exogenous therapy. However, it is unknown whether the symptoms of estrogen deficiency are associated with atherosclerosis in recently menopausal women.
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  • Correlates of Cartoid Artery Intima-Media Thickness in Recently Menopausal Women Screened for the Kronos Early Estrogen Prevention Study
    The timing of initiation of menopausal hormone therapy may be critical to its effects upon atherosclerosis and vascular disease. Common carotid artery intima-media thickness (CIMT), a validated measure of atherosclerosis, is the primary endpoint. There is only limited information on links to subclinical atherosclerosis in this population. We correlated CIMT with a variety of conventional risk markers in 691 women screened to date for the KEEPS.
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  • Relationship of Coronary Calcification to Conventional and Metabolic Risk Factors In Recently Menopausal
    Women The lower rate of coronary heart disease (CHD) events in women vs. men reverses after menopause, but the extent to which conventional risk factors predict clinically silent CHD in perimenopausal women is unknown. We compared historical and biochemical predictors of CHD with CAC in recently menopausal 42-58 year old women screened for KEEPS.
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  • Phenotype of Blood Borne Microparticles: Marker of Premature Atherosclerosis in Recently Menopausal Women
    Circulating microparticles are membrane fragments shed from activated cells which are characterized by surface markers consistent with their cells of origin. Alterations within the microparticle pool may indicate early pre-clinical vascular disease processes. Our study was designed to test the relationship between the phenotype of circulating microparticle and plaque formation quantified by coronary calcification scans in early menopausal women.
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  • Brain Volume Changes in Recently Menopausal Women in a Hormone Replacement Trial
    Estrogens are thought to enhance neurological function and exert neuroprotective effects. Our objective in KEEPS was to quantify the rates of brain volume and ventricular volume change in newly menopausal women in the KEEPS trial.
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  • Baseline Cognitive and Demographic Characteristics of Women Enrolled in the KEEPS Cognitive and Affective Study
    The objective of the KEEPS Cognitive and Affective Study (KEEPS C/A) is to evaluate differential efficacy of oral conjugated equine estrogen (CEE or Premarin®) and transdermal 17 B-estradiol (tE2) with 12 days/month progesterone (Prometrium®) on mood and cognition in healthy non-hysterectomized, women who are within 6 months - 3 years of menopause.
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  • Pilot Study of Sex Differences in Chemokine/Cytokine Markers of Atherosclerosis in Humans
    Atherogenic processes increase in women after menopause, when the risk of cardiovascular adverse events approaches that observed in age-matched men. Experiments were designed to assess the sex distribution of inflammatory chemokines/cytokines, which may be released from platelets in the serum of middle-aged women and men in whom the extent of atherosclerotic coronary disease was defined by coronary arterial calcification (CAC).
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  • Estrogen, Inflammation, and Platelet Phenotype
    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk.
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  • Relationship between Cognition and Vascular Risk Factors in Women Enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS C/A) at Baseline
    Based on initial KEEPS C/A reports, baseline physiological and cognitive data in the KEEPS Study will likely indicate that the cohort is healthy and free of cognitive dysfunction. Although KEEPS participants are healthy, we foresee a negative relationship within participants, such that an increase in VRF will result in a cognitive deficit.
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  • Stroop Task Uniformity in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS C/A)
    Based on initial reports, we foresee a relationship between performance on the paper and pencil and computerized versions of the Stroop Interference task. Additionally, we predict a positive correlation between baseline estradiol levels and performance on both Stroop tasks, such that higher levels of estradiol will yield better cognitive performance.
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  • Endothelial Function and Cardiovascular Risk in Early Menopausal Women
    Peripheral flow-mediated reactive hyperemia (PRH) may indicate early endothelial dysfunction. This study tested the hypothesis that endothelial dysfunction could identify early cardiovascular risk in early menopausal women.
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  • Blood Borne Microvesicles and Coronary Calcification in Early Menopausal Women
    Microvesicles (or microparticles) are a circulating, heterogeneous population of phospholipid-rich spheres formed from membranes of activated cells. Microvesicles carry molecular signatures of their cell of origin and provide surfaces for thrombin generation and thus, could indicate early disease processes. Experiments were designed to determine the relationship between the phenotype of circulating microvesicles to quantifiable vascular lesions in early menopausal women.
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  • Menopausal Age, Endothelial Function and Cardiovascular Risk
    Cardiovascular disease progresses on a continuum throughout life and increases in women at menopause. Therefore, timing of interventions, such as for hormonal therapy, may be critical in order to slow disease progression. Peripheral flow-mediated reactive hyperemia (PRH) is accepted as a marker of endothelial dysfunction and an indicator of early disease processes. This study tested the hypothesis that endothelial dysfunction would increase with time past menopause.
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  • The Muffin Test
    IGT is currently diagnosed by fasting glucose levels (FPG>110 mg/dl) or a 75-g OGTT (2-hr glucose of 140-199 mg/dL). A "Cookie Test" performed in lieu of an OGTT correctly identifies IGT and dyslipidemia and is better tolerated.(2) In recruitment for the KEEPS (Kronos Early Estrogen Prevention Study) Trial, a "Muffin Test-MT" was used to examine glucose metabolism in a sample of recently menopausal women. We hypothesized that a standard breakfast food item provides a more physiologic carbohydrate (CHO) challenge than a concentrated glucose solution.
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  • Copy number of human SULT1A1 gene among newly menopausal Caucasian women
    There is large variation in response to menopausal hormone treatments among women and it remains unclear as to what genetic factors might increase risk of breast cancer in women using such treatments to relieve symptoms of menopause. SULT1A1 is aubiquitous enzyme involved in the metabolism of steroid hormones including estrogen. A number of polymorphisms in the gene for this enzyme are associated with various cancer risks and the activity level of the enzyme is correlated closely with variation in copy number of the gene. This pilot study evaluated SNP variation and copy number of SULT1A1 in a subset of women being screened for KEEPS.
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  • Non-invasive assessment of endothelial function to identify cardiovascular risk in asymptomatic early menopausal women: what to do when Framingham fails?
    Abnormal peripheral flow-mediated reactive hyperemia (PRH) is a surrogate for endothelial dysfunction and an indicator of premature atherosclerosis. This study tested the hypothesis that endothelial dysfunction is associated with atherosclerosis in early menopausal women, deemed low risk by conventional risk assessment.
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KEEPS Manuscripts

 Miller VM, Black DM, Brinton EA, Budoff MJ, Cedars MI, Hodis HN, Lobo RA, Manson JE, Merriam GR, Naftolin F, Santoro N, Taylor HS, Harman SM. Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). J Cardiovasc Transl Res. 2009 Sep;2(3):228-239.

Harman SM, Brinton EA. Biphasic Effects of Hormone Treatment on Risk of Heart Disease. Menopausal Medicine, American Society for Reproductive Medicine's newsletter.

Miller VM, Jayachandran M, Hashimoto K, Heit JA, Owen WG. Estrogen, Inflammation and Platelet Phenotype. Gend Med. 2008;5 Suppl A:S91-S102.

Harman SM. Estrogen Replacement in Menopausal Women: Recent and Current Prospective Studies, the WHI and KEEPS. Gend Med. 2006 Dec;3(4):254-69.

Harman SM, Naftolin F, Brinton EA, Judelson DR. Is the Estrogen Controversy Over? Ann N Y Acad Sci. 2005 Jun;1052:43-56.

Harman 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.

Miller VM, Clarkson TB, Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Naftolin F, Santoro N. Women, Hormones, and Clinical Trials: A Beginning, Not An End. J Appl Physiol. 2005 Aug;99(2):381-3.

Manson JE, Bassuk SS, Harman SM, Brinton EA, Cedars MI, Lobo R, Merriam GR, Miller VM, Naftolin F, Santoro N. Postmenopausal Hormone Therapy: New Questions and the Case for New Clinical Trials. Menopause. 2006 Jan-Feb;13(1):139-47.

Harman 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.

Naftolin F, Taylor HS, Karas R, Brinton E, Newman I, Clarkson TB, Mendelsohn M, Lobo RA, Judelson DR, Nachtigall LE, Heward CB, Hecht H, Jaff MR, Harman SM; Women's Health Initiative.The Women's Health Initiative Could Not Have Detected Cardioprotective Effects of Starting Hormone Therapy During the Menopausal Transition. Fertil Steril. 2004 Jun;81(6):1498-501.


KEEPS Ancillary Studies

KEEPS Ancillary Abstracts

  • Skin Wrinkles and Rigidity in Early Postmenopausal Women Vary by Race and Ethnicity: Baseline Characteristics of Participants enrolled in the Skin Ancillary Study of the KEEPS Trial
    We previously reported a retrospective study showing that long term Hormone Therapy (HT) was associated with less wrinkling and rigidity. Currently this association is being tested in a prospective RCT of participants enrolled in KEEPS.
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KEEPS Ancillary Manuscripts

Jayachandran M, Litwiller RD, Owen WG, Heit JA, Behrenbeck T, Mulvagh SL, Araoz PA, Budoff MJ, Harman SM, Miller VM. Characterization of Blood Borne Microparticles as Markers of Premature Coronary Calcification In Newly Menopausal Women. Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H931-H938.

 

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