The Kronos Early Estrogen Prevention Study (KEEPS): What have we learned?

Virginia M Miller, Fredrick Naftolin, Sanjay Asthana, Dennis M. Black, Eliot A. Brinton, Matthew J. Budoff, Marcelle I. Cedars, N. Maritza Dowling, Carey E. Gleason, Howard N. Hodis, Muthuvel Jayachandran, Kejal M Kantarci, Rogerio A. Lobo, Joann E. Manson, Lubna Pal, Nanette F. Santoro, Hugh S. Taylor, S. Mitchell Harman

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Objective:The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative.Method:The KEEPS was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of HT (oral conjugated equine estrogens [o-CEE] or transdermal 17β-estradiol [t-E2]) in healthy, recently postmenopausal women (n=727) would slow the progression of atherosclerosis as measured by changes in carotid artery intima-media thickness (CIMT).Results:After 4 years, neither HT affected the rate of increase in CIMT. There was a trend for reduced accumulation of coronary artery calcium with o-CEE. There were no severe adverse effects, including venous thrombosis. Several ancillary studies demonstrated a positive effect on mood with o-CEE, and reduced hot flashes, improved sleep, and maintenance of bone mineral density with both treatments. Sexual function improved with t-E2. There were no significant effects of either treatment on cognition, breast pain, or skin wrinkling. Variants of genes associated with estrogen metabolism influenced the age of menopause and variability in effects of the HT on CIMT. Platelet activation associated with the development of white matter hyperintensities in the brain.Conclusions:KEEPS and its ancillary studies have supported the value and safety of the use of HT in recently postmenopausal women and provide a perspective for future research to optimize HT and health of postmenopausal women. The KEEPS continuation study continues to pursue these issues.

Original languageEnglish (US)
Pages (from-to)1071-1084
Number of pages14
JournalMenopause
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2019

Fingerprint

Estrogens
Hormones
Conjugated (USP) Estrogens
Carotid Intima-Media Thickness
Carotid Arteries
Women's Health
Therapeutics
Premature Menopause
Mastodynia
Hot Flashes
Skin Aging
Platelet Activation
Menopause
Venous Thrombosis
Bone Density
Cognition
Estradiol
Atherosclerosis
Coronary Vessels
Sleep

Keywords

  • Cardiovascular disease
  • Cognition
  • Hormone therapy
  • Menopausal symptoms
  • Menopause
  • Osteoporosis

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Miller, V. M., Naftolin, F., Asthana, S., Black, D. M., Brinton, E. A., Budoff, M. J., ... Harman, S. M. (2019). The Kronos Early Estrogen Prevention Study (KEEPS): What have we learned? Menopause, 26(9), 1071-1084. https://doi.org/10.1097/GME.0000000000001326

The Kronos Early Estrogen Prevention Study (KEEPS) : What have we learned? / Miller, Virginia M; Naftolin, Fredrick; Asthana, Sanjay; Black, Dennis M.; Brinton, Eliot A.; Budoff, Matthew J.; Cedars, Marcelle I.; Dowling, N. Maritza; Gleason, Carey E.; Hodis, Howard N.; Jayachandran, Muthuvel; Kantarci, Kejal M; Lobo, Rogerio A.; Manson, Joann E.; Pal, Lubna; Santoro, Nanette F.; Taylor, Hugh S.; Harman, S. Mitchell.

In: Menopause, Vol. 26, No. 9, 01.09.2019, p. 1071-1084.

Research output: Contribution to journalReview article

Miller, VM, Naftolin, F, Asthana, S, Black, DM, Brinton, EA, Budoff, MJ, Cedars, MI, Dowling, NM, Gleason, CE, Hodis, HN, Jayachandran, M, Kantarci, KM, Lobo, RA, Manson, JE, Pal, L, Santoro, NF, Taylor, HS & Harman, SM 2019, 'The Kronos Early Estrogen Prevention Study (KEEPS): What have we learned?', Menopause, vol. 26, no. 9, pp. 1071-1084. https://doi.org/10.1097/GME.0000000000001326
Miller VM, Naftolin F, Asthana S, Black DM, Brinton EA, Budoff MJ et al. The Kronos Early Estrogen Prevention Study (KEEPS): What have we learned? Menopause. 2019 Sep 1;26(9):1071-1084. https://doi.org/10.1097/GME.0000000000001326
Miller, Virginia M ; Naftolin, Fredrick ; Asthana, Sanjay ; Black, Dennis M. ; Brinton, Eliot A. ; Budoff, Matthew J. ; Cedars, Marcelle I. ; Dowling, N. Maritza ; Gleason, Carey E. ; Hodis, Howard N. ; Jayachandran, Muthuvel ; Kantarci, Kejal M ; Lobo, Rogerio A. ; Manson, Joann E. ; Pal, Lubna ; Santoro, Nanette F. ; Taylor, Hugh S. ; Harman, S. Mitchell. / The Kronos Early Estrogen Prevention Study (KEEPS) : What have we learned?. In: Menopause. 2019 ; Vol. 26, No. 9. pp. 1071-1084.
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AU - Naftolin, Fredrick

AU - Asthana, Sanjay

AU - Black, Dennis M.

AU - Brinton, Eliot A.

AU - Budoff, Matthew J.

AU - Cedars, Marcelle I.

AU - Dowling, N. Maritza

AU - Gleason, Carey E.

AU - Hodis, Howard N.

AU - Jayachandran, Muthuvel

AU - Kantarci, Kejal M

AU - Lobo, Rogerio A.

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