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Cited by 660Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsHormonal and reproductive studies

Effect of Postmenopausal Hormones on Inflammation-Sensitive Proteins: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Study

Cushman, Mary, Legault, Claudine, Barrett-Connor, Elizabeth, Stefanick, Marcia L., Kessler, Craig, Judd, Howard L., Sakkinen, Pamela A., Tracy, Russell P.·1999·Circulation
DOI 10.1161/01.cir.100.7.717
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Abstract

Background —Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest. Methods and Results —Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin ( P =0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline. Conclusions —Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.

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  • Inflammation levels fluctuate throughout female life according to hormonal changes owing to phase of menstrual cycle, use of hormonal contraceptives, menopause and use of estrogens.

    “Inflammation levels fluctuate throughout female life according to hormonal changes owing to phase of menstrual cycle, use of hormonal contraceptives, menopause and use of estrogens,6, 7, 8”

    From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [6]

    The Abstract (page not specified) reports that postmenopausal hormone treatment increased C-reactive protein and decreased soluble E-selectin, supporting the claim that estrogen use can change inflammation-sensitive markers. The paper does not establish fluctuations throughout female life or effects of menstrual-cycle phase, hormonal contraceptives, or menopause itself. (LLM, conf=0.88)

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  • Hormonal changes throughout female life (menstrual cycle, hormonal contraceptives, menopause, estrogens) greatly impact inflammation levels.

    “Hormonal changes throughout female life due to phase of menstrual cycle, use of hormonal contraceptives, menopause and use of estrogens greatly impact on inflammation levels,6, 7, 8”

    From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [6]

    The Abstract reports that postmenopausal hormone therapy substantially increased C-reactive protein but decreased soluble E-selectin, supporting an effect of estrogen-containing therapy on inflammation-sensitive markers. The paper does not establish effects of menstrual-cycle phase, hormonal contraceptives, or menopause itself, so it does not support the claim across female life stages. (LLM, conf=0.88)

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Research works printed but not linked: 1

  1. Cushman M, Yanez D, Psaty BM, Fried LP, Heiss G, Lee M, Polak JF, Savage PJ, Tracy RP. Correlates of fibrinogen and coagulation factors VII and VIII in the elderly: results from the Cardiovascular Health Study. Am J Epidemiol. 1996;143:665-676.

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Authors
Cushman, M., Legault, C., Barrett-Connor, E., Stefanick, M. L., Kessler, C., Judd, H. L., Sakkinen, P. A., & Tracy, R. P.
Affiliations
University of Vermont (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1999-08-17
Volume
100
Issue
7
Pages
717-722
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.100.7.717
OpenAlex
W2130451642
Cited by
660
References
27
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 14 · 2013: 12 · 2012: 14
FWCI
43.26
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • George Washington University
  • University of Vermont
  • National Institutes of Health (5u01hl040154-10, 5u01hl040185-07, 5u01hl040195-10)
  • National Heart, Lung, and Blood Institute (U01-HL40154, U01-HL-40195, U01-HL40185)
  • National Institute of Child Health and Human Development
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
hormone replacement therapy, estrogen therapy, inflammation, C-reactive protein, soluble E-selectin, von Willebrand factor, factor VIII, coronary disease risk, cardiovascular risk factors
MeSH terms
Antigens, Blood Glucose, C-Reactive Protein, Cardiovascular Diseases, Double-Blind Method, Estrogens, Conjugated (USP), Factor VIII, Female, Humans, Inflammation, Lipids, Middle Aged, Progesterone, Risk Factors, Smoking, von Willebrand Factor, Biomarkers, Body Mass Index, Treatment Outcome, Medroxyprogesterone Acetate, Postmenopause, E-Selectin, Hormone Replacement Therapy

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