Cited by 1,950Estrogen and related hormone effectsInflammatory mediators and NSAID effectsMenopause: Health Impacts and Treatments

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The Complex Role of Estrogens in Inflammation

Straub, Rainer H.·2007·Endocrine Reviews

DOI 10.1210/er.2007-0001

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Abstract

There is still an unresolved paradox with respect to the immunomodulating role of estrogens. On one side, we recognize inhibition of bone resorption and suppression of inflammation in several animal models of chronic inflammatory diseases. On the other hand, we realize the immunosupportive role of estrogens in trauma/sepsis and the proinflammatory effects in some chronic autoimmune diseases in humans. This review examines possible causes for this paradox. This review delineates how the effects of estrogens are dependent on criteria such as: 1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses (e.g., T cell inhibited by estrogens vs. activation of B cell); 2) the cell types involved during different phases of the disease; 3) the target organ with its specific microenvironment; 4) timing of 17β-estradiol administration in relation to the disease course (and the reproductive status of a woman); 5) the concentration of estrogens; 6) the variability in expression of estrogen receptor α and β depending on the microenvironment and the cell type; and 7) intracellular metabolism of estrogens leading to important biologically active metabolites with quite different anti- and proinflammatory function. Also mentioned are systemic supersystems such as the hypothalamic-pituitary-adrenal axis, the sensory nervous system, and the sympathetic nervous system and how they are influenced by estrogens. This review reinforces the concept that estrogens have antiinflammatory but also proinflammatory roles depending on above-mentioned criteria. It also explains that a uniform concept as to the action of estrogens cannot be found for all inflammatory diseases due to the enormous variable responses of immune and repair systems.

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Authors: Straub, R. H.
Affiliations: University Hospital Regensburg (DE)
Corresponding author: Straub, Rainer H.
ORCID: Straub, Rainer H.
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2007-08-01
Volume: 28
Issue: 5
Pages: 521-574
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/er.2007-0001
OpenAlex: W2159203244
Cited by: 1,950
References: 604
Citations by year: 2026: 118 · 2025: 157 · 2024: 129 · 2023: 136 · 2022: 137 · 2021: 196 · 2020: 123 · 2019: 100 · 2018: 100 · 2017: 98 · 2016: 77 · 2015: 104 · 2014: 81 · 2013: 71 · 2012: 83
FWCI: 5.84
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords: estrogen, inflammation, immunomodulation, estrogen receptor alpha, estrogen receptor beta, estradiol, estrogen metabolism, bone resorption, autoimmune disease, sepsis, trauma (physical injury), T cell activation, B cell activation, hypothalamic-pituitary-adrenal axis, sympathetic nervous system, sensory nervous system, reproductive status
MeSH terms: Animals, Autoimmune Diseases, Cell Movement, Estrogens, Female, Humans, Inflammation, Leukocytes, Neovascularization, Pathologic, Pregnancy, Receptors, Estrogen, Estrogen Replacement Therapy, Apoptosis, Mice

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The Complex Role of Estrogens in Inflammation

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