The DOI matches its Crossref record; 604 of the 604 references it cites were found in a registry or an index.
The Complex Role of Estrogens in Inflammation
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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In the citing paper
“The male mice were used to preclude the effects of sex hormone since liver metabolism and inflammatory responses are highly influenced by estrogen levels and activity of estrogen receptor67,68.”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [68]
In the citing paper
“This discrepancy may be attributed to differences in estrogen metabolism, receptor expression, or interactions with other hormones such as androgens and insulin which can be reviewed here (220).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [220]
In the citing paper
“Prior work has shown estrogen to be both anti- and pro-inflammatory and its effects may depend on a variety of factors, such as cell type, target organ, estrogen concentration, and expression of estrogen receptors (Straub, 2007).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Straub, 2007
In the citing paper
“Thus, B cell-dominated immune reactions that are supported by T helper type 2 immune responses are stimulated, whereas T helper type 1 and macrophage-dominated immune responses are inhibited.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [27]
In the citing paper
“estrogens have a bi-modal pro- and anti-inflammatory role.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [27]
In the citing paper
“Both in vitro and in vivo studies show that while low dose exposure to E2 (doses consistent with oral contraceptive pills) is associated with increased pro-inflammatory cytokine expression [74, 76, 77], high doses (pregnancy levels) tend to generate an anti-inflammatory response [74].”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [74]
In the citing paper
“Estrogens have a divergent effect on inflammation and immune modulation [74, 75] based on the dose and duration of treatment of the drug.”
From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [74]
Citations
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Cited by
Sorted by citations
Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370
Sex, gender, and pain: a review of recent clinical and experimental findings
Fillingim, R. B., King, C. D., Ribeiro-Dasilva, M. C., Rahim-Williams, B., & Riley, J. L. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2008.12.001 · Cited by 2,766
Gender differences in autoimmune disease
Ngo, S. T., Steyn, F. J., & McCombe, P. A. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.04.004 · Cited by 1,074
The G-protein-coupled estrogen receptor GPER in health and disease
Prossnitz, E. R., & Barton, M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.122 · Cited by 925
Challis, J. R., Lockwood, C. J., Myatt, L., Norman, J. E., Strauss, J. F., & Petraglia, F. (2009) · Reproductive Sciences · doi:10.1177/1933719108329095 · Cited by 893
Metadata
- 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
- 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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