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The endocrinology of menstruation – a role for the immune system
Abstract
The human endometrium displays characteristic features, both structural and functional, across the menstrual cycle. It is the sex steroid hormones, oestrogen and progesterone, that drive the endometrium through the different phases of the cycle. Oestrogen and progesterone act sequentially to regulate cellular concentrations of their respective receptors, this interaction initiates gene transcription. Thereafter a cascade of local events prepares the endometrium for implantation, but in the absence of pregnancy, progesterone withdrawal leads to menstruation and cyclic repair. Withdrawal of progesterone from an oestrogen-progesterone primed endometrium is the initiating event for the cascade of molecular and cellular interactions that result in menstruation. Progesterone withdrawal first affects cells with progesterone receptors. Early events in the menstrual process are vasoconstriction and cytokine up-regulation. The activation of lytic mechanisms is a later event and involves cells that may lack progesterone receptors, for example, uterine leucocytes and epithelial cells. Hence progesterone withdrawal results in a local increase of inflammatory mediators and the enzymes responsible for tissue breakdown. The total complex of local factors implicated in normal menstrual and aberrant menstrual bleeding are yet to be fully defined.
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“These mediators and enzymes, in turn, facilitate influx of leukocytes into tissues”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Critchley et al., 2001
In the citing paper
“With withdrawal of progesterone during the premenstrual phase, stroma, endothelium and immune cells undergo changes, inducing local mediators such as chemokines, cytokines, cell regulators and enzymes responsible for prostaglandin synthesis and degradation.”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Critchley et al., 2001
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Mangla, M., Palo, S., Kanikaram, P. K., Raja Shekar, P., & Setty, A. (2025) · Obstetrics & Gynecology Science · doi:10.5468/ogs.25196
Multimodal profiling of repair-associated immune cells in a mouse model of menstruation
Ainslie, R. J., Kirkwood, P. M., Li, H., Gerasimou, S., Saunders, P. T. K., Simitsidellis, I., & Gibson, D. A. (2026) · Journal of Reproductive Immunology · doi:10.64898/2026.02.06.704418
Romero, R. J. (2026) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2026.04.004
Goyal, R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.27.728028
Metadata
- Authors
- Critchley, H. O. D., Kelly, R. W., Brenner, R. M., & Baird, D. T.
- Affiliations
- University of Edinburgh (GB)
- MRC Centre for Reproductive Health (GB)
- Corresponding author
- Critchley, Hilary O. D.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2001-12
- Volume
- 55
- Issue
- 6
- Pages
- 701-710
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2106927311
- Cited by
- 203
- References
- 89
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 13 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 10 · 2014: 6 · 2013: 11 · 2012: 14
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- menstruation, endometrium, progesterone withdrawal, estrogen, progesterone receptor, immune system, inflammation, cytokines, vasoconstriction, endometrial repair, menstrual bleeding, implantation
- MeSH terms
- Adult, Hypoxia, Endometrium, Estradiol, Female, Humans, Immune System, Lymphokines, Menstruation, Progesterone, Endothelial Growth Factors, Receptors, Growth Factor, Inflammation Mediators, Matrix Metalloproteinases, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
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