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Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS

CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade systemic inflammation and increased risk of pregnancy complications. Metformin treatment reduces the risk of late miscarriage and preterm birth in pregnant women with PCOS. Whether the protective effec...

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Autores principales: Ryssdal, Mariell, Vanky, Eszter, Stokkeland, Live Marie T, Jarmund, Anders Hagen, Steinkjer, Bjørg, Løvvik, Tone Shetelig, Madssen, Torfinn Støve, Iversen, Ann-Charlotte, Giskeødegård, Guro F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10438881/
https://www.ncbi.nlm.nih.gov/pubmed/36916886
http://dx.doi.org/10.1210/clinem/dgad145
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author Ryssdal, Mariell
Vanky, Eszter
Stokkeland, Live Marie T
Jarmund, Anders Hagen
Steinkjer, Bjørg
Løvvik, Tone Shetelig
Madssen, Torfinn Støve
Iversen, Ann-Charlotte
Giskeødegård, Guro F
author_facet Ryssdal, Mariell
Vanky, Eszter
Stokkeland, Live Marie T
Jarmund, Anders Hagen
Steinkjer, Bjørg
Løvvik, Tone Shetelig
Madssen, Torfinn Støve
Iversen, Ann-Charlotte
Giskeødegård, Guro F
author_sort Ryssdal, Mariell
collection PubMed
description CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade systemic inflammation and increased risk of pregnancy complications. Metformin treatment reduces the risk of late miscarriage and preterm birth in pregnant women with PCOS. Whether the protective effect of metformin involves immunological changes has not been determined. OBJECTIVE: To investigate the effect of metformin on the maternal immunological status in women with PCOS. METHODS: A post-hoc analysis was performed of two randomized controlled trials, PregMet and PregMet2, including longitudinal maternal serum samples from 615 women with PCOS. Women were randomized to metformin or placebo from first trimester to delivery. Twenty-two cytokines and C-reactive protein were measured in serum sampled at gestational weeks 5 to 12, 19, 32, and 36. RESULTS: Metformin treatment was associated with higher serum levels of several multifunctional cytokines throughout pregnancy, with the strongest effect on eotaxin (P < .001), interleukin-17 (P = .03), and basic fibroblast growth factor (P = .04). Assessment of the combined cytokine development confirmed the impact of metformin on half of the 22 cytokines. The immunomodulating effect of metformin was more potent in normal weight and overweight women than in obese women. Moreover, normoandrogenic women had the strongest effect of metformin in early pregnancy, whereas hyperandrogenic women presented increasing effect throughout pregnancy. CONCLUSION: It appears that metformin has immunomodulating rather than anti-inflammatory properties in pregnancy. Its effect on the serum levels of many multifunctional cytokines demonstrates robust, persisting, and body mass–dependent immune mobilization in pregnant women with PCOS.
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spelling pubmed-104388812023-08-19 Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS Ryssdal, Mariell Vanky, Eszter Stokkeland, Live Marie T Jarmund, Anders Hagen Steinkjer, Bjørg Løvvik, Tone Shetelig Madssen, Torfinn Støve Iversen, Ann-Charlotte Giskeødegård, Guro F J Clin Endocrinol Metab Clinical Research Article CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade systemic inflammation and increased risk of pregnancy complications. Metformin treatment reduces the risk of late miscarriage and preterm birth in pregnant women with PCOS. Whether the protective effect of metformin involves immunological changes has not been determined. OBJECTIVE: To investigate the effect of metformin on the maternal immunological status in women with PCOS. METHODS: A post-hoc analysis was performed of two randomized controlled trials, PregMet and PregMet2, including longitudinal maternal serum samples from 615 women with PCOS. Women were randomized to metformin or placebo from first trimester to delivery. Twenty-two cytokines and C-reactive protein were measured in serum sampled at gestational weeks 5 to 12, 19, 32, and 36. RESULTS: Metformin treatment was associated with higher serum levels of several multifunctional cytokines throughout pregnancy, with the strongest effect on eotaxin (P < .001), interleukin-17 (P = .03), and basic fibroblast growth factor (P = .04). Assessment of the combined cytokine development confirmed the impact of metformin on half of the 22 cytokines. The immunomodulating effect of metformin was more potent in normal weight and overweight women than in obese women. Moreover, normoandrogenic women had the strongest effect of metformin in early pregnancy, whereas hyperandrogenic women presented increasing effect throughout pregnancy. CONCLUSION: It appears that metformin has immunomodulating rather than anti-inflammatory properties in pregnancy. Its effect on the serum levels of many multifunctional cytokines demonstrates robust, persisting, and body mass–dependent immune mobilization in pregnant women with PCOS. Oxford University Press 2023-03-14 /pmc/articles/PMC10438881/ /pubmed/36916886 http://dx.doi.org/10.1210/clinem/dgad145 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research Article
Ryssdal, Mariell
Vanky, Eszter
Stokkeland, Live Marie T
Jarmund, Anders Hagen
Steinkjer, Bjørg
Løvvik, Tone Shetelig
Madssen, Torfinn Støve
Iversen, Ann-Charlotte
Giskeødegård, Guro F
Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS
title Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS
title_full Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS
title_fullStr Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS
title_full_unstemmed Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS
title_short Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS
title_sort immunomodulatory effects of metformin treatment in pregnant women with pcos
topic Clinical Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10438881/
https://www.ncbi.nlm.nih.gov/pubmed/36916886
http://dx.doi.org/10.1210/clinem/dgad145
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