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Archives of Gynecology and Obstetrics

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01-04-2017 | Gynecologic Endocrinology and Reproductive Medicine

Effects of a hyperandrogenaemic state on the proliferation and decidualization potential in human endometrial stromal cells

Authors: Alexander Freis, Tobias Renke, Ulrike Kämmerer, Julia Jauckus, Thomas Strowitzki, Ariane Germeyer

Published in: Archives of Gynecology and Obstetrics | Issue 4/2017

Abstract

Objective

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, involving hyperandrogenaemia and insulin resistance. Treatment options include dexamethasone, as well as the off-label use of metformin. To evaluate the impact of those drugs on cyclic changes in endometrial development, we tested possible effects of metformin and dexamethasone on endometrial stromal cells decidualisation, proliferation, and gene regulation in a hyperandrogenaemic microenvironment in vitro.

Methods/design

Ten endometrial biopsies (of which five were decidualized in vitro) were used from regularly cycling women. Cells were treated with testosterone, dexamethasone, and metformin in different concentrations. Thereafter, cells were assessed for proliferation and decidualization capacity, as well as mTor and MMP-2 gene regulation.

Results

Metformin showed a dose-dependent negative effect on prolactin secretion, a known decidualization marker. This effect was stronger in a hyperandrogenaemic condition and could not be compensated by dexamethasone. Testosterone had a dose dependent negative effect on proliferation in decidualized endometrial stromal cells. Dexamethasone slightly compensated the negative proliferative effect only in low-dose testosterone. High-dose metformin also showed a dose-dependent reduction in endometrial stromal cell proliferation without a major impact by testosterone or dexamethasone in decidualized and non-decidualized cells. High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone. The strongest effect could be observed for the combination with high-dose dexamethasone.

Conclusion

When therapies, such as metformin and dexamethasone, are used to normalize peripheral androgen levels in patients with PCOS, their effect on the endometrial microenvironment should be taken into consideration as well, especially metformin has to be used with caution because of its dose dependent, possibly inhibiting effect at the endometrial proliferation.

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Title: Effects of a hyperandrogenaemic state on the proliferation and decidualization potential in human endometrial stromal cells
Authors: Alexander Freis
Tobias Renke
Ulrike Kämmerer
Julia Jauckus
Thomas Strowitzki
Ariane Germeyer
Publication date: 01-04-2017
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 4/2017
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-017-4295-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of a hyperandrogenaemic state on the proliferation and decidualization potential in human endometrial stromal cells

Abstract

Objective

Methods/design

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods/design

Results

Conclusion

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