Cetin, E., Al-Hendy, A., & Ciebiera, M. (2020). Non-hormonal mediators of uterine fibroid growth. Current opinion in obstetrics & gynecology, 32(5), 361-370. https://doi.org/10.1097/GCO.0000000000000650
Cetin E, Al-Hendy A, Ciebiera M. Non-hormonal mediators of uterine fibroid growth. Current opinion in obstetrics & gynecology. 2020;32(5):361-370. doi:10.1097/GCO.0000000000000650
Cetin, Esra, et al. "Non-hormonal mediators of uterine fibroid growth." Current opinion in obstetrics & gynecology, vol. 32, no. 5, 2020, pp. 361-370.
For EndNote, Zotero or Mendeley:
Open access
Free to read
No reuse license
Open Access
Free full text on PubMed Central (PMC8314923)
RRM Academy Synopsis
Uterine fibroid growth involves non-hormonal pathways as well
A 2020 narrative review of lab and clinical studies reports that fibroid growth involves signals beyond estrogen and progesterone. These include growth factors and inflammation. The authors say far more is known about the hormone side.
Key Findings
The review sorts non-hormonal fibroid biology into six pathway groups, led by growth factors and inflammation and ending with PPAR and retinoic acid signaling.
Sequencing several fibroids revealed tumor-specific changes in the MED12 gene in about 70% of patients, reported by Mäkinen and colleagues in 2011.
TGF-β3 is a key player in fibroids, with roles in cell proliferation and extracellular matrix deposition.
Over 30% of women with fibroids have symptoms, and the authors call drug options limited.
Interpretation
The paper is a narrative review that gathers laboratory, animal and clinical studies. Several of the pathway findings come from cell and animal models. The authors describe data on some pathways, such as PPAR, as scarce. Vitamin D and curcumin appear as natural compounds reported to act on these pathways. The authors describe these pathways as interlocking with hormonal signaling.
RRM Context
The review links obesity, low vitamin D and inflammation to fibroids, and RRM evaluates these factors first.
Our editorial summary of this paper, not the article's abstract.
Abstract
Purpose of Review
Uterine fibroids are the most common benign neoplasms of the female reproductive tract and one of the major public health concerns. Although most women with uterine fibroids are asymptomatic, over 30% of them will present with varying symptoms. This review focuses on the role of non-hormonal mediators and pathways in uterine fibroid biology. Furthermore, it provides data regarding the most recent findings in the field of compounds, which use those non-hormonal pathways in the medical therapy of uterine fibroids.
Recent Findings
Complex signaling pathway alterations are crucial for uterine fibroid development. The topic of the pathophysiology of uterine fibroids focuses mostly on steroids and other hormones. However, other very important pathways exist, and some of them are independent of hormones. Some of the most important pathways, which are non-hormonal, but in some cases still hormone-depended, include growth factors, cytokines and inflammation, Smad proteins, wingless type/β-catenin and others.
Summary
Much more is known about hormonal than about non-hormonal signaling in uterine fibroids. Growth factors, early life exposure and inflammation are key factors in uterine fibroid biology. Numerous agents depend on those pathways and may find their place in the current and future therapy of uterine fibroids.
