Metformin as a Potential Treatment Option for Endometriosis Original paper

What was reviewed?

The paper reviewed the potential use of metformin as a pharmacological treatment for endometriosis, highlighting its diverse biological effects that could beneficially impact the disease. The review extensively explored the role of metformin as an insulin sensitizer, its mechanisms of action, and how these may influence critical aspects of endometriosis pathology, including inflammation, angiogenesis, adhesion, invasion, apoptosis, and interactions with the gut microbiome.

Who was reviewed?

The review examined data from in vitro studies, animal models, and limited human clinical studies on women with endometriosis. The research focused on experimental models that assessed metformin’s effects on endometrial stromal cells, endometrial implants, inflammatory markers, angiogenic factors, and metabolic pathways implicated in endometriosis.

What were the most important findings?

The review reported several crucial findings. Metformin exhibited significant anti-inflammatory properties by reducing cytokines such as IL-6, IL-8, and TNF-α. These anti-inflammatory actions were primarily mediated through the activation of AMP-activated protein kinase (AMPK), which modulates inflammation pathways implicated in endometriosis. Metformin also demonstrated potent anti-angiogenic effects, reducing vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 levels, thus inhibiting the development and growth of new blood vessels necessary for endometriotic lesion survival. Metformin significantly reduced cell proliferation and promoted apoptosis in endometrial cells, partially by suppressing aromatase activity and by disrupting pathways critical for cell survival such as PI3K/Akt/mTOR. Metformin’s impact on adhesion and invasion processes included downregulating adhesion molecules like VCAM-1, potentially reducing lesion formation and attachment.

Metformin influenced the gut microbiota by modulating the estrobolome, the gut microbiome involved in estrogen metabolism. Dysbiosis in endometriosis may exacerbate symptoms by increasing circulating estrogen levels, a mechanism that metformin can positively influence by enhancing beneficial bacterial populations.

What are the greatest implications of this review?

This review holds significant clinical implications. Metformin emerges as a promising candidate for treating endometriosis due to its broad-spectrum actions without serious adverse effects, unlike current hormonal therapies which can have significant side effects or limited long-term usability. The possibility of using metformin either alone or as an adjunct to existing treatments offers a versatile therapeutic strategy. Its beneficial role in managing obesity-associated hyperestrogenism and inflammation, combined with its safety profile, positions metformin as a potential first-line therapy or adjunctive treatment, especially valuable for women seeking to maintain fertility. The need for more extensive clinical trials was emphasized, underscoring metformin’s therapeutic promise.