Metformin, the Rise of a New Medical Therapy for Endometriosis? A Systematic Review of the Literature Original paper

What was reviewed?

The review systematically analyzed existing studies evaluating the potential of metformin as a therapeutic option for endometriosis. It specifically examined the biological mechanisms through which metformin might impact endometriosis, including its anti-inflammatory, anti-angiogenic, and antiproliferative effects. Additionally, the review assessed the results from studies using both animal models and cell cultures, as well as the single clinical study available involving women diagnosed with endometriosis.

Who was reviewed?

The systematic review encompassed in vitro cell culture experiments, animal model studies (primarily rats), and limited clinical data from women with endometriosis. The cell culture studies investigated human endometriotic stromal cells, assessing metformin’s impact on inflammation and proliferation markers. The animal studies involved rats with induced endometriosis, evaluating the reduction of lesion size and biochemical markers after treatment. Researchers drew clinical evidence from a single study involving 90 women diagnosed with stage 1-2 endometriosis who experienced infertility and symptoms such as pelvic pain, dysmenorrhea, and dyspareunia.

What were the most important findings?

The review highlighted multiple significant findings about metformin’s therapeutic potential. In vitro studies demonstrated that metformin effectively reduced inflammation by suppressing key proinflammatory cytokines like interleukin-1β (IL-1β) and IL-8. Metformin also inhibited aromatase activity, crucial in local estrogen production, thereby potentially reducing estrogen-driven endometriosis growth. Another essential finding was metformin’s capacity to modulate the Wnt2/β-catenin signaling pathway, a critical factor in the interaction between stromal and epithelial cells that facilitates lesion proliferation and maintenance. In animal models, metformin treatment significantly regressed endometriotic implants by reducing angiogenic factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and inflammatory mediators IL-1β and IL-8. Notably, metformin reduced adhesion formation, an essential consideration in endometriosis management.

In the single clinical study reviewed, metformin treatment led to marked improvements in symptom relief, including significant reductions in pelvic pain, dysmenorrhea, and dyspareunia. Importantly, metformin use correlated with increased pregnancy rates, suggesting its potential benefits in fertility preservation among women with endometriosis.

What are the greatest implications of this review?

The most critical implication of this systematic review is the promising potential of metformin as a new, non-hormonal treatment option for endometriosis. Metformin’s diverse beneficial effects offer a unique therapeutic profile distinct from conventional hormone-based therapies, which frequently have contraceptive side effects. Given metformin’s general safety, affordability, and extensive use for conditions like PCOS and diabetes, its integration into endometriosis treatment could significantly improve patient outcomes, particularly in individuals contraindicated for or intolerant to hormonal therapy or those desiring pregnancy. The review emphasizes the necessity of further clinical trials to definitively establish metformin’s efficacy and optimal usage guidelines in treating endometriosis.