Injectable Collagenase Clostridium Histolyticum as a Non-surgical Treatment for Uterine Fibroids: A Scoping Review

Uterine fibroids or leiomyomas are the most common benign neoplasms in women and a major source of morbidity, often impairing quality of life and overall well-being. Current management options-ranging from medical therapy to surgery-may be limited by adverse effects, incomplete symptom control, recurrence, or loss of uterine integrity. Given their dense, collagen-rich extracellular matrix, uterine fibroids may be amenable to enzymatic degradation using Clostridium histolyticum collagenase (CCH), a minimally invasive, non-hormonal therapeutic candidate. This scoping review maps the current literature regarding the efficacy, safety, and mechanism of action of CCH for fibroid treatment. A comprehensive literature search was conducted in January 2026 using PubMed, Scopus, Web of Science, Embase, Google Scholar, and ClinicalTrials.gov. This scoping review followed the PRISMA-ScR guidelines. A total of 37 records were identified. After deduplication and screening, 11 full-text articles were assessed, and five unique studies were included: one Phase I clinical trial, one preclinical translational study with ex vivo and in vivo components, and three ex vivo/translational laboratory investigations. Preliminary conference abstracts were excluded when full-text data were available. Ex vivo and in vivo studies consistently showed that CCH was associated with collagen-rich matrix disruption, fibroid softening, liquefaction, and changes in stiffness-related mechanotransduction pathways, including Hippo signalling. A Phase I clinical trial (n = 15) found that transvaginal CCH injection was well tolerated, with no serious treatment-related adverse events reported, a 39% reduction in collagen content, and preliminary improvements in pain and fibroid-related quality of life in the longer-interval cohort. CCH is a promising uterine-preserving investigational intervention that targets the collagen-rich extracellular matrix of uterine fibroids. While current data support its safety and biological activity, evidence is limited to early-phase research. Larger prospective trials are needed to determine optimal dosing, long-term efficacy, durability of effect, and clinical utility as a standalone or adjunctive therapy.