Treatment with the common antibiotic doxycycline may help prevent progression of endometriosis lesions in women who do not respond to standard therapies, results of a pilot study suggest.
The study, “Doxycycline reduces MMP-2 activity and inhibits invasion of 12Z epithelial endometriotic cells as well as MMP-2 and -9 activity in primary endometriotic stromal cells in vitro,” was published in the journal Reproductive Biology and Endocrinology.
Many efforts have been made to better understand the underlying mechanisms involved in endometriosis. Still, no cure has resulted, and for many women surgery is the only valid approach. But a single surgery might not represent a permanent solution, as recurrence of the disease and its symptoms are frequent, often requiring repeated surgeries.
Given this, finding strategies to prevent endometriosis progression or help manage its symptoms is an urgent need.
Doxycycline is a widely used antibiotic, sold under several brand names, that has been shown to inhibit certain enzymes, called matrix metalloproteinases (MMPs).
MMPs are important regulators of organ development and tissue turnover, normally not very active in adult tissues. However, they have been found to be deregulated in several disorders, including endometriosis.
MMP-2 and MMP-9 were found to be increased in endometriosis tissue compared to healthy samples. Also, these molecules are thought to contribute to tissue remodeling mechanisms involved in endometriosis lesions’ growth and invasion.
Researchers from Switzerland’s University Hospital Zurich decided to explore the potential of doxycycline to treat endometriosis.
They found that treatment with different doses of doxycycline could prevent the production of MMP-2 and MMP-9 and reduce activity in both immortalized endometriosis cells (those manipulated in the laboratory to proliferate) and in cells collected from two patients.
Further analysis determined that treatment with low-dose doxycycline could reduce by up to 78% the number of invading cells compared to placebo-treated cells.
Next, the team evaluated doxycycline when used in combination with progesterone, often used to manage endometriosis symptoms. They found that the combo therapy further reduced the levels of activated MMP-2 compared to either of the agents alone.
“Our results demonstrate the potential for use of [low-dose] doxycycline in the treatment of endometriosis,” researchers said.
Low-dose doxycycline has been shown to be well-tolerated in other clinical settings. So it could represent a potential treatment option for endometriosis, particularly severe forms of deep-infiltrating endometriosis that often respond poorly to current treatment options.
Also, “[low-dose] doxycycline might be an interesting alternative for patients who wish to have a non-hormonal medical prevention of recurrence after surgical excision of endometriosis,” researchers stated.