Combination Therapy Proves More Efficient in the Treatment of Endometriosis

This study shows the increased effectiveness of combination therapy, namely telmisartan -an anti-hypertensive-, with parecoxib -an anti-inflammatory-, in the treatment of endometriotic lesions.

Key Points

Highlights:

• Telmisartan can be used in combination with a selective COX-2 inhibitor, namely parecoxib, to treat endometriotic lesions.

Importance:

• Prior treatment of endometriosis lesions using only telmisartan has led to an increase of COX-2, which then exacerbates the endometriosis itself.
• The previous literature showed that selective COX-2 inhibitors may be used to treat endometriosis.
• The authors hypothesized that telmisartan combined with a selective COX-2 inhibitor could be an effective treatment option for endometriosis patients.

What’s done here?

• A study was conducted using a mouse model with endometriotic lesions. Within the scope of the study, the mice were either given daily injections of telmisartan alone, daily injections of parecoxib alone, telmisartan and parecoxib together, or only a vehicle (drug transporter).
• The mice were studied over 4 weeks using not only by high-resolution ultrasound imaging, bu also excised material confirmed by histopathology and techniques such as immunohistochemistry  and Western blot and various characteristics of the endometriosis lesions were examined in terms of growth, cyst formation, vascularization, viability, protein expression, nerve fiber infiltration, and proliferation.

Key results:

• While telmisartan can be used by itself to treat lesions, the combination of telmisartan and parecoxib was the most effective in preventing later progression of the disease.
• The combined therapy showed decreased volume of the lesions and decreased expression of COX-2 ; matrix metalloproteinase-9 ; and p-AKT/AKT, and also decreased microvessel density, ingrowth of nerve fibers that causes pain in endometriosis, and Ki-67 proliferating cells (indicator of expansion and growth), along with increased amount of apoptotic stromal cells.
• The results also showed that the combination drug can lead to regression of endometriotic lesions.

Limitations of the study:

• This is an animal study, further testing in humans is required to confirm the results.
• It is necessary to clarify the synergistic effect (the total effec being greater than the sum of the two) of the drugs under clinical conditions.

Lay Summary

In their recent paper in British Journal of Pharmacology, entitled “Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions,” Nenicu et al. illustrate the increased effectiveness of telmisartan used along with a cyclooxygenase-2 (COX-2) inhibitor (a non-steroidal anti-inflammatory that directly targets the enzyme responsible for inflammation and pain), namely parecoxib, in the treatment of endometriosis lesions. In a previous study the authors proved that telmisartan can be used by itself to treat endometriotic lesions; however, it has been noted that use of this drug causes an increase in COX-2 expression, a factor that is known to exacerbate endometriosis. Various other literature has looked towards selective COX-2 inhibitors in order to treat endometriosis. Using this information along with the results of their own studies, the authors hypothesize that telmisartan along with a selective COX-2 inhibitor would be an effective treatment option for endometriosis patients.

Mice with endometriotic lesions were split into 4 treatment groups and were given either telmisartan, parecoxib or both; and the final group was given a vehicle (drug transporter) only. The mice were observed for 4 weeks using a variety of techniques for endometriotic lesion growth and viability.

The collective results showed that the combination therapy was the most effective method of treatment. The most exciting revelation from the study was the fact that this combined therapy not only halts the progression of endometriosis, but it can also lead to regression of endometriotic tissue.

In conclusion, this study presents a novel approach to treating endometriotic lesions. Additionally, the results of the study show that COX-2 is a potential target that should be further explored in endometriosis research.  

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28548231