Investigational Medical Therapies for Endometriosis: Current Data and Future Trends. 

The Safety and Efficacy of Investigational Hormonal and Non-Hormonal Medical Therapies for Endometriosis

Key Points

Highlight:

• Assessment the safety and efficacy of novel medical treatments, investigational hormonal and non-hormonal medical therapies.

Importance :

• The medical treatment of endometriosis has traditionally relied on hormonal therapies.
• The hormonal therapies preclude fertility or may have unwanted side effects.
• There is a great need for novel hormonal and non-hormonal medical options.

Data:

Hormonal Therapies

• Gonadotropin-Releasing Hormone Antagonists: A novel nonpeptide GnRH antagonist, exhibited regression of endometriotic implants without bone loss.
• Aromatase Inhibitors: AI in combination with progestin therapy does not seem to be associated with bone loss, but more clinical trials are needed.
• Dienogest: DNG is superior to placebo in improving endometriosis-associated pain, but have side effects such as vaginal bleeding, headache, breast pain, and weight gain.

Non-hormonal Therapies

• Immunomodulators: Although TNF-α inhibitors show the potential for the treatment of endometriosis, more studies are needed to confirm the safety of new TNF-α inhibitors.
• Antiangiogenic Agents: Anti-VEGF/VEGFR agents reduce the incidence of endometriosis by 74%, but there are concerns about the safety of long-term use.
• Other Medications/Possible Remedies: A study using a mouse model showed that rosiglitazone did not have any adverse effect on offspring.

Lay Summary

The medical treatment of endometriosis has traditionally relied on hormonal therapies. Because these hormonal therapies preclude fertility or may have unwanted side effects, there is a great need for novel hormonal and non-hormonal medical options. Therefore, this review focuses on investigational medical therapies based on in vitro and in-vivo models of endometriosis and assesses the safety and efficacy.

It has been suggested that endometriosis, currently treated with GnRH agonists, may be more effectively treated with GnRH antagonists. Several animal studies have demonstrated the efficacy of GnRH antagonists. SKI2670, a novel nonpeptide GnRH antagonist, exhibited regression of endometriotic implants in a rat model without bone loss. Aromatase Inhibitors (AIs) are efficacious in reducing endometriotic pelvic pain as well as endometriotic lesion regression. AI in combination with progestin add-back hormone therapy does not seem to be associated with bone loss at six months of use. A systemic review including nine randomized clinical trials concluded that dienogest (DNG, 2 mg/day) is superior to placebo in improving endometriosis-associated pain. However, there are side effects such as vaginal bleeding, headache, breast pain, and weight gain.

Among non-hormonal therapies, anti-TNF-a treatment decreased the extent of endometriosis compared with placebo, reducing both the number and surface area of red lesions. Although TNF-α inhibitors show a significant potential, more studies are needed to validate the safety. A systematic review found that anti-VEGF/VEGFR agents reduced endometriotic lesion size, weight, and endometriosis score. Also, this may reduce the incidence of endometriosis by 74%, but there are concerns about the safety of long-term use. Lastly, rosiglitazone suppressed the establishment and growth of auto-transplanted lesions in human endometrial cells. Rosiglitazone also did not have any adverse effects on offspring using a mouse model.

"Investigational medical treatments for endometriosis have been found to be efficacious in in-vitro and in-vivo studies. However, the safety and efficacy of such novel therapies continue to be evaluated." added authors. The minireview published recently in the scientific journal named "Seminars in Reproductive Medicine." 

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29036739