Is it the new gold mine for endometriosis: oral GnRH antagonists

Are GnRH antagonists the new promised treasure or do they come with a price?

Key Points

Highlights:

• Oral GnRH antagonists are promising for progestin-resistant endometriosis patients, but they might come with side effects caused by lower estrogen levels.

Importance:

• The effects and side effects of the oral GnRH antagonist drugs on the market were summarized and the need for trials to entertain their use on endometriosis treatment.

What's done here:

• A literature search was performed from PubMed and Embase including studies from 2010 to 2021.
• The keywords as ‘GnRH antagonist and add-back therapy, endometriosis’ have been used, among 83 manuscripts, 27 original papers evaluated.

Key Results:

• The reviewers analyzed the advantages of oral GnRH antagonists as easy use, immediate suppression of FSH and LH, and tunable dose option allowing dose-dependent suppression of E2 and quick reversibility of hormones after drug cessation.
• The oral GnRH antagonists on the market have been found as, elagolix, linzagolix and relugolix.
•  The use of Elagolix twice daily was summarized as causing strong suppression of E2 and also symptoms but coming with hot flushes and bone loss.
• The use of Linzagolix once a day, found to have a real impact on dyspareunia and quality of life while causing higher rates of hypoestrogenic symptoms after 6 months.
• Oral Relugolix, again once daily, significantly reduced dysmenorrhea and nonmenstrual pelvic pain and was also well tolerated with lesser vasomotor symptoms and bone loss after 6 months.

Limitations:

• While GnRH antagonists look like a good option for patients who cannot use COCs and progestins, the side effects caused by lower E2 levels and the requirement of add-back therapy have not been optimized yet.
• Future studies comparing the efficacy of GnRH antagonists with an add-back therapy option are needed before allowing them in the guidelines.

Lay Summary

Progestins and combined oral contraceptive pills are the first step hormonal options for women with endometriosis. But the more the use expands the more cases are seen with resistance to progestins. This gave birth to a need for different therapeutic options.

In the review summarized by Donnez et al., the use of oral GnRH antagonists on endometriosis has been analyzed. A literature search was done from PubMed and Embase including studies from 2010 to 2021. The keywords as ‘GnRH antagonist and add-back therapy, endometriosis’ have been used on the search. When 83 manuscripts were filtered for peer-reviewed and English language studies, the authors selected and reviewed 27 original papers on oral GnRH antagonists in the management of endometriosis in symptomatic premenopausal women.

The reviewers first analyzed the advantages of oral GnRH antagonists as easy use, immediate suppression of FSH and LH secretion, and tunable dose option allowing dose-dependent suppression of E2 levels and quick reversibility of hormones after cessation of the drugs.The oral GnRH antagonists on the market are elagolix, linzagolix and relugolix. The use of elagolix twice daily was summarized as causing strong suppression of E2 and also symptoms but coming with the cost of hot flushes and bone loss. The use of linzagolix once a day, found to have a real impact on dyspareunia and quality of life while causing higher rates of hypoestrogenic symptoms after 6 months. Oral relugolix, again once daily, significantly reduced dysmenorrhea and non-menstrual pelvic pain and was also well tolerated with lesser vasomotor symptoms and bone loss after 6 months.

While GnRH antagonists look like a good option for patients who cannot use COCs and progestins, the side effects caused by lower E2 levels and the requirement of add-back therapy have not been optimized yet. And the authors suggested organizing future studies comparing the efficacy of GnRH antagonists with an add-back therapy option before allowing them in the guidelines.

Research Source: https://pubmed.ncbi.nlm.nih.gov/34768770/