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Approval of Elagolix (Orilissa), the first Orally Active GnRH Antagonist, and Relevance for Transfeminine People

By Aly W. | First published August 2, 2018 | Last modified October 6, 2020

Elagolix is a new gonadotropin-releasing hormone (GnRH) antagonist and is the first oral GnRH antagonist to be introduced for medical use. Unlike all other marketed GnRH modulators (agonists/antagonists), elagolix is not a GnRH analogue, is not a peptide, and is orally active. It was approved by the FDA for the treatment of endometriosis on July 24th, 2018. It’s approved specifically for endometriosis and it’s very expensive right now (US$875 without insurance). But in time the price should go down. In particular, once other oral GnRH antagonists like relugolix and linzagolix finish clinical development and are introduced for medical use as well, I anticipate that these medications will become more affordable. And eventually the patent protection of these oral GnRH antagonists will expire and they should become pretty inexpensive. The fact that they are non-peptides/small-molecules and don’t require fancy drug formulations (since they can just be taken orally; no implant or depot injection technology needed) may mean that they’ll be far less expensive than GnRH analogues once they become generics in the future. Of course, generic availability of oral GnRH antagonists is a long ways off though (10 to 15 years or so).

Oral GnRH antagonists will allow pre-op/non-op transgender women to easily and conveniently abolish gonadal testosterone production, without concerns about efficacy, tolerability, or safety. In addition, the level of testosterone suppression is adjustable via the use of lower oral GnRH antagonist dosages, which, if you’re the type that would prefer non-castrate levels of testosterone, may be desirable. I anticipate that the combination of physiological-dose parenteral (non-oral) estradiol plus an oral GnRH antagonist (and/or progesterone, if one so pleases) may someday become the gold standard for transfeminine hormone therapy in pre-op/non-op transgender women. No more excessively high doses of estradiol to suppress testosterone (which may theoretically compromise breast development and may have health/safety issues with long-term therapy). And no more having to depend on antiandrogens with undesirable side effects (e.g., spironolactone and cyproterone acetate), safety issues (e.g., spironolactone, cyproterone acetate, and bicalutamide), or efficacy concerns (e.g., spironolactone).

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