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GnRh Antagonists

Some new medications have been introduced onto the market in the past few years:

  • 2018 – Orilissa by Abbvie: generic name elagolix

  • 2022 – MyFembree / Ryeqo by Myovant/Pfizer: generic name relugolix (this also has “add back therapy” in the form of estradiol and norethindrone acetate)

  • 2022 – Yselty by ObsEva: generic name linzagolix

Important: this page is about GnRh antagonists. This is not the same as GnRh agonists, like Lupron, Zoladex, Synarel, Prostrap, etc.

They are symptom management only

GnRh antagonists are pills that lower estrogen by affecting the way your brain talks to your ovaries on the hypothalamus – pituitary – gonadal axis. The medications block the production of ovarian-stimulating hormones by competitively binding to the GnRh receptors. (The medications block the receptor, therefore “competing” with the natural GnRh so it cannot bind with the receptor as it normally would). In turn, this reduces the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), therefore reducing estrogen and progesterone. However, endometriosis can continue making its own estrogen locally via the aromatase enzyme.
GnRh drugs are commonly prescribed by misinformed doctors as a treatment for endometriosis. However, they cannot diagnose, treat, remove, or shrink endometriosis lesions. What they may do is provide symptom management only (although many patients find the drug side effects intolerable). 

They can have serious side effects

On the prescribing information for GnRh antagonists, there’s typically a long list of potential side effects including suicidal thoughts or actions, bone mineral density loss, abnormal liver scans, hot flashes and night sweats, headache, nausea, difficulty sleeping, absence of periods, anxiety, joint pain, depression, and mood changes.
Orilissa has been approved by the FDA for the management of endometriosis symptoms for 6 months on the higher dose and 2 years on the lower dose. Myfembree and Ryeqo are also only approved for 2 years. This is due to the risk for bone loss on this drugs. You should speak to your doctor about having a bone density scan to periodically check your bone density.

They are not your only option

For many gynecologists, who are not endometriosis specialists and don’t often see patients with endometriosis in their practice, GnRh antagonists (and/or Lupron) are the only “tool” they have for patients with endometriosis. GnRh drugs (antagonists or agonists) are supposed to be second-line therapies, meaning that they are prescribed when first-line therapies (oral contraceptive pills and progestins) are ineffective, not tolerated or contraindicated. Studies have shown that in about 2/3 of people with endometriosis, first-line therapies provide symptom relief.
Yet some doctors put their patients on GnRh drugs right away, as soon as they suspect endometriosis, and for much longer than the FDA approved time frame. Additionally, various studies comparing GnRh drugs to other hormonal medications such as the Mirena, Dienogest, Depo Provera, combined birth control pills, and others, have shown these other hormones (which a patient can be on for longer and that have a much lower side effect profile) to provide similar symptom relief to patients as GnRh drugs. This is another reason why GnRh drugs are second-line therapies, but unfortunately many gynecologists are giving them out as soon as they suspect endometriosis, without any conversation around the side effects, treatment time limitations, or equally viable options.

In summary

  • GnRh drugs don’t do anything to the endometriosis itself like shrink it or dry it up.

  • Endometriosis can still progress while you’re on GnRh drugs.

  • Various studies comparing GnRh drugs to other hormonal medications show these all to provide similar symptom relief.

  • GnRh drugs are supposed to be second-line treatments, prescribed when first-line hormones like contraceptive pills, progestin shots, IUDs, etc are ineffective, not tolerated or contraindicated.

  • GnRh drugs have a higher side effect profile than first-line treatments, and you can’t be on them as long.

Is this the best option for me?

That’s something that only you can decide after doing ample research on Orilissa or Myfembree/Ryeqo. I put together a lot of detailed information in my podcast episodes below on the efficacy and risks of Lupron and Orilissa, so please check that out!

The only way to actually treat endometriosis is excision surgery and removing the disease at the root. However, not everyone can access excision surgery and we need a way to reduce our symptoms and improve our quality of life. Orilissa and Myfembree/Ryeqo only help some people with lowering their endometriosis symptoms while they are taking the drug, and it’s considered a “band aid” because it’s only temporary, and once the person stops the drug, their endometriosis symptoms typically come back quite quickly.

With any treatment or management option, we should assess if the benefits outweigh the risks. Some helpful questions we can ask ourselves are:

  • What other options do I have? (Excision surgery, diet and lifestyle changes, other hormonal medications such as the IUD, progestins, and birth controls which have a lower side effect profile and provide similar pain relief to GnRh drugs.)

  • What options have I already tried?

  • What risks are there to this medication vs the other options?

  • Is my doctor actually knowledgeable in endometriosis?

It can be hard to make choices about our endometriosis care. Between the misinformed doctors, to the difficulty of accessing a true specialist, to the daily symptoms which make everything 10 times harder, it can be difficult to gather all the facts to make a fully informed decision. We should be given all the facts and options from the start when we go to the doctor for endometriosis care, but unfortunately that typically doesn’t happen and a heavy burden falls on our shoulders to educate and advocate for ourselves. Which is unfair and exhausting.

Sometimes we judge ourselves, or others judge us, for the choices we make about our care, but there shouldn’t be any judgement on our decision choices, especially from other people! Whatever choices you make for yourself are based on what you think is best at the time, and that’s all we can do for ourselves: gather information and make a decision based on it. We don’t know how we will respond to a certain treatment, and we are all making the best decisions that we can based on our personal risk/benefit analysis as individuals.

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