Lupron and GnRh Agonists

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The information on my platforms is educational information only and not medical advice. Always check with your qualified medical professional before making any changes to your treatment plan. Keep in mind that while I strive to share evidenced-based information on endometriosis, this doesn’t always mean that my information is accurate or complete. See my full disclaimer here.

Forms of GnRh agonists

These are medications like Lupron, Zoladex, Synarel, Prostrap, Decapeptyl, etc.

Important: this page is about GnRh agonists. This is not the same as GnRh antagonists, like Orilissa, Myfembree, Ryeqo, etc.)

How do GnRh agonists work?

GnRh is a hormone in the body that’s released by the hypothalamus in your brain. Normally, it is released in pulses, binds to receptors in the pituitary gland, and tells them to send LH and FSH to the ovaries, which is the signal to make estrogen.

GnRh agonists mimic the GnRh hormone in the body and binds directly to the GnRh receptor on the pituitary gland, therefore “tricking the gland” into thinking it’s been bonded with GnRh hormone. GnRh agonists, however, isn’t released in pulses and when they bind to the receptor, they overstimulate it. LH and FSH then flood the body, which tell the ovaries to make the sex hormones, especially estrogen. That’s why estrogen surges during the first 1-2 weeks on GnRh agonists, and many people see a worsening of their symptoms during that estrogen spike.

After that, the level of the sex hormones, including estrogen, begins to fall (through the desensitization and downregulation of the pituitary GnRh receptors) and continue to do so until they reach menopausal or near menopausal levels.

However, it’s important to know that endometriosis can continue making its own estrogen locally via the aromatase enzyme. 

“GnRH agonists affect only the hypothalamo-pituitary-gonadal axis, but not extraglandular sites of estrogen biosynthesis. Therefore, estrogen production occurs in the adipose tissue, the skin and local endometriotic lesions during these treatments.” (1)

GnRh agonists don’t treat the disease

GnRh drugs cannot diagnose, treat, remove, or shrink* endometriosis lesions.

*Although the prescribing information claims that Lupron shrinks the disease, this was based on a flawed study design which I talk about in my Instagram post here.

“It has been shown that the visual appearance of endometriosis at the end of GnRH agonist therapy may seem improved, while 3 months later it can seem worse. This indicates that some of the visual changes associated with endometriosis, such as adjacent capillary bleeding, inflammation, and swelling, may regress during treatment. However, once the drug wears off, the disease becomes more active once again, and the surrounding visual changes can recur. All of this happens without anything being done to the endometriosis itself.” (2)

Unfortunately, many doctors spread this misinformation because that’s how the drug has been marketed or explained to them. What GnRh drugs may do for some patients is provide symptom management only (although many people find the drug side effects intolerable).

How long can you take GnRh agonists?

For Lupron, the FDA has only approved it for 6 months without add-back treatment, and 12 months total if add-back is used the second six months. Add-back therapy is a medication you take at the same time at the same time as a GnRH agonist: a low-dose oestrogen, a low-dose progestin, or tibolone alone. If you decide to stay on Lupron or another GnRh agonist for longer than the FDA recommended time limit, you should speak to your doctor about having a bone density scan to periodically check your bone density.

Lupron* can have serious side effects

*Although some people report similar long term side effects after using other GnRh agonists, this next section focuses specifically on Lupron.

Apart from the side effects one may have while taking Lupron, it may also cause long-term, irreversible side effects even after stopping the drug. Some people report having permanent side effects after taking Lupron, some of which lowered their quality of life or left them disabled. In fact, there are Facebook groups called “Lupron Victims” and “Lupron Survivors” because these people’s health was so seriously affected by Lupron that they feel they survived taking it! This isn’t to scare anyone, but rather to say that in terms of side effects, some people have found them to be serious, permanent, and even disabling (3). 

If you decide that taking Lupron is right for you, then I hope it provides you symptom relief! However, make sure to adequately research Lupron to see if you feel that the potential benefits outweigh the potential risks of taking this serious medication. Many people who take Lupron later say, “I wish I had known XYZ about Lupron before taking it.”