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Gonadotropin-Releasing Hormone (Gn-RH) Agonists

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By Editorial Team

3 min read

Reviewed by: HU Medical Review Board | Last reviewed: March 2023

Gonadotropin-releasing hormone agonists (Gn-RH agonists) are drugs that decrease ovarian function by reducing levels of estrogen and other hormones in the body. Gn-RH agonists may reduce pain caused by endometriosis.1

How do Gn-RH agonists work?

Tissue builds up in the uterus every menstrual cycle. However, uterine-like tissue sometimes grows outside of the uterus, causing pain. This is called endometriosis. Hormones, like estrogen, can stimulate the growth of this tissue outside the uterus.2

Endometriosis tissue does not respond in the same way that tissue inside the uterus responds. The tissue inside the uterus sheds with every menstrual cycle. Endometriosis tissue can grow, bleed, and form scars.2

Gn-RH agonists desensitize Gn-RH receptors, which ultimately reduces hormone release. When estrogen is decreased, endometriosis growth slows. This decrease in estrogen also decreases the pain caused by endometriosis.2

A similar type of drug called Gn-RH antagonists also decrease estrogen levels in the body. But unlike Gn-RH agonists, they do not contain hormones.

Examples of Gn-RH agonists

Different Gn-RH agonist drugs are used to treat endometriosis, including:3-6

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  • Lupron – Leuprolide injections
  • Lupaneta Pack – Leuprolide injections with an oral add-back therapy containing the progestin norethindrone. Add-back therapy allows “adding back” a small amount of estrogen to decrease symptoms from low estrogen (including low bone density, which can lead to fractures).
  • Zoladex – Implant containing goserelin
  • Synarel – Nafarelin nasal spray

What are the possible side effects of Gn-RH agonists?

Side effects can vary depending on the specific drug you are taking. Some possible side effects of Gn-RH agonists include:3-6

  • Hot flashes
  • Decreased interest in sex
  • Decrease in bone mineral density
  • Headaches
  • Unexpected vaginal bleeding
  • Dizziness
  • Trouble sleeping
  • Nausea and vomiting
  • Weight changes
  • Changes in mood or behavior such as depression, anxiety, or other signs of emotional instability

These are not all the possible side effects of Gn-RH agonists. Talk to your doctor about what to expect when taking Gn-RH agonists. You also should call your doctor if you have any changes that concern you when taking Gn-RH agonists.

Things to know about Gn-RH agonists

Gn-RH agonists can increase the risk of heart or vessel complications, such as heart attack or stroke. They may also cause increased calcium levels in your blood and high blood sugar levels (hyperglycemia).3-6

Gn-RH agonists can cause a loss of bone mineral density. This can decrease bone density, which increases the risk of fracture. For these reasons, long-term use is not recommended. Gn-RH agonists can harm an unborn baby. Talk to your doctor about your options for birth control and breastfeeding while taking this type of drug.3-6

Seek immediate medical attention if you experience any of the following:3-6

  • Vision problems, such as bulging eyes, double vision, or sudden loss of vision
  • Severe migraine-like headaches
  • Depression or worsening depression
  • Severe signs of mental or emotional instability
  • Severe swelling
  • Pregnancy
  • Signs of an allergic reaction, such as swelling of your face or mouth, breathing problems, chest pain, dizziness, itching, or skin rash

Before you start taking a Gn-RH agonist, tell your doctor if you have:3-6

  • A history of blood clots
  • A history of any heart problems
  • Diabetes
  • Kidney or liver problems
  • A history of cancer, especially hormone-sensitive cancers like breast cancer
  • A history of mental illness such as depression
  • A history of seizures or epilepsy
  • A history of osteoporosis (thinning of the bones) or a family history or osteoporosis
  • High cholesterol
  • A history of migraines
  • Are pregnant or planning to become pregnant
  • Are breastfeeding or planning to breastfeed
  • Are a smoker
  • Regularly drink alcohol

Before beginning treatment for endometriosis, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.