Gonadotropin-Releasing Hormone (Gn-RH) Antagonists

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

How do Gn-RH antagonists 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 endometriosis tissue outside the uterus.¹

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 lesions can grow, bleed, and form scars.¹

One way to treat pain caused by endometriosis is to decrease the amount of estrogen your body produces. Gn-RH antagonists work like this, leading to a reduction of estrogen.²

Gn-RH antagonists do not contain hormones, but they stop the body from making as much estrogen. When less estrogen is made, less fuel is made for endometriosis. This leads to a decrease in the growth of endometriosis lesions.²

A similar type of drug called Gn-RH agonists also decrease estrogen levels in the body. But unlike Gn-RH antagonists, they contain hormones.

Examples of Gn-RH antagonists

Gn-RH antagonist drugs approved to treat endometriosis include:^2,3

• Myfembree (relugolix/estradiol/norethisterone acetate)
• Orilissa (elagolix)

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

Gn-RH antagonists are taken in pill form by mouth. Common side effects include:^2,3

• Bone loss
• Changes in menstrual pattern. This leads to a decreased ability to recognize pregnancy.
• Thoughts of self-harm or worsening of mood disorders
• Potential for liver damage, shown by increased blood liver enzymes

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

Things to know about Gn-RH antagonists

Unlike Gn-RH agonists, Gn-RH antagonists do not typically cause low estrogen effects (mood swings, vaginal dryness, and hot flashes).³

Do not take Gn-RH antagonist drugs if you:³

• Are pregnant or may become pregnant
• Have bone disease
• Have severe liver problems
• Are taking certain anticancer drugs

Gn-RH antagonists can harm an unborn baby. People using Gn-RH antagonists should use birth control during treatment and for some time after the last dose. You should also not breastfeed during treatment with these drugs and for some time after the last dose. Talk to your doctor about your options for birth control and breastfeeding while taking a Gn-RH antagonist.³

Before taking a Gn-RH antagonist, tell your doctor if you:³

• Have broken bones, now or in the past
• Have other conditions or take medicines that may cause bone problems
• Experience depression, mood problems, or thoughts of self-harm
• Have liver problems
• Use birth control pills

Seek medical attention if you experience any of the following while taking a Gn-RH antagonist:³

• Thoughts of self-harm or worsening of mood
• Sudden changes in your mood, behaviors, thoughts, or feelings
• Abnormal liver tests

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.