Gonadotropin-Releasing Hormone Agonist (GnRH-a) Therapy for Endometriosis

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Gonadotropin-Releasing Hormone Agonist (GnRH-a) Therapy for Endometriosis


Gonadotropin-releasing hormone agonists

Generic NameBrand Name
leuprolide Lupron Depot

How these medicines are taken

  • Leuprolide is injected into muscle (intramuscularly) once a month. It is also available in a dose that lasts for 3 months.
  • Nafarelin is sprayed into the nose (intranasally) twice a day.
  • Goserelin 3.6 mg pellet is injected under the skin of the abdomen (subcutaneously) once every 28 days. Your body gradually absorbs the pellet.

How It Works

GnRH-a therapy decreases production of the hormone estrogen to the levels women have after menopause. This decrease:

  • Stops menstrual periods.
  • Stops the growth and reduces the size of endometriosis sites.

GnRH-a therapy is limited to a short period of time (3 to 6 months). For some women, the benefits of treatment are only a temporary solution, lasting several months. For others, relief is long-lasting.

Why It Is Used

Gonadotropin-releasing hormone agonist (GnRH-a) therapy is widely used to shrink endometriosis implants, which relieves pain. GnRH-a therapy is usually a second-choice treatment that is used when several months of birth control pill therapy have not been effective.

GnRH-a therapy is sometimes used before surgery to make implants easier to remove. This can help reduce the amount of scar tissue created by the surgery.

GnRH-a therapy can't be used as an infertility treatment. (But it may be used before in vitro fertilization.1)

How Well It Works

Like all hormone therapies and surgery for endometriosis, GnRH-a therapy does not cure the disease.

Up to 90% of women report full or partial pain relief after 6 months of GnRH-a therapy. Treatment also shrinks endometriosis implants in about 90% of women.2

GnRH-a therapy after surgery can extend pain relief by preventing the growth of new or returning endometriosis.3

Pain recurrence

After GnRH-a treatment, or any other hormone therapy, endometriosis pain can return.2

  • Each year, up to 20% of all women treated will have pain return after hormone treatment.
  • About 37% of women who use hormone therapy for mild endometriosis have pain 5 years later.
  • About 74% of women who use hormone therapy for severe endometriosis have pain 5 years later.

Side Effects

All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine.

Here are some important things to think about:

  • Usually the benefits of the medicine are more important than any minor side effects.
  • Side effects may go away after you take the medicine for a while.
  • If side effects still bother you and you wonder if you should keep taking the medicine, call your doctor. He or she may be able to lower your dose or change your medicine. Do not suddenly quit taking your medicine unless your doctor tells you to.

Call 911 or other emergency services right away if you have:

  • Trouble breathing.
  • Swelling of your face, lips, tongue, or throat.

Call your doctor if you have:

  • Hives.
  • A fast or irregular heartbeat.
  • Bone, muscle, or joint pain.
  • Anxiety, depression, or other mood changes.
  • Bleeding between menstrual periods.

Common side effects of this medicine include:

  • An irregular menstrual period (or no menstrual period at all).
  • Hot flashes.
  • Vaginal burning, itching, or dryness.
  • Decreased sexual interest.
  • Thinning of the bones.
  • Increased acne or oily skin or hair.
  • An irritated or runny nose (nafarelin only).

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

These medicines are given as a shot or a nasal spray. You will get instructions on how to give the shot or use the nasal spray. Ask your doctor or pharmacist if you have any questions about how to take your medicine correctly.

Add-back therapy. Many doctors are prescribing GnRH-a therapy in combination with other medicines such as low-dose estrogen and progestin to control bone thinning and decrease the side effects of menopause, such as hot flashes.

Taking medicine

Medicine is one of the many tools your doctor has to treat a health problem. Taking medicine as your doctor suggests will improve your health and may prevent future problems. If you don't take your medicines properly, you may be putting your health (and perhaps your life) at risk.

There are many reasons why people have trouble taking their medicine. But in most cases, there is something you can do. For suggestions on how to work around common problems, see the topic Taking Medicines as Prescribed.

Advice for women

Do not use this medicine if you are pregnant, breast-feeding, or planning to get pregnant. If you need to use this medicine, talk to your doctor about how you can prevent pregnancy.


Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take.

Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.



  1. American Society for Reproductive Medicine (2006). Endometriosis and infertility. Fertility and Sterility, 86(Suppl 4): S156–S160.
  2. Fritz MA, Speroff L (2011). Endometriosis. In Clinical Gynecologic Endocrinology and Infertility, 8th ed., pp. 1221–1248. Philadelphia: Lippincott Williams and Wilkins.
  3. American College of Obstetricians and Gynecologists (2010). Management of endometriosis. ACOG Practice Bulletin No. 114. Obstetrics and Gynecology, 116(1): 225–236.


ByHealthwise Staff
Primary Medical ReviewerAdam Husney, MD - Family Medicine
Specialist Medical ReviewerKirtly Jones, MD - Obstetrics and Gynecology
Last RevisedMay 14, 2012

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