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 acetateLupron Depot
nafarelin acetateSynarel

How these medicines are taken

  • Leuprolide acetate is injected into muscle (intramuscularly) once a month. It is also available in a dose that lasts for 3 months.
  • Nafarelin acetate 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 cannot be used as an infertility treatment. (But it may be used before in vitro fertilization.3)

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.1

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

GnRH-a side effects are like menopause symptoms. They are caused by low estrogen levels. These side effects last as long as you are taking a GnRH-a. Side effects include:

  • Rapid bone loss of up to 1% a month. This is partially reversed by also taking low-dose estrogen.2 Most women regain their pretreatment bone density after stopping GnRH-a therapy.
  • No menstrual periods. (Treatment is meant to stop menstrual periods. Call your doctor if your regular periods continue.)
  • Hot flashes.
  • Mood swings.
  • Vaginal dryness.
  • Reduced sexual interest.
  • Increased cholesterol level.
  • Decreased high-density lipoprotein (HDL, or "good") cholesterol.
  • Insomnia.
  • Headaches.

These low-estrogen side effects are greatly relieved by taking estrogen add-back therapy along with GnRH-a therapy (see below). After stopping treatment, bone density slowly recovers, although not completely in some women.2

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

What To Think About

When considering GnRH-a therapy, weigh the short-term benefits against the side effects, which can be bothersome. You also may have long-term health effects, such as permanent bone-thinning (osteopenia) and increased cholesterol.

  • Add-back therapy may further raise your cholesterol levels.
  • If you are worried about your cholesterol levels and coronary artery disease, danazol (also used for endometriosis) is not a good hormone therapy choice for you. It is likely to have an even worse effect on cholesterol levels than GnRH-a plus add-back therapy.

Consider your risk for bone loss before starting GnRH-a therapy:

  • For more information on protecting bone density and for risk assessment, see the topic Osteoporosis.
  • If you have a high osteoporosis risk, talk to your doctor about a different treatment.
  • Add-back therapy with estrogen helps to reduce bone loss from GnRH-a therapy (see below).
  • To protect your bones, you may need to wait at least 1 year before starting a second course of hormone therapy. Typically, only two courses of treatment are recommended.

During GnRH-a therapy, pregnancy is highly unlikely because the menstrual cycle is shut down. But use a barrier method of birth control, such as condoms, to prevent pregnancy while using this medicine. Do not use a GnRH-a if you are pregnant.

GnRH-a therapy is expensive (several hundred dollars a month). This does not include the cost of add-back therapy.

Add-back therapy Many doctors are prescribing GnRH-a therapy in combination with other medicines to control bone-thinning and decrease menopausal side effects, such as hot flashes. The most proven add-back therapy is low-dose estrogen and progestin. This is thought to raise your hormone levels enough to benefit your bones, but not enough to encourage endometriosis growth.2 The decrease in bone mineral density partially recovers after stopping treatment. But it does not necessarily return to normal. Medicine combinations include:

  • GnRH-a and estrogen.
  • GnRH-a, progestin, and low-dose estrogen.
  • GnRH-a, estrogen with or without progestin, and etidronate disodium (Fosamax).

Experts disagree about the timing and treatment intervals of this therapy. Talk with your doctor about add-back therapy.

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



  1. Winkel CA (2003). Evaluation and management of women with endometriosis. Obstetrics and Gynecology, 102(2): 397–408.
  2. Speroff L, Fritz MA (2005). Endometriosis. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 1103–1133. Philadelphia: Lippincott Williams and Wilkins.
  3. American Society for Reproductive Medicine (2006). Endometriosis and infertility. Fertility and Sterility, 86(Suppl 4): S156–S160.


By Healthwise Staff
Primary Medical Reviewer Sarah Marshall, MD - Family Medicine
Primary Medical Reviewer Anne C. Poinier, MD - Internal Medicine
Specialist Medical Reviewer Deborah A. Penava, BA, MD, FRCSC, MPH - Obstetrics and Gynecology
Last Revised December 8, 2009

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