Gonadotropin-releasing hormone agonist (GnRH-a) therapy for endometriosis

Examples

Gonadotropin-releasing hormone agonists

Generic Name	Brand Name
goserelin	Zoladex
leuprolide acetate	Lupron Depot
nafarelin acetate	Synarel

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.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

Some studies of women with severe endometriosis have found that 6 months of GnRH-a therapy before in vitro fertilization improve the chances of a healthy pregnancy.¹

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

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% per 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 health professional 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. Generally, 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 per month). This does not include the cost of add-back therapy.

Add-back therapy Many health professionals are now 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. Some doctors believe in starting treatment with GnRH-a alone before using the add-back agents.⁴ But recent research has shown that starting add-back therapy right away does not interfere with endometriosis relief from GnRH-a therapy. Talk with your doctor about add-back therapy.

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Author:	Kathe Gallagher, MSW Ralph Poore Monica Rhodes	Last Updated: August 1, 2007
Medical Review:	Kathleen Romito, MD - Family Medicine Deborah A. Penava, BA, MD, FRCSC, MPH - Obstetrics and Gynecology
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