Gonadotropin-releasing hormone analogue (GnRH-a) therapy

Examples

gonadotropin-releasing hormone analogue (GnRH-a)

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

• Leuprolide is injected into a 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. The pellet is gradually absorbed by the body.

Gonadotropin-releasing hormone analogue (GnRH-a) therapy is approved for the treatment of endometriosis and uterine fibroids. A GnRH-a is rarely used for dysfunctional uterine bleeding.

GnRH-a therapy is usually taken for only 3 to 6 months to avoid long-term side effects.

How It Works

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

• Prevents ovulation and stops menstrual periods (but it does not provide dependable pregnancy prevention).
• Stops the growth of and reduces the size of endometriosis sites (implants).
• Reduces uterine size.
• Stops uterine fibroid growth and promotes fibroid shrinkage.¹

Why It Is Used

GnRH-a therapy is used to help diagnose or treat disorders that are linked to menstrual hormones, such as endometriosis and uterine fibroids. GnRH-a therapy may be used:

• For dysfunctional uterine bleeding or ovarian cysts.
• For endometriosis.
• When an ultrasound has confirmed that uterine fibroids are present, and they cause significant symptoms.

Dysfunctional uterine bleeding. GnRH-a therapy is used under special circumstances, such as when no other medical treatment has reduced uterine bleeding and a woman wants to avoid surgery.

GnRH-a therapy is sometimes used to thin the endometrium before endometrial ablation for dysfunctional uterine bleeding. This is the most effective medicine for this use.^{2, 3}

A GnRH-a is a good choice for women who have heavy menstrual periods after organ transplant procedures, especially a liver transplant. If they are used for long-term therapy after organ transplant, then additional treatment with daily estrogen and progesterone is recommended to prevent bone loss (osteoporosis).⁴ This is called "add-back" therapy.⁵

Uterine fibroids. GnRH-a therapy is usually limited to presurgery treatment to:

• Shrink fibroids before removal by myomectomy or hysterectomy.
• Correct anemia caused by heavy bleeding. (Iron supplements are another option for correcting anemia.)

GnRH-a therapy is not usually used to relieve fibroid symptoms only, because fibroids grow back fairly quickly after GnRH-a therapy ends. But for women who are close to menopause (when fibroids shrink), short-term relief with GnRH-a therapy may be a reasonable option.

Before gynecologic surgery. GnRH-a therapy may be used before surgery to:⁶

• Reduce the size of fibroids or endometriosis sites (implants), allowing for easier removal of the problem growths or the uterus (hysterectomy).
• Attempt to prevent scarring that might occur after surgery.

GnRH-a therapy is usually used for short periods of time (3 to 6 months). It can weaken the bones when used for longer periods of time.⁷

How Well It Works

Dysfunctional uterine bleeding. GnRH-a therapy causes a significant reduction in severe menstrual bleeding. This relieves anemia and reduces the need for blood transfusions. But blood loss returns to pretreatment levels when this treatment is stopped.⁵

Uterine fibroids. Fibroids usually shrink to 40% to 60% of their original size.^{8, 9}

• Smaller fibroids are easier to remove surgically (myomectomy).
• Smaller fibroids result in fewer surgical complications and less blood loss during surgery.
• Small fibroids may completely disappear after 12 weeks of treatment.
• A vaginal hysterectomy may be possible, which would avoid an abdominal hysterectomy.

Ovarian cysts. GnRH-a therapy may reduce or prevent ovarian cysts that are related to ovulation.

Chronic pelvic pain. Women report improvement in pelvic pain at the end of treatment with:

• Leuprolide (Lupron Depot).
• Nafarelin (Synarel).

Recurrence

• These medicines are only a temporary solution. When treatment stops, chronic pelvic pain and fibroid growth will gradually return.
• 1 year after the end of treatment with leuprolide (Lupron Depot), over half of women reported the return of some painful periods.
• 6 months after the end of treatment with nafarelin (Synarel), many women reported mild pelvic pain.

Side Effects

GnRH-a therapy controls symptoms by producing a condition similar to menopause, with many of the same effects. Side effects that go away when the medicine is stopped include:

• Hot flashes.
• Mood swings.
• Vaginal dryness.
• Decreased sexual interest.
• Increased LDL (low-density lipoprotein) cholesterol level.
• Decreased HDL (high-density lipoprotein) cholesterol.
• Insomnia.
• Headaches.

Pregnancy may be possible during and after therapy.

A woman's bones can weaken when she takes GnRH-a for longer than 6 months. After treatment, bone loss slows down. Then the bones get stronger, though they may not completely return to normal. ⁷

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

What To Think About

During GnRH-a therapy, pregnancy is highly unlikely because the menstrual cycle is shut down. However, 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 ($250 to $600 per month). This does not include the cost of add-back therapy.

GnRH-a therapy is rarely used for dysfunctional uterine bleeding—only when symptoms are severe enough and treatment options are limited enough that the possible benefit outweighs the severity of the medicine's side effects.

• Consider your risk of bone loss (osteoporosis) before starting GnRH-a therapy.⁵ Because of the lack of data on bone mineral density changes during longer or repeated courses of treatment, GnRH-a therapy is currently only approved for a single 6-month treatment period. For information on protecting bone density, see the topic Osteoporosis.
• Consider your risk of heart disease. GnRH-a therapy may raise your level of LDL cholesterol and decrease your HDL cholesterol.

GnRH-a therapy is only a temporary solution for the treatment of uterine fibroids and dysfunctional uterine bleeding. When treatment stops:

• Uterine fibroids usually grow back quickly.¹⁰
• Uterine bleeding returns to pretreatment levels.⁵

GnRH-a add-back therapy When a GnRH-a is used for longer than 3 to 6 months, you can use other medicines (add-back therapy) to decrease bone density loss. Some experts recommend using add-back therapy from the start, because it also relieves menopausal symptoms. Treatment combinations include GnRH-a, supplemental calcium, and:

• Progestin and low-dose estrogen.
• Progestin.
• Progestin and a bisphosphonate (an osteoporosis medicine).

New medicine combinations may soon be available.

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Author:	Kathe Gallagher, MSW	Last Updated: August 16, 2007
Medical Review:	Kathleen Romito, MD - Family Medicine Kirtly Jones, MD - Obstetrics and Gynecology
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