Gonadotropin-releasing hormone analogue (GnRH-a) therapy

Examples

gonadotropin-releasing hormone analogue (GnRH-a)

• 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.

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

References

Citations

1. Wallach E, Vlahos NF (2004). Uterine myomas: An overview of development, clinical features, and management. Obstetrics and Gynecology, 104(2): 393-406.

2. Tierney R, et al. (2000). Menstrual blood loss measured 5 to 6 years after endometrial ablation. Obstetrics and Gynecology, 95(2): 251-254.

3. Donnez J, et al. (2001). Goserelin acetate (Zoladex) plus endometrial ablation for dysfunctional uterine bleeding: A 3-year follow-up evaluation. Fertility and Sterility, 75(3): 620-622.

4. Speroff L, Fritz MA (2005). Dysfunctional uterine bleeding. In L Speroff, MA Fritz, eds., Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 548-571. Philadelphia: Lippincott Williams and Wilkins.

5. Mishell DR Jr, et al. (2001). Abnormal uterine bleeding. In MA Stenchever et al., eds., Comprehensive Gynecology, 4th ed., pp. 1079-1097. St. Louis: Mosby.

6. Lethaby A, et al. (2002). Efficacy of pre-operative gonadotropin hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: A systematic review. British Journal of Obstetrics and Gynaecology, 109(10): 1097-1108.

7. Speroff L, Fritz MA (2005). The uterus. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 113-144. Philadelphia: Lippincott Williams and Wilkins.

8. American College of Obstetricians and Gynecologists (2000). Surgical alternatives to hysterectomy in the management of leiomyomas. ACOG Technical Bulletin No. 16. Obstetrics and Gynecology, 95(5): 1-9.

9. Haney AF (2003). Leiomyomata. In JR Scott et al., eds., Danforth's Obstetrics and Gynecology, 9th ed., pp. 869-887. Philadelphia: Lippincott Williams and Wilkins.

10. Lethaby A, Vollenhoven B (2006). Fibroids (uterine myomatosis, leiomyomas). Online version of Clinical Evidence (15).

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