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Uterine fibroids and hysterectomy

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of uterine fibroids

Alternative Names

Hysterectomy and uterine fibroids; Leiomyoma; Myoma

Medications

Because fibroid growth tends to stop and regress after menopause, the important reproductive hormones--estrogen, progesterone, or both--most likely play a critical role in their survival. Some drugs that block either of these hormones are used to treat severe fibroids with some success.

Contraceptives

Oral contraceptives (OCs) are sometimes used to control the heavy menstrual bleeding (menorrhagia) associated with fibroids, but they do not help prevent fibroid growth. Intrauterine devices (IUDs) that release progestin may be very beneficial for menorrhagia. Specifically, the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena, FibroPlant), has shown excellent results. Many experts now recommend the LNG-IUS as a first-line treatment for menorrhagia, particularly for women who may face hysterectomy (removal of uterus), conservative surgery such as endometrial resection (removal of endometrial lining), or endometrial ablation (destruction of endometrial lining). [For more information, see In-Depth Report #100: Menstrual disorders.]

GnRH Agonists

Gonadotropin releasing hormone (GnRH) blocks the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and nafarelin (Synarel), a nasal spray. Such drugs may be used to alone or in preparation for procedures used to destroy the uterine lining.

These drugs may be used in the following situations:

• As preoperative treatment 3 to 4 months before uterine surgery. In a major analysis, the use of GnRH agonists reduced fibroid size and uterus volume, helped correct any existing anemia due to blood loss, reduced blood loss during surgery, and reduced the duration of hospital stay. (Some experts question, however, whether the benefits outweigh the costs.)
• For women with fibroids nearing menopause. (Such women only need them for a short period.)
• Possibly helpful in improving subsequent fertility. (However, women should not try to become pregnant while taking these drugs, as they pose a risk for birth defects.)

While GnRH agonists can reduce fibroids by between 30 - 90% of original size, they have certain limitations:

• They are not permanent cures and fibroids regrow after the drugs are discontinued
• They are injected drugs and cannot be taken orally
• They are expensive
• Long-term use of GnRh agonists causes bone density loss, which can lead to osteoporosis

Before using these drugs, the doctor should be certain that no other complicating conditions are present, particularly leiomyosarcoma (cancer). The use of these drugs can delay treatment of the malignancy and cause severe complications.

Commonly reported side effects, which can be severe in some women, include menopausal-like symptoms. These symptoms include hot flashes, night sweats, changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women should not take these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

• Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist.
• Intermittent leuprolide, which uses repeated 6-month courses of GnRH agonists followed by an average of 9 months of symptom control only.
• Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
• Adding a bone-protective drug may be helpful. The standard ones are bisphosphonates, which include alendronate (Fosamax), risedronate (Actonel), and etidronate (Didronel). Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include the parathyroid hormone teriparatide (Forteo) and selective estrogen-receptor modulators (SERMs), such as raloxifene (Evista).

GnRH treatments used alone do not prevent pregnancy. Furthermore, if a woman becomes pregnant during their use, there is some risk for birth defects. Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Androgens

Danazol (Danocrine) resembles a male hormone. It suppresses estrogen and is effective for heavy menstrual bleeding caused by fibroids. In some women it produces male characteristics such as facial hair and voice change. Other side effects include weight gain, acne, and dandruff. It may increase the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have been reported. At present there is no long-term experience using danazol for fibroids.

Antiprogestins

Gestrinone. Antiprogestins are promising drugs for fibroids. Gestrinone has been shown to reduce uterine volume and stop bleeding. In addition, benefits appear to persist. In one study, 89% of the women maintained a smaller uterine for at least 18 months after stopping the treatment. In another study, bone density even increased slightly. Adverse effects of gestrinone include male hormone symptoms, such as acne, and possibly the development of unhealthy cholesterol levels.

Mifepristone. Mifepristone (Mifeprex) is used for emergency contraception, but is controversial because it is one of the drugs used in the abortion pill. This drug is an anti-progestin that has reduced fibroid size in some studies. In one study, it reduced fibroids as significantly as GnRH agonists and the fibroids were less likely to recur. However, it can have severe side effects.

Asoprisnil. A promising new antiprogestin called Asoprisnil has been shown to reduce fibroids. The drug is in late-stage clinical trials.

Investigative Drugs

A number of other drugs are under investigation for treating fibroids:

• Selective estrogen-receptor modulators (SERMs) are drugs that have some of the effects of estrogen but do not produce some of its complications, such as a higher risk for uterine cancer. Raloxifene (Evista) is proving to help prevent bone loss in patients taking GnRH agonists for uterine fibroids, and may also be helpful as a single drug for preventing fibroid growth.
• Drugs that block growth factors believed to play a role in fibroids are also under investigation. Pirfenidone is one such drug, which blocks fibroid cell reproduction. Another is interferon alpha, substance that inhibits angiogenesis (the growth of new blood vessels).
• Drugs derived from retinoids (vitamin A compounds) may inhibit cell proliferation in fibroid tissue.
• Fulvestrant (Faslodex) blocks estrogen and has been studied for uterine fibroids and endometriosis, although progress in these areas has stalled in favor of research for its use in breast cancer.

• Review Date: 6/13/2006
• Reviewed By: Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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