Leiomyomata

Background

Leiomyomata (fibroids) are the most common benign soft tissue tumors in women. Up to 77% of women have microscopic or macroscopic uterine fibroids at the time of menopause (Cramer 1990); fibroids occur in all ethnic groups examined, but are more common in African-American than Caucasian women. Leiomyomata may be 1 mm to 20 cm in diameter.

Leiomyomata are almost always benign in pre-menopausal women but may be indistinguishable from leiomyosarcomas, a rare tumor most common in post-menopausal women. The latter condition is more likely in older women and when the tumors grow rapidly in size.

While these tumors may not cause symptoms, they frequently have clinical manifestations, such as excessive uterine bleeding, chronic pelvic pain or pressure, or dysmenorrhea, especially when large. Miscarriage and infertility are associated with fibroids as well. However, it is the location, rather than the size of the fibroid that appears related to these last two clinical problems.

Treatment

The treatment of fibroids depends on the symptoms, location and size of the tumor(s), and the age of the woman. Observation (no treatment) is recommended for asymptomatic women and medical treatment for those with excessive bleeding. In some small studies, induction of a “medical menopause” with low estradiol and progesterone levels by GnRH agonists led to rapid shrinkage of the tumors. However, medical therapy with GnRH agonists causes hot flushes and osteoporosis (the latter when given for more than six months), so they are recommended for use only up to six months. The selective progesterone receptor modulator Mifepristone also reduced fibroid size at daily doses of 10 – 50 mg (Murphy 1995, Stewart 1998). However, this drug is not widely available.

Because there are no safe and effective long-term medical therapies for leiomyomata, surgical extirpation by hysterectomy or myomectomy is the major therapeutic option for symptomatic women (Farquhar 2002). The American College of Obstetricians and Gynecologists (ACOG) has defined conditions under which hysterectomy is an appropriate therapy of fibroids for women who do not wish to maintain fertility (ACOG Practice Bulletin 1994). These include excessive bleeding, pelvic discomfort or increased urinary frequency or uterine enlargement greater than 12 weeks gestation size that is a concern to the patient. Laparoscopic or hysteroscopic myomectomies may be an alternative to laparotomy or hysterectomy depending on the skill of the laproscopist and whether the fibroids are submucosal and can be accessed by the hysteroscope (ACOG Practice Bulletin 2000). Endometrial ablation to destroy the endometrium targets the source of endometrial bleeding and may be effective when that is the primary symptom. A number of small studies with limited follow-up suggest that uterine artery embolization can decrease bloodflow to the uterus, and reduce leiomyoma and uterine size. However, the procedure may be painful and cause infection and bleeding that leads to surgery. Because of damage to the uterine and ovarian blood supply, it is not recommended for pre-menopausal women interested in preserving fertility. Pregnancy outcomes following this procedure are not well studied.

Clinicians would welcome new medical treatments to reduce fibroid symptoms – either before menopause or before surgery. Ideally, these treatments would exploit information about the cause or maintenance of leiomyomata. This study evaluates a possible new medical treatment.

Farquhar CM, Steiner CA. Hysterectomy rates in the United States 1990-1997. Obstet Gynecol. 99:229-34, 2002

ACOG practice bulletin. Surgical alternatives to hysterectomy in the management of leiomyomas. Number 16, May 2000. Int J Gynaecol Obstet. 2001 Jun;73(3):285-93, 2001.

Stewart EA, Nowak RA. New concepts in the treatment of uterine leiomyomas. Obstet Gynecol. Oct 92(4 Pt 1):624-7, 1998.

Murphy AA, Morales AJ, Kettel LM, Yen SS. Regression of uterine leiomyomata to the antiprogesterone RU486: dose-response effect. Fertil Steril. 64:187-90, 1995.

ACOG technical bulletin Uterine leiomyomata. Number 192--May 1994. Int J Gynaecol Obstet. 46:73-82, 1994.

Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol. 94:435-8, 1990.