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Disorders of the Uterus

Leiomyomata Uteri

Leiomyomata uteri are benign smooth muscle tumors of the uterus. They are also referred to as fibroids or uterine myomas. Myomas are the most common pelvic tumor in women, occurring in 20% of women of reproductive age. Approximately 30% of hysterectomies are performed because of myomas.

Etiology

A small number of genes have been determined to have mutated in uterine myomas. Mutations in these genes may cause uterine myomas. Myomas were discovered to be monoclonal tumors both by glucose-6-phosphate dehydrogenase isoform analysis and by analysis of polymorphisms in the androgen receptor gene. Myomas also were discovered to contain nonrandom cytogenetic abnormalities. Approximately 45% of myomas are cytogenetically abnormal, with normal karyotypes observed in normal myometrium from the same woman. The most frequently affected chromosomes are 1, 6, 7, 12, and 14. The most frequently reported cytogenetic abnormalities in myomas are: del (7)(q21), del (7)(q21 q32), t( 12; 14) (q 13 - 15 ,q23 -24), and t(1 ;2)(p36,p24). Using molecular biology techniques, investigators launched a positional cloning project to identify a consensus translocation site on chromosome 12. A gene at 12ql 5, the high-mobility group protein gene, was discovered to be mutated in many cases of uterine myomas. The high-mobility group protein gene is an architectural factor that binds to the minor groove of DNA and may play a role in organizing satellite chromatin. The gene is a phosphoprotein that is a substrate for cell regulatory kinases such as casein kinase II and p34/cdc2. The high-mobility group protein gene is a member of a family of proteins

The relationship between leiomyomas and leiomyosarcomas remains uncertain. Of women with a preoperative diagnosis of uterine myoma, fewer than 0.5% are discovered to have a leiomyosarcoma. Most leiomyosarcomas occur in uteri with coexisting myomas. In some cases, leiomyomas and coexisting leiomyosarcomas share the same cytogenetic abnormality [eg, del (7)(q22q32)]. These data support the concept that the sarcoma evolved, through ad ditional mutations, from the myoma. However, in many cases leiomyosarcomas contain clonal cytogenetic abnormalities that are not

Recent epidemiologic studies indicate that the peak occurrence of myomas is in women between 40 and 45 years of age. African-American women appear to have a threefold increase in the risk of developing myomas compared with white, Asian, and Hispanic women. The mechanisms that account for the high rate of myomas in African-American women are unknown. Pregnancy appears to protect

Uterine myomas contain estradiol and progesterone receptors. Both estradiol and progestins appear to regulate the size of myomas. In premenopausal women with myomas, suppression of estradiol and progesterone to the menopausal range decreases myoma volume by approximately 50%; the maximal decrease in myoma volume is reached by 3 months. Progestins also play a role in the size of myomas and fibroids.