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Abstract
One distinctive feature of leiomyomata is the presence of abundant fibrous connective tissue elements and ECM. It is also thought that this overproduced ECM itself may play a dynamic role in the metabolic processes leading to tumor growth, by influencing cellular proliferation and differentia¬tion and serving as a repository for biologically active growth factors and cyto¬kines.
The sex steroid hormones play an important role in myoma maintenance and growth as evidenced by clinical, molecular, biological, and pharmacological models. It was found that leiomyomas develop only after the commencement of menstrual cycles and be¬come symptomatic usually in the 30s or 40s. At the time of menopause, leio¬myomas start to regress in most patients. The ovary is thought to be the major source of sex steroids for leiomyoma growth. There’s evidence that there were increased numbers of ERs in leiomyomas versus normal myometrium. Clinicians are developing some understanding of mechanisms of action of estrogen. Estrogen may directly increase proliferation of leiomyoma cells by possibly altering the expression of a large number of genes and growth factors or indirectly increase growth by enhancing progesterone action in human leiomyomas. Although the details of the role of estrogen in myoma growth are still elusive, the potential therapeutic benefit of agents that interrupt ovulation provided important clues. The use of gonadotropin-releasing hormone showed a significant reduction in fibroid size, while the use of selective ER modulators as clomiphene citrate and tamoxifen may cause rapid increase in size of fibroid due to its estrogenic effect. However raloxifene causes significant decrease in overall uter¬ine size and in the size of the fibroids. Studies proved that leiomyomas express aromatase at strikingly higher levels than the surrounding myometrium which is needed for local estrogen production even in perimenopausal or postmenopausal females where the ovarian function declines or stops. Studies suggest that progesterone (and possibly the up-regulation of progesterone receptors by estrogen) plays a significant role in the cellular proliferation of leiomyoma. Because the evidence for a direct mitogenic action of progesterone is incomplete, however, one may