One distinctive feature of leiomyomata is the presence of abundant fibrous connectivetissue elements and ECM. It is also thought that this overproduced ECM itself mayplay a dynamic role in the metabolic processes leading to tumor growth, by influencingcellular proliferation and differentiation and serving as a repository for biologically activegrowth factors and cytokines.The sex steroid hormones play an important role in myoma maintenance and growthas evidenced by clinical, molecular, biological, and pharmacological models. It wasfound that leiomyomas develop only after the commencement of menstrual cycles and becomesymptomatic usually in the 30s or 40s. At the time of menopause, leiomyomas start toregress in most patients. The ovary is thought to be the major source of sex steroids forleiomyoma growth. There's evidence that there were increased numbers of ERs inleiomyomas versus normal myometrium. Clinicians are developing some understanding ofmechanisms of action of estrogen. Estrogen may directly increase proliferation ofleiomyoma cells by possibly altering the expression of a large number of genes andgrowth factors or indirectly increase growth by enhancing progesterone action in humanleiomyomas. Although the details of the role of estrogen in myoma growth are still elusive, thepotential therapeutic benefit of agents that interrupt ovulation provided important clues. Theuse of gonadotropin-releasing hormone showed a significant reduction in fibroid size, whilethe use of selective ER modulators as clomiphene citrate and tamoxifen may causerapid increase in size of fibroid due to its estrogenic effect. However raloxifene causessignificant decrease in overall uterine size and in the size of the fibroids. Studies provedthat leiomyomas express aromatase at strikingly higher levels than the surroundingmyometrium which is needed for local estrogen production even in perimenopausal orpostmenopausal females where the ovarian function declines or stops. Studies suggest thatprogesterone (and possibly the up-regulation of progesterone receptors by estrogen)plays a significant role in the cellular proliferation of leiomyoma. Because the evidence for adirect mitogenic action of progesterone is incomplete, however, one may