A benefit-risk assessment of medical treatment for uterine leiomyomas

The growth of a uterine leiomyoma growth stops and regresses after the menopause suggesting that leiomyoma growth is dependent on ovarian steroids. Therefore, estrogen has received much attention as the major factor responsible for the development of uterine leiomyomas, but progesterone also plays an important role in development of this disease. Cytogenetic analyses of resected samples has revealed that about 40 to 50% of leiomyomas show karyotypically detectable chromosomal abnormalities. Gonadotrophin releasing hormone (GnRH) agonists exert their action through the suppression of endogenous gonadotrophins and gonadal steroid secretion. Significant reductions of uterine/leiomyoma volume under GnRH agonist therapy has been reported in several studies. However, the leiomyoma generally returns to its pretreatment volume within a few months after discontinuation of the GnRH agonist. To minimise the adverse effects of hypoestrogenism during GnRH agonist treatment, add back therapy can be used (estrogen-progestin, progestin alone and recently tibolone). Antiprogestins have a potential clinical utility in uterine leiomyomas. Mifepristone is a synthetic steroid with both antiprogesterone and antiglucocorticoid activities, that may have an inhibitory effect on growth of leiomyoma. Danazol is an isoxazole of 17beta-ethinyl testosterone, a synthetic steroid, which has a suppressive effect on sex hormone binding globulin concentrations, resulting in efficacy in the short-term treatment of uterine leiomyomas. Gestrinone is a tri-enic steroid with antiestrogen and antiprogesterone properties and has been shown to reduce uterine volume and stop bleeding. Growth factors play a relevant role on the pathophysiology of uterine leiomyoma and probably the inhibition of the action of growth factors on the myometrium will be the basis for future therapy. A number of agents are under investigation for treating uterine leiomyoma. Agents developed from increasing genetic knowledge of this condition could represent, in the next few years, new trends in the medical treatment of uterine leiomyomas.