Future research directions in the GnRH-Analogue treatment of endometriosis and uterine fibroids.

A variety of new data on the biology, pathophysiology and metabolic changes occur-ring in leiotnyonias and in the ectopic endometrium have opened new avenues for research in a neglected arest, that of benign proliferations of the fanale reproductive tract. In addition, the avallabUity of potent inhibitors of ovarian function which, like the super-agonist analogues of GnRH, have no hormonal activity (oestrogenic, progestogenic or androgenic) has allowed for the first time to evalu-ate -the effect of oestrogen deprivation on dontetriosis and uterine fibrosis. The results, although impressive, are only telnpOrnrys in both cases hypoestrogcnism produce@ an in> portant relief of symptoms, but--once treat-ment is discontinued—both conditions usuaUy continue to evolve. For this reason, much re-mains to be done to optimize Gn-RH analogue utilization. In the case of endometriosis, there seem to be three main areas for future researcht pain, infertility and the possibility of rnodifying its natura& history. In addition, the role of combined, medico-surgical therapy re- to be established, especially in the case of severe disease. In the treatment of abroga, analogues can be utilized as pre-treatment be-fere conservative or dentolitive surgery, or as an alternative to hysterectomy. The role of analogues as a pre-surgical adjuvant has probably becn overemphasized and it is time to carry out weU controlled studles to 11111TOW down indications. At present they Include se-vere anemia caused by chronic heavy uterine bleeding, and the need to minimfre intraoper-ative blood lotte. Musch remains to be done be-fare analogues can become a real alternative to surgery. Todate no single sequential therapeutic regimen has been identifled which is capable of prolonging the benefichial effects of agonists without their well known negative consequences. Temporary results can be obtained interrupting analogue therapy and substituting it with the administration of a progestogen. Finally analogue administration can be prolonged by assoclating an oestrogen-progestogen sequential coniblmttion as in HRT. In all of instances, what are urgently needed are well controlled randomized clinical trials.