[Directions of future research on GnGH analogs in the treatment of endometriosis and uterine fibromyoma]

Abstract

A variety of new data on the biology, pathophysiology and metabolic changes occurring in leiomyomas and in the ectopic endometrium have opened new avenues for research in a neglected area, that of benign proliferations of the female reproductive tract. In addition, the availability 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 evaluate the effect of oestrogen deprivation on endometriosis and uterine fibrosis. The results, although impressive, are only temporary: in both cases hypoestrogenism produces an important relief of symptoms, but--once treatment is discontinued--both conditions usually continue to evolve. For this reason, much remains to be done to optimize Gn-RH analogue utilization. In the case of endometriosis, there seem to be three main areas for future research: pain, infertility and the possibility of modifying its natural history. In addition, the role of combined, medico-surgical therapy remains to be established, especially in the case of severe disease. In the treatment of fibrosis, analogues can be utilized as pre-treatment before conservative or demolitive surgery, or as an alternative to hysterectomy. The role of analogues as a pre-surgical adjuvant has probably been overemphasized and it is time to carry out well controlled studies to narrow down indications. At present they include: severe anemia caused by chronic heavy uterine bleeding, and the need to minimize intraoperative blood loss. Much remains to be done before analogues can become a real alternative to surgery. To date no single sequential therapeutic regimen has been identified which is capable of prolonging the beneficial 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 associating an oestrogen-progestogen sequential combination as in HRT. In all of these instances, what are urgently needed are well controlled randomized clinical trials.