Treatment of Endometrial Cancer with GnRH Analogs

Abstract

In many Western countries, endometrial carcinoma is now considered to be the most common gynecological malignancy, but mortality from this disease is less than that for ovarian malignancies. Nearly 20% of patients with endometrial carcinoma get second primaries, mostly in the breast and colon, indicating common denominators for many of these tumors. Certain factors predispose to this cancer. Many patients are obese, nulliparous, and have a history of irregular menses suggesting a basic abnormality in the hypothalamic-pituitary-ovarian hormonal axis. Long periods of unopposed estrogen stimulation of the endometrium may be a factor in carcinogenesis, since the endometrium is a highly sensitive end-organ to estrogens, regardless of whether they are of gonodal origin or exogenously administered. When the estrogen-induced growth is unopposed by progesterone (due to a lack of ovulations or for other reasons) the endometrium first shows hyperplasia. If the epithelial activity is excessive, adenomatous hyperplasia with prominent mitoses and changes that are difficult to distinguish from frank adenocarcinoma appear. The risk factors are also shared by these two conditions. Although treatment with progesterones may in some cases reverse an adenomatous hyperplasia so that even a desired pregnancy will be possible, in the somewhat older woman hysterectomy is considered to be the safest approach. In particular, the presence of cytonuclear atypia raises concern for premalignancy and progression to can]cer. It has also been proposed that such lesions should be referred to as endometrial intraepithelial neoplasia (EIN).