Endometrial Pathology and Its Relation to Estrogen Therapy in Patients With Hypogonadism

Abstract

Clinical observations suggest that estrogen levels above physiologic plasma concentration can result in pathologic endometrial changes. Patients with feminizing ovarian tumors and those with the polycystic ovary syndrome who have excessive amounts of endogenous estrogens have a high incidence of endometrial cancer.1-4 Several investigators have noted the development of atypical hyperplasia and adenocarcinoma in women receiving prolonged treatment with various estrogen preparations, including the sequential oral contraceptives.5-11 Until recently, the association of exogenous estrogens with carcinoma of the endometrium had been based on clinical impression, but convincing epidemiological data had been lacking. Recent reports by Smith et al.12 and Ziel and Finkle13 indicate that the risk of endometrial cancer is 5 to 14 times greater in women taking exogenous estrogens. Patients with hypogonadism are frequently treated with estrogenic substances to initiate the development of breasts and menstrual bleeding. Most of these patients are then maintained on estrogenic preparations for years. Therefore, this group of subjects provides a model for the study of possible development of endometnial changes in response to estrogen therapy. To date, there have been 12 reported cases of endometrial adenocarcinoma in gonadal dysgenesis patients who received estrogen therapy.14-19 Eleven of these women were known to have received diethylstilbestrol; one patient was taking a sequential ethinyl estradiol-dimethisterone preparation at the time of the study and had previously taken an unknown estrogen preparation for four years. This article presents information about the relationship of estrogen therapy and endometrial histology in 43 hypogonadal patients followed up in the Pediatric Endocrine Clinic and the Department of Gynecology and Obstetrics at The Johns Hopkins Hospital, Baltimore.