Recent independent case-control studies have indicated that treatment with exogenous estrogen is associated with an increase in the risk of endometrial cancer. This question was studied in Olmsted County, Minnesota, by identifying all cases of endometrial cancer among residents over a 30 year period (1945 through 1974) and by matching four controls to each of the 145 patients. The rate of past exposure to any exogenous estrogen for any duration was about the same for patients as for controls. However, the estimated relative risk of endometrial cancer associated with conjugated estrogen treatment of 6 months or longer was 4.9 (P less than 0.01), and this increased to 7.9 (P less than 0.01) with exposure for 3 years or longer. The risk increased with larger doses (1.25 mg. or more) and continuous administration of conjugated estrogens. The incidence of endometrial carcinoma over the three decades of the study, corrected for an increasing rate of hysterectomy, was constant. Thus to this time, the low rate of use of conjugated estrogens in this region over the past 30 years apparently has not had an appreciable impact on the incidence of endometrial cancer.
PIP: A relationship between exposure to exogenous estrogens and endometrial carcinoma has been reported in numerous studies. The incidence among those so exposed has been estimated to have been increased from 7.5 to 8 times that of those not exposed. Long-term therapy with estrogens for menopausal symptoms has been the usual history. Breast cancer patients treated with estrogens and young women taking sequential oral contraceptives have had increased risks. In this study, the records of Olmsted County, Minnesota, residents with endometrial uterine cancer diagnosed between 1945-1974 at the Mayo Clinic or at other medical facilities were reviewed. There were 122 adenocarcinomas and 23 adenoacanthomas. In 3 instances, adenocarcinomas contained zones of uterine sarcoma. For each of the 146 patients there were 4 age-matched controls. Estrogen use for 6 months or more was recorded for 39 (27%) of the 145 cases and for 163 (28%) of the 580 controls. The controls had more frequent histories of short-term estrogen therapy. Cancer patients had relatively more estrogen use for menopausal symptoms. The relative risk of endometrial cancer tended to increase with the duration of exposure to conjugated estrogens from 2.0 with any exposure to 4.9 (p less than .01) after 6 months or more and to 7.9 after 3 years or more. The risk increased with larger doses (1.25 mg or more) and with continuous administration of conjugated estrogen. Myometrial invasion was superficial in 77 cases and deep in 44 cases. Long-term use of conjugated estrogen was frequently associated with low-stage low-grade superficially invasive endometrial malignancy. The 5-year survival rate of the 145 patients was 85%. Patients with Stage 1 had a 95% relative 5-year survival rate. Those with Stages 2, 3, or 4 had 50% survival rates. Of other risk factors, obesity and nulliparity were noted. Patients had more frequent records of benign cystic adenoma and of adenomatous hyperplasia than controls. The corrected age-specific rate for endometiral cancer increased to a maximum of about 90/100,000 population per year in the group aged 55-64 and then diminished with age. An increase in endometrial cancer among those at risk may have been nullified by an increase in those who have had a hysterectomy. In this study the incidence of endometrial carcinoma in Olmsted County does not show an increase in the last 3 decades. It is noted that the long-term use of conjugated estrogens in this area has been relatively low.