Uterine Effects Of Estrogen Plus Progestin Therapy And Raloxifene: Adjudicated Results From The Euralox Study

OBJECTIVE: To compare the incident rate of abnormal endometrial findings in postmenopausal women receiving treatment with either 60 mg of raloxifene or a continuous combined estrogen plus progestin therapy containing 2 mg of 17beta-estradiol plus 1 mg of norethisterone acetate for a duration of up to 12 months.METHODS: One thousand eight asymptomatic postmenopausal women with osteoporosis or cardiovascular risk factors with an endometrial thickness of less than 5 mm at baseline participated in this prospective, randomized, double-blind trial that lasted 6 months; 347 of these women also participated in a 6-month extension. Women with repeated bleeding or an increase in endometrial thickness to above 5 mm were subjected to saline-infused sonohysterography or hysteroscopy with biopsy. Sonographic, histologic, and clinical findings were adjudicated by a panel of 4 experts blinded with respect to patients' treatments. All adjudicated patients were grouped into 15 diagnostic categories according to predefined criteria.RESULTS: Three hundred thirty-four women needed adjudication during the core phase, 73 (14.7%) of those taking raloxifene and 261 (50.9%) taking continuous combined estrogen plus progestin therapy (P < .001). Compared with raloxifene, women using continuous combined estrogen plus progestin therapy had significantly higher rates of benign endometrial proliferation (8.8 versus 1.2%, P < .001), endometrial polyps (4.3 versus 2.0%, P = .048), and cystic atrophy (5.5 versus 1.2%, P < .001).CONCLUSION: Women using continuous combined estrogen plus progestin therapy more often have benign endometrial pathology and, in our study, more often required the protocol-specific gynecological follow-up assessments for safety reasons, as compared with those using raloxifene. These findings are of clinical relevance when choosing the most appropriate therapy for postmenopausal health risks such as osteoporosis. ((C) 2004 by The American College of Obstetricians and Gynecologists.).