Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene.

Idoxifene is a novel selective estrogen receptor modulator that has shown beneficial effects on bone turnover and lipid metabolism in clinical studies. Preclinical studies have demonstrated that idoxifene has estrogen antagonist activities on the endometrium. This paper describes the results of a double-blind, placebo-controlled, and dose ranging study involving 331 osteopenic postmenopausal women who were treated with either placebo or idoxifene (2.5, 5, or 10 mg/day) for 12 weeks. In these women, endometrial assessment was carried out by transvaginal sonography and endometrial biopsy on selected patients at baseline and on all women at the end of treatment. Women with an endometrial thickness greater than 10 mm were excluded from the study. Aspiration endometrial biopsy was performed on women with an endometrial thickness between 6 and 10 mm at baseline and on all women after treatment. Of the 298 biopsies performed in the subjects at the end of treatment, 99% of the women were reported to have either a benign or atrophic endometrium (85%) or insufficient tissue for diagnosis (14%). Proliferative histologic features were reported in two cases (1%) (2.5 mg idoxifene) and atypical hyperplasia in one placebo patient. Even though idoxifene use was associated with a dose related increase in endometrial thickness as evaluated by transvaginal sonography, no relationship was established between endometrial histologic features and change in endometrial thickness. On histologic analysis, the increase in endometrial thickness seen on transvaginal sonography was not associated with proliferative or hyperplastic change in the epithelial (glandular) endometrial tissue. In 48 patients (16% of total) transvaginal sonography showed endometrial thickening of 5 mm or more over the study period. The endometrial histologic features were benign in all these patients. Nineteen percent of women developed intraluminal fluid, even though endometrial thickness was normal and unchanged and histologic features were normal. Our data show that after 3 months of treatment, no significant pathologic changes of the endometrium were observed. Our data indicate that measurements of endometrial thickness by transvaginal sonography may falsely suggest the presence of endometrial pathologic changes in some postmenopausal women treated with idoxifene. Additional testing using saline infusion sonohysterography is an important part of the transvaginal sonography protocol in equivocal or abnormal cases to exclude focal lesions such as polyps. In addition, our data indicate that pathologic changes of the endometrium are extremely rare in the treated group, indicative of its short term safety. Continued investigation such as this will be needed to establish long term safety.

RCT Entities:   Population Interventions Outcomes