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

Idoxifene is a novel selective estrogen receptor modulator that has shown b eneficial effects on bone turnover and lipid metabolism in clinical studies . Preclinical studies have demonstrated that idoxifene has estrogen antagon ist activities on the endometrium. This paper describes the results of a do uble-blind, placebo-controlled, and dose ranging study involving 331 osteop enic postmenopausal women who were treated with either placebo or idoxifene (2.5, 5, or 10 mg/day) for 12 weeks. In these women, endometrial assessmen t was carried out by transvaginal sonography and endometrial biopsy on sele cted patients at baseline and on all women at the end of treatment. Women w ith an endometrial thickness greater than 10 mm were excluded from the stud y. 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 endometriu m (85%) or insufficient tissue for diagnosis (14%). Proliferative histologi c features were reported in two cases (1%) (2.5 mg idoxifene) and atypical hyperplasia in one placebo patient. Even though idoxifene use was associate d with a dose related increase in endometrial thickness as evaluated by tra nsvaginal sonography, no relationship was established between endometrial h istologic features and change in endometrial thickness. On histologic analy sis, the increase in endometrial thickness seen on transvaginal sonography was not associated with proliferative or hyperplastic change in the epithel ial (glandular) endometrial tissue. In 48 patients (16% of total) transvagi nal sonography showed endometrial thickening of 5 mm or more over the study period. The endometrial histologic features were benign in all these patie nts. Nineteen percent of women developed intraluminal fluid, even though en dometrial thickness was normal, and unchanged and histologic features were normal. Our data show that after 3 months of treatment, no significant path ologic changes of the endometrium were observed. Our data indicate that mea surements of endometrial thickness by transvaginal sonography may falsely s uggest the presence of endometrial pathologic changes in some postmenopausa l women treated with idoxifene. Additional testing using saline infusion so nohysterography is an important part of the transvaginal sonography protoco l in equivocal or abnormal cases to exclude focal lesions such as polyps. L n addition, our data indicate that pathologic changes of the endometrium ar e 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.