Journal of Ultrasound in Medicine, Vol 18, Issue 7 503-512, Copyright © 1999 by American Institute of Ultrasound in Medicine
Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene
A. C. Fleischer, J. E. Wheeler, I. T. Yeh, B. Kravitz, C. Jensen and B. MacDonald
Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2675, USA.
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.
