The purpose of this study was to evaluate the effect of tamoxifen therapy on the endometrium by transvaginal color Doppler sonography, hysteroscopy and endometrial sampling. The study group (tamoxifen group) was composed of 38 asymptomatic postmenopausal women. All had been treated with tamoxifen (20-30 mg/day) for breast cancer for at least 1 year. The patients of the tamoxifen group underwent transvaginal color Doppler sonography, hysteroscopy and, if necessary, endometrial biopsy. Thirty asymptomatic postmenopausal women (control group) and 25 asymptomatic postmenopausal breast cancer patients not on tamoxifen therapy (no-tamoxifen group) served as the control groups. The endometrium was scanned by transvaginal ultrasound to evaluate thickness, echotexture, border and intraluminal fluid. Color and pulsed Doppler were used to evaluate the pulsatility (PI) and resistance (RI) indices of the uterine and endometrial arteries when possible. The patients receiving tamoxifen had a significantly thicker endometrium compared to the control groups. Endometrial pathology was observed in 61% (23/38) of cases and an endometrial thickness of "> or =" 10 mm was always associated with an endometrial lesion. Nineteen benign endometrial polyps were found, most of them having a typical sonographic endometrial pattern with regular borders and small hypoechoic cystic areas which we define as polypoid. Four endometrial hyperplasias, one of these atypical were observed. There were no endometrial cancers. The mean PI and RI of the uterine arteries in the tamoxifen group were 2.04 +/- 0.77 and 0.82 +/- 0.1, respectively and were significantly lower than those of the control group (2.93 +/- 0.9 and 0.93 +/- 0.06) and the no-tamoxifen group (2.53 +/- 0.7 and 0.89 +/- 0.1). The blood velocity changes were very similar to those described in postmenopausal women receiving estrogen replacement therapy. A correlation between the time of beginning tamoxifen therapy after menopause and development of endometrial pathology was observed: in patients who started therapy many years after the onset of menopause, the risk of developing endometrial pathology was higher than in those who began therapy a few years after the onset of menopause. Patients receiving tamoxifen, particularly those who start therapy many years after the onset of menopause, should be closely monitored by transvaginal ultrasound and color Doppler imaging to detect endometrial lesions.