Variation in endometrial thickening in women with amenorrhea on tamoxifen

Tamoxifen is reported to increase the risk of endometrial cancers mostly in postmenopausal women. In the Royal Marsden chemoprevention programme, we noted that premenopausal women at the start of tamoxifen/placebo who developed amenorrhea may be at special risk of endometrial cancer. The aim of this report was to investigate recently amenorrheic women by measuring plasma estradiol (E₂), follicular stimulating hormone (FSH), and endometrial thickness (ET) by transvaginal ultrasound (TVUS). ET readings and E₂ levels were available in the same proportion of women on tamoxifen or placebo. Women on placebo developed amenorrhea with upper limit of E₂ readings of 450 pmol/L. In both postmenopausal women and recently amenorrheic women with low E₂ (≤ 450 pmol/L), tamoxifen significantly increased endometrial thickening (p < 0.0001 and < 0.005 respectively). Conversely, tamoxifen did not result in endometrial thickening in women with high E₂ (> 450 pmol/L), with a trend to lower ET readings (p = 0.07). Finally, all five women who developed endometrial cancer were premenopausal at the start of tamoxifen/placebo. Two of these five women were asymptomatic with increased ET readings (17 mm and 17 mm) and low E₂ levels (32 and 51 pmol/L). These results indicate that women who develop amenorrhea on tamoxifen may be at special risk of endometrial cancer. Tamoxifen causes endometrial thickening in amenorrheic women with low E₂ but has an opposite antiestrogenic effect in women with high E₂. We recommend that women who develop amenorrhea on tamoxifen especially in the presence of endometrial thickening, low E₂ levels, and/or gynaecological symptoms warrant further investigations.