Endometrium endometrial hyperplasia

Uterine fibroids and endometrial polyps (sometimes with bleeding) have been reported in menopausal women who had taken tamoxifen for periods of months or years (SEDA-16, 466) (92,93). In view of this, the question of whether tamoxifen increases the risk of endometrial cancer has been widely discussed. The authors of a 1993 review of the outcome of six major trials tended strongly to the conclusion that tamoxifen can cause both endometrial hyperplasia and endometrial cancer proportional to the total dose (94) the figures pointed to an overall incidence of endometrial cancer of 0.5 % in tamoxifen users and 0.1% in controls. Another major review up to 1992 concluded that in the world literature there were 70 cases of uterine malignancies with tamoxifen, including 61 cases of adenocarcinoma of the endometrium and four cases of uterine sarcoma (95). 

In addition to its limited duration of beneficial effects in breast cancer, a serious problem associated with tamoxifen is its stimulatory effect on the endometrium, leading to endometrial hyperplasia and even cancer (Fisher etal., 1996 Kedar etal., 1994 Robinson etal., 1995). We thus have the example of a compound for which the benefits exerted on breast cancer and bone are accompanied by adverse effects in another tissue. In fact, as mentioned above, even the beneficial effects observed in breast cancer deserve some important comments because of the limit of 5 years of treatment, which raises practical questions about the use of this compound for prevention of breast cancer (Fisher et al., 1996) while, in fact, long-term use is required. Analogues of tamoxifen have... 

Also, lower doses of estrogen may be associated with a lower risk of endometrial hyperplasia. Raloxifene does not resnlt in endometrial hyperplasia, has no effect on endometrial thickness, is not associated with polyp formation, and has virtnally no proliferative effect on the endometrium. A 4-year trial of raloxifene in women with osteoporosis showed no increased risk of endometrial cancer." ... 

The presence of an enlarged endometrium (> 5 mm) may be associated with endometrial abnormalities, principally polyps, hyperplasia, or even adenocarcinoma of the endometrium, in the postmenopausal woman (Dijkhuizen et al. 1996 Granberg et al. 1991 Holbert 1997). It seems that treatment with tamoxifen in postmenopausal women sustains this association. Thus, in the previously mentioned study by Cohen et al. (1994), the only endometrial abnormalities were found in those women whose endometrium had a thickness... 

A randomized placebo-controlled trial found that 39% of the tamoxifen-treated women had an endometrial abnormality, a percentage that was reduced to 10% of women on placebo (p < 0.0001) (Kedar et al. 1994), though no cases of endometrial cancer were diagnosed in this study. The histological abnormalities found in the tamoxifen group were atypical hyperplasia (16%), proliferative endometrium (13%), polyps (8%), or presence of mitosis (2%). The authors concluded that the predicative value of an endometrium thickness... 

In fact, the most widely recognized adverse effects of tamoxifen are those related to the stimulatory effects on the endometrium. These effects include proliferation of the endometrium (Dijkhuizen et al., 1996 Hann et al., 1997 Lahti et al., 1993), formation of endometrial polyps (Cohen et al., 1997 Hann et al., 1997 Kedar et al., 1994a Lahti et al., 1993), hyperplasia (Cohen, 1997 Lahti et al, 1993), and cancer (Fisher et al, 1994 Rutqvist et al., 1995 Stearns and Gelmann, 1998 Wilking et al, 1997). Other reproductive side effects of tamoxifen are worsening of endometriosis (Buckley, 1990 Hajjar et al, 1993 Ismail and Maulik, 1997), adenomyosis (Cohen etal, 1997), and proliferation of benign uterine tumors (Cohen, 1997 Kang et al, 1996). 

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