Tamoxifen uterus

The effects of pure antiestrogens in the uterus have also been extensively studied, since it is an estrogen-dependent organ and the target of the main side effects of tamoxifen therapy, such as endometrial hyperplasia, hypertrophy of glandular epithelium, or even focal cellular atypia (Sourla et al. 1997). 

Raloxifene is a SERM devoid of stimulating effects on the uterus as is known from the initial studies (Delmas et al. 1997). Eliminating one of the major concerns raised by the experience gained with tamoxifen studies, both in prevention and adjuvant treatments, puts raloxifene in a place of privilege to be a rational alternative agent. At the same time it improves bone density, prevents osteoporosis and vertebral fracture, and reduces cardiovascular events in a subset of high-risk patients (Silverman et al. 2004). The evidences on the effects of raloxifene on the uterus are explained in detail in Chap. 10 of this book. 

The partial agonistic effect of tamoxifen on the uterus has caused concern not only regarding an increased incidence of endometrial pathology but also... 

According to results from clinical trials, the agonistic effects of tamoxifen detected in animals were also observed in the human uterus as it produces a trophic effect and an increase in the incidence of endometrial pathology, which is related to endometrial thickening (> 4 mm). Its use seems to be associated with an increase in endometrial cancer, which is related to the length of treatment and the accumulated dose of tamoxifen. Nevertheless, these tumors do not seem to be more aggressive or to have a worse prognosis than those found in women who do not follow this treatment or who receive hormone therapy. 

Achiron R, Grisaru D, Golan-Porat, Lipitz S (1996) Tamoxifen and the uterus an old drug tested by new modalities. Ultrasound Obstet Gynecol 7 374-378... 

Huynh HT, Poliak M (1993) Insulin-like growth factor I gene expression in the uterus is stimulated by tamoxifen and inhibited by the pure antiestrogen ICI 182780. Cancer... 

Kedar RP, Bourne TH, Powles TJ, Collins WP, Ashley SE, Cosgrove DO, et al. (1994) Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet 343 1318-1321... 

Rivera-Gonzalez R, Petersen DN, Tkalcevic G, Thompson DD, Brown TA (1998) Estrogen-induced genes in the uterus of ovariectomized rats and their regulation by droloxifene and tamoxifen. J Steroid Biochem Mol Biol 64(1-2) 13—24... 

Stewart HJ, Knigth GM (1989) Tamoxifen and the uterus and endometrium. Lancet 1 375-376... 

The effects of tamoxifen on uterine leiomyomas have been studied also in postmenopausal patients with breast cancer (Schwartz et al. 1998). After an average treatment of about 1 year, uterine and leiomyoma volumes increased significantly, confirming an agonistic effect of tamoxifen on the uterus. No significant difference in agonist effect on the uterus has been detected between tamoxifen and toremifene (Tomas et al. 1995). 

At present, the only SERMs routinely used in clinical practice are tamoxifen and raloxifene. Tamoxifen is used essentially as adjuvant treatment in women with breast cancer. Its use is related to estrogenic effects on the uterus. Specifically, tamoxifen can be associated with an increase not only in endometrial hyperplasia and cancer risk but also in uterine leiomyoma dimensions and in a risk of developing active endometriotic lesions. 

Tomas E, Kauppila A, Blanco G, Apaja-Sarkkinen M, Laatikainen T (1995) Comparison between the effects of tamoxifen and toremifene on the uterus in postmenopausal breast cancer patients. Gynecol Oncol 59 261-266... 

Alternatives to steroid hormone therapy for osteoporosis include raloxifene, bisphosphonates, sodium fluoride, vitamin D and calcium supplementation, calcitonin, and parathyroid hormone. Tamoxifen has estrogenic effects on bone and delays bone loss in postmenopausal women. However as a result of estrogenic activity in the uterus, long-term tamoxifen administration has been associated with an increased risk of... 

Prevention of the expected loss of lumbar spine bone density and plasma lipid changes consistent with a reduction in the risk for atherosclerosis have also been reported in tamoxifen-treated patients following spontaneous or surgical menopause. However, this agonist activity also affects the uterus and may increase the risk of endometrial cancer. 

Boudouris O, Ferrand S, Guillet JL, Madelenat P. Effets paradoxaux du tamoxifene sur l uterus de la femme. [Paradoxical effects of tamoxifen on the woman s uterus. 

Ascher SM, Johnson JC, Barnes WA, Bae CJ, Patt RH, Zeman RK. MR imaging appearance of the uterus in postmenopausal women receiving tamoxifen therapy for breast cancer histopathologic correlation. Radiology 1996 200(1) 105-10. 

Jessop FA, Roberts PF. Mullerian adenosarcoma of the uterus in association with tamoxifen therapy. Histopathology 2000 36(l) 91-2. 

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