Tamoxifen estrogenicity

Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S (1996) Time dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats effects of raloxifene HC1, tamoxifen, estrogen and alendronate. Bone 18 621-627... 

Tamoxifen Estrogen receptor antagonist. Prevents endogenous estrogens from stimulating tumor growth. Used to treat estrogen receptor-positive breast cancer in postmenopausal women. 

For the purposes of this article, antiestrogens are compounds that counteract the biological activity of estrogens at the receptor level. In the late 1970s, there were no steroidal antiestrogens in widespread clinical use. Clomiphene [911 -45-5]( ) and tamoxifen/7(954(9-25 -/7(9) were nonsteroidal antiestrogens that had been employed for the treatment of female infertility and breast cancer, respectively. 

A stmcturally related series of phenyfiiydrazones resulted ia the selection of compound A-007 [2675-35-6] (DEKK-TEC)(37) for the treatment of hormone-dependent tumors. A-007 is an antiestrogen that, ia contrast to tamoxifen, demonstrated inhibitory activity both ia the presence and absence of estradiol ia ZR-75-1 estrogen-dependent human breast cancer cells, and afforded more protection than tamoxifen ia the 7,12-dimethylbenz[i7]anthracene... 

Aromatase inhibitors are relatively well tolerated however have a number of distinct side effects are observed that stem from the state of estrogen deprivation induced by aromatase inhibitors. Side effects include hot flashes, joint and muscle aches, vasomotor symptoms and vaginal dryness. Variable effects of aromatase inhibitors on lipid levels have been observed. Trials comparing third generation aromatase inhibitors to tamoxifen have also repotted an increased risk of cardiovascular events in the group receiving aromatase inhibitors. 

EM-800 is a pure estrogen receptor antagonist that has recently been used clinically for breast cancer patients who have failed tamoxifen therapy. 

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

Bicalutamide may increase the effect of oral anticoagulants. Flutamide enhances the action of leuprolide. Additive antineoplastic effects may occur when leuprolide is administered with megestrol or flutamide. Estrogens decrease the effectiveness of tamoxifen. 

Yamaguchi and Gao, 1998 Rat femoral-metaphyseal tissues cultured for 48 h with bone resorbing factors PTH, PGE2 or EPS) +/- genistein measured bone calcium content, acid and alkaline phosphatases Genistein (10 Yi O M) inhibited bone resorption. Effect reversed by anti-estrogen, tamoxifen. 

YCUNG H J, DCERGE D R, KIMBERLY F A, ALLRED C D and HELFERICH W G (2002) Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res 62,2474-77. 

Several Grignard reactions are used on an industrial scale in drug synthesis.95 The syntheses of both tamoxifen and droloxifene, which are estrogen antagonists used in treatment of breast cancer and osteoporosis, respectively, involve Grignard addition... 

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