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Enclomifene (INN Tooltip International Nonproprietary Name), or enclomiphene (USAN Tooltip United States Adopted Name), a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group, acts by antagonizing the estrogen receptor (ER) in the pituitary gland, which reduces negative feedback by estrogen on the hypothalamic-pituitary-gonadal axis, thereby increasing gonadotropin ...
Tamoxifen is a pure antiestrogenic trans-isomer and has differential actions at estrogen target tissues throughout the body. Tamoxifen is selectively antiestrogenic in the breast but estrogen-like in bones and endometrial cancer. [24] Tamoxifen undergo phase I metabolism in the liver by microsomal cytochrome P450 (CYP) enzymes.
N-Desmethyltamoxifen (developmental code name ICI-55,548) is a major metabolite of tamoxifen, a selective estrogen receptor modulator (SERM). [1] [2] N-Desmethyltamoxifen is further metabolized into endoxifen (4-hydroxy-N-desmethyltamoxifen), which is thought to be the major active form of tamoxifen in the body.
Clomifene is a prodrug being activated via similar metabolic pathways as the related triphenylethylene SERMs tamoxifen and toremifene. [36] [37] The affinity of clomifene for the ER relative to estradiol ranges from 0.1 to 12% in different studies, which is similar to the range for tamoxifen (0.06–16%).
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. [13] It is also being studied for other types of cancer. [13] It has been used for Albright syndrome. [14] Tamoxifen is typically taken daily by mouth for five years for breast cancer. [14]
Toremifene appears to be safer than tamoxifen. [15] It has a lower risk of venous thromboembolism (VTE) (e.g., pulmonary embolism), stroke, and cataracts. [15] The lower risk of VTE may be related to the fact tamoxifen decreases levels of the antithrombin III to a significantly greater extent than either 60 or 200 mg/day toremifene. [15]
Endoxifen is an active metabolite of tamoxifen and has been found to be effective in patients that have failed previous hormonal therapies (tamoxifen, aromatase inhibitors, and fulvestrant). [3] [4] [5] The prodrug tamoxifen is metabolized by the CYP2D6 enzyme to produce endoxifen and afimoxifene (4-hydroxytamoxifen). [6]
Hormonal therapy is used for several types of cancers derived from hormonally responsive tissues, including the breast, prostate, endometrium, and adrenal cortex. Hormonal therapy may also be used in the treatment of paraneoplastic syndromes or to ameliorate certain cancer- and chemotherapy -associated symptoms , such as anorexia .
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