Disease relevance of Deamino-hydroxytoremifene

• CONCLUSIONS: Ospemifene at daily doses of 30 to 90 mg did not stimulate endometrium or aggravate hot flashes but clearly had a rather strong estrogenic effect on the vaginal epithelium during a 3-month treatment period [1].
• Similarly to other SERMs, ospemifene exhibits antiestrogenic effects in breast tissue, which led to the hypothesis that it may be a potential breast cancer chemopreventive agent [2].
• As hypothesized, ospemifene greatly reduced the incidence of mammary carcinomas compared to control mice (p = 0.003), similar to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant effect was seen in mammary tumor prevention (p = 0.20) [2].
• CONCLUSION: Tamoxifen and ospemifene inhibit the growth of premalignant mammary lesions and the progression to invasive carcinoma in a transplantable mouse model of DCIS [3].
• Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo) [4].

High impact information on Deamino-hydroxytoremifene

• CONCLUSIONS: Ospemifene, at the dose of 90 mg/day, was more estrogenic than raloxifene, as shown by changes in serum follicle-stimulating hormone and sex hormone-binding globulin levels [5].
• In comparison with raloxifene, follicle-stimulating hormone levels decreased significantly more in the 90-mg ospemifene group and sex hormone-binding globulin levels increased more in all ospemifene groups [5].
• All ospemifene groups demonstrated a clear estrogenic effect on the vaginal epithelium, as seen in Pap smears [5].
• OBJECTIVE: Ospemifene, a novel selective estrogen receptor modulator, shows a potential for prevention and treatment of osteoporosis in postmenopausal women [1].
• Ospemifene had no effect on the appearance of proliferation marker Ki-67 in the endometrium as compared with placebo, and endometrial thickness increased by mean 0.4 to 0.6 mm (P < 0.01, P < 0.05 and P < 0.05 for 30, 60 and 90 mg ospemifene, respectively) [1].

Chemical compound and disease context of Deamino-hydroxytoremifene

• The results of the follow-up study, which extended the treatment to 52 weeks, confirmed the results of our previous study, with ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary carcinomas compared to controls [2].

Biological context of Deamino-hydroxytoremifene

• Ospemifene was not observed to aggravate climacteric symptoms or cause adverse events, nor did it suppress climacteric symptoms [1].
• Of the markers reflecting coagulation and fibrinolysis, plasma fibrinogen was significantly reduced in the 60- and 90-mg groups of ospemifene (8.7% and 8.5%, respectively) when compared with the placebo group [6].
• The uterine or carotid arteries and 24-h ambulatory blood pressure were not affected by ospemifene [6].
• No other differences in bone formation markers emerged between ospemifene and raloxifene [7].
• Ospemifene exerted a very weak estrogenic effect on endometrial histology [8].

Anatomical context of Deamino-hydroxytoremifene

• In the vast majority of participants, the endometrium remained atrophic after 3 months of treatment with ospemifene [1].
• To investigate the differential short-term effects of selective estrogen receptor (ER) modulators (SERMs) on uterus, we treated adult ovariectomized rats with a novel SERM, ospemifene (Osp), two previously established SERMs (tamoxifen and raloxifene (Ral)) and estradiol [9].

Associations of Deamino-hydroxytoremifene with other chemical compounds

• We first assessed the ability of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sencar mice [2].
• For MCF-7 cells, FC-1271a and its main metabolite, toremifene VI (TOR VI) displayed anti-estrogenic effects in vitro as shown through growth inhibition and decreased expression of pS2 [10].

Gene context of Deamino-hydroxytoremifene

• The results of these two studies suggest that women taking ospemifene for osteoporosis and/or urogenital atrophy may further benefit from ospemifene's breast cancer chemopreventive effects [2].
• Comparative study of the short-term effects of a novel selective estrogen receptor modulator, ospemifene, and raloxifene and tamoxifen on rat uterus [9].

Analytical, diagnostic and therapeutic context of Deamino-hydroxytoremifene

• In vivo, the effects of treatment with 10, 25, 50, or 100 mg/kg FC-1271a on MCF-7 and MDA-MB-231 human tumor xenografts in athymic, ovariectomized mice were determined [10].
• The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months [7].
• In summary, we have developed and validated an HPLC assay to quantitate FC-1271a in human plasma [11].
• A highly sensitive and precise high-performance liquid chromatography (HPLC) assay was developed and validated for the quantitation of Z-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl) phenoxy]ethanol (FC-1271a) in human plasma [11].

References