Endocrine Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Depending on regulatory approval in different world regions, raloxifene is used for the treatment and prevention of osteoporosis in postmenopausal women, for the reduction of risk and treatment of invasive breast cancer, or to reduce breast density. It was first approved by the FDA to prevent and treat osteoporosis (bone thinning) in postmenopausal women based on its estrogenic effect in bone tissue. Unlike some other hormone replacement therapies, raloxifene does not reduce menopausal vasomotor symptoms. Later clinical studies showed that, taken once a day, it works almost as well as tamoxifen in lowering the relative risk of breast cancer by up to approximately 40%. It was shown to reduce breast density in postmenopausal women, a known risk factor for breast cancer. However, in comparative clinical trials it was shown to cause fewer cases of uterine cancer than tamoxifen (due to the negligible estrogenic activity in the uterus), and did not increase the risk of cataracts, a common tamoxifen side effect. Furthermore, although both groups of patients developed more blood clots in the veins and lungs compared to a control group, this side effect was more common with tamoxifen than raloxifene.
Current and emerging pharmacological agents in the treatment of osteoporosis
Peter V. Giannoudis, Thomas A. Einhorn in Surgical and Medical Treatment of Osteoporosis, 2020
Raloxifene is a benzothiophene nonsteroidal derivative that binds to estrogen receptors. It is a second-generation SERM that acts as an estrogen receptor agonist or antagonist depending on the target tissue. The ideal SERM acts as estrogen receptor agonist by exerting a protective effect on bone, while maintaining breast and uterine safety via its estrogen receptor antagonist activity (4). Raloxifene was initially approved by the U.S. Food and Drug Administration for the treatment and prevention of osteoporosis in postmenopausal women. In 2007, the indications were extended to reduce invasive breast cancer risk in postmenopausal women with osteoporosis (5). Raloxifene is currently the only drug in its class that is approved for long-term treatment in the prevention of fragility fractures.
Breast Cancer
Mary J. Marian, Gerard E. Mullin in Integrating Nutrition Into Practice, 2017
Adjuvant endocrine therapy is instituted for breast cancers that are estrogen or progesterone receptor-positive (ER-positive and PR-positive).27 The two SERMs used for treatment of breast cancer, tamoxifen and raloxifene (Evista®), compete with estrogen for receptor sites in target tissues such as the breast. Tamoxifen is used for adjuvant treatment for premenopausal breast cancer. This drug exerts estrogen-like activity on the skeletal and cardiovascular systems, reducing bone loss and improving lipid levels. Side effects of tamoxifen include hot flashes, night sweats, and vaginal dryness. Serious adverse effects include an increased risk of cataracts, endometrial cancer, and pulmonary embolism. The U.S. Food and Drug Administration approved raloxifene for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. The STAR trial that compared Tamoxifen and Raloxifen suggested near equal efficacy supporting a 50% reduction in risk, but with less thrombotic events in the Raloxifen group.28
Successes and failures of uterine leiomyoma drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Mohamed Ali, Zunir Tayyeb Chaudhry, Ayman Al-Hendy
Raloxifene, a second-generation SERM, is commonly used to reduce the risk of breast cancer as well as both prevent and treat osteoporosis in postmenopausal women [34]. Raloxifene does not have agonistic activity on the endometrium, allowing it to be explored as a potential treatment for UF. Moreover, owing to raloxifene’s potential for dual-therapeutic effects on leiomyoma size and osteoporosis, it has been an attractive research target [35]. A 2012 Cochrane review explored the use of SERMs in UFs and summarized studies evaluating the use of raloxifene [33]. A 180 mg daily dose of raloxifene was found to reduce mean leiomyoma size by 22.2% at three months when compared to no treatment. However, after considering adverse effects and the limitations of conducted studies, the authors concluded that there is insufficient evidence to support SERM use in uterine fibroids and, if prescribed, it should be used with caution [33]. The literature appears to agree on the need for larger controlled trials before raloxifene can be recommended for fibroid management.
Pharmacological Management of Postmenopausal Osteoporosis: a Level I Evidence Based - Expert Opinion
Published in Expert Review of Clinical Pharmacology, 2021
Filippo Migliorini, Giorgia Colarossi, Alice Baroncini, Jörg Eschweiler, Markus Tingart, Nicola Maffulli
The decline in estrogen plays a role in the pathogenesis of postmenopausal osteoporosis [110], reducing the activity of osteoblasts and osteocytes and promoting apoptosis in osteoblasts [2]. Raloxifene works as an estrogen agonist in bone and on lipid metabolism, and as an antagonist on estrogen receptors in breast and endometrial tissue [111]. The effectiveness of Raloxifene in reducing fractures is uncertain [112], but this drug did reduce vertebral and non-vertebral fractures and showed good tolerability with an improvement in the quality of life in Japanese postmenopausal women [113]. In the present meta-analysis, although it resulted in less effective in reducing fractures, Raloxifene showed low rates of serious adverse events. Of note, serious adverse events were those declared as such in the RCTs included; however, we acknowledge that the definition of serious adverse events was not always clear.
Estrogen and estrogen receptors in kidney diseases
Published in Renal Failure, 2021
Hao-Yang Ma, Shuang Chen, Yang Du
Selective estrogen receptor modulators (SERMs) are antiestrogens designed to compete with estrogen and modulate ER activity in a tissue-specific manner [70,71]. For instance, tamoxifen can exhibit antagonistic effect on mammary tissue, whereas it can have agonistic effects on other tissues such as the uterus, bone, and heart [72]. Raloxifene acts as an estrogen agonist in bone and an estrogen antagonist in uterine and breast tissues [73]. Similarly, bazedoxifene functions as a pure antagonist in the breast and an agonist in the bone [74]. Since ERs are nuclear transcription factors involved in the regulation of a variety of physiological and pathological processes in humans, modulation of the receptors either by SERMs or by agonists/antagonists might be beneficial for the prevention and treatment of various diseases [27].
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