China
Africa
Explore chapters and articles related to this topic
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Initially developed for the treatment of osteoporosis, raloxifene was found to significantly diminish the incidence of breast cancer, and so was subsequently studied in breast cancer clinical trials after which it was developed to the approval stage. Arzoxifene (LY353381) was identified by Ely Lilly as a potentially more potent drug than raloxifene with an improved side-effect profile. However, in 2009 the company announced the preliminary results of a five-year clinical study which showed that arzoxifene had failed to meet three important secondary endpoints and so development was discontinued. Bazedoxifene (ViviantTM; ConbrizaTM) was developed by Pfizer and has been approved for the prevention (rather than treatment) of postmenopausal osteoporosis. However, at the time of writing, clinical trials are still underway to investigate its possible use in the treatment of breast cancer.
Systemic complications of osteoporosis medical treatment
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Konstantinos G. Makridis, Stamatina-Emmanouela Zourntou
Bazedoxifene is relatively safe and well tolerated without exhibiting breast or endometrial stimulation and having a lower risk for venous thromboembolism. Its advantage over raloxifene is that it increases endothelial nitric oxide synthase activity and does not antagonize the effect of 17β-estradiol on vasomotor symptoms (26).
Iatrogenic disease
Published in T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng, Richard Wing-Cheuk Wong, Hao Chen, Diagnostic Endometrial Pathology, 2019
T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng
The increased risk of developing endometrial cancer for women taking tamoxifen is well established; this risk increases with cumulative dose and duration of treatment.29 Many studies have found that the stage, grade, histology and biology of tumors that develop in tamoxifen-treated women are no different from those that arise in the general population. Some smaller series studies have reported a worse prognosis for tamoxifen-treated women with endometrial malignancies due to the finding of more aggressive subtypes such as endometrial stromal sarcomas, adenosarcoma, malignant mixed Müllerian tumors or later stage endometrioid carcniomas.30 Women using raloxifene demonstrate a lower risk of endometrial cancer when compared with those who used tamoxifen and with SERM nonusers,31 while women treated with bazedoxifene alone for postmenopausal osteoporosis had a lower rate of endometrial carcinoma and no increase in endometrial hyperplasia.32 There may be an increased risk of endometrial cancer in subfertile women exposed to clomiphene, but the quality of evidence and the confounding factors underlying subfertility for which clomiphene is used render the association unclear.33
Medical treatment of osteoporosis
Published in Climacteric, 2022
Clinical trials have shown that the SERM bazedoxifene has positive effects on BMD, bone turnover markers and lipid profiles, and also reduces the risk of new vertebral fractures [21,22]. Moreover, different meta-analyses have shown that bazedoxifene has at least the same efficacy as bisphosphonates regarding the risk of vertebral and non-vertebral fractures [23,24]. Another meta-analysis showed that, compared with placebo, bazedoxifene reduced the risk of vertebral fractures by 39% but without a significant impact on the risk of hip or non-vertebral fractures [17]. Venous thromboembolism, hot flushes and leg cramps have been described with the use of bazedoxifene [25]. Of note, bazedoxifene has been combined with conjugated equine estrogen for the treatment of hot flushes and the prevention of osteoporosis by reducing bone resorption, and also improves the lipid profile [26,27].
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].
Pharmacotherapeutic considerations and options for the management of osteoarthritis in women
Published in Expert Opinion on Pharmacotherapy, 2020
Sunny Trivedi, William Fang, Ishan Ayyalasomayajula, C. Thomas Vangsness
Another emerging field of pharmacological therapy for OA is hormonal treatment. Estrogen has been shown to play a role in bone growth and development [142]. Although multiple studies link estrogen deficiency to the development of Osteoarthritis [38], currently, there is insufficient research into the mechanism of involvement of estrogen in the disease development [143]. Research has shown that post-menopausal women who underwent hormone therapy were at reduced risk for osteoarthritis [143]. Further investigations of the pathophysiology of estrogen in osteoarthritis are necessary to improve treatment options specific to women. In recent years, there have been clinical studies testing the efficacy of estrogen and selective estrogen receptor modulators (SERMs) on treating OA. Studies testing the effects of estrogen on OA treatment have produced inconclusive results [143]. In these studies, estrogen has been shown to prevent joint degradation in OA patients as well as having negative effects on OA. Previous work has indicated that SERMs have dual agonist and antagonist effects in various tissues. Low doses of SERMs have been shown to affect chondrocytes, resulting in increased extracellular matrix deposition and increased resistance to damage [143]. Specifically, bazedoxifene has been shown to reduce bone loss and maintain bone mass density by reducing bone breakdown in post-menopausal women. Similarly, recent research indicates that levormeloxifene reduced cartilage degeneration [143].