Iatrogenic disease
T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng, Richard Wing-Cheuk Wong, Hao Chen in Diagnostic Endometrial Pathology, 2019
Selective estrogen receptor modulators (SERMs) are agents that exert agonist and antagonist activity at estrogen receptors depending on the target tissue. The first-generation triphenylethylene derivatives, tamoxifen and toremifene, are used for treating premenopausal women with hormone receptor–positive breast cancer and, in the case of tamoxifen, in the prevention of breast cancer. Tamoxifen use can be extended, lasting up to ten years. Tamoxifen also improves bone density. Clomiphene (clomifene) is also a first-generation triphenylethylene derivative and is indicated for ovulation induction. The second generation benzothiopene derivative SERM, raloxifene, is indicated for the treatment and prevention of postmenopausal osteoporosis and for reducing the risk of breast cancer while bazedoxifene, a third-generation SERM, is indicated for the treatment of osteoporosis.24
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Selective estrogen receptor modulators (SERMs) are structurally different compounds that interact with intracellular estrogen receptors in target organs as estrogen agonists and antagonists. The molecular basis of SERM activity involves binding of the ligand SERM to the estrogen receptor, causing conformational changes that facilitate interactions with coactivator or corepressor proteins and later initiate or suppress transcription of target genes (Shelly et al. 2008). SERMs currently approved for use in patients include tamoxifen, raloxifene, and toremifene. Tamoxifen, a triphenylethyleneamine derivative, is one of the most widely used SERMs for the treatment of postmenopausal, hormone-sensitive, estrogen receptor–positive breast cancer (Jordan 2007; Jordan and O’Malley 2007). Tamoxifen is first approved in 1977 by the US FDA for the treatment of meta-static breast cancer and in ensuing years for adjuvant treatment of breast cancer. Other triphenylethylene SERMs, analogs of tamoxifen, have been studied for breast cancer prevention and treatment, including droloxifene (3-hydroxytamoxifen) (Buzdar et al. 2002; Roos et al. 1983; Ruenitz et al. 1982), idoxifene (pyrrolidino-4-iodotamoxifen) (Arpino et al. 2003; Chander et al. 1991; Coombes et al. 1995; Johnston et al. 2004), and ospemifene (Komi et al. 2005).
Role of Aromatase Inhibitors (AIs) and Selective Estrogen Receptor Modulators (SERMs) in the Treatment of Uterine Leiomyoma
John C. Petrozza in Uterine Fibroids, 2020
Currently selective estrogen receptor modulators (SERMs) are more frequently used for the treatment of osteoporosis and breast cancer, with documented proven benefits [17]. Early generation SERMs such as clomiphene citrate have been used for ovulation induction in polycystic ovarian syndrome (PCOS) related infertility. Newer SERM therapies have been developed for the treatment of postmenopausal vasomotor symptoms in patients with an intact uterus and are also indicated in the treatment of vaginal atrophy and dyspareunia associated with hypoestrogenism. Most of the estrogen representation is mediated by either estrogen receptor (ER)-α or ERβ receptors [17–19]. SERMs are chemically diverse nonsteroidal compounds that belong to one of two different chemical families: the triphenylethylenes and the benzothiophenes, with the exception of fulvestran (downregulator) that acts on the ligand binding domain (LBD) located in the ER carboxyl-terminal site, causing conformational changes which facilitate interactions as a co-activator or co-repressor proteins, and subsequently initiate or suppress the transcription of target genes [17–19]. Different types of SERMs can have both agonist and antagonist action in different target tissues; for example, tamoxifen has agonist action on bone and is an antagonist on the breast ERs and, in addition, it can also have an agonist effect on endometrial tissue.
Is there still a role for SERMs in menopause management?
Published in Gynecological Endocrinology, 2020
Stefano Lello, Anna Capozzi, Giovanni Scambia
Selective Estrogen Receptor Modulators (SERMs) are non-hormonal compounds that can act as estrogen-agonist or antagonist according to the different target tissues. For instance, a SERM may be an estrogen agonist on bone tissue and, conversely, a potent estrogen antagonist on breast tissue [1]. The concept of SERM arises from the recognized existence of a spectrum of action from agonist-to-antagonist activity in nature. In other words, the same hormone can exert an agonist or antagonist function under different conditions in different cell types. Estrogen receptors (ERs), and their signaling system, are important targets found in bone tissue, as clearly demonstrated by the effects observed under aromatase inhibitors (AIs), on one hand, and hormone therapy (HT), SERMs, and Tissue Selective Estrogen Complex (TSEC), on the other hand.
Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators
Published in Climacteric, 2019
Selective estrogen receptor modulators (SERMs) are molecules that exhibit both estrogen agonist and antagonist effects, depending on the target tissues, and function almost exclusively through estrogen receptor (ER) α and β receptors1. The promise of SERMs lies in their ability to provide mixed functional ER agonist or antagonist activity2. The best choice for an individual woman is determined based on the goals of treatment and the unique properties of the SERM, which in turn depend on the desired target genes and target tissues. Effects on the breast, bone, heart, uterus3, brain, and coagulation are important considerations in clinical development of SERMs, with less known about long-term effects on cognition. Postmenopausal women have almost a 50% chance of developing progressive genitourinary syndrome of menopause4, and thus the effect on the vulva, vagina, and bladder becomes important as women progress further from menopause5.
Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs
Published in Drug Metabolism Reviews, 2023
Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher
In addition, the results noticed in the study conducted by Wang at al. (Wang et al. 2019) that the administration of Escherichia coli Nissle 1917 had protective effects on intestinal injury induced by irinotecan. The key findings were that irinotecan treatment altered the diversity of gut microbiota composition. This drug increased the Proteobacteria relative abundance, compared with its abundance in control group. Therefore, Escherichia coli Nissle application improved the gut microbiota dysbiosis (Wang et al. 2019). In recent years, there were many studies (Diot et al. 2021) that have been developing a model system by using the nematode Caenorhabditis elegans to assess the response of the animals to different drugs such as tamoxifen. It belongs to the class of drugs called SERMs, selective estrogen receptor modulators that is the standard treatment for breast cancers positive for estrogen receptors together with chemotherapy and radiation therapy. The authors of this study (Diot et al. 2021) changed the diet of larval stage animals with one of the three following bacteria: C.aquatica, B. subtilis or E. coli. After the tamoxifen administration to C.elegans, it was proven that tamoxifen toxicity increased in animals fed by C.aquatica and B. subtilis that showed a delay in development.
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