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Lifestyle Medicine in Menopause and Bone Health
Published in Michelle Tollefson, Nancy Eriksen, Neha Pathak, Improving Women's Health Across the Lifespan, 2021
The two primary types of estrogen receptors are alpha and beta receptors. Endogenous and synthetic estrogens act as nonselective agonists at both receptor types. Drugs that are considered “anti-estrogen” such as fulvestrant, used to treat metastatic breast cancer, are nonselective antagonists at all estrogen receptors. Mixed agonist-antagonists such as synthetic selective estrogen receptor modifiers (SERMs), like tamoxifen, and phytoestrogens act selectively and primarily on beta-receptors.14
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Estrogen receptors are DNA-binding transcription factor proteins that represent the main class of the nuclear hormone family group of intracellular receptors and are activated by estrogen. Other members of the nuclear hormone family include the G protein-coupled receptor GPR30. The ERs are cytoplasmic receptors when not bound to estrogen, but labeling studies have shown that a fraction of the ERs reside permanently in the nucleus. Once estrogen has bound to the ER and activated it, the protein translocates into the nucleus and binds to a particular sequence of DNA (i.e., its recognition site) which regulates the activity of various genes. However, it has some additional functions independent of DNA binding (i.e., ligand-independent regulation – see below).
Endocrine, paracrine and intracrine mechanisms of growth regulation in normal and malignant endometrial epithelium
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
Tamoxifen has an estrogen-like effect on the gene expression of IGFs and their receptors in the endometrium of postmenopausal breast cancer patients. IGF-I gene expression is up-regulated and, simultaneously, the expression of IGFBP-3 is suppressed to less than one-third of control values36. A complete estrogen receptor antagonist had opposite effects. In another study, the levels of IGF/IGF receptor mRNAs in the endometrium of tamoxifen-treated postmenopausal breast cancer patients were found to be as high as those in proliferative and early secretory phase endometrium and in endometrioid-type endometrial carcinoma37. Stimulation of uterine IGF-I and IGF receptor expression in parallel with inhibition of IGFBP-3 may therefore be another mechanism accounting for the endometrial effects of unopposed estradiol or tamoxifen treatment.
Mat Pilates improves lower and upper body strength and flexibility in breast cancer survivors undergoing hormone therapy: a randomized controlled trial (HAPiMat study)
Published in Disability and Rehabilitation, 2023
Josefina Bertoli, Ewertton de Souza Bezerra, Kerri M. Winters-Stone, Luis Alberto Gobbo, Ismael Forte Freitas
When considering hormone therapy, which involves administration of aromatase inhibitors (AIs) or selective modulators of estrogen receptors (SMREs), different side effects are reported [4]. Among the musculoskeletal side effects of AIs are joint stiffness and pain [5], as well as loss of lean mass and muscle strength. In contrast, SMREs are associated with fatigue, and lower and upper body numbness [1], which might be related to muscle strength loss [6]. Morales et al. [7] showed a large decrease in handgrip strength after six months of hormone therapy that appears to be related to tendon and joint changes, mainly in AIs compared to tamoxifen (TMX), which is an SMRE. In this context, a recent study [8] showed that BCS undergoing hormone therapy presented lower force production in knee flexor–extensors, trunk extensors, and right and left shoulder abductors compared with women without a cancer history. The decrease in range of motion due to tendon joint stiffness and the muscle strength loss can negatively impact functional capacity, and, consequently, quality of life in BCS [9].
Impacts of menopause hormone therapy on mood disorders among postmenopausal women
Published in Climacteric, 2022
P. Feng, L. Lin, Y. Wang, L. Chen, J. Min, Y. Xie, M. Liu, S. Wei, S. Lin, Q. Yu
MHT is a critical medical intervention in the health management of postmenopausal women. Emotional disorders tend to occur during the period of sex hormone fluctuations. However, there are also different points of view that menopause will not directly lead to emotional problems and that neurotransmitters cause emotional disorders [3]. Existed studies have been mainly devoted to exploring the emotional disorders during menopausal transition or early menopausal stages and the role of MHT in improving emotional disorders. At present, most studies have confirmed that MHT could improve mood disorders in the perimenopausal period [11,14]. Amygdala, hippocampal and several non-mesial temporal structures are the central areas involved in emotional regulation [3]. Estrogen therapy could protect the aforementioned structural changes during menopausal and postmenopausal periods and improve depression [41]. Estrogen receptor (ER) subtypes mainly consist of ERα and ERβ. Different subtypes of receptors have various actions on anxiety. ERα has an anxiety effect, while ERβ has a universal antianxiety impact [2,42]. We also found that long-term use of MHT could improve the emotional problems of postmenopausal women. For depression, there was a significant difference in CES-D scores between the two groups. In terms of anxiety status, no significant difference between the two groups was detected. Plasma estrogen levels were reported to be significantly lower in depressed women, suggesting that low estrogen could potentially lead to mood disorders or related symptoms [43].
Increasing importance of breast cancer in Nepal
Published in Hospital Practice, 2022
Ruqaiyyah Siddiqui, Ajnish Ghimire, Jibran Sualeh Muhammad, Naveed Ahmed Khan
There are various hallmarks for the identification of the signaling pathway for a breast tumor. For the breast tumor subtyping, the most common immunohistochemistry (IHC) markers include Estrogen Receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) [21]. These receptors are known for mediating the signals for cell growth. ER was first discovered in the 1960s and for clinical management purpose, it was started in the 1970s as a predictive factor for the recurrence of breast cancer [22]. For the gene expression profiling (GEP) studies, the ER status is used as a major prognostic factor for molecular analysis of breast cancer [23]. ER+ breast cancer tumor reports about 75% of all breast cancer patients and it plays a crucial role in carcinogenesis [24]. The endocrine signaling induces PR, and this activation causes active signaling in ER [25]. A 65–75% of breast cancer is PR positive, and this is used for the classification of a tumor [26]. HER2 is a proto-oncogene that encodes for tyrosine kinase activity and overexpression of its product induces cell transformation. HER2 overexpression is found in 15–30% of breast cancer and hence is used as a suitable biomarker [27].