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1.
The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause.
Robeva, R, Mladenović, D, Vesković, M, Hrnčić, D, Bjekić-Macut, J, Stanojlović, O, Livadas, S, Yildiz, BO, Macut, D
Maturitas. 2021;:22-30
Abstract
The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT.
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2.
Phytoestrogens (Resveratrol and Equol) for Estrogen-Deficient Skin-Controversies/Misinformation versus Anti-Aging In Vitro and Clinical Evidence via Nutraceutical-Cosmetics.
Lephart, ED
International journal of molecular sciences. 2021;(20)
Abstract
The overarching theme for this review is perspective. Superfoods (a marketing term for fruits and vegetables, etc.) have a positive connotation, while many superfoods contain phytoestrogens, a term that is alarming to the public and has a negative connotation because phytoestrogens are endocrine-disruptors, even though they are strong antioxidants that have many health benefits. To understand phytoestrogens, this paper provides a brief summary of the characteristics of: (a) estrogens, (b) estrogen receptors (ER), (c) estrogen-deficient skin, (d) how perspective(s) get off track, (e) phytoestrogen food sources, and (f) misconceptions of phytoestrogens and food safety, in general, that influence person(s) away from what is true. Finally, a brief history of cosmetics to nutraceuticals is covered plus the characteristics of phytoestrogens, resveratrol and equol on: (g) estrogen receptor binding, (h) topical and oral dosing, and (i) in vitro, molecular mechanisms and select clinical evidence, where both phytoestrogens (resveratrol and equol) demonstrate promising applications to improve skin health is presented along with future directions of nutraceuticals. Perspective is paramount in understanding the controversies associated with superfoods, phytoestrogens, and endocrine-disruptors because they have both positive and negative connotations. Everyone is exposed to and consumes these molecules everyday regardless of age, gender, or geographic location around the world, and how we understand this is a matter of perspective.
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3.
Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications.
Emmanuelle, NE, Marie-Cécile, V, Florence, T, Jean-François, A, Françoise, L, Coralie, F, Alexia, V
International journal of molecular sciences. 2021;(4)
Abstract
Bone is a multi-skilled tissue, protecting major organs, regulating calcium phosphate balance and producing hormones. Its development during childhood determines height and stature as well as resistance against fracture in advanced age. Estrogens are key regulators of bone turnover in both females and males. These hormones play a major role in longitudinal and width growth throughout puberty as well as in the regulation of bone turnover. In women, estrogen deficiency is one of the major causes of postmenopausal osteoporosis. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens not only in females but also in males, during different life stages. Effects of estrogens on bone involve either Estrogen Receptor (ER)α or ERβ depending on the type of bone (femur, vertebrae, tibia, mandible), the compartment (trabecular or cortical), cell types involved (osteoclasts, osteoblasts and osteocytes) and sex. Finally, we will discuss new ongoing strategies to increase the benefit/risk ratio of the hormonal treatment of menopause.
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4.
The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.
Bertoldo, E, Adami, G, Rossini, M, Giollo, A, Orsolini, G, Viapiana, O, Gatti, D, Fassio, A
Frontiers in endocrinology. 2021;:620920
Abstract
The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.
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5.
A new hypothesis linking oxytocin to menstrual migraine.
Bharadwaj, VN, Porreca, F, Cowan, RP, Kori, S, Silberstein, SD, Yeomans, DC
Headache. 2021;(7):1051-1059
Abstract
OBJECTIVE To highlight the emerging understanding of oxytocin (OT) and oxytocin receptors (OTRs) in modulating menstrual-related migraine (MRM). BACKGROUND MRM is highly debilitating and less responsive to therapy, and attacks are of longer duration than nonmenstrually related migraine. A clear understanding of the mechanisms underlying MRM is lacking. METHODS We present a narrative literature review on the developing understanding of the role of OT and the OTR in MRM. Literature on MRM on PubMed/MEDLINE database including clinical trials and basic science publications was reviewed using specific keywords. RESULTS OT is a cyclically released hypothalamic hormone/neurotransmitter that binds to the OTR resulting in inhibition of trigeminal neuronal excitability that can promote migraine pain including that of MRM. Estrogen regulates OT release as well as expression of the OTR. Coincident with menstruation, levels of both estrogen and OT decrease. Additionally, other serum biochemical factors, including magnesium and cholesterol, which positively modulate the affinity of OT for OTRs, both decrease during menstruation. Thus, during menstruation, multiple menstrually associated factors may lead to decreased circulating OT levels, decreased OT affinity for OTR, and decreased expression of the trigeminal OTR. Consistent with the view of migraine as a threshold disorder, these events may collectively result in decreased inhibition promoting lower thresholds for activation of meningeal trigeminal nociceptors and increasing the likelihood of an MRM attack. CONCLUSION Trigeminal OTR may thus be a novel target for the development of MRM therapeutics.
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Herbal supplements interactions with oral oestrogen-based contraceptive metabolism and transport.
Hlengwa, N, Muller, CJF, Basson, AK, Bowles, S, Louw, J, Awortwe, C
Phytotherapy research : PTR. 2020;(7):1519-1529
Abstract
The increased use of herbal supplements as complementary or alternative medicines has become a clinical conundrum due to the potential for herb-drug interactions. This is exacerbated by an increased supply of new herbal supplements in the market claiming various health advantages. These herbal supplements are available as over-the-counter self-medications. Herbal supplements are generally perceived as efficacious without side effects commonly associated with conventional drugs. However, despite regulations, claims related to their therapeutic effects are mostly unsupported by scientific evidence. These products often lack suitable product quality controls, labelled inadequately and with batch to batch variations, potentially compromising the safety of the consumer. Amongst health practitioners, the greatest concern is related to the lack of chemical characterization of the active compounds of the herbal supplements. The interaction between these different active components and their concomitant effects on other conventional drugs is generally not known. This review will focus on herbal supplements with the potential to effect pharmacokinetic and pharmacodynamic properties of oestrogen-based oral contraceptives. The use of herbal supplements for weight management, depression, and immune boosting benefits were selected as likely herbal supplements to be used concomitantly by women on oral contraceptives.
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7.
Association between FTO gene polymorphisms and breast cancer: the role of estrogen.
Gholamalizadeh, M, Jarrahi, AM, Akbari, ME, Bourbour, F, Mokhtari, Z, Salahshoornezhad, S, Doaei, S
Expert review of endocrinology & metabolism. 2020;(2):115-121
Abstract
Introduction: The fat mass and obesity-associated (FTO) gene may be associated with breast cancer risk. This study aimed to systematically investigate the association between FTO gene polymorphisms and breast cancer and the possible role of estrogen in this association.Areas covered: We performed an extensive search of electronic databases such as PubMed, Science Direct, Scopus, and Cochran for published original studies on the association of FTO gene polymorphisms with breast cancer risk. Keywords such as breast cancer and/or FTO gene and/or polymorphism were used in order to identify the related articles. We excluded studies unrelated to the FTO genotype and the outcome of breast cancer.Expert opinion: FTO gene may have a significant association with the risk of breast cancer. The association between FTO gene polymorphisms and breast cancer was influenced by the status of estrogen receptors. Estrogen may promote breast cancer cell proliferation through up-regulation of FTO gene expression and activation of the PI3 K/Akt signaling pathway in estrogen receptor positive patients. Further studies are warranted to identify the underlying mechanisms and signaling pathways involved in the interactions between FTO gene, estrogen, and the risk of breast cancer.
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8.
Sex Differences in Adipose Tissue Function.
Gavin, KM, Bessesen, DH
Endocrinology and metabolism clinics of North America. 2020;(2):215-228
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Abstract
Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number of products from adipose tissue are under the control of sex steroids, which act through a wide variety of mechanisms, both direct and indirect, to tailor metabolism to the unique needs of each sex. A fuller understanding of sex-based differences in adipose tissue function may help with tailored strategies for disease prevention and treatment and provide insights into fundamental differences in the processes that regulate nutrient homeostasis and body weight.
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9.
Decreased bone mineral density and reproductive axis dysfunction: more than oestrogen.
DeLoughery, EP, Dow, ML
The Netherlands journal of medicine. 2020;(2):50-54
Abstract
Decreased bone mineral density (BMD) in oestrogendeficient states has long been thought to be a direct outcome of the reduction in oestrogen. In physiologic and many pathologic hypo-oestrogenic states, oestrogen supplementation improves BMD. However, the relationship between oestrogen replacement and BMD is less clear in the case of reproductive axis dysfunction secondary to decreased caloric intake or increased energy expenditure, such as in female athletes or anorexia nervosa. This decrease in oestrogen is associated with decreased BMD, but oestrogen replacement in these states fails to conclusively improve BMD. This suggests that the decrease in BMD in these states is not driven solely by low oestrogen. Cortisol and other markers of inflammation may play a role in BMD reduction but further research is needed. What is clear is that increased caloric consumption and restoration of menses and the reproductive axis are essential to improving BMD, while pharmacologic therapy, including oestrogen replacement through hormone therapy or contraceptives, does not provide conclusive benefit.
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10.
Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy.
Bai, J, Qi, QR, Li, Y, Day, R, Makhoul, J, Magness, RR, Chen, DB
International journal of molecular sciences. 2020;(12)
Abstract
Normal pregnancy is associated with dramatic increases in uterine blood flow to facilitate the bidirectional maternal-fetal exchanges of respiratory gases and to provide sole nutrient support for fetal growth and survival. The mechanism(s) underlying pregnancy-associated uterine vasodilation remain incompletely understood, but this is associated with elevated estrogens, which stimulate specific estrogen receptor (ER)-dependent vasodilator production in the uterine artery (UA). The classical ERs (ERα and ERβ) and the plasma-bound G protein-coupled ER (GPR30/GPER) are expressed in UA endothelial cells and smooth muscle cells, mediating the vasodilatory effects of estrogens through genomic and/or nongenomic pathways that are likely epigenetically modified. The activation of these three ERs by estrogens enhances the endothelial production of nitric oxide (NO), which has been shown to play a key role in uterine vasodilation during pregnancy. However, the local blockade of NO biosynthesis only partially attenuates estrogen-induced and pregnancy-associated uterine vasodilation, suggesting that mechanisms other than NO exist to mediate uterine vasodilation. In this review, we summarize the literature on the role of NO in ER-mediated mechanisms controlling estrogen-induced and pregnancy-associated uterine vasodilation and our recent work on a "new" UA vasodilator hydrogen sulfide (H2S) that has dramatically changed our view of how estrogens regulate uterine vasodilation in pregnancy.