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1.
[Effects of the use of 17 β-estradiol and genistein in Alzheimer's disease in women with menopause].
Chávez-Pérez, C, Ceballos-Ramírez, A, Suárez-Castro, A
Revista espanola de geriatria y gerontologia. 2021;(4):236-240
Abstract
The use of 17 β-estradiol and genistein in women with menopause helps in the reduction of vasomotor symptoms and cognitive improvement. There is evidence on the use of certain flavonoids such as genistein, which has a potentially neuroprotective role in neurodegenerative diseases such as Alzheimer's. Scientific evidence on the effects of phytoestrogens and genistein during menopause and their effect on cognition are scarce, however, in the present review it was found that the intervention with 17 β-estradiol has positive effects on cognition in women with Alzheimer's disease. In addition, the use of genistein, daidzein or any supplement based on isoflavones may influence vasomotor symptoms. 17 β-estradiol supplements in women in early menopause and with some degree of cognitive impairment may have beneficial effects.
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2.
Sarcopenia and Menopause: The Role of Estradiol.
Geraci, A, Calvani, R, Ferri, E, Marzetti, E, Arosio, B, Cesari, M
Frontiers in endocrinology. 2021;:682012
Abstract
During aging and menopausal transition in women, a progressive muscle degeneration (i.e. decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women.
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3.
Elagolix, Estradiol, and Norethindrone Kit (Oriahnn) for the Management of Heavy Menstrual Bleeding Associated with Fibroids.
Antoun, J
American family physician. 2021;(8):505-506
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4.
Effect of menstrual cycle and female hormones on TRP and TREK channels in modifying thermosensitivity and physiological functions in women.
Uchida, Y, Izumizaki, M
Journal of thermal biology. 2021;:103029
Abstract
Thermoregulation is crucial for human survival at various ambient temperatures. Transient receptor potential (TRP) and TWIK-related K+ (TREK) channels expressed in sensory neurons play a role in peripheral thermosensitivity for temperature detection. In addition, these channels have various physiological roles in the skeletal, nervous, immune, vascular, digestive, and urinary systems. In women, the female hormones estradiol (E2) and progesterone (P4), which fluctuate during the menstrual cycle, affect various physiological functions, such as thermoregulation in hot and cold environments. The present review describes the effect of female hormones on TRP and TREK channels and related physiological functions. The P4 decreased thermosensitivity via TRPV1. E2 facilitates temporomandibular joint disease (TRPV1), breast cancer (TRPM8), and calcium absorption in the digestive system (TRPV5 and TRPV6), inhibits the facilitation of vasoconstriction (TRPM3), nerve inflammation (TRPM4), sweetness sensitivity (TRPM5), and menstrual disorders (TRPC1), and prevents insulin resistance (TRPC5) via each channel. P4 inhibits vasoconstriction (TRPM3), sweetness sensitivity (TRPM5), ciliary motility in the lungs (TRPV4), menstrual disorder (TRPC1), and immunity (TRPC3), and facilitates breast cancer (TRPV6) via each channel as indicated. The effects of female hormones on TREK channels and physiological functions are still under investigation. In summary, female hormones influence physiological functions via some TRP channels; however, the literature is not comprehensive and future studies are needed, especially those related to thermoregulation in women.
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5.
Modulation of Human Sperm Capacitation by Progesterone, Estradiol, and Luteinizing Hormone.
López-Torres, AS, Chirinos, M
Reproductive sciences (Thousand Oaks, Calif.). 2017;(2):193-201
Abstract
Sperm residency in female reproductive tract is essential to undergo functional changes that allow the cell to encounter the oocyte and fertilize it. Those changes, known as capacitation, are modulated by molecules located in the uterotubal surface and fluids. During the fertile window, there is a notable increase in some reproductive hormones such as progesterone, estradiol, and luteinizing hormone in the female reproductive tract, so spermatozoa are exposed to these hormones in an environment that must favor gamete encountering and fusion. This spatiotemporal coincidence suggests that they are suitable candidates to modulate sperm function in order to synchronize the events that ultimately allow the success of fertilization. The presence of receptors for these hormones in the human sperm has been described, but their physiological relevance and mechanisms of action have been either subject of controversy or not properly investigated. This review intends to summarize the evidence that support the participation of these hormones in the regulation of sperm capacitation.
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6.
Going off the grid: ERα breast cancer beyond estradiol.
Perone, Y, Magnani, L
Journal of molecular endocrinology. 2016;(1):F1-5
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Abstract
Novel studies have linked cholesterol biosynthesis to drug resistance in luminal breast cancer. Structural data suggest that cholesterol metabolites, including 27-hydroxycholesterol (27HC), can act as ERα ligands in these cells. Additionally, hypercholesterolemia has now been linked to breast cancer progression. The focus of this review is to briefly summarize these recent findings and discuss how epigenetic reprogramming is definitively connected to endogenous cholesterol biosynthesis. We elaborate on how these data support a working model in which cholesterol biosynthesis promotes autocrine, pro-invasive signaling via activation of a series of closely related transcription factors. Importantly, we discuss how this mechanism of resistance is specifically associated with aromatase inhibitors. Finally, we examine how the field is now considering the development of anticholesterol therapeutics and companion biomarkers to stratify and treat ERα breast cancer patients. In particular, we review recent progress in pharmaceutical strategies targeting the cholesterol molecular machinery in primary and secondary breast cancers.
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7.
Hormones, herbal preparations and nutriceuticals for a better life after the menopause: part I.
Comhaire, FH, Depypere, HT
Climacteric : the journal of the International Menopause Society. 2015;(3):358-63
Abstract
In developed countries, women spend more than one-third of their life in the menopause and at least half of them experience vasomotor symptoms that impair their normal function and well-being. Long-term estrogen replacement therapy (HRT) with estrogen can suppress typical menopausal symptoms and prevents osteoporosis. When estrogen-only HRT is started within 10 years after the menopause, the prevalence of cardiovascular disease is reduced, mortality is lower, and the risk of breast cancer is not significantly increased. Postmenopausal genital and urinary problems with recurrent infections, incontinence, and dyspareunia can effectively be treated by vaginal application of estriol, which seems to be safe for women treated for breast cancer. HRT after the age of 60 years is associated with a lower number needed to treat than number needed to harm, implying that there would be one unfavorable side-effect for up to ten women experiencing a positive effect. However, further studies are needed regarding the risk-benefit ratio of HRT in women over 70 years. It is concluded that transdermal substitution therapy with estradiol may increase the number of quality-adjusted life years of postmenopausal women. The combination with nutriceutical food supplementation may add to this benefit, but complementary prospective trials are still needed.
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Hormones, herbal preparations and nutriceuticals for a better life after the menopause: part II.
Comhaire, FH, Depypere, HT
Climacteric : the journal of the International Menopause Society. 2015;(3):364-71
Abstract
Long-term estrogen replacement therapy with estrogen has benefits for many postmenopausal women. However, some women prefer non-steroidal substitution with herbal preparations. The effectivity against vasomotor symptoms has been evidenced for the extracts of pine bark, of linseed and of Lepidium meyenii (Maca), whereas there is controversy about the effectiveness of genistein-rich soy extract. The extracts of cruciferous vegetables such as Broccoli and of linseed induce changes in the metabolism of estrogens, and antioxidants may reverse altered epigenetic DNA methylation, possibly reducing the risk of breast cancer or its recurrence. Indirect evidence from the literature and from clinical trials supports that a nutriceutical composed of plant extracts, low-dose vitamins and minerals may improve the quality of life by delaying certain age-related diseases. On the basis of epidemiologic studies, physiopathological considerations and controlled prospectieve trials, it is suggested that transdermal substitution therapy with estradiol together with nutriceutical food supplementation may increase the number of quality-adjusted life years of postmenopausal women, but complementary, large-scale, prospective trials are still needed.
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9.
Regioselective hydroxylation of steroid hormones by human cytochromes P450.
Niwa, T, Murayama, N, Imagawa, Y, Yamazaki, H
Drug metabolism reviews. 2015;(2):89-110
Abstract
This article reviews in vitro metabolic activities [including Michaelis constants (Km), maximal velocities (Vmax) and Vmax/Km] and drug-steroid interactions [such as induction and cooperativity (activation)] of cytochromes P450 (P450 or CYP) in human tissues, including liver and adrenal gland, for 14 kinds of endogenous steroid compounds, including allopregnanolone, cholesterol, cortisol, cortisone, dehydroepiandrosterone, estradiol, estrone, pregnenolone, progesterone, testosterone and bile acids (cholic acid). First, we considered the drug-metabolizing P450s. 6β-Hydroxylation of many steroids, including cortisol, cortisone, progesterone and testosterone, was catalyzed primarily by CYP3A4. CYP1A2 and CYP3A4, respectively, are likely the major hepatic enzymes responsible for 2-/4-hydroxylation and 16α-hydroxylation of estradiol and estrone, steroids that can contribute to breast cancer risk. In contrast, CYP1A1 and CYP1B1 predominantly metabolized estrone and estradiol to 2- and 4-catechol estrogens, which are endogenous ultimate carcinogens if formed in the breast. Some metabolic activities of CYP3A4, including dehydroepiandrosterone 7β-/16α-hydroxylation, estrone 2-hydroxylation and testosterone 6β-hydroxylation, were higher than those for polymorphically expressed CYP3A5. Next, we considered typical steroidogenic P450s. CYP17A1, CYP19A1 and CYP27A1 catalyzed steroid synthesis, including hydroxylation at 17α, 19 and 27 positions, respectively. However, it was difficult to predict which hepatic drug-metabolizing P450 or steroidogenic P450 will be mainly responsible for metabolizing each steroid hormone in vivo based on these results. Further research is required on the metabolism of steroid hormones by various P450s and on prediction of their relative contributions to in vivo metabolism. The findings collected here provide fundamental and useful information on the metabolism of steroid compounds.
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Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone.
Talbot, JN, Gligorov, J, Nataf, V, Montravers, F, Huchet, V, Michaud, L, Ohnona, J, Balogova, S, Cussenot, O, Daraï, E, et al
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2015;(1):4-17
Abstract
Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-[¹⁸F]fluoro-17β-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV(max) or FES/FDG SUV(max) ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical utility in those settings; only initial results are available. The indication of PET and PET/CT has been even more disputed in prostate carcinoma, due to the lack of significant FDG uptake in most cases, at least before the castration-resistant stage. Using FDHT, a fluorinated testosterone analogue, PET is able to detect the over-expression of the androgen receptor (AR) in lesions, at a whole-body level. At least partly due to the rather large number of alternative tracers that are in development or even routinely available in some countries, few FDHT studies have been published until now. From absorbed dose values previously published for FES by the team of University of Washington School of Medicine at Seattle, and for FDHT by the teams of Memorial Sloan-Kettering Cancer Center at New York and of Washington University at St. Louis, we applied the coefficients of ICRP publication 103 and calculated an effective dose per unit of injected activity of 0.023 mSv/MBq for FES and 0.018 mSv/MBq for FDHT. The radiation exposure is of the same order of magnitude as with FDG.