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The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial.
Amini, S, Amani, R, Jafarirad, S, Cheraghian, B, Sayyah, M, Hemmati, AA
Nutritional neuroscience. 2022;(1):22-32
Abstract
Objectives: Postpartum depression (PPD) is a major depressive disorder. Vitamin D deficiency may play a role in PPD pathogenesis. This study was designed to determine the effect of vitamin D and calcium supplementation on the severity of symptoms and some related inflammatory biomarkers in women with PPD.Materials and Methods: Eighty-one women with a PPD score >12 participated in this study. A total of 27 patients were randomly assigned into three groups (1:1:1 ratio) to receive either 50,000 IU vitamin D3 fortnightly + 500 mg calcium carbonate daily; or 50,000 IU vitamin D3 fortnightly + placebo of calcium carbonate daily, or placebo of vitamin D3 fortnightly + placebo of calcium carbonate daily (placebo group) for 8 weeks. At the baseline and end of the study, the severity score of PPD, levels of 25-hydroxy vitamin D, calcium, tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6) and estradiol were measured.Results: The PPD score had more reduction in the vitamin D + calcium and vitamin D + calcium placebo groups than that of the placebo group (-1.7 ± 3.44, -4.16 ± 5.90 and 0.25 ± 2.81, respectively; p = 0.008). The effect of vitamin D on the PPD score was larger when vitamin D was given alone than given together with calcium (p = 0.042 and p = 0.004, respectively). No significant differences in estradiol, IL6 and TNFα were observed between the three groups.Discussion: Vitamin D may be effective in improving the clinical symptoms of PPD; however, the mechanism of the effect might not entirely operate through inflammatory and/or hormonal changes.
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Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19.
Infante, M, Pieri, M, Lupisella, S, D'Amore, L, Bernardini, S, Fabbri, A, Iannetta, M, Andreoni, M, Morello, M
European review for medical and pharmacological sciences. 2021;(19):5889-5903
Abstract
OBJECTIVE Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.
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The effect of dehydroepiandrosterone (DHEA) supplementation on estradiol levels in women: A dose-response and meta-analysis of randomized clinical trials.
Zhu, Y, Qiu, L, Jiang, F, Găman, MA, Abudoraehem, OS, Okunade, KS, Zhang, M
Steroids. 2021;:108889
Abstract
Estradiol, an estrogen steroid hormone, serves as the dominant female hormone and its levels fluctuate during lifetime. In women, after the menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from dehydroepiandrosterone (DHEA). However, the effect of DHEA supplementation on estradiol levels in women is unclear as previously published data has resulted in conflicting findings. Thus, we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women. The PubMed/Medline, Embase, Web of Science and Scopus databases were systematically searched for articles published on this topic until May 10, 2021. No time or language restrictions were applied. The data were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CI), and a P-value of less than 0.05 was considered to be statistically significant. The pooled results were obtained using the generic inverse of variance method with a random effects model. A total of 21 arms, including 1223 participants (case = 610, and control = 613), reported estradiol concentrations as an outcome measure. The overall results demonstrated that estradiol significantly increased following the administration of DHEA (WMD: 7.02 pg/mL, 95% CI: 5.43, 8.62, P = 0.000). The stratified analyses revealed that the elevation of estradiol concentrations was more pronounced in subjects aged ≥60 years old (WMD: 8.56 pg/mL, 95% CI: 6.97, 10.16, I2 = 94%) and in those receiving DHEA supplements for ≥26 weeks (WMD: 7.30 pg/mL, 95% CI: 6.28, 8.32, I2 = 61%). Moreover, estradiol levels increased significantly with DHEA dosages of 50 mg/day (WMD: 7.75 pg/mL, 95% CI: 9.12, 9.39, I2 = 94%) and when DHEA was prescribed to postmenopausal women (WMD: 7.61 pg/mL, 95% CI: 5.97, 9.24, I2 = 93%). This meta-analysis has provided a comprehensive overview of the effects of DHEA administration on circulating estradiol levels, far beyond the available evidence from different RCTs. Subsequent subgroup analyses revealed that postmenopausal women, females aged 60 years and above, those on DHEA dosages of 50 mg/day and those receiving DHEA for ≥26 weeks registered a more pronounced elevation of the circulating estradiol levels.
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[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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Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.
Singhal, V, Bose, A, Slattery, M, Haines, MS, Goldstein, MA, Gupta, N, Brigham, KS, Ebrahimi, S, Javaras, KN, Bouxsein, ML, et al
The Journal of clinical endocrinology and metabolism. 2021;(7):2021-2035
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Abstract
CONTEXT Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
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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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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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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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Effect of estrogen-active compounds on the expression of RACK1 and immunological implications.
Buoso, E, Masi, M, Galbiati, V, Maddalon, A, Iulini, M, Kenda, M, Sollner Dolenc, M, Marinovich, M, Racchi, M, Corsini, E
Archives of toxicology. 2020;(6):2081-2095
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Abstract
We previously demonstrated the existence of a balance among steroid hormones, i.e. glucocorticoids and androgens, in RACK1 (receptor for activated C kinase 1) expression and innate immunity activation, which may offer the opportunity to use RACK1 expression as marker to evaluate immunotoxicity of hormone-active substances. Because of the existence of close interconnections between the different steroid hormone receptors with overlapping ligand specificities and signaling pathways, in this study, we wanted to investigate a possible effect of estrogenic active compounds, namely 17β-estradiol, diethylstilbestrol, and zearalenone, on RACK-1 expression and innate immune responses using THP-1 cells as experimental model. All compounds increased RACK1 transcriptional activity as evaluated by reporter luciferase activity, mRNA expression as assessed by real time-PCR and protein expression by western blot analysis, which paralleled an increase in LPS-induced IL-8, TNF-α production, and CD86 expression, which we previously demonstrated to be dependent on RACK1/PKCβ activation. As the induction of RACK1 expression can be blocked by the antagonist G15, induced by the agonist G1 and by the non-cell permeable 17β-estradiol conjugated with BSA, a role of GPER (previously named GPR30) activation in estrogen-induced RACK1 expression could be demonstrated. In addition, a role of androgen receptor (AR) in RACK1 transcription was also demonstrated by the ability of flutamide, a nonsteroidal antiandrogen, to completely prevent diethylstilbestrol-induced RACK1 transcriptional activity and protein expression. Altogether, our data suggest that RACK1 may represent an interesting target of steroid-active compounds, and its evaluation may offer the opportunity to screen the immunotoxic potential of hormone-active substances.
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Adsorption of 17β-estradiol from aqueous solution by raw and direct/pre/post-KOH treated lotus seedpod biochar.
Liu, N, Liu, Y, Zeng, G, Gong, J, Tan, X, JunWen, , Liu, S, Jiang, L, Li, M, Yin, Z
Journal of environmental sciences (China). 2020;:10-23
Abstract
Five biochars derived from lotus seedpod (LSP) were applied to examine and compare the adsorption capacity of 17β-estradiol (E2) from aqueous solution. The effect of KOH activation and the order of activation steps on material properties were discussed. The effect of contact time, initial concentration, pH, ionic strength and humic acid on E2 adsorption were investigated in a batch adsorption process. Experimental results demonstrated that the pseudo second-order model fitted the experimental data best and that adsorption equilibrium was reached within 20 hr. The efficiency of E2 removal increased with increasing E2 concentration and decreased with the increase of ionic strength. E2 adsorption on LSP-derived biochar (BCs) was influenced little by humic acid, and slightly affected by the solution pH when its value ranged from 4.0 to 9.0, but considerably affected at pH 10.0. Low environmental temperature is favorable for E2 adsorption. Chemisorption, π-π interactions, monolayer adsorption and electrostatic interaction are the possible adsorption mechanisms. Comparative studies indicated that KOH activation and the order of activation steps had significant impacts on the material. Post-treated biochar exhibited better adsorption capacity for E2 than direct treated, pre-treated, and raw LSP biochar. Pyrolyzed biochar at higher temperature improved E2 removal. The excellent performance of BCs in removing E2 suggested that BCs have potential in E2 treatment and that the biochar directly treated by KOH would be a good choice for the treatment of E2 in aqueous solution, with its advantages of good efficiency and simple technology.