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Dry olive leaf extract attenuates DNA damage induced by estradiol and diethylstilbestrol in human peripheral blood cells in vitro.
Topalović, D, Dekanski, D, Spremo-Potparević, B, Pirković, A, Borozan, S, Bajić, V, Stojanović, D, Giampieri, F, Gasparrini, M, Živković, L
Mutation research. Genetic toxicology and environmental mutagenesis. 2019;:402993
Abstract
Phenolic groups of steroidal or nonsteroidal estrogens can redox cycle, leading to oxidative stress, where creation of reactive oxygen species are recognized as the main mechanism of their DNA damage properties. Dry olive (Olea europaea L.) leaf extract is known to contain bioactive and antioxidative components and to have an ability to modulate the effects of various oxidants in cells. The main goal of this study was to investigate antigenotoxic potential of a standardized dry olive leaf extract on DNA damage induced by 17β-estradiol and diethylstilbestrol in human whole blood cells in vitro, using comet assay. Our results indicated that both hormones showed a genotoxic effect at a concentration of 100 μM (P < 0.05, n = 6). Dry olive leaf extract was efficient in reducing number of cells with estrogen-induced DNA damage at tested concentrations (0.125, 0.5 and 1 mg/mL) (P < 0.05, n = 6) and under two experimental protocols, pre-treatment and post-treatment, exhibiting antigenotoxic properties. Analysis of antioxidant properties of the extract revealed moderate ABTS radical scavenging properties and reducing power. Overall, our results suggested that the protective potential of dry olive leaf extract could arise from the synergistic effect of its scavenging activity and enhancement of the cells' antioxidant capacity.
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2.
Estrogen down regulates COMT transcription via promoter DNA methylation in human breast cancer cells.
Wu, Q, Odwin-Dacosta, S, Cao, S, Yager, JD, Tang, WY
Toxicology and applied pharmacology. 2019;:12-22
Abstract
Catechol-O-methyltransferase (COMT) acts as a 'gate-keeper' to prevent DNA damage during estrogen metabolism. Both experimental and epidemiological studies suggest the role of COMT in pathogenesis of human breast cancer (BCa). It was previously reported that inhibition of COMT enzyme activity in estradiol-treated human breast epithelial carcinoma-derived MCF-7 cells caused increased oxidative DNA damage and formation of mutagenic depurinating adducts. To improve our understanding of factors influencing estrogen metabolism in BCa, it requires a mechanistic study illustrating the regulation of this 'gate-keeper'. We investigated the epigenetic mechanisms underlying decreased COMT transcription in MCF-7 cells exposed to 17ß-estradiol (E2) and the phytoestrogen, genistein (GEN). CpG site-specific methylation at promoters for both soluble (S) and membrane-bound (MB) COMT transcripts were assessed. Both E2 and GEN induced CpG site-specific methylation within the distal promoter of MB-COMT. In addition, ChIP analysis showed that there was increased binding of DNMT3B, MBD2 and HDAC1 within this promoter. These epigenetic changes were associated with decreased COMT transcript levels. Interestingly, sulforaphane, an antioxidant commonly found in cruciferous vegetables, was able to reverse the estrogen-induced epigenetic changes and gene silencing of COMT. Our data provide a new insight in epigenetically targeting COMT transcription. Since reactive estrogen metabolites may contribute to breast cancer, our findings may help in developing prevention and/or intervention strategies for human BCa.
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Intermittent light and microbial action of mixed endogenous source DOM affects degradation of 17β-estradiol day after day in a relatively deep natural anaerobic aqueous environment.
Gu, L, Huang, B, Han, F, Xu, Z, Ren, D, He, H, Pan, X, Dionysiou, DD
Journal of hazardous materials. 2019;:40-49
Abstract
All kinds of wastewaters containing steroid estrogens (SEs) and mixed endogenous source dissolved organic matter (DOM) enter natural water environments with intermittent illumination where microbial action occurs in a relatively deep natural aqueous environment. The role of mixed endogenous source DOM in SEs' biodegradation and photochemical degradation in such environments was studied using 17β-estradiol (E2) in laboratory experiments under anaerobic conditions. The experimental results show that microbial action can improve the optical properties and electron transfer capability of mixed endogenous source DOM, promoting photodegradation and biodegradation. Intermittent illumination attenuates DOM's electron transfer capacity and its chromophore groups, but it improves the bioavailability of low molecular weight dissolved organic matter which promotes microbial growth under anaerobic conditions. DOM-mediated co-degradation by light and microbial action over three days was better than either individually. The presence of Fe(III) promoted electron transfer, and Fe(III)-DOM complexes accelerated energy transfer under irradiation, enhancing photodegradation. Any remaining estrogens will continue to degrade, most effectively in well-aerated waters with sufficient illumination.
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Long-term weight loss maintenance, sex steroid hormones, and sex hormone-binding globulin.
Duggan, C, Tapsoba, JD, Stanczyk, F, Wang, CY, Schubert, KF, McTiernan, A
Menopause (New York, N.Y.). 2019;(4):417-422
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Abstract
OBJECTIVE We tested the effects of weight loss on serum estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG) in overweight/obese women 18 months after completing a year-long, 4-arm, randomized-controlled dietary weight loss and/or exercise trial. METHODS From 2005 to 2008, 439 overweight/obese, postmenopausal women (BMI >25 kg/m), 50 to 75 years, were randomized to a year-long intervention: diet (reduced calorie, 10% weight loss, N = 118), exercise (225 min/wk moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). At 12 months, 399 women provided blood; of these, 156 returned at 30 months and gave a blood sample. Hormones and SHBG were measured by immunoassay. Changes were compared using generalized estimating equations, adjusting for confounders. RESULTS At 30 months, participants randomized to the diet + exercise intervention had statistically significant increases in SHBG levels versus controls (P = 0.001). There was no statistically significant change in SHBG in the exercise or diet intervention arms. Hormone levels did not vary by intervention arm from baseline to 30 months. Participants who maintained weight loss at 30 months had statistically significantly greater decreases in free estradiol and free testosterone (Ptrend = 0.02 and Ptrend = 0.04, respectively) and increases in SHBG (Ptrend < 0.0001) versus those who did not have sustained weight loss. Levels of other analytes did not vary by weight loss at 30 months. CONCLUSIONS Sustained weight loss results in reductions in free estradiol and testosterone and increases in SHBG 18-month post-intervention.
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Comparison Of Cimicifuga foetida extract and different hormone therapies regarding in causing breast pain in early postmenopausal women.
Wang, YP, Ma, D, Cheng, XT, Zhang, SJ, Xue, W, Deng, Y, Wang, YF, Sun, AJ
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(2):160-164
Abstract
This study aimed to compare the influence between Cimicifuga foetida extract and different hormone therapies on breast pain in early postmenopausal women. A prospective, randomized, controlled clinical trial was conducted among 96 early postmenopausal women. Participants were randomly assigned to three groups: group A received 1 mg/day estradiol valerate plus 4 mg/day medroxyprogesterone acetate on days 19-30; group B received 1 mg/day estradiol valerate plus 100 mg/day micronized progesterone on days 19-30; group C received C. foetida extract, 1talet (contains 33.3 mg extract), t.i.d. Breast pain diary and numerical rating scale was used to access the breast pain. For 6 months' treatment, the total incidence of breast pain in group A and B was significantly higher than that in group C (p < .05). The duration (day) of breast pain in each month decreased over time in group A and B while it was continuously low and without significant change in group C (p > .05). The intensity of breast pain was mild in most participants and did not differ among three groups (p > .05). During treatment of early postmenopausal women with C. foetida extract for 6 months, the incidence and duration of breast pain were lower than upon treatment with E2 plus cyclic MPA or m-P and did not change over time.
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The Effect of Macronutrients on Reproductive Hormones in Overweight and Obese Men: A Pilot Study.
Pearce, KL, Tremellen, K
Nutrients. 2019;(12)
Abstract
Hypogonadal obese men find it difficult to lose weight. We investigated whether the modification of macronutrient intake can alter testosterone levels independently of the body mass index. Fasted overweight or obese fertile men were asked to consume meals of polyunsaturated fats (PUFA), monounsaturated fats (MUFA), refined carbohydrates (CHO, orange juice, OJ), whey and egg albumin and mixed meals of PUFA and CHO, PUFA and egg albumin, and CHO and egg albumin. Blood was collected at fasting, then hourly for 5 h and analysed to determine the levels of testosterone and other hormones. We found PUFA and MUFA or a mixed meal of PUFA and CHO significantly reduced serum testosterone production to a similar degree over a 5 h period. PUFA decreased serum testosterone levels by 3.2 nmol/L after 1 h compared to baseline (p = 0.023), with this suppression remaining significant up to 5 h postprandially (2.1 nmol/L; p = 0.012). The net overall testosterone levels were reduced by approximately 10 nmol/L × h by PUFA, MUFA and PUFA combined with CHO. CHO alone had little effect on testosterone levels, whereas egg albumin was able to increase them (7.4 cf 2.0 nmol/L × h). Therefore, for men wishing to optimize their testosterone levels, it may be wise to avoid a high fat intake, drink liquids such as water or OJ or even consider fasting. ANZCTR, Australia; ACTRN12617001034325.
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Adsorption studies of 17β-estradiol from aqueous solution using a novel stabilized Fe-Mn binary oxide nanocomposite.
Dai, MY, Liu, YG, Zeng, GM, Liu, SB, Ning, QM
Environmental science and pollution research international. 2019;(8):7614-7626
Abstract
The removal of 17β-estradiol (E2) from contaminated water on nanoscale Fe-Mn binary oxide-loaded multiwalled carbon nanotubes (MWCNTs/FMBO) was evaluated in this work. The characterizations of the mesoporous adsorbent were analyzed by using SEM, TEM, VSM, XRD, XPS, and FTIR measurements. The effects of experimental conditions in E2 removal, including stabilizer additional level, adsorption time, initial E2 concentration, solution pH, reaction temperature, and foreign ions, were examined. The maximum monolayer adsorption capacity (qm) of MWCNTs/FMBO for E2 in the experiment was 47.25 mg/g as verified by the Langmuir sorption isotherm study. The adsorption process was pH-sensitive with an optimum pH of 7.0. On the kinetics study, the adsorption data could be satisfactorily fitted by the pseudo-second-order kinetics. Thermodynamic parameters indicated that the adsorption process was spontaneous and exothermal. In addition, the foreign ions did not show any noticeable inhibition for E2 removal from the water solution except for PO43- that was adversely affected for E2 uptake than other anions in a certain concentration. The adsorption capacities of the mesoporous adsorbent remained at 86.16% even after five adsorption-desorption cycles without significant loss of capacity, which demonstrated the stability and reusability for further removal of E2. Moreover, both hydrogen bond and π-π interaction might be the dominating adsorption mechanisms for E2 adsorption onto MWCNTs/FMBO.
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A novel molecularly imprinted electrochemical sensor based on double sensitization by MOF/CNTs and Prussian blue for detection of 17β-estradiol.
Duan, D, Si, X, Ding, Y, Li, L, Ma, G, Zhang, L, Jian, B
Bioelectrochemistry (Amsterdam, Netherlands). 2019;:211-217
Abstract
In this paper, we constructed MIL-53 (AlOHbdc, bdc = benzene-1,4-dicarboxylate) /CNTs and Prussian blue (PB) as the double sensitization material of the sensing platform, in which the MIL-53/CNTs hybrid can not only increase the specific surface area but also increase the conductivity of the sensor and PB can play a role in amplifying electrical signals and accelerating electron transmission. Pyrrole was used as monomer and E2 was used as template for electropolymerization to form conductive film. Moreover, the overoxidation/dedoping elution method were used to simplify the experimental process. Under optimal conditions, the MIECS exhibited an excellent sensitivity and high selectivity with a wide linear response range between 10-14 to 10-9 mol L-1 and an estimated detection limit of 6.19 × 10-15 mol L-1.
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The resting metabolic rate in women with polycystic ovary syndrome and its relation to the hormonal milieu, insulin metabolism, and body fat distribution: a cohort study.
Romualdi, D, Versace, V, Tagliaferri, V, De Cicco, S, Immediata, V, Apa, R, Guido, M, Lanzone, A
Journal of endocrinological investigation. 2019;(9):1089-1097
Abstract
PURPOSE To evaluate possible alterations of a major determinant of energy expenditure, the resting metabolic rate (RMR), in women with polycystic ovary syndrome (PCOS) compared with age-BMI similar controls. To assess whether the hormonal milieu, the body fat distribution and the insulin metabolism may affect energy consumption in these patients. METHODS This is a monocentric observational prospective cohort study, including 109 Caucasian PCOS subjects and 31 healthy control women. (Median age PCOS 26.0 ± 9.2 years, controls 25.5 ± 8.5 years; median BMI-body mass index PCOS 26.4 ± 9.4 kg/m2, controls 27.2 ± 12.8 kg/m2). RMR was evaluated by the SenseWear Armband (SWA), a reliable and validated metabolic holter, never previously used in the PCOS population to this purpose. Hormonal assessment, insulin metabolism evaluated by HOMA-IR and OGTT, anthropometric features (BMI and WHR) were also assessed. RESULTS Median RMR resulted similar in PCOS and control women: 1520.0 ± 248.00 kcal/day vs 1464.0 ± 332.70 kcal/day (p = 0.472), even after adjusting for BMI, fat distribution, insulin metabolism parameters. RMR resulted significantly correlated with BMI, WHR, estradiol levels, SHBG, total cholesterol, triglycerides, basal glycaemia, basal insulinemia, AUC insulin 240', and HOMA. In the subgroup of patients with WHR > 0.85, PCOS women showed a significantly lower RMR compared with controls. CONCLUSIONS The higher prevalence of obesity, which negatively influences the reproductive and general health of PCOS women, could be related to factors other than an intrinsic alteration of the RMR. Further studies are needed to clarify the possible role of the visceral fat in modulating the energy balance in PCOS. TRIAL REGISTRATION NUMBER clinicaltrials.gov Identifier NCT03132545.
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Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial.
Carr, BR, Stewart, EA, Archer, DF, Al-Hendy, A, Bradley, L, Watts, NB, Diamond, MP, Gao, J, Owens, CD, Chwalisz, K, et al
Obstetrics and gynecology. 2018;(5):1252-1264
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Abstract
OBJECTIVE To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas. METHODS This double-blind, randomized, placebo-controlled, parallel-group study evaluated efficacy and safety of elagolix in cohorts 1 (300 mg twice daily) and 2 (600 mg daily) with four arms per cohort: placebo, elagolix alone, elagolix with 0.5 mg estradiol/0.1 norethindrone acetate, and elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate. A sample size of 65 per group was planned to compare elagolix with add-back to placebo on the primary end point: the percentage of women who had less than 80 mL menstrual blood loss and 50% or greater reduction in menstrual blood loss from baseline to the last 28 days of treatment. Safety assessments included changes in bone mineral density. RESULTS From April 8, 2013, to December 8, 2015, 571 women were enrolled, 567 were randomized and treated (cohort 1=259; cohort 2=308), and 80% and 75% completed treatment, respectively. Participants had a mean±SD age of 43±5 years (cohort 2, 42±5 years), and 70% were black (cohort 2, 74%). Primary end point responder rates in cohort 1 (cohort 2) were 92% (90%) for elagolix alone, 85% (73%) for elagolix with 0.5 mg estradiol/0.1 mg norethindrone acetate, 79% (82%) for elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate, and 27% (32%) for placebo (all P<.001 vs placebo). Elagolix groups had significant decreases compared with placebo in lumbar spine bone mineral density, which was attenuated by adding 1.0 mg estradiol/0.5 mg norethindrone acetate. CONCLUSION Elagolix with and without add-back significantly reduced menstrual blood loss in women with uterine leiomyomas. Add-back therapy reduced hypoestrogenic effects on bone mineral density. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.