Estrogen Drugs Research Articles

Exploring the inhibitory potential of hormone replacement therapy drugs on glutathione transferase P1-1

Aim: Glutathione transferase P1-1 (GST P1-1) plays a crucial role in the human phase II detoxication system and is implicated in drug resistance in certain cancer cells. Analogs of drugs used in Hormone Replacement Therapy (HRT) have been reported to exhibit inhibition of various GSTs. This study aims to investigate the inhibitory potential of several HRT drugs on GST P1-1 for the possible use of counteracting drug resistance and for other therapeutic purposes. Materials and Methods: GST P1-1 was expressed and then purified in a single step using Nickel Sepharose affinity chromatography. Synthetic drugs that are used in HRT were screened for inhibition of GST P1-1 using 1-chloro-2,4-dinitrobenzene as the substrate. The IC50 value of the most potent compound was calculated and binding location and formation of bonds to GST P1-1 were identified through docking analysis. Results: Screening the inhibitory effect of eight synthetic estrogenic drugs reveals that estradiol valerate is the most potent inhibitor, showing 72 ± 4% inhibition of GST P1-1. This effect is followed by estradiol cypionate 53 ± 5%, mestranol 39 ± 4%, and estradiol propionate 35 ± 2%. The most potent compound estradiol valerate has an IC50 value of 30 ± 2 μM. According to docking analysis, it binds to the H-site of the enzyme where the residues Phe9, Arg14, Val36, Trp39, Ile105, Tyr109, Pro203, Asn207, and Gln210 were within 5 Å proximity of the ligand. Estradiol valerate forms Pi-alkyl interactions with Phe9 and Val36, as well as an alkyl interaction with Ile104. Conclusion: Estradiol valerate is a modest inhibitor for hGST P1-1, however it fits in the area of H-site of the enzyme and forms bonds with critical key residues. Understanding its binding site on the enzyme is critical for designing other inhibitors targeting GSTs or possibility for the potential use as a substrate with other GSTs.

Effects of soybean isoflavone aglycone on osteoporosis in ovariectomized rats.

Postmenopausal osteoporosis is one of the most common metabolic diseases in old women, and supplementing estrogen through bioactive substances is one of the important ways to improve menopausal syndrome. Some studies have confirmed that soybean isoflavone has estrogenic activity, and the main active component of soybean isoflavones is isoflavone aglycones. However, few studies have investigated the improvement effect of high-purity soy isoflavone aglycones on postmenopausal osteoporosis. Thus, the effect of different doses of high-purity soybeans isoflavone aglycone on the ovariectomized female osteoporosis rat model was evaluated by oral gavage. The rats were divided into seven experimental groups including SHAM, OVX, EE, SIHP, AFDP-L, AFDP-M, and AFDP-H, which was administered for 60 days from 30 days after ovariectomy. We collected blood from the abdominal aorta of rats on the 30th, 60th, and 90th days respectively, analyzed its serum biochemistry, and took out the femur for micro-CT imaging and bone microstructure parameter analysis. Results showed that the intervention effect of AFDP-H group on osteoporosis rats at 60 and 90 days was similar to that of EE group, and superior to the OVX group, SIHP group, AFDP-L group, AFDP-M group. The AFDP-H group inhibited the decrease in serum bone markers, bone density, trabeculae quantity, trabeculae thickness, and bone volume fraction, and increased the trabecular separation caused by ovariectomy, thereby significantly improving bone microstructure. It also prevented continuous weight gain and increased cholesterol levels in female rats. This study provided theoretical to application of soybean isoflavone aglycone in the intervention of osteoporosis. and confirmed that could replace chemical synthetic estrogen drugs.

The Hidden Dangers of Plant-Based Diets Affecting Bone Health: A Cross-Sectional Study with U.S. National Health and Nutrition Examination Survey (NHANES) Data from 2005-2018.

The plant-based dietary pattern has been recommended for its potential health and environmental benefits, but its association with bone loss needs to be further explored. This study aimed to investigate the association between three plant-based diet indexes and bone loss in 16,085 adults, using data from the National Health and Nutrition Examination Survey. Three plant-based diet indexes (PDI, hPDI, and uPDI) were calculated from two NHANES 24-h dietary recall interviews, to characterize a plant-based diet. A multinomial logistic regression model was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Higher hPDI and PDI were associated with increased risk of bone loss (ORQ5 vs. Q1 = 1.50; 95% CI: 1.24-1.81 for hPDI; ORQ5 vs. Q1 = 1.22; 95% CI: 1.03-1.45 for PDI), while higher uPDI was associated with increased risk of osteoporosis (ORQ5 vs. Q1 = 1.48; 95% CI: 1.04-2.11). A harmful association between plant-based diet indexes (hPDI and PDI) and osteopenia was observed at the lumbar spine rather than the femoral neck. We conducted several sensitivity analyses to ensure the robustness of results, including subgroup analysis, exclusion of people taking anti-osteoporotic and estrogenic drugs, further adjustment for menopausal status, corticosteroid usage, and dietary supplements, and calculation of E-value. Our study demonstrates the deleterious effects of a plant-based diet on bone health and emphasizes the importance of a balanced diet.

First‐degree relatives of patients with systemic lupus erythematosus: Autoreactivity but not autoimmunity?

Systemic lupus erythematosus (SLE) is a disorder with a complex immunopathogenesis. It is well known that the disease begins with immunological alterations and autoantibody appearance in the serum years before clinical onset. As SLE has a strong tendency to familial aggregation, first-degree relatives (FDRs) constitute a group at elevated risk. The current understanding is that external risk factors trigger underlying immune dysregulations, leading to overt disease in those with elevated genetic risk. This cross-sectional study investigates the degree to which clinical features, external risk factors, and immunological profiles differ in SLE FDRs from healthy individuals and SLE patientts. Three groups were studied: Lupus patient FDRs (n=56), healthy controls (n=20), and SLE patients (n=20). FDRs and healthy participants completed a detailed clinical questionnaire that included questions regarding smoking and estrogen drug history. All participants were tested for the presence of the following antinuclear autoantibodies (ANAs) against: nRNP/Sm, Sm, Ro60, Ro-52, La, Scl-70, PM-Scl, PM- Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosomes, histones, RibP, AMA M2, DFS70, and eight soluble cytokines, including transforming growth factor-β (TGF-β), vitamin D levels, and antibodies against Epstein-Barr virus (EBV). Compared with the healthy controls, FDRs had higher titers of ANA, more specific staining immunofluorescent patterns, and more autoantibody specificities. Furthermore, FDRs differed significantly in their TGF-β levels from the other two groups. In FDRs, some clinical features (hair loss, skin, and oral ulcer-like lesions) were associated with higher ANA titers and some (oral ulcer-like lesions) with the anti-Ro60-specific antibody. Interestingly, there was an association between ANA titers and levels of antibodies against EBV only in the FDR group. First-degree relatives display unique clinical and immunological profiles, placing them between healthy individuals and SLE patients, with a balance between compensated immune dysregulation and disease-developing potential. A possible association between ANA titer and the number of clinical complaints is observed, which needs to be confirmed in more extensive studies.

Забруднювач довкілля бісфенол А порушує програмування статевої поведінки у жіночого потомства щурів

Bisphenol A (BPA) is a common environmental pollutant and, due to its estrogenic properties, can cause disorders of the reproductive and other physiological systems of the body, especially in males. It is known that in male rats it disrupts the sexual differentiation of the brain (SDB) of the fetus in utero. Studies of the effects of perinatal exposure of fetuses and newborn females through the mother’s body under the conditions of long-term administration of BPA during pregnancy and lactation did not reveal significant changes in SDB. Identification of long-term endocrine, neuromorphological, and behavioral consequences of exposure of female rat fetuses to a low dose of BPA administered to mothers during the last week of pregnancy, which corresponds to the temporal period of SDB, was the aim of this study. Rats were orally administered BPA suspended in Dorfman gel at a daily dose of 25 μg/kg b.w., which is 200 times less than the NOAEL (no observed adverse effect level) for rats, via a gavage, or, as a positive control, estradiol diacetate (E2D) subcutaneously at a dose of 10 μg/kg b.w., during 15-21 days of pregnancy. Control animals received gel without BPA. The levels of estradiol, testosterone, and corticosterone in blood plasma, the response of the hypothalamic-pituitary-adrenal (HPA) axis to acute immobilization stress, sexual behavior, and the histological structure and karyometric parameters of neurocytes of the medial-preoptic nuclei (MPN) of the hypothalamus were studied in adult female offspring. Prenatal exposure to BPA or E2D decreased the concentration of estradiol in the blood plasma, while the levels of testosterone and corticosterone remained normal. In the females of the BPA and E2D groups, a masculinization of sexual behavior (mounting to a receptive female, approaching her, etc.) was observed, which, according to the number of lordosis reactions in the presence of a sexually experienced male, not accompanied by her defeminization. Changes in the morphology of the MPN, which belongs to the sex-dimorphic area of the brain, conformed to the masculinization of female sexual behavior due to prenatal exposure to a low dose of BPA. Karyometry of neurocytes of the hypothalamic MPN of rats revealed no difference between the control and the BPA group. The response of the HPA axis to immobilization stress did not change in both experimental groups. It is found for the first time that maternal exposure of in utero female rat fetuses to an ultra-low relative to the NOAEL dose of BPA during the last gestational week, which corresponds to the critical period of SDB impairs programming of sexual behavior in the direction of its masculinization and causes hypoestrogenemia at adulthood. Disorders of sexual behavior conformed to morphological changes of the hypothalamic MPN. The unidirectionality of functional disorders induced by prenatal exposure to BPA and the reference estrogenic drug E2D indicates that they are caused by the estrogenic properties of both substances.

FL-DTD: an integrated pipeline to predict the drug interacting targets by feedback loop-based network analysis.

Drug target discovery is an essential step to reveal the mechanism of action (MoA) underlying drug therapeutic effects and/or side effects. Most of the approaches are usually labor-intensive while unable to identify the tissue-specific interacting targets, especially the targets with weaker drug binding affinity. In this work, we proposed an integrated pipeline, FL-DTD, to predict the drug interacting targets of novel compounds in a tissue-specific manner. This method was built based on a hypothesis that cells under a status of homeostasis would take responses to drug perturbation by activating feedback loops. Therefore, the drug interacting targets can be predicted by analyzing the network responses after drug perturbation. We evaluated this method using the expression data of estrogen stimulation, gene manipulation and drug perturbation and validated its good performance to identify the annotated drug targets. Using STAT3 as a target protein, we applied this method to drug perturbation data of 500 natural compounds and predicted five compounds with STAT3 interacting activities. Experimental assay validated the STAT3-interacting activities of four compounds. Overall, our evaluation suggests that FL-DTD predicts the drug interacting targets with good accuracy and can be used for drug target discovery.

Medicinal plants with lactogenic effect: A review

Milk production is essential for optimal feeding of infants. The most common lactogenic drugs are dopamine 2 antagonists, oxytocin, recombinant bovine somatotropin (rBST), thyrotropin releasing hormone (TRH) and estrogenic drugs. However, many medicinal plants possess lactogenic effects in humans and animals. The current review focused on medicinal plants with lactogenic effect as natural sources of galactogogues characterized by efficacy and safety.

Robust strategies to eliminate endocrine disruptive estrogens in water resources

The widespread occurrence and ubiquitous distribution of estrogens, i.e., estrone (E1), estradiol (E2), and estriol (E3) in our water matrices, is an issue of global concern. Public and regulatory authorities are concerned and placing joint efforts to eliminate estrogens and related environmentally hazardous compounds, due to their toxic influences on the environmental matrices, ecology, and human health, even at low concentrations. However, most of the available literature is focused on the occurrence of estrogens in different water environments with limited treatment options. Thus, a detailed review to fully cover the several treatment processes is needed. This review comprehensively and comparatively discusses many physical, chemical, and biological-based treatments to eliminate natural estrogens, i.e., estrone (E1), estradiol (E2), and estriol (E3) and related synthetic estrogens, e.g., 17α-ethinylestradiol (EE2) and other related hazardous compounds. The covered techniques include adsorption, nanofiltration, ultrafiltration, ultrasonication, photocatalysis of estrogenic compounds, Fenton, Fenton-like and photo-Fenton degradation of estrogenic compounds, electro-Fenton degradation of estrogenic compounds, ozonation, and biological methods for the removal of estrogenic compounds are thoroughly discussed with suitable examples. The studies revealed that treatment plants based on chemical and biological approaches are cost-friendly for removing estrogenic pollutants. Further, there is a need to properly monitor and disposal of the usage of estrogenic drugs in humans and animals. Additional studies are required to explore a robust and more advanced oxidation treatment strategy that can contribute effectively to industrial-scale applications. This review may assist future investigations, monitoring, and removing estrogenic compounds from various environmental matrices. In concluding remarks, a way forward and future perspectives focusing on bridging knowledge gaps in estrogenic compounds removal are also proposed.

Oral-contraceptive related ischemic colitis in young women: A case report

Ischemic colitis is the most common form of gastrointestinal (GI) ischemia. The mechanism of ischemic colitis is the lack of colonic blood supply, and the causes are numerous and can be divided into two groups: vascular occlusive and non-occlusive diseases. Despite being common in elderly patients, ischemic colitis is rare in the young and usually associated with some estrogenic drugs, sickle cell anemia, vasculitis, and lupus erythematosus. In Vietnam, estrogen is a rare cause of ischemic colitis. We encountered a clinical case of ischemic colitis in a young female patient taken oral contraceptives for a long time. She visited the hospital for acute abdominal pain and bloody stools. Blood tests and abdominal computed tomography were normal. Endoscopy appearance showed a “single-stripe” sign at the descending colon to the splenic flexure. The biopsy result revealed acute mucosal damage. The patient was managed conservatively with bowel rest, intravenous fluids, and empirical antibiotics. The symptoms were improved with abdominal pain relief and yellow stools after four days. Through this case report, we warn about the risk of ischemic colitis in young women taking oral contraceptives

New opportunities for using transdermal forms of estradiol in ART programs

Objective of this review is to summarize the accumulated data on the use of estradiol transdermal gel in the form of a bottle with a pump-dispenser Oestrogel® in the treatment of "thin" endometrium and in assisted reproductive technologies (ART) programs."Thin" is the endometrium with thickness on ultrasound not exceeds 7 mm during ovulation and is characterized by complete or partial absence of conditions for ovum implantation. Endometrial thickness of 8 mm is referred to as hypoplastic endometriopathy. This endometrium thickness is used to predict the possibility of pregnancy in ART cycles.Estrogen and progesterone are the two main hormones responsible for morphological changes in the endometrial structure during the menstrual cycle. Estradiol promotes the expression of progesterone receptors, thus increasing the tissue sensitivity to progesterone.Today in Ukraine, oral and transdermal estrogens are widely used in ART programs. Transdermal estrogens are preferred due to their lack of a primary hepatic transit effect, which provides a higher safety profile compared to oral forms.A number of researches have been study the effectiveness of the Oestrogel®. It has been established that this drug is highly effective and safe for preparing patients for cryo-transfer of thawed embryos in ART programs. It has also been proven that the efficacy of estradiol transdermal gel in terms of pregnancy rate in patients treated in ART programs with gonadotropic releasing hormone antagonists is comparable to that of oral estradiol valerate and a transdermal patch. In another study, the frequency of miscarriages was significantly lower in patients treated with Oestrogel® compared with patients in the oral estradiol valerate group. Long-term pregnancy and live birth rates were also statistically significantly higher in the transdermal estradiol group. Conclusion. The estrogen drug Oestrogel® is an effective in improving the indicators of prolonged pregnancy and live birth. It can be effectively used for the treating "thin" endometrium and ART programs.

A Review Article on Pharmacologic Evaluation, Botanical report and Calming uses of Dioscorea bulbifera Linn. and Dioscorea pentaphylla Linn.

The present-day investigation focuses on the Pharmacologic revision of the climbers of D. bulbifera L &. D. pentaphylla L. (Dioscoreaceae). Climbers have been deliberate from diverse angles of morphological and, residue scrutiny, and extractive standards. Morphological analysis discovered nature, dimensions, aroma and flavour of tubers. The genus Dioscorea have its place to the family Dioscoreaceae, universally recognized as yam, consist of nearly 600 sps. Scattered all over the earth realm, but customarily in steamy section. Most sps. encompass steroid saponins and correspondingly sapogenins, such as diosgenin, which is preparatory quantifiable for blend of various steroidal hormones castoff as anti-inflammatory, androgenic estrogenic and contraceptive drugs. Associates of the genre Dioscorea are one of ancient tuber crop cultured or garnered from uninhabited in steamy constituency all over earth realm and set up one of the key food element for various indigenous groups. Genus is reflected to be amid the most primeval angiosperms and was recognized to occur and broaden the horizons nearly 75 M. Yrs. past in segments of southern celestial-sphere at the termination of the cretaceous period

The First Dive into the Ocean of Non-Face-to-Face Learning

Introduction Students’ self-learning time that takes place outside of the classroom is an unmeasured learning time. In medical education, students’ learning in the presence and the absence of a teacher are ‘Face-to-Face’ (F2F) and ‘Non-Face-to-Face’ (NF2F) learning, respectively. Traditionally, the content of a topic delivered by a teacher in a one-hour lecture is recognized as F2F learning time. However, its mirror NF2F learning time that is students’ self-learning remains unknown. The objective of this study was to reckon the NF2F learning time for pharmacology topics taught by F2F one-hour lecture method. Methods In a cross-over study, following convenience sampling, two cohorts of undergraduate medical students (N=200) were randomly divided into two equal subgroups; group I and group II. For data purposes, novice and expert faculty categorized based on their teaching experience taught two pharmacology topics (Aminoglycosides drugs and Estrogen drugs) by lecture method. Respondents gave their perceived NF2F (self-learning) time on a Five-point Likert scale. The association of teaching experience and NF2F learning time of students was observed by applying the chi-square test. Results For contents delivered in a one-hour lecture, the NF2F learning time by most students was ≥ 3 hours. There was a significant statistical association between students NF2F learning time and teachers’ experience for ‘Aminoglycosides drugs’ [X2, 95% CI: 4.985, 2.062 (1.087, 3.193), p 0.026]. It was noted that the NF2F learning time had no association with gender (P> 0.05). Conclusion Mostly, the required NF2F learning time is more than double the time of F2F time. The implication of this study suggests that the estimation of students’ NF2F learning time may likely be estimated for other topics of pharmacology in a controlled manner.

Bazedoxifene effects on osteoprotegerin, insulin-like growth factor, tumor necrosis factor and bone mineral density

112 patients with postmenopausal osteoporosis who received Bazedoxifene drugs in our hospital from January to December 2018 were collected as a study group, and 56 patients treated with calcium alone were collected as a control group. the risk of adverse events such as bone mineral density, osteoprotegerin (OPG), insulin-like growth factor (IGF), tumor necrosis factor (TNF-α), and fracture after treatment were analyzed before and after treatment. There was no significant difference in the mean lumbar positive position (L2-4) and right femoral neck bone density and OPG, IGF, TNF-α level between the two groups before treatment (P>0.05). The total effective rate of clinical treatment in the study group was 88.39%, the control group was 23.21%, the difference between the two groups was statistically significant (P˂0.05). After treatment, the mean lumbar positive position (L2-4) and the right femoral neck bone density and OPG, IGF in the study group were higher than those in the control group, lower than those in the control group (P<0.05). the occurrence of adverse events such as fracture, spinal deformation and fatigue in the study group after 12 months of treatment was significantly lower than that in the control group (P<0.05), but there was no significant difference in the occurrence of hot flashes and venous thromboembolism between the two groups (P>0.05). Bazedoxifene is an effective drug for the treatment of postmenopausal osteoporosis. It can not only prevent the rapid loss of bone mass, effectively relieve the symptoms of menopause, but also improve bone density and reduce the risk of fracture.

Preparation of endometrium for frozen embryo transfer cycles

Aim. Aim of the study was to the effectiveness of various endometrial preparation protocols in IVF frozen embryo transfer cycles.
 Materials and methods. The study included 288 women, which were stratified into two groups depending on the onset of pregnancy: group 1 pregnancy + (n=92), group 2 pregnancy - (n=196). Then endometrium preparation features were evaluated.
 Results. The pregnancy rate after frozen-thawed embryo transfer was a bit higher in the natural menstrual cycle (41.2%) compared to the hormonal replacement therapy (30.0%); p=0.083. There were no significant differences in the use of various estrogen and progestogen drugs, the average estrogen dose, progestogen administration and the endometrium thickness. In the natural cycle, the odds ratio of pregnancy with the duration menstrual cycle from 28 to 30 days was 4.25 (95% CI 1.15; 17.23).
 Conclusion. Thus, the pregnancy rate is slightly higher in natural cycle frozen-thawed embryo transfer. However, the duration of the menstrual cycle (from 28 to 30 days) has a key effect on the effectiveness of the IVF program in this case.

Estrogen receptor 1 expression and methylation of Esr1 promoter in mouse fetal prostate mesenchymal cells induced by gestational exposure to bisphenol A or ethinylestradiol.

Fetal/neonatal environmental estrogen exposures alter developmental programing of the prostate gland causing onset of diseases later in life. We have previously shown in vitro that exposures to 17β-estradiol (E2) and the endocrine disrupting chemical bisphenol A, at concentrations relevant to human exposure, cause an elevation of estrogen receptor α (Esr1) mRNA in primary cultures of fetal mouse prostate mesenchymal cells; a similar result was observed in the fetal rat urogenital sinus. Effects of these chemicals on prostate mesenchyme in vivo are not well understood. Here we show effects in mice of fetal exposure to the estrogenic drug in mixed oral contraceptives, 17α-ethinylestradiol (EE2), at a concentration of EE2 encountered by human embryos/fetuses whose mothers become pregnant while on EE2-containing oral contraceptives, or bisphenol A at a concentration relevant to exposures observed in human fetuses in vivo. Expression of Esr1 was elevated by bisphenol A or EE2 exposures, which decreased the global expression of DNA methyltransferase 3A (Dnmt3a), while methylation of Esr1 promoter was significantly increased. These results show that exposures to the environmental estrogen bisphenol A and drug EE2 cause transcriptional and epigenetic alterations to expression of estrogen receptors in developing prostate mesenchyme in vivo.

Estrogen Receptor‐α Counterbalances the Endotoxic Inflammatory Response and Associated Arterial Baroreflex Dysfunction in Ovariectomized Rats

Evidence from clinical and experimental studies suggests that the female population is tolerant to inflammatory and cardiovascular anomalies of endotoxemia. In this study we investigated the possibilities that female rats are also protected against the arterial baroreceptor depressant effect of endotoxemia and that this interaction is modulated by gonadal hormones. The effect of i.v. lipopolysaccharides (LPS, 10 mg/kg) on baroreflex chronotropic activity were assessed in conscious sham‐operated (SO) female rats as well as in ovariectomized (OVX) rats supplemented with or without gonadal hormones. Baroreflex curves relating changes in chronotropic responses to increases or decreases in blood pressure evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed and slopes of the curves were taken as measures of baroreflex sensitivity (BRSPE, BRSSNP). While LPS had no effect on baroreflex activity tested by PE in SO rats, it caused downward shifts in baroreflex curves generated by SNP and significant reductions (by ~ 25%) in slopes of the curves (BRSSNP). Compared with SO rats, significantly greater reductions in BRSSNP were caused by LPS in OVX rats (~ 50%), inferring a restraining influence for gonadal hormones on LPS‐BRSSNP interaction. The BRSSNP depressant effect of LPS in OVX rats was largely eliminated after supplementation with PPT (estrogen receptor‐α agonist), in contrast to no effect for DPN (estrogen receptor‐β agonist), estrogen, or medroxyprogesterone. Immunohistochemical studies revealed that PPT was more effective than estrogen or DPN in attenuating the LPS‐evoked increases in myocardial expressions of NF‐κB and iNOS in OVX rats. Further, the three estrogenic drugs caused comparable increases in myocardial HSP70 expression in the same rat model. None of these molecular entities was improved by medroxyprogesterone. These findings preferentially implicate antiinflammatory pathways of estrogen receptor‐α in the alleviation of baroreflex dysfunction induced by endotoxemia in female rats.Support or Funding InformationSupported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Estrogen sulfotransferase in the metabolism of estrogenic drugs and in the pathogenesis of diseases

ABSTRACTIntroduction: Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. The expression of SULT1E1 can be detected in many tissues, including the liver. SULT1E1 catalyzes the transfer of a sulfate group from 3ʹ-phosphoadenosine-5ʹ-phosphosulfate (PAPS) to any available hydroxyl group in estrogenic molecules. The substrates of SULT1E1 include the endogenous and synthetic estrogens. Upon SULT1E1-mediated sulfation, the hydrosolubility of estrogens increases, preventing the binding between the sulfated estrogens and the estrogen receptor (ER). This sulfated state of the estrogens is not irreversible, as the steroid sulfatase (STS) can convert sulfoconjugated estrogens to free estrogens. The expression of SULT1E1 is inducible by several diseases that involve tissue inflammation, such as type 2 diabetes, sepsis, and ischemia-reperfusion injury.Areas covered: This systematic literature review aims to summarize the role of SULT1E1 in the metabolism of estrogenic drugs and xenobiotics, and the role of SULT1E1 in the pathogenesis of several diseases, including cancer, metabolic disease, sepsis, liver injury, and cystic fibrosis. Meanwhile, ablation or pharmacological inhibition of SULT1E1 can affect the outcomes of the aforementioned diseases.Expert opinion: In addition to its role in metabolizing estrogenic drugs, SULT1E1 is unexpectedly being unveiled as a mediator for the disease effect on estrogen metabolism and homeostasis. Meanwhile, because the expression and activity of SULT1E1 can affect the outcome of diseases, the same sulfotransferase and the reversing enzymes STS can be potential therapeutic targets to prevent or manage diseases. Accumulating evidence suggest that the physiological and pathophysiological effects of SULT1E1 can be estrogen-independent and it is necessary to elucidate what other possible substrates may be recognized by the enzyme. Moreover, human studies are paramount to confirm the human relevance of the animal studies.

The Influence of hormonal therapy on bone tissue: myths and reality

The paper presents a review of the current literature on the impact of estrogen, progesterone, and estrogen-progestin drugs (combined oral contraceptives, drugs for menopausal hormone therapy), thyroid, and glucocorticoid hormones on bone tissue. In this review, we discuss the pathogenetic mechanisms of the effects of various bioactive compounds on bone, and the results of domestic and foreign research.

The effectiveness and safety of mht depending on the type, route of administration of estrogens, and the type of progestogen. Analysis of data from clinical trials and international recommendations

The hormone therapy remains the most effective method for treating of the vasomotor symptoms and genitourinary syndrome in menopause. The evidence available to date suggests that for women younger than 60 and with a postmenopause no more than 10 years without contraindications, the benefits of administering systemic hormone therapy for the treatment of vasomotor symptoms, sleep disorders and prevention of bone loss exceed possible risks. In addition, the data about statistically significant reduction in all-cause mortality in women who initiate hormone therapy before the age of 60 and/or 10 years after the onset of menopause have been obtained.Menopausal hormone therapy (MHT) includes a wide range of hormonal drugs and administration routes that potentially have different risks and benefits, and therefore the term “class effect” is misleading and inappropriate. The risks of menopausal hormone therapy vary depending on the composition, dose and route of administration of hormones, as well as the timing of the onset and duration of use of both estrogens and progesterone. The use of transdermal estrogens in combination with progesterone seems safer for venous thromboembolism, especially in high-risk women. The use of transdermal estrogen drugs in comparison with oral estrogens is associated with a lesser likelihood of developing thrombotic risk, and possibly the risk of developing stroke and coronary heart disease. If progesterone is needed, micronized progesterone is a safer alternative.MHT requires a periodic reassessment of the benefits and risks for deciding whether to continue or stop using it. The use of postmenopausal hormone therapy in women with menopausal disorders should be based on an assessment of all risk factors for cardiovascular disease, age and time from the onset of menopause. The duration of therapy should be motivated by the indications, and the decision should be taken in conjunction with the doctor.

A model of natural degradation of 17-α-ethinylestradiol in surface water and identification of degradation products by GC-MS.

Over the past decade, the environment has been polluted by a wide spectrum of exogenous chemicals and environmental analysis has become one of the most progressive parts of analytical research. The aim of this work was to determine the kinetics of natural degradation, and to identify the degradation products of the massively used estrogenic drug, 17-α-ethinylestradiol. The photodegradation, oxidation and thermostability conditions were selected according to ICH requirements for pharmaceutical stability testing. A simple 72-h photodegradation study in purified water exhibited significant first-order kinetics with the kinetic constant k=0.0303h-1, and degradation halftime 22.8h. The basic halftime could be reduced to 17.1h by the addition of sea salt, and increase in temperature. Monohydroxy, dihydroxy and dehydrogenated derivatives of ethinylestradiol with intact steroidal structure were identified as major degradation products resulting from simple photodegradation. The addition of an oxidative agent significantly accelerated the degradation rate; combined with higher temperature, the degradation halftime was reduced to 1.1h with the first-order kinetic constant k=0.632h-1. TOC analysis showed a notable decrease of organic mass (18% in 3days) during oxidation experiments, and confirmed the degradation of steroidal structure.