Effects Of Female Sex Hormones Research Articles

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury.

The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.

The effects of female sex hormones on the human cornea across a woman’s life cycle

The cornea is a hormone-responsive tissue that responds to changing levels of female sex hormones. This review focuses on the structural and functional changes in the human cornea associated with the hormonal milestones of menarche, pregnancy, and menopause, as well as consequences stemming from the use of exogenous sex hormones for fertility control and replacement. Articles were identified by searching PubMed without language or region restrictions. The primary outcomes evaluated were changes in central corneal thickness (CCT), intraocular pressure (IOP), and quality of the ocular tear film. The potential impact of hormone-associated changes on the diagnosis and surgical management of common eye diseases, as well as the potential use of sex hormones as therapeutic agents is also considered. Understanding the physiological effects of female sex hormones on the cornea is important because that knowledge can shape the management decisions physicians and women face about ocular health across their life stages.

Differential angiogenic response contributes to sexual dimorphism in right ventricular adaptation in male and female Fischer CDF rats subjected to pulmonary artery banding model

Background: Female sex has been associated with better right ventricular (RV) adaptation and survival in patients with elevated RV afterload; however, the mechanisms underlying these differences remain unclear. Therefore, we studied the mechanisms underlying sex differences in RV remodeling and development of RHF using the rat pulmonary artery banding (PAB) model. Methods: Adult male and female Fischer CDF rats were subjected to PAB or sham surgery and echocardiography was performed at 1- or 2-weeks post-PAB to evaluate RV structure and function. RV systolic pressure (RVSP) was measured using a pressure catheter and Fulton Index (RV/ left ventricle + septum) was measured to evaluate RV hypertrophy (RVH). To explore the mechanisms, a focused PCR array was performed to assess the expression of angiogenic genes in the RV of male and female rats subjected to sham or PAB procedure. RV endothelial cells (RVECs) were isolated from Fischer CDF rats and effects of female sex hormones on angiogenic ability of RVECs was assessed using Matrigel network formation assay. We also assessed the role of sphingosine kinase-1 (Sphk1) inhibitor, PF-543, in mediating the effects of female sex hormones on angiogenic potential of RVECs. Results: At 1- and 2-week post-PAB, RVSP and RVH were significantly elevated in PAB rats compared to control rats; however, no differences were observed between male and female rats. Cardiomyocyte surface area (330 vs 234 mm2, p<0.05) and fibrosis (6.96 vs 4.58%, p<0.05) were both significantly higher in male compared to female rats. RV end-diastolic diameter was also increased in male rats compared to female rats (3.33 vs 2.05 mm; p<0.05). On the contrary, RV function was preserved in female rats as indicated by higher cardiac index and fractional area change compared to male rats. Up-regulation of angiogenic genes, including Sphk1, was observed in the RV of female rats compared to male rats at 2 weeks post-PAB. Estradiol treatment increased network forming ability of RVEC isolated from Fischer CDF rats and this effect was inhibited by PF-543. Conclusions: Female Fischer CDF rats develop adaptive RV remodeling in response to PAB compared to mal-adaptive RV remodeling in male rats. Moreover, the better RV adaptation in female rats involves increased RV angiogenesis and these effect may be mediated through Sphk1. Research Nova Scotia, Dalhousie University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences and the effect of female sex hormones on auditory function: a systematic review.

First, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and progesterone) affect auditory function in pre-menopausal and post-menopausal women. Second, to systematically review the literature concerning the discussed patterns in order to give an overview of the methodologies used in research. Last, to identify the gap in knowledge and to make recommendations for future work. Population, Exposure, Control, Outcome and Study design (PECOS) criteria were used in developing the review questions. The review protocol follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO; CRD42020201480). Data Sources: EMBASE, PubMed, MEDLINE (Ovid), PsycINFO, ComDisDome, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, and scanning reference lists of relevant studies, and internet resources (i.e., Mendeley) were used. Only studies published between 1999 and 2022, in English, or in English translation, were included. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). Sex differences: Women had more sensitive hearing (measured at the level of peripheral and central auditory system) than men. Cyclic fluctuations: Auditory function in women fluctuated during the menstrual cycle, while no such fluctuations in men over the same time period were reported. Hearing sensitivity improved in women during the late follicular phase, and decrease during the luteal phase, implying an effect of female sex hormones, although the specific effects of estradiol and progesterone fluctuations on the central auditory system remain unclear. Hearing sensitivity in women declined rapidly at the onset of menopause. The review has shown the following. Consistent sex differences exist in auditory function across the auditory pathway with pre-menopausal women often showing better function than age-matched men. Moreover, pre-menopausal women show fluctuations in hearing function across the menstrual cycle with a better function during the peak of estradiol or when the ratio of estradiol to progesterone is high. Third, menopause marks the onset of hearing loss in women, characterized by a rapid decline in hearing sensitivity and a more pronounced loss than in age-matched men. Finally, the systematic review highlights the need for well-designed and -controlled studies to evaluate the influence of estradiol and progesterone on hearing by consistently including control groups (e.g., age-matched man), using objective tests to measure hormonal levels (e.g., in saliva or blood), and by testing participants at different points across the menstrual cycle. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201480, identifier CRD42020201480.

Current evidence shows no influence of women's menstrual cycle phase on acute strength performance or adaptations to resistance exercise training.

The bias towards excluding women from exercise science research is often due to the assumption that cyclical fluctuations in reproductive hormones influence resistance exercise performance and exercise-induced adaptations. Hence, the purpose of this umbrella review was to examine and critically evaluate the evidence from meta-analyses and systematic reviews on the influence of menstrual cycle phase on acute performance and chronic adaptations to resistance exercise training (RET). We observed highly variable findings among the published reviews on the ostensible effects of female sex hormones on relevant RET-induced outcomes, including strength, exercise performance, and hypertrophy. We highlight the importance of comprehensive menstrual cycle verification methods, as we noted a pattern of poor and inconsistent methodological practices in the literature. In our opinion, it is premature to conclude that short-term fluctuations in reproductive hormones appreciably influence acute exercise performance or longer-term strength or hypertrophic adaptations to RET.

GENDER-RELATED VARIATIONS IN PATHOPHYSIOLOGICAL RESPONSES TO METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS PNEUMONIA AND SEPSIS.

In preclinical studies, the protective effects of female sex hormones and the immunosuppressive effects of male sex hormones were demonstrated. However, gender-related differences in multiorgan failure and mortality in clinical trials have not been consistently explained. This study aims to investigate gender-related differences in the development and progression of sepsis using a clinically relevant ovine model of sepsis. Adult Merino male (n=7) and female (n=7) sheep were surgically prepared with multiple catheters before the study. To induce sepsis, bronchoscopy instilled methicillin-resistant Staphylococcus aureus into sheep's lungs. The time from the bacterial inoculation until the modified Quick Sequential Organ Failure Assessment (q-SOFA) score became positive was measured and analyzed primarily. We also compared the SOFA score between these male and female sheep over time. Survival, hemodynamic changes, the severity of pulmonary dysfunction, and microvascular hyperpermeability were also compared. The time from the onset of bacterial inoculation to the positive q-SOFA in male sheep was significantly shorter than in female sheep. Mortality was not different between these sheep (14% vs. 14%). There were no significant differences in hemodynamic changes and pulmonary function between the two groups at any time point. Similar changes in hematocrit, urine output, and fluid balance were observed between females and males. The present data indicate that the onset of multiple organ failure and progression of sepsis is faster in male sheep than in female sheep, even though the severity of cardiopulmonary function is comparable over time. Further studies are warranted to validate the above results.

Endocrine background of meningioma carcinogenesis

Meningiomas, being mostly benign tumors, are derived from the arachnoid cap cells, their etiopathogenesis is based on various factors. The etiology of sporadic meningiomas is not yet known. Many factors have been identified as possible causes of the development of intracranial meningiomas. These include head trauma, viral infections, deletion in the NF2 gene, the use of cell phones, and sex hormones. The review is based on a endocrine factors, playing a role in meningioma carcinogenesis.
 The carcinogenesis of meningioma appeals to be profoundly dependent from hormonal factors. Mayor ones, usually underlined in according to their prognostic significance, are female sex hormones. Due to this, meningiomas are twice as more likely to occur in female than in male patients. The other group of hormones appointed to play a role in meningioma carcinogenesis are adipokines in general – and leptin in particular. Leptin secretion correlates with BMI elevation, what may explain the confirmed linking between obesity and brain tumors. The scientific literature has documented the occurrence of meningioma in five patients with CAH, but the role of cortical axis and/or ACTH secretion impairments is still under consideration. Authors didn’t find any publication about the role of thyroid disorders in meningioma carcinogenesis.
 The carcinogenesis of meningioma appeals to be profoundly dependent from hormonal factors. The effects of female sex hormones and adipokines are under a significant consideration, and may be useful in severity prediction. Basic science research should be focused on ACTH secretion in meningioma and possible common genetic etiopathogenesis of meningioma and CAH.

COVID-19 and sex differences: role of estrogen

Introduction. Sex differences in the course and outcomes of the disease were found during the COVID- 19 pandemic.Aim. To summarize the knowledge about the mechanisms underlying sex differences in COVID-19, with a focus on the role of estrogen.Materials and methods. We conducted a study using various databases until September 2022 for the keywords “estrogen” and “COVID-19”. All articles were published in English.Results. The review discusses the involvement of estrogen in the implementation of the immune response in viral infection. Individual paragraphs of the article are devoted to the effect of female sex hormones on coagulation, inflammation, and the renin-angiotensin system.Conclusion. At the end of the paper, it is concluded that there is great potential for future work deciphering hormonal effects on human physiology to explain the heterogeneity in pathogenic responses and may facilitate the development of more effective and personalized interventions.

Oestrogen inhibits psoriasis-like dermatitis induced by imiquimod in mice in relation to increased IL-10 producing cells despite elevated expression of IL-22, IL-23, IL-17 mRNA.

Sex hormones influence the development and natural course of psoriasis. Here, we examined the effects of female sex hormones, particularly oestrogen, on psoriasis-like dermatitis induced using topical imiquimod in mice that underwent either sham operation (Sham) or ovariectomy (OVX), with (hormone replacement treatment: HRT) or without 17β-oestradiol targeting the maximum physiological levels. The number of neutrophils in the skin was higher in the order of OVX-, Sham-, and HRT-treated mice. However, no significant difference was detected in the clinical scores among the three groups due to severe erythema and scale in a few mice out of HRT-treated mice in a set of experiments. OVX- and HRT-treated mice showed increased mRNA levels of interleukin (IL)-22 and IL-23 compared with Sham-treated mice; increased IL-10 mRNA levels were found in HRT-treated mice, possibly due to an increased proportion of forkhead box P3 (Foxp3)- and IL-10 positive large cells (possibly macrophages). In addition, HRT-treated mice had a more compact stratum corneum with higher expression of loricrin and involucrin than OVX- and Sham-treated mice. This study suggests that oestrogen has a dual potential in the pathogenesis of psoriasis: suppression of inflammation by enhancing IL-10 production and enhancement of inflammation by induction of IL-22 and IL-23 expression.

What Is Hidden Behind The Gender Differences Of Carotid Atherosclerosis?

This review article reveals possible causes that may underlie gender differences of carotid atherosclerosis: vascular anatomy, localization and morphology of atherosclerotic plaques, different effects and prevalence of known risk factors between genders (arterial hypertension, hypercholesterolemia, obesity, smoking, alcohol consumption, depression / stress). A separate place in the review is given to markers of inflammation and the protective effect of female sex hormones.

Loss of Female Sex Hormones Does Not Further Elevate Blood Pressure in Obese Female Mice but Preserves the Contribution of Leptin to Hypertension

Obesity, which is a major risk factor for hypertension and cardiovascular disease, abolishes the cardioprotective effects of female sex hormones and predisposes women to hypertension. Although 40% of postmenopausal women are obese and 75% are hypertensive, the mechanisms whereby obesity and menopause interact to elevate blood pressure (BP) remains unknown. Formerly, our laboratory demonstrated that hypertension involves leptin‐mediated increases in aldosterone production in obese female mice of reproductive age. Herein, we hypothesized that loss of female sex hormones with ovariectomy (OVX) will further elevate BP and impairs vascular function in obese female mice. Obese agouti yellow mice (Ay) on a KK background and lean controls underwent OVX or sham surgery at 12‐week of age. At 15 weeks, mice were implanted with radiotelemeters to record BP under baseline conditions and in response to leptin receptor blockade (Allo‐Aca, 0.05mg/kg/day s.c. osmotic minipump). To ascertain the effects of OVX on autonomic control of BP, we recorded BP and heart rate (HR) responses to ganglionic blockade (hexamethonium), atropine, and propranolol. At 18 weeks, mice were euthanized and mesenteric arteries isolated to measure endothelial function via wire myography. Obesity significantly increased mean arterial pressure (MAP), systolic BP, diastolic BP, and HR but OVX did not further elevate BP. Interestingly, obesity also disrupted circadian rhythm. Unexpectedly, OVX significantly reduced MAP response to ganglionic blockade (2‐way ANOVA, P<0.05) in obese mice but preserved HR responses to propranolol and atropine respectively suggesting lower neurogenic control of BP. Allo‐Aca treatment significantly decreased (2‐way ANOVA, P<0.05) MAP in both sham and OVX obese mice, indicating BP elevation remains leptin‐dependent. Obesity significantly impaired relaxation to acetylcholine (2‐way ANOVA, P<0.05) but OVX did not further impair relaxation. Compared to lean controls, LNAME further reduced (2‐way ANOVA, P=0.054) relaxation responses to acetylcholine in obese OVX mice suggesting greater contribution of nitric oxide synthase activity to vascular relaxation. Quantitative real‐time PCR showed a trend for decreased adrenal aldosterone synthase (CYP11B2) expression in obese OVX mice. Interestingly, menopause induced a similar decrease in CYP11B2 expression in human adrenal tissue collected from kidney donors with elevated BMIs (postmenopausal 56 yo female: BMI 27.4, vs. premenopausal 43 yo female, BMI 32). Quantification of mouse plasma aldosterone levels via LC‐MS revealed no significant difference in circulating aldosterone levels, suggesting that tissue(s) other than the adrenals could potentially produce aldosterone in obese OVX mice. Plasma analysis also revealed Allo‐Aca treatment increased ANG II, ANG I and ANG 1‐7 in obese mice. In conclusion, these data suggest that obesity‐associated hypertension remains leptin dependent in the absence of female sex hormone and that female sex steroids play limited role in the control of the development of hypertension associated with obesity.

Hypertensive Female Mice Are Protected from Impaired Parenchymal Arteriolar TRPV4‐Mediated Dilation and Reactive Astrogliosis

Hypertension is a leading risk factor for cerebral small vessel disease. Our lab has previously demonstrated that cerebral parenchymal arterioles (PAs) are dependent on transient receptor potential vanilloid 4 (TRPV4) function for endothelium‐dependent dilation, and that this dilation is impaired in angiotensin II (AngII)‐hypertensive male mice. This PA dilation impairment is associated with cognitive deficits and increased inflammation. However, sex differences in hypertension‐associated dementia development are not well understood. To better understand the effect of female sex hormones during hypertension, we tested the hypothesis that young, cycling hypertensive female mice will be protected from impaired TRPV4‐mediated PA dilation and reactive astrogliosis observed in male mice. AngII‐filled osmotic minipumps (800ng/kg/min, 4 weeks) were implanted in 16‐18‐week‐old male C56BL/6 mice. Age‐matched female mice received either an AngII dose that matches the dose used in male mice (800ng/kg/min) or a higher dose (1200ng/kg/day) that produces an elevation in blood pressure similar to male mice. Sham mice served as control. Blood pressure was measured by tail‐cuff plethysmography. Pressure myography was used to assess TRPV4‐mediated dilation in PAs. An anti‐glial fibrillary acidic protein (GFAP) antibody was used in paraformaldehyde‐fixed 40μm coronal brain sections to assess the quantity and morphology of astrocytes. Data are presented as means ± SEM (n=5‐10). Male data were compared by Student’s t‐test and female data were compared by one‐way ANOVA unless otherwise stated. Systolic blood pressure was elevated in AngII‐treated male mice (sham: 133 ± 10, AngII: 181 ± 11mmHg; p=0.005) and in 1200ng AngII‐treated female mice (sham: 146 ± 8, 800ng AngII: 161 ± 13, 1200ng AngII: 179 ± 7mmHg; p=0.0482) vs sham. PA dilation in response to the TRPV4 agonist GSK1016790A (10‐9‐10‐5M) was not impaired in AngII‐treated female mice (sham: 85 ± 5, 800ng AngII: 73 ± 7, 1200ng AngII: 77 ± 8% maximum dilation; p=0.4381), contrasting with what we have previously reported in male mice. There was an increase in astrocytes in the corpus callosum of hypertensive male mice (sham: 65 ± 2; AngII: 77 ± 5; p=0.039). Interestingly, sham female mice had more astrocytes than sham male mice, and AngII infusion reduced the quantity (sham: 81 ± 3, 800ng AngII: 71 ± 3, 1200ng AngII: 69 ± 3; p=0.011). Sholl analysis was used to assess astrocyte morphology. Astrocytes from hypertensive male mice had more arborization further from the soma compared to sham (p=0.0348 at 14‐15μm from the soma, by two‐way ANOVA and Bonferroni correction). Female mice receiving the 1200ng dose AngII, however, had fewer arborizations away from the soma compared to sham (p=0.0263 at 13‐15μm from the soma, by two‐way ANOVA and Bonferroni correction). Female mice are resistant to AngII‐induced hypertension and protected from the associated deleterious cerebrovascular effects, supporting our hypothesis.

Maternal body estrogen exposure influences the mice offspring ovaries’ morphology

Background. The question of the effect of female sex hormones and their analogues on humans and experimental animals is of great interest in medicine.
 Aim. The aim of the work was to study the morphological features of the ovaries of the offspring of laboratory mice during the administration of estrogens to the maternal body.
 Materials and methods. Female laboratory mice after fertilization were divided into groups: two control and two experimental, which at the stage of development of gestation E11.5 underwent intramuscular, single administration of experimental doses of estrogens. The first experimental group was injected with the synthetic drug synestrol in the form of a 2% oil solution at a total dose of 50 mcg / kg (n = 5; S-50), the first control group was injected with olive oil at a dose of 0.2 m/kg (n = 5). The second experimental group was injected with a 0.4 ml 0.0005% fulvestrant oil solution at a dose of 100 mcg/kg (n = 5; F-100), the second control group (n = 5) received sterile castor oil at a dose of 0.8 m/kg.
 Results. Persistent morphological changes are observed in the ovaries of the offspring of the first experimental group S-50: an increase in the average area of the cortical substance, a decrease in the area of the medulla, an increase in the average number of yellow bodies, an increase in the average number of luteal cells in the yellow body, a decrease in the total number of follicles and atretic bodies, indicating a violation of the folliculogenesis process, an increase in the average diameter of blood vessels demonstrating increased blood circulation. With the introduction of the drug fulvestrant 100 mcg / kg in the second experimental group F-100, morphological changes in the form of an increase in the average area of the cortical substance, a decrease in the average area of the medulla, sclerosis of the stromal component, accompanied by a restructuring of the vascular network with signs of atresia and cystic degeneration of the follicular epithelium in secondary and tertiary follicles are considered on a slice of the ovaries of the offspring.
 Conclusions. The obtained results of the study confirm the urgency of the problem of implementing complex measures aimed at limiting the effects of estrogenetic drugs introduced into the maternal body during pregnancy, in order to prevent adverse effects on the development of the ovaries of offspring.

Effect of female Sex hormones on irritable bowel syndrome induced by water avoidance stress in experimental rat model of menopause.

Effect of female Sex hormones on irritable bowel syndrome induced by water avoidance stress in experimental rat model of menopause.

Effect of Female Sex Hormones on the Immune Response against Chlamydia abortus and on Protection Conferred by an Inactivated Experimental Vaccine in a Mouse Model.

Mice are valuable models extensively used to test vaccine candidates against Chlamydia abortus and to clarify immunopathological mechanisms of the bacteria. As this pathogen has the ability to reactivate during pregnancy, it is important to deepen the knowledge and understanding of some of the effects of female hormones on immunity and vaccination. This study is aimed at describing the role of sex hormones in the pathology of OEA during chlamydial clearance using ovariectomised mice and also gaining an understanding of how 17-oestradiol or progesterone may impact the effectiveness of vaccination. Animals were treated with sex hormones and infected with C. abortus, and the kinetics of infection and immune response were analysed by means of bacterial isolation, histopathology, and immunohistochemistry. In a second phase of the study, protection conferred by an experimental vaccine after hormone treatment was assessed. Oestradiol showed a stimulatory effect on the immune response during infection, with a more efficient recruitment of macrophages and T-cells at the infection site. Furthermore, after vaccination, oestradiol-treated animals showed a stronger protection against infection, indicating that this hormone has a positive effect, stimulating a specific memory response to the pathogen.

Periodontitis to placenta: An awareness-based survey

Introduction: Surprising how a small part of our body, the mouth, can alter and result in a variety of systemic complications if not taken care of. The primary factor for maternal and newborn morbidity and mortality is thought to be periodontitis. Gynecologists have a crucial role in educating their patients about the need of keeping good dental health because it can improve the success of pregnancies and reduce mouth pain. Objective: The objective of this study was to understand the awareness of gynecologists practicing in Pune, Maharashtra, about periodontal status and its outcome in pregnant women. Materials and Methods: A questionnaire-based study was conducted on 60 gynecologists. We evaluated people's knowledge of the negative effects of female sex hormones on periodontal health. Results: Eighty percent were aware of the correlation between periodontal health and female sex hormones. 56.7% agreed that periodontal microorganisms can pass through the placenta and harm the fetus. 76.7% were unaware that the possibility of prenatal growth restriction has increased. Most participants did not motivate pregnant women for an oral health checkup. Conclusion: It can be inferred that gynecologists are not aware of the connection between mouth findings and worse pregnancy outcomes.

МЕНОПАУЗАЛЬНАЯ ГОРМОНАЛЬНАЯ ТЕРАПИЯ И РИСКИ ВЕНОЗНЫХ ТРОМБОЭМБОЛИЧЕСКИХ ОСЛОЖНЕНИЙ: СОВРЕМЕННЫЙ АСПЕКТ ПРОБЛЕМЫ

Age-related aspects of women's health have been in the focus of attention of cardiologists, gynecologists, and endocrinologists for many years. The physiological features of the course of the peri- and postmenopausal periods and the possible consequences of estrogen deficiency are already well-studied. For nearly 20 years, there has been a debate about the benefit-risk ratio of menopausal hormone therapy. The evidence for its protective effect on age-related cases is overwhelming: prevention of osteoporosis development, cardiovascular diseases, cognitive decline, and improvement of the overall quality of life. The article presents current data on the association of menopausal hormone therapy with venous thromboembolic complications, depending on the type of estrogen and progestogen components, dose, regimen and methods of application. The feasibility and safety of menopausal hormone therapy in the context of the COVID-19 coronavirus pandemic is considered. The probability of increased risk of thromboembolic complications in case of COVID-19 infection during menopausal hormone therapy has not been proven in clinical practice. The data from the latest publications are presented, indicating the likely positive effect of female sex hormones on the course of SARS-CoV-2 and the recommendations of the leading international communities on menopause measurement regarding the admissibility of menopausal hormone therapy during the pandemic and limited ability to counsel patients.

Possible involvement of female sex steroid hormones in intracellular signal transduction mediated by cytokines following traumatic brain injury

IntroductionThe aim of this study was to determine the anti-inflammatory effect of female sex hormones on the level of intracellular molecules of cytokine signaling pathway after diffuse traumatic brain injury (TBI) in ovariectomized rats. MethodsFemale rats were divided into 10 groups: control, sham, TBI, Vehicle (oil), Vehicle E1 (33.3 µg/kg), E2 (1 mg / kg), P1 (1.7 mg/kg), P2 (8 mg / kg), E2 + P1. All drugs were injected 0.5 h after TBI. Brain edema and the brain levels of P-STAT-3, NFκB-P52, NFκB-P65, P-IκB, and SOCS-3 by immunohistochemistry measured at 24 h after TBI. ResultsIncreased brain edema after TBI was inhibited by different doses of estrogen, progesterone (P < 0.001), and E2 + P1 (P < 0.05). The brain levels of P-STAT-3, NFκB-P52, NFκB-P65, and p-IκBα that increased after TBI was decreased only by E2 (P < 0.05). E2 and E2 + P1 have increased the SOCS-3 level after TBI (P < 0.05). Also, there was a difference between the E2 with E1 and two progesterone doses (P < 0.05). So that in all cases, the effects of E2 were more significant than the other groups. The target cells for these effects of E2 were microglia and astrocytes. ConclusionThe results indicate that one of the probable mechanism(s) of estrogen anti-inflammatory effect after TBI is either reduction of p-STAT-3, NFκB-P52, p-NFκB-P65, and p-IκBα or increase in SOCS-3 molecules involved in the signaling pathway of inflammatory cytokines.

Gender-related response of body systems in COVID-19 affects outcome

Severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is the seventh member of the coronaviruses (CoVs) family that infects humans and causes coronavirus disease 2019 (COVID-19), which is currently a global pandemic. Widespread secretion of cytokines has been shown to occur early in severe cases of the disease and can be an effective factor in the rapid progression of the disease. Systemic inflammation indicates an advanced stage of acute disease, which is characterized by multiple organ failure and elevated key inflammatory markers. Studies have shown a gender difference between the incidence and mortality of COVID-19. In this review, we investigated the gender difference in the systemic effects of COVID-19 and found that this gender difference exists especially in the respiratory, cardiovascular, liver, gastrointestinal and kidney systems. Due to the worse outcome of COVID in males, the role of female sex hormones in causing these gender differences is noticeable. There can be a systemic and local effect of female sex hormones, especially estrogen and possibly progesterone, on various cells. Among the effects of these hormones is the regulation of localized angiotensin-converting enzyme 2 (ACE2) levels. ACE2 is the route of entry for SARS-CoV-2 virus into the cell. It is hoped that this review would address gender differences for better management of COVID-19 treatment.

Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes.

Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes.