Low Estrogen Levels Research Articles

Do steroid abusers have more temporomandibular joint symptoms? A study with 97 bodybuilders

ABSTRACT Objectives Anabolic androgenic steroids (AAS) are derivatives of testosterone, used to treat gonadal disturbances, performance enhancement, and aesthetic purposes. AAS abuse can lead to side effects, including androgenic, cardiovascular, and liver disturbances, effects on libido, gynecomastia, and behavioral effects. There is a hypothesis that some joint tissues may be targets for sex hormones, and the use of AAS without medical follow-up may exacerbate temporomandibular joint problems in patients seeking performance and aesthetics. Methods In this study, a cross-sectional survey was conducted on AAS abusers who voluntarily presented themselves for clinical evaluation. Patients were subdivided by sex and age group, and the length of AAS use and symptoms such as headache, tinnitus, and temporomandibular joint pain were evaluated. Results It was observed that drug usage is related to symptoms. Conclusion The results suggest that AAS use without medical follow-up may exacerbate temporomandibular joint problems, especially in patients with low estrogen levels.

The profile of steroid hormones in human fetal and adult ovaries.

Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries. We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles. Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures. Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction.

Abstract SS02-02: Hormone Replacement and Alternatives for Relief of Vasomotor Symptoms in Women at Increased Risk for Breast Cancer

Abstract 70% of women will experience vasomotor symptoms sufficient to impact their quality of life during menopause transition and the early menopause. These symptoms are thought result from neurotransmitter imbalances resulting from ovarian hormone reductions and hypersecretion of gonadotropins. Increases in gonadotropins result in neurotransmitter triggered stimulation of the neurokinin 3 (NK3) receptor and thermoregulatory imbalance. Estrogen deficiency also reduces serotonin which can also trigger increases in hot flashes, and sleep disturbances. Vasomotor symptoms last on the average for 7 years until acclimation to persistent low estrogen levels occurs. Estrogen +/- progestin replacement therapy is associated with the greatest likelihood of vasomotor symptom relief as it reduces gonadotropin and NK3 receptor signaling and increases serotonin. Progestins also increase the neuroinhibitory transmitter gamma-aminobutyric acid (GABA) which improves sleep quality. There continues to be confusion on the part of providers and patients regarding the excess risk of breast cancer and thromboembolic events as these risks are affected by type of agent, route of delivery, age, duration of treatment, and presence of obesity. The majority of placebo controlled randomized clinical trial data on hormone replacement with estrogen or estrogen + a progestin comes from the Women’s Health Initiative (WHI) for women 50-79 in which oral conjugated estrogen (CE) 0.625 mg was used as the estrogen for women without a uterus and medroxyprogesterone acetate (MPA) was added to CE for women with a uterus to protect against endometrial hyperplasia and cancer. The median age at entry to WHI that trial was 63 and a substantial proportion had previously taken hormones. Large longitudinal cohort studies have been helpful in assessing risks in women starting hormones at a more clinically relevant age (45-55) and with hormonal preparations other than oral CE and MPA. Five to seven years of estrogen alone results in minimal if any increased risk for breast cancer. However, combined estrogen+ progestin replacement for women over 50, necessary for women with a uterus, results in an ~ 30 % relative increased risk for breast cancer if taken for up to 5 years and a doubling of risk with 10 years of treatment. So called bioidentical hormones often compounded as oral troches of estradiol, progesterone, and testosterone, are also associated with increased breast cancer risk. Vaginal hormones have not been found to increase risk for breast cancer. Increased risk of thromboembolism is predominately observed in women over 50 using oral as opposed to transdermal preparations. Increased risk for stroke and dementia was observed in the WHI again with oral hormones in women over 65. In the WHI there was no increase in cancer related, cardiovascular or overall mortality with estrogen or estrogen and progestin. For high-risk peri and post-menopausal women with who would like to reduce/alleviate their vasomotor symptoms with no increase in risk for breast cancer there are several options: 1) the tissue selective estrogen complex bazedoxifene (BZA) combined with conjugated estrogen (CE) 2) the non-hormonal option of NK3 receptor antagonists such as fezolinetant ( 3) non-hormonal options of gabapentin, selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine uptake inhibitors (SNRI). BZA and CE and fezolinetant are reported to reduce hot flashes in 70% or more of individuals with paroxetine effectiveness reported as 50%. All three are FDA approved for reduction of vasomotor symptoms. The combination of BZA and CE is also being investigated for breast cancer risk reduction. These agents differ with respect to side effects with increased risk of blood clots for bazedoxifene and conjugated estrogen, increased risk of nausea, diarrhea, and liver dysfunction for fezolinetant and drowsiness and dry mouth for SSRIs. Drug costs may also dramatically affect insurance coverage and patient uptake of a particular strategy. A recent online perusal of a popular site for finding the lowest drug price suggested substantial differences in the cost of drugs for relief of vasomotor symptoms. The approximate cost for a 30- day supply of oral estradiol was $30, estradiol transdermal patches $35, oral progesterone $15, combined estradiol and levonorgestrel transdermal patches $240, oral CE $200, oral CE + medoxyprogesterone acetate $240, and for BZA+ CE $200. For non-hormonal therapies the cost of 30 days of gabapentin was $11, paroxetine $30 and fezolinetant $550. Crandall, Mehta, and Manson JAMA 2023 329:405-420 Collaborative Group on Hormonal Factors in Breast Cancer Lancet 2019 394: 1159-1168 Fabian et al Ca Prev Res 2019 10:711-720 Modi and Dhillo Neuroendocrinology 2019 109:242–248 Citation Format: C. Fabian. Hormone Replacement and Alternatives for Relief of Vasomotor Symptoms in Women at Increased Risk for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SS02-02.

Infertility in POMC-deficient mice

The pro-opiomelanocortin (POMC) gene is expressed in the hypothalamus and pituitary and its product is cleaved into several peptides including the melanocyte stimulating hormones (α, β, or γ-MSH), adrenocorticotropic hormone (ACTH), and beta-endorphin. Alpha-MSH is involved in regulating appetite, sexual behavior, and melanin, while ACTH regulates secretion of glucocorticoids from the adrenal cortex. Humans who have a POMC mutation either produce an abnormally short version of POMC or are missing the protein completely and therefore lack these hormones. This has biological consequences including red hair and fair skin, early-onset obesity (due to severe hyperphagia), and potentially hypothyroidism, hypogonadism, and infertility. Many of these same effects are seen with mice containing this deficiency. We are interested in studying infertility through a mouse model of hypothalamic-specific POMC-deficiency. These mice also experience early-onset obesity and infertility. Estradiol is a key reproductive hormone that is essential for fertility. POMC deficiency may lead to hypogonadism, which can cause low levels of estrogen so we hypothesize that POMC-deficient mice have reduced estrogen levels, which may contribute to their infertility. To test this hypothesis, we will measure estrogen levels in POMC-deficient mice at different stages of the estrus cycle using an estradiol ELISA kit. We expect the POMC-deficient mice to have lower estrogen levels than control mice. We also plan to use liquid chromatography mass spectrometry (LC-MS) to measure estrogen levels. Before collecting the blood samples, vaginal cell samples are obtained and viewed under a microscope to analyze the ratio of cells and determine which stage the females were in—proestrus, estrus, metestrus, or diestrus. Blood samples are then collected into 1.5 mL microcentrifuge tubes with 10 microliters of 0.5 M EDTA to prevent blood clotting. After blood is collected, it is centrifuged at 2,000 g for 20 minutes at 4 degrees Celsius. The plasma is then stored at -80 degrees Celsius until analysis. Based on preliminary results we expect the POMC deficient mice to have reduced estrogen and/or altered levels throughout the cycle. So far, our results have indicated that POMC-deficient female mice have abnormal estrus cycles and also reduced uterine weights. The conclusions from this study will help us understand more about the causes of infertility in POMC-deficient mice, which may also lead to greater understanding on how to treat humans with infertility due to a POMC mutation. Support for this research was provided by IRACDA grant NIHK12GM111725 to Z.T. and UVU Scholarly Activities Grant to A.G. This is the full abstract presented at the American Physiology Summit 2024 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.

Physical Activity, Self-Care, and Menopausal Symptoms among Women in Al-Ahsa, Saudi Arabia: Adherence to Postmenopausal Guidelines (PMGs).

Menopause is a physiological change in which the menstrual period permanently ends. Every woman experiences this transition in different ways between the ages of 40 and 55. Women may have menopausal symptoms as a result of low estrogen levels. Self-care is a practice which women can use to maintain their wellness. This study aimed to assess physical activity, self-care, and menopausal symptoms and their associations with selected variables. The results showed that women should adhere to postmenopausal guidelines (PMGs). A cross-sectional study was conducted among 212 menopausal women randomly selected from health centers in Al-Ahsa, Saudi Arabia. The international physical activity tool, a self-care questionnaire, and the Kupperman menopausal index scale were used to assess women's physical activity, self-care, and menopausal symptoms, respectively. The chi-square and Pearson correlation tests were used for analysis. The women were 55.01 ± 6.87 years old, and 40.6% reached menopause between the ages of 46 and 50 years; 57.1% of the women had low physical activity, which was associated with menopausal symptoms (p < 0.022). The highest mean score (29.63 ± 5.83) was obtained for physical health, while the lowest (11.92 ± 3.58) was found in self-care screening tests. Regarding menopausal symptoms, 25.9% had mild, 69.8% had moderate, and 4.3% had severe symptoms. A significant association was found between menopausal symptoms and age, menopausal age, education, body mass index, and PMGs awareness at p < 0.001. Self-care positively correlated with menopausal symptoms (p < 0.001). Therefore, attention should be given to women's adherence to PMGs so that they can enjoy healthier lives after menopause.

A study to assess the prevalence of menopausal symptoms and its impact on quality of life in the menopausal women in a selected Urban community, Kolkata, West Bengal

Menopause is the end of menstruation. Menopause is cessation of menstruation for 12 months or a period that equivalent to three previous cycles or as time of cessation of ovarian function resulting in permanent amenorrhea. Menopause is a part of a women’s natural ageing process when lower level of estrogen &amp; progesterone is produced by ovaries. This cross-sectional study was conducted on a total of 400 women in the age group of 45-50 years in a selected urban community, Kolkata, West Bengal in 2020. Menopause Specific Quality of Life scale was used to assess the prevalence of menopausal symptoms and its impact. Data analysis was performed calculating mean, frequency and percentage and chisquare. Among the vasomotor symptoms prevalence of sweating was maximum (98%), among psychological symptoms anxiety and nervousness was the maximum prevalent symptoms(98%), most prevalent physical symptom was lack of energy (89.25%). Vasomotor symptoms had mild moderate and severe impact on quality of life where the other symptoms had mild and moderate impact on quality of life. Menopausal symptoms had significant association with socio demographic variables. The results support the popular belief that menopause causes vasomotor, physical and psychological problems. From the findings of the present study it can be concluded that almost all areas or domains evaluated were impaired in menopausal women but the vasomotor and psychological symptoms affects women’s quality of life more than the physical and sexual symptoms of menopause

Associations Between Serum Estrogen Levels and Urinary Incontinence in Women: A Cross-sectional Analysis of NHANES 2013 to 2016

ObjectiveTo explore the relationship between serum estrogen levels and UI in a nationally representative female population. Materials and MethodsWe included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education and menopause. ResultA total of 4114 individuals were ultimately included in our study. Of these women 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR = 1.885; 95% CI = 1.042 - 3.412, p = 0.039). No association was noted between serum estrogen levels and SUI or MUI. ConclusionOur study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications.

Hubungan Antara Kadar Hormon Dengan Perdarahan Di Luar Siklus Menstruasi Pada Wanita Usia Subur

Bleeding disorders outside the menstrual cycle are reproductive system disorders commonly experienced by women during their reproductive years. These disorders are characterized by changes in menstrual periods, including alterations in cycle length, duration of menstruation, or volume of bleeding, with a worldwide prevalence ranging from 3% to 30%. Hormonal factors are often implicated as causes of bleeding disorders outside the menstrual cycle. Preliminary findings from a study conducted at RSIA Puri revealed that three female patients seeking treatment experienced bleeding disorders outside the menstrual cycle, with two of them exhibiting low estrogen levels (below 20 pg/ml) upon examination. The purpose of this study was to analyze the relationship between hormone levels, particularly estrogen, and bleeding outside the menstrual cycle in women of childbearing age at RSIA Puri Malang. The research employed a quantitative analysis through a cross-sectional approach. Primary and secondary data were obtained from laboratory examinations of estrogen levels in blood serum on the third day of menstruation. The sample consisted of 34 mothers who met the criteria of experiencing menstrual disorders and visited RSIA Puri Malang, and who willingly participated as respondents, selected through quota sampling. Data analysis was conducted using the Chi-square test, and the results revealed a significant relationship between estrogen levels and bleeding outside the menstrual cycle, or metrorrhagia (p-value = 0.018; OR = 0.107). This suggests that estrogen hormone regulation plays a crucial role in preventing menstrual irregularities. In conclusion, maintaining optimal estrogen hormone levels is essential for preventing and managing menstrual irregularities and bleeding disorders outside the menstrual cycle.

Effect of Submaximal Exercise on Trained and Untrained Intensity on Estrogen Levels in Female White Rats (Rattus Norvegicus) Wistar Strains

Background: Trained and continuous physical activity can increase estrogen levels in women, while irregular activity can increase excessive Estrogen levels. Submaximal exercise is a recommended exercise to improve a woman's physiological function The purpose of this experiment was to determine the effect of submaximal exercise on trained and untrained intensity on Estrogen levels in female white rats (Rattus norvegicus) Wistar strains. Methods: This research was an experimental study using a post-test-only control group design using 30 female Wistar rats which were divided into 5 groups: control group not treated (K1), experimental group of animals with exercise intensity without intervention (K2), group of experimental animals with untrained intensity without intervention (K3), group of experimental animals with exercise intensity with intervention (K4), and experimental group of animals with exercise intensity with intervention (K4). experimental animals with untrained intensity treatment with intervention (K5). The intervention was swimming at moderate intensity with a duration of 85% of the maximum time to swim and a load of 8% of the rat's body weight. After the treatment period, all groups were terminated to take intracardiac blood measured using ELISA. Results: The data results were analyzed using statistical tests. The results of this study found that the trained group had lower Estrogen levels compared to the untrained group, but higher than the control group. The Kruskal-Wallis test show a significance value (p = 0.157), p&gt; 0.05. Conclusion: In this study, there was no effect of submaximal exercise between trained and untrained intensity on Estrogen levels in Wistar strain female white rat.

Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats.

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

THE EFFECT OF BARIATRIC SURGERY ON BREAST CANCER INCIDENCE AND CHARACTERISTICS: A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Obesity elevates estrogen levels and pro-inflammatory cytokines, increasing breast cancer risk via macrophage migration to breast tissue and stimulating epithelial proliferation. Observational studies suggest that intentional weight loss, such as through bariatric surgery, can mitigate this risk. This study aims to conduct a comprehensive systematic review, focusing on the impact of bariatric surgery on breast cancer incidence and characteristics using recent literature. Methods: The systematic review followed PRISMA 2020 standards and examined full-text English literature published between 2014 and 2024. This review excluded editorials, review papers from the same journal, and submissions without a DOI. Literature was sourced from online platforms such as PubMed, SagePub, and SpringerLink. Result: A total of 1,011 articles s were retrieved from online databases (PubMed, SagePub, and SpringerLink). After three rounds of screening, five articles directly relevant to the systematic review were selected for full-text reading and analysis. Conclusion: Bariatric surgery decreases overall cancer risk in women, especially for breast cancer, by lowering estrogen levels and altering tumor biology. It also improves glucose homeostasis and reduces insulin resistance, both linked to higher cancer risk.

Postmenopausal Hormone, Hematology and Immune Modulation in Rheumatoid Arthritis Patients

Background: There is a significant hormonal shift in Postmenopausal women with low levels of estrogen and progesterone. These changes may cause the pathogenesis of autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), which exhibit a higher prevalence in women. It is crucial to determine the pathophysiology and treatment strategies and to understand the hematological, hormonal, and immunological differences in postmenopausal women with RA and SLE. This study determined the hematological, hormonal, and immunological parameters in postmenopausal RA and SLE patients. Methods: 75 postmenopausal women (aged 52-65 years) were recruited in this study, comprising 25 with RA, 25 with SLE, and 25 with healthy controls. Blood samples were collected for complete blood count (CBC), erythrocyte sedimentation rate (ESR), and serum hormone and immunoglobulin assays. Statistical analyses were conducted using Fisher's test, t-test, and ANOVA, with significance at p &lt; 0.05. Results: In postmenopausal RA and SLE patients, significant blood parameter differences were observed versus controls. RA showed elevated WBC count (18.189±0.782) and PLT (373.778±14.644), lower RBC (4.009±0.149) and Hb (11.705±0.328). SLE had lower WBC (3.016±0.595), RBC (4.293±0.112), and Hb (12.270±0.312), and higher RDW (18.830±1.719) and lower MPV (8.327±0.314). Hormonal differences included higher FSH and lower LH, estrogen, and testosterone in both groups, while RA exhibited decreased cortisol and increased progesterone, and both diseases showed elevated rheumatoid factor (RF), ESR, and immunoglobulin E (IgE). Conclusion: Postmenopausal women with RA and SLE showed distinct hematological, hormonal, and immunological profiles compared to healthy controls. This study demonstrated the complex interplay between hormonal changes and autoimmune diseases, warranting further investigation into their underlying mechanisms and potential implications for treatment strategies.

Abstract TP287: Estrous Cycle Stages and Cerebral Blood Flow: Implications for Ischemic Tolerance in Stroke

Introduction: Previous stroke studies in female rodents have demonstrated that the severity of ischemic damage is differentially impacted by the estrous cycle. Estrogen is considered to be neuroprotective, but it is unclear whether this protection is dependent on the vasodilator properties of estrogen. In this study, we investigated the impact of estrus cycle stage on stroke lesion volume and whether that impact was dependent on cerebral blood flow (CBF) changes during stroke. Methods: Ischemia was induced in adult ( 10 weeks) male and female Sprague-Dawley rats by 30 minutes middle cerebral artery occlusion (MCAO) using the suture model. Prior to the stroke procedure, the phases of the estrous cycle (proestrus(P), estrus(E), metestrus(M) and diestrus (D)) were determined by vaginal smear tests in female rats. Cerebral blood flow (CBF) was measured by laser doppler and infarct volume were measured by TTC staining at d2 post-stroke. Results: Females in proestrus and diestrus (P/D) stages of the estrous cycle, which have reportedly high levels of estrogen, had significantly (p&lt;0.05) smaller CBF decreases during ischemia and a trend for smaller infarcts than those in estrous and metestrus stages, which have lower estrogen levels. This suggests that the protective effects of estrogen may be related to effects on blood flow. However, when compared to male rats, females in P/D stages had significantly (p&lt;0.05) smaller brain infarcts despite having similar CBF decreases. This implies that additional mechanisms are responsible for the neuroprotection observed in females when compared to males. Conclusion: Estrous cycle stage affects CBF decrease during ischemia, but this does not account for the difference in infarct size observed between male and female rats. Our study indicates that multiple mechanisms are responsible for ischemic tolerance in specific stages of the estrous cycle. Keywords: stroke, estrous cycle, CBF, estrogen

Insights into estrogen impact in oral health & microbiome in COVID-19

BackgroundCOVID-19 emerged in late 2019 and has occasioned more than 765 millions cumulative cases and 6.9 millions of deaths globally. Notably, around 70% of patients with severe COVID-19 are men. Therefore, it is to be presumed that women have a hormonal protector factor in inflammation and ACE2 expression. On the other hand, oral health status, and local microbiome can be key factors to respiratory viral infections control. Nevertheless, it has been poorly investigated. In our study 20 premenopausal, 18 postmenopausal and 22 men with COVID-19 were included. Oral health status, viral load, lingual ACE2 expression, as well as microbiome, estrogens and cytokines in saliva were analyzed.ResultsOur results showed a lower expression of ACE2 in tongue cells of postmenopausal compared with premenopausal (p = 0.05), and a strong negative correlation between saliva estrogen and viral load (r = -0.76; p = 0.001). Respect to IFN-γ (p = 0.05), IL-1β, TNF-α, IL-18, and IL-23 levels were increased in postmenopausal. Oral microbiome signature of premenopausal was characterized by Prevotella melaninogenica (Log2 = 26.68; p = 1.34e-10), Haemophilus (Log2 = 23.99; p = 2.96e-9), and Alloprevotella (Log2 = 7.92; p = 0.0001). On the other hand, Leptotrichia (Log2 = -18.74; p = 0.001), Tanerella (Log2 = -17.08; p = 0.004), and Clostridiales (Log2 = -2.88; p = 0.04) represented the poor oral health group compared with the adequate group which was enriched with the commensal microorganism Neisseria perflava (Log2 = 26.70; p = 1.74e-7). Furthermore, the high viral load group was characterized by Prevotella nanceiensis (Log2 = 19.60; p = 6.06e-8), Prevotella melaninogenica (Log2 = 21.45; p = 9.59e-6), Alloprevotella (Log2 = 23.50; p = 2.70e-7) and bacteria from the red complex Porphyromonas endodentalis (Log2 = 21.97; p = 1.38e-7).ConclusionsPostmenopausal and men have a poor oral health status which could be related to a detrimental progression of COVID-19 also linked to a lower expression of ACE2, lower saliva estrogen levels and oral dysbiosis. Nevertheless, functional studies are required for a deeper knowledge.

The Role of Estrogen Signaling and Exercise in Drug Abuse: A Review.

Discovering how sex differences impact the efficacy of exercise regimens used for treating drug addiction is becoming increasingly important. Estrogen is a hormone believed to explain a large portion of sex differences observed during drug addiction, and why certain exercise regimens are not equally effective between sexes in treatment. Addiction is currently a global hindrance to millions, many of whom are suffering under the influence of their brain's intrinsic reward system coupled with external environmental factors. Substance abuse disorders in the U.S. alone cost billions of dollars annually. Studies involving the manipulation of estrogen levels in female rodents, primarily via ovariectomy, highlight its impact regarding drug addiction. More specifically, female rodents with higher estrogen levels during the estrus phase increase cocaine consumption, whereas those in the non-estrus phase (low estrogen levels) decrease cocaine consumption. If estrogen is reintroduced, self-administration increases once again. Exercise has been proven to decrease relapse tendency, but its effect on estrogen levels is not fully understood. Such findings and results discussed in this review suggest that estrogen influences the susceptibility of females to relapse. Therefore, to improve drug-abuse-related treatment, exercise regimens for females should be generated based on key sex differences with respect to males.

Oestrogen and Gastroesophageal Reflux Disease Dynamics in Premenopausal and Postmenopausal Women: A Cross-sectional Study

Introduction: Gastroesophageal Reflux Disease (GERD) is a common clinical disorder characterised by the reflux of stomach contents into the oesophagus, primarily due to the temporary relaxation of the Lower Oesophageal Sphincter (LES). The aetiology of GERD is multifactorial. The prevalence of GERD in females has been found to sharply increase throughout the postmenopausal period compared to the reproductive phase. Aim: To study the relationship between serum oestrogen levels in premenopausal and postmenopausal women with GERD. Materials and Methods: In this cross-sectional study, 60 patients with GERD were divided into 30 premenopausal and 30 postmenopausal groups. The study subjects underwent high-resolution oesophageal manometry. The Cobas e 411 immunoassay analyser was utilised to measure serum oestrogen levels through electrochemiluminescence. The independent, unpaired Student's t-test was employed to analyse the collected data. Results: The statistical analysis revealed that the mean reduced LES pressure of 9.76±3.80 mmHg and the mean reduced Oesophagogastric Junction Contractile Integral (EGJ-Cl) of 14.503±10.64 mmHg were lower in women with postmenopausal GERD who exhibited lower oestrogen levels compared to those with premenopausal GERD. An increase in LES pressure was also associated with an increase in EGJ-CI, demonstrating a statistically significant positive linear correlation between LES pressure and EGJ-CI. The p-value &lt;0.05 was deemed highly statistically significant. Conclusion: Parameters such as basal LES pressure and EGJCl were observed to be reduced in postmenopausal women with GERD who had low oestrogen levels. This study suggests that oestrogen plays a crucial role in safeguarding the oesophageal epithelium against the reflux of gastric contents.

Treatment of D-galactose-induced rat polycystic ovarian condition using Lepidium sativum and secondary antibodies.

There is still much to be discovered regarding the etiopathogenesis and management of polycystic ovarian syndrome (PCOS). Four groups of female Wister-Albino rats were established, each with a normal estrous cycle: control, D ( + ) galactose (D-galactose), Lepidium sativum (L. sativum), and prepared secondary antibody (Ab2). Serum samples were collected, and histopathological examination was performed on ovaries and spleen tissues. Immunoreactive anti-ovarian antibody (AOA) quantities were determined using a modified antigen-based ELISA procedure. ELISA assay kits were used to quantify FSH, LH, and estradiol 17 β concentrations. The study found that AOA concentration in undiluted samples was significantly higher in the second and fourth weeks after PCOS induction by D-galactose (p < 0.001). However, antibody index% and titer elevated in the D-galactose group. L. sativum's late efficacy was observed in the fourth week, while the concentration of undiluted samples in the D-galactose + Ab2 group lowered (p < 0.001). Higher basal FSH and LH levels and lower estrogen levels are associated with PCOS development. L. sativum's immunomodulatory properties may contribute to this association. Estradiol-17ß concentrations increased in D-galactose + L. sativum and D-galactose + Ab2 groups, respectively. Careful extrapolation of experimental models is crucial for clinical applications, as technical advancements make Ab2 production easier. Further study is needed to fully understand its potential in immunotherapy.

OP52 Treating Osteoporosis In Postmenopausal Women With Denosumab (Prolia®): A Systematic Review And Network Meta-Analysis

IntroductionIt is estimated that osteoporosis affects over 200 million people globally. Postmenopausal women (PMW) have an increased risk of developing osteoporosis due to low estrogen levels. This study assessed the safety and effectiveness of denosumab (Prolia®) relative to placebo, selective estrogen receptor modulators (SERMs) (bazedoxifene and raloxifene), and bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) for the treatment of osteoporosis in PMW.MethodsSystematic searches were conducted in three biomedical databases (PubMed, the Cochrane Library, and Embase) to identify randomized controlled trials (RCTs) of PMW with osteoporosis allocated to denosumab, placebo, bisphosphonates, or SERMs. The Cochrane Risk of Bias 2.0 tool was used to critically appraise included RCTs. Pairwise and Bayesian network meta-analyses were performed on the following predetermined outcomes: fractures (vertebral and nonvertebral); adverse events (AEs); mortality; serious AEs (SAEs); withdrawals due to AEs; bone mineral density (BMD); and AEs caused by denosumab discontinuation.ResultsThe analyses included 12 RCTs (22 publications, 25,879 participants). Denosumab, ibandronate, alendronate, zoledronate, and risedronate produced a statistically significant improvement in total hip (TH) and lumbar-spine (LS) BMD, compared with placebo. Similarly, ibandronate, risedronate, and alendronate showed a statistically significant improvement in femoral neck (FN) BMD. Risedronate produced a statistically significant decrease in nonvertebral fractures (risk ratio 0.20, 95% confidence interval: 0.00, 0.97) relative to placebo. However, there were no significant differences between any of the interventions for rates of vertebral fractures, AEs, SAEs, withdrawals due to AEs, or mortality, compared with placebo.None of the included trials reported evidence on AEs caused by denosumab discontinuation.ConclusionsDenosumab was associated with significant improvements in both LS and TH BMD relative to placebo. Similarly, compared with placebo, denosumab was not associated with significant changes in nonvertebral or vertebral fractures. Denosumab was not associated with significant changes in safety outcomes relative to placebo. Given that some of the analyses suffered from statistical imprecision, these findings should be interpreted with caution. Regarding policy, continued funding of denosumab needs to be reviewed.

Estrogen-induced phenotype in hiPSC-derived cardiomyocytes of a woman affected by both Long QT Syndrome Type 2 and Polycystic Ovary Syndrome

Abstract Introduction Long QT Syndrome (LQTS) is an arrhythmogenic disorder caused either by genetic alteration or by exogenous factors. Polycystic Ovary Syndrome (PCOS) is a disease associated with high levels of testosterone and low levels of estrogen (E2). It has been suggested that hormones can influence the occurrence of malignant cardiac events in LQTS type 2 (LQT2) women, carriers of mutations on the potassium channel (hERG). However, the precise mechanisms governing this process still need to be clarified. Purpose We studied a patient affected by both LQT2 and PCOS who started experiencing cardiac symptoms after initiation of hormonal replacement therapy. We observed a correlation with the occurrence of arrhythmic events and the irregular assumption of the hormonal replacement therapy, thus we aim to dissect the underlying mechanism in patient-in-a-dish cardiac cellular model. Methods Induced Pluripotent Stem Cells (hiPSC) were generated from a woman affected by both LQT2 and PCOS and from a healthy donor, and then differentiated into cardiomyocytes (hiPSC-CMs). hiPSC-CMs were stimulated with E2 10nM for five time points (1, 5, 10, 15 and 30 minutes). The expression of potassium channel hERG, and of the G-coupled estrogen receptor (GPER) regulating the fast non-genomic pathway, were quantified after E2 stimulation at different time points by In Cell Western (ICW). The Unstimulated sample were used to normalize GPER and hERG expression to 100%. Electrophysiological experiments were performed using the whole-cell patch-clamp technique in current-clamp mode to record spontaneous action potentials (APs). AP duration at 30%, 50% and 90% repolarization (APD30, APD50 and APD90) was quantified. During spontaneous activity, AP duration values were rate-corrected with Bazett’s formula, thus obtaining cAPD. Results LQT2 hiPSC-CMs express higher levels of GPER (p&amp;lt;0.05) and hERG (p&amp;lt;0.01) than healthy hiPSC-CMs. A significant decrease in GPER expression was detected during 10nM E2 stimulation in healthy cardiomyocytes at the five time points (p&amp;lt;0.0001), while any difference was detected in hERG expression levels. E2 stimulation at different time points did not affect neither GPER nor hERG expression in LQT2 hiPSC-CMs. In LQT2 hiPSC-CMs, APDC values were significantly increased (p&amp;lt;0.0001) compared to healthy cells; pre-incubation with E2 for 10 minutes significantly shortened cAPD50 and increased spontaneous firing rate. In healthy hiPSC-CMs, E2 had no effect. Conclusions The hiPSC-CM model reproduces the LQT2 clinical phenotype. cAPD50 shortening by E2 was unexpected based on the proarrhythmic effect in the patient. The mechanism of LQT2-specific effects of E2 are under investigation.

Maternal steroids during pregnancy and their associations with exposure to lifetime stressful life events, prenatal stress appraisal and psychological functioning

BackgroundDuring pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied. AimTo assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22–40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334). MethodsSerum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects. ResultsHigh prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [β (95%CI): androgens: −0.13 (−0.25;−0.01); estrogens: −0.16 (−0.31;−0.01)], particularly among women carrying males [androgens: −0.22 (−0.39;−0.05); estrogens: −0.28 (−0.50;−0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite—5alpha-androstan-3alpha,17alpha-diol disulfate—negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males. ConclusionsIncreased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.