Low Estrogen Levels Research Articles

Multicenter, prospective, single-arm clinical study to investigate the efficacy and safety of Zoladex (Goserelin acetate) 10.8 mg prior to surgery in Chinese premenopausal women with symptomatic uterine fibroids

Objectives To assess the effect and safety of Zoladex (Goserelin acetate) 10.8 mg in patients with uterine fibroids. Methods Fifty-three patients received Goserelin acetate 10.8 mg once and surgery was conducted at 12 weeks ± 7 days after drug injection. All assessments form baseline to week12/before surgery were carried out: fibroids volume, uterine volume, serum hormone (E2, FSH, LH), hemoglobin concentration, uterine arterial resistance index (UA-RI), fibroid arterial RI (FA-RI) and improvements of symptoms (Uterine Fibroid Symptom and Quality of Life (UFS-QOL) and Health-Related Quality of Life (HRQL) scores). Adverse events (AEs) were recorded to evaluate the safety. Results After 12 weeks of treatment, the volume of uterine fibroids was significantly smaller than before (249.19 ± 297.04 vs. 195.77 ± 418.27 cm3, p < 0.0001). The volume of the uterus was also smaller than before (372.02 vs. 263.58 cm3, p < 0.0001). Serum levels of E2, FSH, and LH showed significant decreasing trend (61.13 pmol/L, 5.23 IU/L and 4.75 IU/L respectively, p < 0.0001) and hemoglobin levels were increased significantly (108.30 ± 26.28 VS. 134.90 ± 9.21g/L, p < 0.0001). Left and right UA-RI showed slight increase of 0.04 and 0.02 respectively from baseline without significance. Mean FA-RI showed slight decrease of 0.03 from baseline (p = 0.22). Patient symptoms were alleviated after treatment. In addition, AEs occurred in 81.1% of enrolled patients and all AEs were well tolerably. Conclusions Goserelin acetate 10.8 mg pretreatment can effectively reduce the volume of uterine fibroids and uterus, lower estrogen levels and improve anemia symptoms. It could also improve the quality of life of patients, showing good safety and tolerance. This pretreatment was effective, safe, and generally well tolerated.

Review on Natural Agents as Aromatase Inhibitors: Management of Breast Cancer.

Breast cancer is a prevalent type of cancer that is typically hormone-dependent, caused by estrogen. Aromatase inhibitors are frequently utilised in the treatment of hormonereceptor- positive breast cancer because they prevent the enzyme aromatase from converting androgens to estrogens. Natural medicines with aromatase inhibitory characteristics have attracted interest as potential alternatives or complementary therapy to manufactured medications. This review discusses the function of natural agents as aromatase inhibitors in treating breast cancer. A variety of natural compounds have been investigated for their capacity to inhibit aromatase activity and lower estrogen levels. These agents include resveratrol from red wine and grapes, curcumin from turmeric extract and green teahigh in catechins, and other flavonoids such as genistein, luteolin and quercetin. It has been demonstrated that by decreasing estrogen synthesis, they can slow the growth of breast cancer cells that are dependent on estrogen. However, the clinical evidence supporting their efficacy and safety in breast cancer treatment is inadequate. More research is required to investigate the therapeutic potential of natural medicines, such as aromatase inhibitors, in treating breast cancer. The clinical trials are required to assess their efficacy, appropriate doses, and potential interactions with other therapies. In conclusion, natural aromatase inhibitory drugs are promising adjuncts in the treatment of hormone receptor-positive breast cancer. Their clinical value and safety profile, however, require additional investigation.

The deleterious effect of orally administered aqueous extract of &lt;i&gt;Acalypha wilkesiana&lt;/i&gt; (Red Acalypha) on female reproductive organs in Sprague Dawley rats

Acalypha wilkesiana is a herbaceous plant that has been traditionally used to treat and/or manage a variety of illnesses, including respiratory issues, diabetes, jaundice, hypertension, fever, diarrhea, and inflammation of the liver. The effects of taking Acalypha wilkesiana orally on the uterus and ovaries were examined in this study. Twenty (20) adult female Sprague-Dawley rats (165±20g) were purchased and given a two-week period to get used to the laboratory environment. Aqueous extract of Acalypha wilkesiana was given orally for four weeks at concentrations of 0, 100, 200, and 400 mg/kg of BW following acclimatization. Groups A-D provided as the control, low, medium, and high doses, respectively. The rats' weight gain and behavioral patterns were periodically examined. Following their euthanasia, blood was drawn via the ocular sinuses to measure hormonal parameters, and the uterus and ovaries were exercised to examine histology and oxidative stress markers. Significantly lower levels of FSH, LH, estrogen, and progesterone were observed in the treatment groups, while significantly lower levels of SOD and CAT and higher levels of MDA were observed. In both the 40 and 80 mg/kg groups, histological sections of the ovaries and uterus revealed vascular congestion in the ovaries and moderate to severe damage within the uteri. The findings demonstrated that long-term use of Acalypha wilkesiana increased levels of oxidative stress, altered hormone levels, and negatively affected the histoarchitecture of the uterus and ovaries.

8230 Adrenal Crisis, Unrevealing the Impact of Immigration on Central Adrenal Insufficiency

Abstract Disclosure: D.H. Sacoto: None. K. Madani: None. D. Patel: None. A. De Rosairo: None. G. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel: None. Introduction: Even though patients with secondary adrenal insufficiency (AI) may go through life without an episode of adrenal crisis, there is a 50% chance of developing it. Around 90% have a known precipitating, with infections and surgery being frequent causes. However, emotional stress is unrecognized. With the recent increase in worldwide immigration, it is important to recognize these as potential triggers in those with AI. Here, we present a case of adrenal crisis triggered by immigration. Case presentation: A 41-year-old female diagnosed eighteen years ago with Sheehan syndrome, with unknown replacement therapy status, is brought to ED for altered mental status. One week before, she crossed the Mexican-US border as an illegal immigrant and was hospitalized in Arizona after developing mutism and mood lability. She was initiated and discharged on hormone replacement therapy. She arrived in New York confused with flat affect and impaired recent memory. She was hypotensive (BP: 92/64 mmHg), hyponatremic (Na: 133 mEq/L), and anemic (Hb: 10.6 g/dL). She had an inappropriate normal ACTH of 25 pg/mL (7.2-63.3 pg/mL). MRI findings confirmed empty sella, suggestive of central AI. Additional studies revealed central hypothyroidism (low normal TSH (1.36 uIU/mL), low-normal Free T4 (1.4 ng/dL), gonadotroph dysfunction with low FSH (2.7 IU/L), and low estrogen levels (20 pg/mL) for her age, and low normal prolactin (4.6 ng/mL). After initiating a stress dose of IV hydrocortisone and IV levothyroxine, her affect, memory, mental status, and vital signs (BP: 128/80 mmHg) improved. She was educated regarding the need for maintenance doses as an outpatient. At the one-month follow-up, she continued with a positive response. Discussion: Patients with chronic AI are unable to produce sufficient cortisol and are at risk of acute adrenal crisis when under stress. Stressful situations, including accidents, job interviews, or death in the family, have been described. However, with almost doubling the number of people entering the US without prior authorization between 2022 and 2023, immigration, which poses physical and emotional stress, certainty will become a matter of importance for those with AI. Guidelines to manage cortisol replacement in times of fever, infections, trauma, surgery, or severe pain are available. However, it is more difficult to define how emotional and psychological challenges affect the stress response, mainly because each challenge is unique. Therefore, it is important to advocate for policies to provide medical alert bracelets to immigrants with known AI in addition to providing education about emergency injection kits in cases of impending crisis. Presentation: 6/3/2024

8684 Lifetime Duration of Amenorrhea Is Associated With Monetary Decision-Making and Hedonic Eating In Females With a Low-Weight Eating Disorder

Abstract Disclosure: F. Plessow: None. M. Wronski: None. M. Rogers: None. M.G. Turley: None. E.R. Golden: None. M. Slattery: None. J.J. Thomas: None. E.A. Lawson: None. M. Misra: None. K.T. Eddy: None. Background: Low estrogen levels and oligomenorrhea are common characteristics in females with a low-weight eating disorder (LWED). In animal models, estrogen status is associated with neural activity in dopaminergic reward pathways affecting reward processing and decision-making. Whether a similar link exists in humans is unknown but important to understand, as reduced reward-driven behavior and an increased delay of gratification driving decision-making hinder recovery from a LWED. To fill this knowledge gap, we studied the relationship between lifetime duration of amenorrhea and hedonic eating and monetary decision-making in a group of females with a LWED. We hypothesized that longer lifetime duration of amenorrhea is associated with reduced hedonic food intake and a smaller delay discounting rate (indicating an increased delay of gratification) in females with a LWED (independent of age and illness severity). Methods: Fifty-six females with a LWED (mean age±SD: 19.84±2.98 years, range: 13.6-23.5 years) and 34 female healthy controls (HC; 19.08±2.41 years, 13.4-22.2 years) underwent a menstrual history to determine the number of missed menses since menarche, Eating Disorder Examination (EDE) to assess ED psychopathology, anthropometric measurements to calculate body mass index (BMI), Cookie Taste Test as a laboratory-based assessment of reward-related eating beyond satiety, and a monetary Delay Discounting Task to determine their delay discounting rate. Between-group differences were tested using Mann-Whitney U-tests, and associations between duration of amenorrhea and caloric intake at the Cookie Taste Test and delay discounting rate in the LWED group were examined using partial Spearman correlations adjusted for age and BMI as a marker for illness severity. Results: By study design, females with a LWED had a lower BMI (17.97±2.16 vs. 21.71±2.57 kg/m2, U=1,802.50, p&amp;lt;0.001, r=0.75) and more pronounced ED psychopathology (EDE Global Score: 2.38±2.50 vs. 0.00±0.00, U=22.50, p&amp;lt;0.001, r=0.83) than HC. They had missed 16.50±22.64 menses since menarche. When controlling for age and BMI, longer lifetime duration of amenorrhea was correlated with lower caloric intake in the Cookie Taste Test (rs=-0.34, p=0.011) and a smaller delay discounting rate indicating an increased delay of gratification (rs=-0.40, p=0.004). Conclusions: This is the first demonstration that lifetime duration of amenorrhea is associated with hedonic food intake and monetary decision-making in females with a LWED, pointing towards a potential role of cumulative estrogen status in reward processing and decision-making in this population. Future research avenues include investigating whether estrogen replacement can increase reward responsiveness and reduce delay of gratification to promote a faster recovery from a LWED. Presentation: 6/1/2024

8684 Lifetime Duration of Amenorrhea Is Associated With Monetary Decision-Making and Hedonic Eating In Females With a Low-Weight Eating Disorder

Abstract Disclosure: F. Plessow: None. M. Wronski: None. M. Rogers: None. M.G. Turley: None. E.R. Golden: None. M. Slattery: None. J.J. Thomas: None. E.A. Lawson: None. M. Misra: None. K.T. Eddy: None. Background: Low estrogen levels and oligomenorrhea are common characteristics in females with a low-weight eating disorder (LWED). In animal models, estrogen status is associated with neural activity in dopaminergic reward pathways affecting reward processing and decision-making. Whether a similar link exists in humans is unknown but important to understand, as reduced reward-driven behavior and an increased delay of gratification driving decision-making hinder recovery from a LWED. To fill this knowledge gap, we studied the relationship between lifetime duration of amenorrhea and hedonic eating and monetary decision-making in a group of females with a LWED. We hypothesized that longer lifetime duration of amenorrhea is associated with reduced hedonic food intake and a smaller delay discounting rate (indicating an increased delay of gratification) in females with a LWED (independent of age and illness severity). Methods: Fifty-six females with a LWED (mean age±SD: 19.84±2.98 years, range: 13.6-23.5 years) and 34 female healthy controls (HC; 19.08±2.41 years, 13.4-22.2 years) underwent a menstrual history to determine the number of missed menses since menarche, Eating Disorder Examination (EDE) to assess ED psychopathology, anthropometric measurements to calculate body mass index (BMI), Cookie Taste Test as a laboratory-based assessment of reward-related eating beyond satiety, and a monetary Delay Discounting Task to determine their delay discounting rate. Between-group differences were tested using Mann-Whitney U-tests, and associations between duration of amenorrhea and caloric intake at the Cookie Taste Test and delay discounting rate in the LWED group were examined using partial Spearman correlations adjusted for age and BMI as a marker for illness severity. Results: By study design, females with a LWED had a lower BMI (17.97±2.16 vs. 21.71±2.57 kg/m2, U=1,802.50, p&amp;lt;0.001, r=0.75) and more pronounced ED psychopathology (EDE Global Score: 2.38±2.50 vs. 0.00±0.00, U=22.50, p&amp;lt;0.001, r=0.83) than HC. They had missed 16.50±22.64 menses since menarche. When controlling for age and BMI, longer lifetime duration of amenorrhea was correlated with lower caloric intake in the Cookie Taste Test (rs=-0.34, p=0.011) and a smaller delay discounting rate indicating an increased delay of gratification (rs=-0.40, p=0.004). Conclusions: This is the first demonstration that lifetime duration of amenorrhea is associated with hedonic food intake and monetary decision-making in females with a LWED, pointing towards a potential role of cumulative estrogen status in reward processing and decision-making in this population. Future research avenues include investigating whether estrogen replacement can increase reward responsiveness and reduce delay of gratification to promote a faster recovery from a LWED. Presentation: 6/1/2024

7609 Androgen Receptor Positive DCIS in a Transmasculine Individual on Testosterone Therapy

Abstract Disclosure: J. Kelly: None. B. Cohen: None. Introduction: The rate of breast cancer in transgender men is lower than in cisgender women, perhaps due to lower estrogen levels in the setting of suppression from exogenous testosterone, lack of clear guidelines on screening after top surgery, and increase in mastectomies. However, the impact of testosterone therapy on existing breast cancer is not known. Concerns regarding use of testosterone in patients with breast cancer include the potential for conversion of testosterone to estradiol, as well as direct androgen receptor (AR) stimulation. However, for some patients, hormone therapy is lifesaving and stopping gender affirming hormone therapy (GAHT) will negatively impact patient well-being. This creates a challenging clinical scenario when transgender patients on testosterone are diagnosed with breast cancer.Case Presentation: We present a case of a 29-year-old self-identified transmasculine nonbinary individual (assigned female at birth) who underwent chest reconstruction surgery after several months on daily transdermal testosterone therapy. A 4 cm DCIS ER+/AR+ with possible micro invasion was incidentally noted on pathology. They had no family history of breast cancer. The patient underwent chest MRI which was negative for persistent disease. The treating oncologist did not recommend Tamoxifen. The patient chose to discontinue testosterone therapy due to uncertainty regarding future breast cancer risk. However, due to worsening depression and fatigue, the patient chose to resume GAHT after receiving counseling of possible risk, though likely low, of cancer recurrence. Given that they had undergone bilateral mastectomy which, unlike chest reconstruction surgery where some breast tissue is left for contouring, all breast tissue was removed and given that chest MRI was negative for disease, cancer recurrence was felt to be low. Furthermore, though AR positivity was noted, the clinical implications are unclear and it is not known whether testosterone would stimulate tumor growth or potentially have antagonistic effects on ER signaling. Additionally, any stimulatory effects of AR signaling may be balanced by androgen suppression of gonadotroph production and reduction in estrogen production; this is more clearly associated with stimulatory effects on cancer growth. And finally, the potential risks of therapy must be weighed against the benefits provided to the patient’s well-being and mental health. Ultimately, the patient resumed testosterone therapy and has been doing well.Teaching Point: This case illustrates the uncertainties regarding the management of gender affirming testosterone therapy in patients with DCIS or breast cancer. It also highlights the need for a patient centered approach to decisions regarding changes to GAHT, to appropriately weigh the risks and benefits of continuing therapy. Presentation: 6/2/2024

Osteoporosis in older men

Osteoporosis, characterized by reduced bone mass and compromised skeletal microarchitecture, significantly increases the risk of fractures and is the most prevalent metabolic bone disease. While it is commonly associated with post-menopausal women, osteoporosis and subsequent fractures are also substantial concerns in men. Men experience sustained bone loss after the sixth decade, with estimates indicating that 20% of Americans with osteopenia or osteoporosis are men. Approximately one in eight men over 50 will suffer an osteoporotic fracture, with hip fractures in men leading to a two- to threefold increase in mortality compared to women. The prevalence of osteoporosis in men has risen, doubling in prevalence since the early 1990s. Men generally have higher peak bone mass and greater bone size, offering some protection against osteoporosis; however, aging leads to increased bone resorption and decreased bone formation, exacerbated by lower androgen and estrogen levels. Secondary causes, such as hypogonadism and chronic glucocorticoid use, are prevalent in men. Diagnosis primarily involves bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA), with fracture risk assessment tools like FRAX and MORES aiding in clinical decisions. Treatment includes calcium and vitamin D supplementation, bisphosphonates, denosumab, and anabolic agents like teriparatide and abaloparatide. Special considerations are necessary for men undergoing androgen deprivation therapy for prostate cancer due to accelerated bone loss. Effective management requires early diagnosis, lifestyle modifications, and appropriate pharmacological interventions to reduce fracture risk and improve patient outcomes.

Retrospective Investigator-Initiated Trial on Tocopherol Acetate Vaginal Administration in Pre-and Postmenopausal Women.

Menopause, a natural phase in a woman's life, often adversely affects physical, mental, sexual, and emotional well-being due to low estrogen levels. This study examines the impact of vaginal ovules with tocopherol acetate (Filme Gyno-V® ovules, manufactured by Panin Srl and distributed by Hulka Srl, Italy), 500 mg per ovule, on vaginal health in pre- and menopausal women. Fifty women aged 50-70 were divided into menopausal (28) and premenopausal (22) cohorts and treated with the ovules for two weeks, with assessments before and after treatment. The findings showed that distressing symptoms of vaginal atrophy, such as dryness, itching, and pain during intercourse, were resolved post-treatment. A molecular analysis revealed a reduction in Escherichia coli in both cohorts and an increase in three species of Lactobacillus in premenopausal patients. This study concludes that Filme Gyno-V ovules may benefit vaginal health by alleviating atrophy symptoms and promoting healthy vaginal microbiota.

Cardiovascular Disease in Women and the Role of Hormone Replacement Therapy.

Cardiovascular disease (CVD) is the leading cause of death in women and manifests more severely and at a later stage in life compared to men. The low estrogen levels during menopause are linked to an increased CVD risk. This association has promoted research regarding the role of hormone replacement therapy (HRT) in reducing the symptoms and diseases related to menopause, including CVD. This review article aims to discuss the biological changes associated with menopause and their impact on CVD. It also examines the effects of HRT in women with comorbidities related to CVD,its indications, risks, and contraindications.

Switch-like Gene Expression Modulates Disease Susceptibility.

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five (~18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold, p<10-4) and vaginal atrophy (44-fold, p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like gene ALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.

Association of phthalates exposure and sex steroid hormones with late-onset preeclampsia: a case-control study

BackgroundThis study aimed to investigate the relationship between phthalates exposure and estrogen and progesterone levels, as well as their role in late-onset preeclampsia.MethodsA total of 60 pregnant women who met the inclusion and exclusion criteria were recruited. Based on the diagnosis of preeclampsia, participants were divided into two groups: normotensive pregnant women (n = 30) and pregnant women with late-onset preeclampsia (n = 30). The major metabolites of phthalates (MMP, MEP, MiBP, MBP, MEHP, MEOHP, MEHHP) and sex steroid hormones (estrogen and progesterone) were quantified in urine samples of the participants.ResultsNo significant differences were observed in the levels of MMP, MEP, MiBP, MBP, MEHP, MEOHP, and MEHHP between women with preeclampsia and normotensive pregnant women (P > 0.05). The urinary estrogen showed a negative correlation with systolic blood pressure (rs= -0.46, P < 0.001) and diastolic blood pressure (rs= -0.47, P < 0.001). Additionally, the urinary estrogen and progesterone levels were lower in women with preeclampsia compared to those in normotensive pregnant women (P < 0.05). After adjusting for confounding factors, we observed a significant association between reduced urinary estrogen levels and an increased risk of preeclampsia (aOR = 0.09, 95%CI = 0.02–0.46). Notably, in our decision tree model, urinary estrogen emerged as the most crucial variable for identifying pregnant women at a high risk of developing preeclampsia. A positive correlation was observed between urinary progesterone and MEHP (rs = 0.36, P < 0.05) in normotensive pregnant women. A negative correlation was observed between urinary estrogen and MEP in pregnant women with preeclampsia (rs= -0.42, P < 0.05).ConclusionsPhthalates exposure was similar in normotensive pregnant women and those with late-onset preeclampsia within the same region. Pregnant women with preeclampsia had lower levels of estrogen and progesterone in their urine, while maternal urinary estrogen was negatively correlated with the risk of preeclampsia and phthalate metabolites (MEP).Trial registrationRegistration ID in Clinical Trials: NCT04369313; registration date: 30/04/2020.

Urethral Caruncle: A Case Report

The urethral caruncle is the most frequent benign tumor in postmenopausal women due to their low levels of estrogen. The main differential diagnosis is the urethral carcinoma, which is why a clinical case of a patient with a urethral caruncle is presented. The clinical and radiological characteristics are reviewed to ensure an appropriate patient approach, treatment, and histopathological correlation.

Effects of Clinical Mastitis on Reproductive Performances in Dairy Cows

The study was undertaken to study the productive and reproductive performances in clinical mastitis (CM) affected and apparently, healthy dairy crossbred cows and to analyze the effects of mastitis considering age, lactation, and severity of mastitis on reproductive performances in crossbred cows. A survey using a questionnaire was done to record different parameters of the cows during the period November 2021 to March 2022. A total of 58 lactating cows included in this study were divided into two groups named mastitis (n=24) and controlled (n=34). Cows of the mastitis groups were divided into subgroups depending on the age, lactation number and severity of mastitis. Prolactin (PRL), progesterone (P4) and estrogen (E2) levels of cows at the time of AI were analyzed. The results showed that cows of the mastitis group had substantially (P&lt;0.01) higher values for Days to first heat detection after parturition (96.16±6.20), Days to first insemination after parturition (105.00±6.64), Days open (140.58±7.40), and number of services per conception (2.33±0.11). The results also indicated that the greatest values were seen in the cows of Sub-group age &gt;8 for Milking Yield (16.21±2.39 Lt), Days to first heat detection after parturition (109.29±13.57), Days to first insemination following parturition (122.14±15.87), and Days open (165.79±16.70), and in cows of Sub-group 7-8 had for the Days of incidence of mastitis following parturition (51.57±12.73). Considering the number of lactations, we observed the highest values of Milking Yield (16.69±2.20 Lt), Days to first heat detection after parturition (108.75±11.58), Days to first insemination following parturition (120.00±13.96), and Days open (160.63±15.20) in cows of Sub-group lactation number &gt;3 and the highest Days of occurrence of mastitis after parturition in cows of Sub-group lactation number 3. Based on the degree of clinical mastitis, it was found that cows of the severe mastitis sub-group had the greatest Milking Yield (24.80±5.40 Liter) at a significant level (P&lt;0.05). This result indicates an association of severe CM with a high yield of milk. Whereas, there was no significant (P&gt;0.05) variation observed in different parameters in terms of reproductive performances in all sub-groups. In addition, significantly (P&lt;0.01) higher prolactin levels (16.10 ±1.17 ng/ml) and low estrogen levels (13.86±0.57 pg/ml) were present in CM-affected cows. This study could help veterinarians in taking strategies to minimize and control the negative effect of clinical mastitis on the reproduction of dairy cows. J. of Sci. and Tech. Res. 5(1): 01-07, 2023

Switch-like Gene Expression Modulates Disease Susceptibility.

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five (~18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold, p<10-4) and vaginal atrophy (44-fold, p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like gene ALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.

Investigating the Impact of Estrogen Levels on Voiding Characteristics, Bladder Structure, and Related Proteins in a Mouse Model of Menopause-Induced Lower Urinary Tract Symptoms.

Lower urinary tract symptoms (LUTS) are common in postmenopausal women. These symptoms are often linked to decreased estrogen levels following menopause. This study investigated the relationship between estrogen levels, alterations in bladder tissue structure, bladder function, and the incidence of urinary frequency. An age-appropriate bilateral ovariectomized mouse model (OVX) was developed to simulate conditions of estrogen deficiency. Mice were divided into three groups: a sham-operated control group, OVX, and an estradiol-treated group. The assessments included estrogen level measurement, urination frequency, cystometry, histological analysis, immunofluorescence staining, and real-time quantitative PCR. Additionally, we quantified the expression of the mechanosensitive channel proteins Piezo1 and TRPV4 in mouse bladder tissues. Lower estrogen levels were linked to increased voiding episodes and structural changes in mouse bladder tissues, notably a significant increase in Collagen III fiber deposition. There was a detectable negative relationship between estrogen levels and the expression of Piezo1 and TRPV4, mechanosensitive proteins in mouse bladder tissues, which may influence voiding frequency and nocturia. Estrogen treatment could improve bladder function, decrease urination frequency, and reduce collagen deposition in the bladder tissues. This study explored the connection between estrogen levels and urinary frequency, potentially setting the stage for novel methods to address frequent urination symptoms in postmenopausal women.

Impact of obesity on the perinatal vaginal environment and bacterial microbiome: effects on birth outcomes.

Introduction. Lactobacillus species predominate the human vagina and are associated with positive vaginal health, including an acidic pH (<4.5). The prevalence of vaginal Lactobacilli increases with increased oestrogen due to increased glycogen production within the vagina. Lactobacilli produce lactic acid, thereby lowering vaginal pH, preventing growth of other bacteria, and lowering microbial diversity. Lower placental oestrogen levels in obese pregnant women could dampen the mechanism to initiate this process, which may be associated with vaginal dysbiosis and unfavourable pregnancy outcomes.Hypothesis. We hypothesize that oestrogen and glycogen levels will be lower, vaginal pH will be higher, and vaginal microbiome diversity will be greater during pregnancy in obese and overweight women compared to healthy weight women.Aim. Pregnancy complications (e.g. preterm birth) are more common in overweight and obese women. If vaginal dysbiosis plays a role, and quantifiable predictors of this increased risk can be determined, these measures could be used to prospectively identify women at risk for pregnancy complications early in pregnancy.Methodology. Vaginal samples were collected at 10-14, 18-24, 26-30, and 34-37 weeks gestation and at delivery from 67 pregnant participants (23 healthy weight, 22 overweight, 22 obese). A blood sample to quantify serum oestrogen was collected at 10-14 weeks. Vaginal samples were collected to test vaginal pH using pH paper, glycogen abundance using fluorometry, and the vaginal microbiome using 16S rRNA amplicon sequencing.Results. Vaginal pH was higher in obese participants compared to healthy weight participants (P=<0.001). Vaginal glycogen levels increased over time in obese participants (P=0.033). The vaginal bacterial alpha diversity was higher in obese participants compared to healthy weight participants (P=0.033). The relative abundances of Peptoniphilus and Anaerococcus were increased in overweight and obese participants, as well as in complicated pregnancies, at 10-14 weeks gestation.Conclusion. The relative abundance of specific vaginal bacteria, like Peptoniphilus and Anaerococcus, in early pregnancy could predict pregnancy outcomes. Our goal is to use the information gathered in this pilot study to further determine the feasibility of assessing the vaginal environment during pregnancy to identify women at risk for negative pregnancy and birth outcomes in the context of a larger study.

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition

PurposeAntipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD.MethodsThis cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models.ResultsIn women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β−estradiol = 0.24, βprolactin = -0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r = -0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β−estradiol = -0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027).ConclusionsIn women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD.

Changes in Rehmanniae Radix processing and their impact on ovarian hypofunction: potential mechanisms of action.

This study evaluates the research developments concerning Rehmanniae Radix in ovarian hypofunction diseases. It explores the processing methods of Rehmanniae Radix, the variations in its compounds before and after processing, the mechanism of Rehmanniae Radix and its active compounds in improving ovarian function, and the advancements in clinical applications of traditional Chinese medicine (TCM) compound that include Rehmanniae Radix. Comprehensive literature search was conducted using databases such as China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, National Science and Technology Library, the Pharmacopoeia of the People's Republic of China, Pubmed, and the Web of Science Database. The search utilized the following Medical Subject Headings (MeSH) and keywords: "Rehmanniae Radix," "Drying Rehmannia Root," "Rehmannia glutinosa," "Rehmanniae Radix Praeparata," "Traditional Chinese Medicine Processing," "Pharmacological Effects," "Ovarian Aging," "Diminished ovarian reserve," "Premature ovarian insufficiency," "Premature Ovarian Failure," "Ovarian hypofunction diseases". The ancient Chinese medical books document various processing techniques for Rehmanniae Radix. Contemporary research has identified changes in its compounds processing and the resultant diverse therapeutic effects. When processed into Rehmanniae Radix Praeparata, it is noted for its ability to invigorate the kidney. TCM compound containing Rehmanniae Radix is frequently used to treat ovarian hypofunction diseases, demonstrating significant clinical effectiveness. The key changes in its compounds processing include cyclic dilute ether terpene glycosides, phenylethanol glycosides, sugars, and 5-hydroxymethylfurfural. Its pharmacological action is primarily linked to the improvement of granulosa cell proliferation, antioxidative and anti-aging properties, and modulation of the immune and inflammatory microenvironment. Furthermore, Rehmanniae Radix also offers therapeutic benefits for cardiovascular and cerebrovascular diseases, osteoporosis and cognitive dysfunction caused by low estrogen levels. Thereby Rehmanniae Radix mitigates both the short-term and long-term health risks associated with ovarian hypofunction diseases. Processed Rehmanniae Radix has shown potential to improve ovarian function, and its compound prescriptions have a definite effect on ovarian dysfunction diseases. Therefore Rehmanniae Radix was garnering interest for both basic and clinical research, with promising application prospects as a future therapeutic agent for ovarian hypofunction diseases. However, further studies on its toxicology and the design of standardized clinical trials are necessary to fully establish its efficacy and safety.

P-644 Effect of Letrozole co-stimulation with gonadotropin in women with normal ovarian reserve on oocyte maturation: a Randomized controlled trial

Abstract Study question To define whether letrozole co-stimulation with gonadotropin in normal-ovarian reserve women will improve the number of oocyte maturation. Summary answer Letrozole co-stimulation in normal ovarian reserve resulted in a reduced number of MII. What is known already Letrozole functions as an aromatase inhibitor. By inhibiting this enzyme, letrozole effectively lowers estrogen levels. Thus, letrozole prevents the estrogen-negative feedback to the HPO axis, which can increase the secretion of gonadotropins from the pituitary gland to promote folliculogenesis. The application of letrozole co-stimulation in women with a normal ovarian reserve is still debated. Study design, size, duration This study is an open-labeled, randomized controlled trial. Letrozole co-stimulation with gonadotropin in women with normal ovarian reserve. The RCT was conducted at the Fertility and Reproductive Biology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital in Thailand, from March 2023 to October 2023. Participants/materials, setting, methods One hundred forty-four infertile women 18-40 years old with normal ovarian reserve (AMH 1.2-7 ng/ml, AFC ≥ 5) were random to gonadotropin co-stimulation with letrozole 5 mg once daily (n = 72) and gonadotropin alone (n = 72). The number of MII oocytes, follicle-to-oocyte index, GDF-9 and BMP-15 in follicular fluid were assessed. Main results and the role of chance Letrozole co-stimulation resulted in a significantly reduced number of MII [8 (4,12) vs 9 (5, 15.8), p = 0.042] and the rate of MII [ 71.7(60, 83.8) vs 80 (66.7, 90), p = 0.013]. However, the number of retrieved oocytes [12 (6,16.8) vs. 12 (6,16), p = 0.335] and FOI [85.7 (57.4,107.5) vs 84.2 [61.8, 112.5], p = 0.396] remained unchanged. The total dose of gonadotropin in the letrozole group was no different from the control group [1,350 (1,200, 1,650) vs 1,500 (1,350, 1,718.8) I.U., p = 0.137]. The duration of ovarian stimulation was shortened in the letrozole group compared to the control group [9 (8, 10) vs 9 (8.3, 10) days, p = 0.027]. The letrozole and control group had a similar level of GDF-9 (0.036 ± 0.003 A.U. vs. 0.028 ± 0.004 A.U., p = 0.119, letrozole and control group, respectively) and BMP-15 (0.034 ± 0.002 A.U. vs. 0.033 ± 0.004 A.U., p = 0.923, letrozole and control group respectively) in follicular fluid. Limitations, reasons for caution This study was open-label, with limited generalizability due to 91% of ovarian stimulation being strict to the research protocol (r-FSH and antagonist protocol) and no pregnancy outcome. Wider implications of the findings The study showed no benefit of letrozole co-stimulation in women with normal ovarian reserve. Trial registration number TCTR20221125002