Search

Objective: B-type natriuretic peptide (BNP) is a neurohormone primarily secreted from cardiac ventricles in reaction to increased volume and pressure. The plasma level of BNP is used to measure the mechanical function of the heart and the risk of developing chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin (AAT) is a glycoprotein that acts as an inhibitor of serine proteases and plays a crucial role in protecting the lungs against potential harm. AAT deficiency also causes COPD. The data on the prevalence of BNP and AAT in African Americans (AA) are limited and inconsistent. No previous studies have investigated whether any association exists between BNP and AAT. We collected fasting blood samples from 114 AA subjects who provided informed consent. The plasma levels of the biomarkers were measured using ELISA., Results: Our findings revealed a significant negative correlation between AAT and BNP (r=-0.266, p = 0.01) as well as between AAT and TNF-α (r=-0.242, p = 0.01). Sex hormones (estrogen and testosterone) have a significant relationship with the levels of AAT and BNP. Increasing the AAT and reducing the levels of inflammation can lower the levels of BNP, which in turn could help lower the risk of heart disease in the AA population., (© 2024. The Author(s).)

Human chorionic gonadotropin (hCG) is widely used to treat reproductive dysfunction by enhancing testicular blood flow and stimulating hormonal activity. This study investigates the seasonal variations in the response to hCG treatment in male dogs, focusing on its effects on testicular blood flow and plasma concentrations of testosterone and oestrogen. Conducted across different seasons (spring, summer, fall and winter), the study utilised colour Doppler ultrasonography to measure testicular haemodynamics and analysed hormonal levels at multiple time points post-hCG injection. The findings revealed that the response to hCG is modulated by seasonal factors, with significant variations in both blood flow and hormone levels. A significant negative relationship was indicated between testicular blood flow and testosterone levels, particularly during spring and summer. These results suggest that seasonality should be considered when administering hCG for reproductive treatments in canines., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Purpose: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization., Results: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district., Conclusion: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance., (© 2024. The Author(s).)

Purpose: This study aimed to investigate the impact of short-term low energy availability (LEA) on vascular function in young, regularly menstruating women., Methods: Participants were 19 women, aged 22.9 ± 4.2 years, with body mass index 18-30 kg·m 2 . They were divided into two groups and completed two conditions in a crossover design: a 3-day control condition (CON) with an energy availability of 45 kcals·kgFFM -1 ·day -1 and a 3-day LEA condition of 15 kcals·kgFFM -1 day -1 . Assessments were conducted during the early follicular phase of the menstrual cycle. Outcome measures included forearm blood flow (FBF), heart rate, blood pressure, arterial stiffness, resting energy expenditure (REE), metabolic blood markers and body composition., Results: Significant time-by-condition interactions were found for resting FBF (p = .004), REE (p = .042), triiodothyronine (p = .006), β-hydroxybutyrate (p = .002) and body mass (p < .001). Resting FBF was 1.43 ± 1.01 and 1.31 ± 0.61 (arbitrary units) at pre and post, respectively, in LEA and 1.52 ± 0.7 and 1.76 ± 0.57 at pre and post in CON. The LEA condition led to a decrease in triiodothyronine (pre: 1.54 ± 0.28, post: 1.29 ± 0.27 ng ml -1 ), REE (pre: 1588 ± 165, post: 1487 ± 160 kcals day -1 ) and body mass (pre: 61.4 ± 7.5, post: 59.6 ± 7.3 kg). Changes in resting FBF were significantly correlated with changes in REE in the LEA condition (r = 0.53; p = 0.02)., Conclusion: Short-term LEA modifies regional blood flow and this might contribute to the observed decreased in REE. Findings emphasize the need for careful management of energy availability in populations at risk of LEA., (© 2024. The Author(s).)

The aim of this systematic review is to evaluate the impact of estrogen levels on the occurrence of temporomandibular disorders (TMDs) in humans. Searches were conducted in the same databases as follows: PubMed, the Cochrane Collaboration database, and the Scopus database. In accordance with the MeSH database and previous work, the following keywords were used: 'estrogens' and 'temporomandibular joint disorders'. Twelve studies were included in the review and were assessed for the quality of evidence. Estrogen levels are associated with pain modulation in the temporomandibular joint and the entire orofacial region. There is insufficient evidence to either confirm or refute the influence of estrogen on the occurrence of TMDs. The study was registered under the identifier: 10.17605/OSF.IO/BC7QF.

Increased circulating tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have been observed in patients with acute lung injury (ALI). However, the sex-specific regulation of TIMP-1 and the underlying molecular mechanisms have not been well elucidated. In this study, we found that plasma TIMP-1 levels were significantly higher in COVID-19 and H1N1 patients compared with those in healthy subjects (n = 25). TIMP-1 concentrations were significantly different between males and females in each disease group. Among female but not male patients, TIMP-1 levels significantly correlated with the PaO 2 /FiO 2 ratio and hospital length of stay. Using the mouse model of ALI induced by the H1N1 virus, we found that TIMP-1 is strikingly induced in PDGFRα-positive cells in the murine lungs. Moreover, female mice showed a higher Timp-1 expression in the lungs on day 3 postinfection. Mechanistically, we observed that estrogen can upregulate TIMP-1 expression in lung fibroblasts, not epithelial cells. In addition, overexpression of estrogen receptor α (ERα) increased the TIMP-1 promoter activity. In summary, TIMP-1 is an estrogen-responsive gene, and its promoter activity is regulated by ERα. Circulating TIMP-1 may serve as a sex-specific marker, reflecting the severity and worst outcomes in female patients with SARS-CoV2- and IAV-related ALI., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS)., Methods: Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection., Results: Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GM yes 0.46 [95% CI:0.37-0.57] vs. GM no 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GM yes 11.1 [95% CI:8.95-13.9] pmol/L vs. GM no 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GM yes 6.50 [95% CI:5.05-8.37] vs. GM no 4.92 [95% CI:4.00-6.05])., Conclusion: While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: This study aimed to investigate the effect of the MC and endogenous sex hormone concentrations on performance-determining variables in three distinct MC phases in endurance-trained females., Methods: Twenty-one eumenorrheic trained/highly trained endurance athletes completed a standardized test battery during the early follicular phase (EFP), ovulatory phase (OP), and midluteal phase (MLP) for either one ( n = 7) or two test cycles ( n = 14). MC phases were determined using calendar-based counting, urinary ovulation testing, and verified with serum hormone analysis. MCs were retrospectively classified as eumenorrheic or disturbed. Disturbed MCs were excluded from analysis. The test battery consisted of 4-6 × 5-min submaximal stages with stepwise speed increases, a 30-s all-out double-poling ski ergometer test, and a maximal incremental treadmill running test., Results: At a group level, there was no effect of MC phase or the serum concentrations of estrogen and progesterone on peak oxygen uptake (V̇O 2peak ), oxygen uptake at 4 mmol·L -1 blood lactate concentration, time to exhaustion, running economy, or mean 30-s power output (MPO 30s ). Serum testosterone concentration was positively associated with MPO 30s ( P = 0.016). Changes in V̇O 2peak from EFP to MLP were inconsistent between individuals and across cycles., Conclusions: None of the measured performance-determining variables were influenced by MC phase or serum estrogen or progesterone concentrations. Although some individual patterns could be observed, there was no indication that any single MC phase is consistently associated with improved or impaired V̇O 2peak on a group level., (Copyright © 2024 by the American College of Sports Medicine.)

Detection of doping with steroids that are also endogenous in the horse can be challenging, and a variety of approaches to distinguish exogenous administration from their natural presence are employed. Knowledge of endogenous concentrations of various steroids in different genders of horses (intact male, castrated male and female) and factors that could naturally affect them is beneficial for establishing ways for detection of their use. The current internationally adopted approaches include concentration-based thresholds in urine and plasma, steroid ratios in urine and targeting the administered intact steroid esters in plasma and hair. However, these have their limitations, and therefore, other strategies, such as additional biomarkers and steroid profiling based on longitudinal testing and multivariate analysis, have been investigated and could potentially improve detection of the use of endogenous steroids in horses. This paper aims to provide a comprehensive overview of the steroids (androgens, oestrogens and progestogens) that have been reported to be endogenous to horses in literature, their concentration ranges in different genders and factors potentially affecting them as well as current and possible future approaches to detect their use., (© 2023 John Wiley & Sons, Ltd.)

Introduction: Growth Differentiation Factor 15 (GDF15) increases substantially during pregnancy and is primarily produced by the placenta. Elevated levels of GDF15 have been associated with mental health problems in non-perinatal populations, higher corticosterone levels, and decreased estrogen receptor activity. However, the role of GDF15 in mental health during the perinatal transition remains unknown. This longitudinal study is the first to evaluate pregnancy levels of GDF15 in cerebrospinal fluid (cGDF15), plasma (pGDF15) and placenta GDF15 mRNA, along with mapping plasma GDF15 (pGDF15) level changes from late pregnancy to early postpartum. Moreover, we aimed to evaluate the association between pregnancy cGDF15 levels and cortisol early postpartum, evaluate the association between pregnancy cGDF15 levels and mental health in pregnancy and postpartum, and evaluate the association between pGDF15 and estrogens and high-sensitivity C-reactive protein (CRP)., Methods: We included data from 95 women scheduled for a planned cesarean section and obtained cerebrospinal fluid (CSF) and plasma levels of GDF15. We quantified GDF15 mRNA levels in placenta biopsies. Estrogens, high-sensitivity CRP, and mental health measures were further collected on the day or one day before the cesarean section. At five weeks postpartum, mental health measures and saliva samples for cortisol analyses were collected. Correlation analyses for GDF15 in CSF, plasma, and placenta mRNA were performed, along with association analyses for pregnancy cGDF15, Cortisol Awakening Response, and mental health outcomes., Results: We demonstrated a strong correlation between cGDF15 and pGDF15 (r=0.52; p<0.001) and found that both cGDF15 and pGDF15 correlated with placenta GDF15 mRNA*placental weight (r=0.62, p<0.001 and r=0.44, p=0.008, respectively). During late pregnancy, both estradiol (E2) and estriol (E3) were significantly associated with pGDF15 levels (E2: p=0.002; E3: p(corrected)<0.001). Finally, we found that cGDF15 levels were not associated with self-reported mental well-being or the Cortisol Awakening Response or absolute cortisol at awakening postpartum., Conclusion: This novel study points to the unique hormonal landscape during the perinatal transition and the specific role of GDF15 in pregnancy, which appears uncoupled with perinatal mental health and cortisol outcomes. Our data also strongly imply that the overall amount of circulating GDF15 in late pregnancy is closely related to placenta size., Competing Interests: Declaration of Competing Interest VGF discloses that she has received honorarium in form of consulting fees from SAGE Therapeutics, Lundbeck Pharma A/S, Janssen Cilag A/S and Gedeon-Richter A/S. ABK and CC are co-founders of Ousia Pharma ApS. All other authors disclose no potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

When a naïve observer meets with a familiar conspecific in pain, mice may have a myriad of social (sniffing, allolicking, allogrooming, huddling) and non-social (self-grooming) behaviors under dyadic social interaction (DSI) paradigm. Unlike male, female observers express more allolicking behavior toward injury site of a familiar female in pain, but with less body allogrooming. In current study, we investigated roles of natural estrus cycle phases and ovarian estrogen in these behaviors and results showed that: (1) there was no changes in above behaviors in terms of latency, time and bouts across different natural estrus cycle phases in intact female. (2) however, ovariectomy (OVX) changed estrus cycle phases, lowered circulating level of ovarian estrogen, reduced time and bouts of allolicking behavior and increased time of self-grooming without affecting other behaviors. Moreover, OVX in observers decreased social buffering effect of DSI on spontaneous pain-related behavior in demonstrator relative to naïve and sham controls. (3) treatment of OVX-female with β-estradiol (E 2 ) or progesterone (PROG) as replacement therapies, only E 2 reversed impairment of allolicking behavior. (4) Additionally, socially transferred pain could be identified in intact female across all estrus cycle phases post-DSI, but disappeared in OVX-female, which could be reversed completely by E 2 but not by PROG. (5) Finally, serum levels of estrogen, PROG, oxytocin, arginine vasopressin (AVP), prolactin, norepinephrine and 5-HT were examined by ELISA after E 2 , results showed only AVP level was significantly increased. These results suggest both injury site-targeted caring behavior and socially transferred pain are selectively dependent on ovarian estrogen. This article is part of the Special Issue on "Empathic Pain"., Competing Interests: Declaration of competing interest The authors hereby declare that there are no conflicts of interest, financial or otherwise, that could have influenced the integrity and objectivity of the research conducted and presented in this paper. This includes, but is not limited to, the following aspects: 1. Financial Conflicts of Interest: All authors affirm that they have not received any direct or indirect financial support that could influence the outcomes of this research. Furthermore, no author is employed by, consults for, owns shares in, or receives funding from any company or organization that would benefit from the results of this study. 2. Personal and Academic Relationships: All authors declare that they have no personal relationships or academic competition related to the subject matter of this research that could interfere with the objectivity or fairness of the research. 3. Transparency in Data and Methods: To ensure transparency, the data and methodologies used in this study are openly available for peer review and public scrutiny. 4. Other Potential Conflicts: All authors confirm that there are no other potential conflicts of interest, beyond those disclosed, that could undermine the integrity of this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Reproductive hormones might impact disease course in cognitive decline. We examined the association between male and female endogenous reproductive hormones and subjective cognitive decline (SCD) score., Design, Patients and Measurements: A cross-sectional study design was used with baseline data from the Pingyin cohort study, involving 1943 participants aged 45-70 years. Oestrogen (E2), testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured in females and E2 and testosterone were measured in males. We categorised hormones into three levels of low, intermediate and high level. The 9-item subjective cognitive decline questionnaire (SCD-Q9) scores were collected to assess the symptoms of SCD. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) between categorised hormone levels and SCD status. Multivariable linear regression models were also used., Results: Overall, 1943 participants were involved and 1285 (66.1%) were female. The mean age at baseline was 59.1 (standard deviation 7.1) years. Women with high testosterone levels had a higher probability of having SCD compared with those with low testosterone levels (OR 1.43, 95% CI 1.01-2.05). Men with a high level of testosterone (0.59, 0.35-0.98) and high testosterone/E2 ratio (0.55, 0.33-0.90) were related to decreased chances of having SCD. Each one-unit increase of testosterone was linked to reduced SCD score in males [(β: -.029, 95% CI (-0.052, -0.007)]., Conclusion: There was sex-specific relationship between hormone levels and SCD abnormal. Those with higher testosterone levels in females may increase likelihood of experiencing SCD. Males with higher testosterone levels and higher testosterone/E2 ratio may be associated with reduced likelihood of SCD. The roles of endogenous reproductive hormone levels and their dynamic changes in cognitive function need further investigation., (© 2024 John Wiley & Sons Ltd.)

Objective: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted., Results: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels ( t =-3.546, P < 0.001), lower testosterone levels ( t =-2.089, P =0.037), and a higher rate of hyperglycemia ( χ 2 =12.772, P =0.002) compared with those with non-vascular ED. The patients with arterial ED were older ( t =3.953, P < 0.001), had a higher rate of hyperglycemia ( χ 2 =9.518, P =0.009), and a higher estrogen/testosterone ratio ( t =2.330, P =0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age ( t =3.567, P < 0.001), lower testosterone levels ( t =-2.288, P =0.022), a higher rate of hyperglycemia ( χ 2 =12.877, P =0.002), and a larger estrogen/testosterone ratio ( t =2.096, P =0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED ( OR =1.009, 95% CI : 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor ( OR =0.381, 95% CI : 0.219-0.661). Older age was a risk factor for arterial ED ( OR =0.960, 95% CI : 0.938-0.982). Additionally, older age ( OR =0.976, 95% CI : 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L ( OR =0.591, 95% CI : 0.399-0.876) were also risk factors for mixed arterio-venous ED., Conclusion: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.

Estradiol (E2) deficiency arising from menopause is closely related to changes in body composition and declines of muscle mass and strength in elderly women. Whole-body vibration training (WBV) is an emerging approach expected to improve muscle mass and strength of older person, but the underlying mechanisms remain unclear. The balance between protein synthesis and degradation is a determining factor for muscle mass and strength, which is regulated by Akt-mTOR and FoxO1 signal pathway, respectively. In the present study, we firstly determined whether the effects of WBV on muscle mass and strength in ovariectomized female mice was affected by estrogen level, then investigated whether this was associated with Akt-mTOR and FoxO1 signal pathways. We found that (1) WBV, E2 supplementation (E) and WBV combined with E2 supplementation (WBV+E) significantly increased serum estradiol content, quadriceps muscle mass and grip strength in ovariectomized mice, accompanied with alterations of body composition (reducing fat content, increasing lean body mass and lean percent), furthermore, the altered degrees of these indicators by WBV+E were greater than WBV alone; (2) WBV, E and WBV+E remarkably increased the activities of Akt and mTOR and decreased FoxO1 activity, and the changed degrees by WBV+E were greater than WBV alone; (3) Pearson correlation coefficient revealed that serum estradiol content was positively correlated with Akt and mTOR activities, while inversely associated with FoxO1 activity. We concluded that WBV could significantly increase muscle mass and strength in ovariectomized mice, which might achieve through activating Akt-mTOR and suppressing FoxO1 signal pathways, and the improving effect of WBV on muscle mass and strength was better when in the presence of estrogen., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Previous studies have suggested that the effects of androgens on body weight (BW) and appetite are affected by the estrogen milieu in females; however, the mechanism underlying these effects remains unclear. We hypothesized that androgens may affect endogenous oxytocin (OT), which is a hypothalamic anorectic factor, and that these effects of androgens may be altered by the estrogen milieu in females. To investigate this hypothesis, in the present study, we examined the effects of testosterone on peripheral and central OT levels in ovariectomized female rats that did or did not receive estradiol supplementation. Ovariectomized female rats were randomly divided into non-estradiol-supplemented or estradiol-supplemented groups, and half of the rats in each group were concurrently supplemented with testosterone (i.e., rats were divided into four groups, n = 7 per each group). We also measured peripheral and central OT receptor (OTR) gene expression levels. As a result, we found that testosterone increased serum and hypothalamic OT levels and OT receptor mRNA levels in non-estradiol-supplemented rats, whereas it had no effects on these factors in estradiol-supplemented rats. In addition, testosterone reduced food intake, BW gain, and fat weight in non-estradiol-supplemented rats, whereas it did not have any effects on BW, appetite, or fat weight in estradiol-supplemented rats. These findings indicate that the effects of androgens on OT may be affected by the estrogen milieu, and elevated OT levels may be related to the blunting of appetite and prevention of obesity under estrogen-deficient conditions.

The abnormal estrogens levels in human body can cause many side effects and diseases, but the quantitative detection of the trace estrogens in complex biological samples still remains great challenge. Here we reported the fabrication of a novel core-shell structured magnetic cyclodextrin microporous organic network (Fe 3 O 4 @CD-MON) for rapid magnetic solid phase extraction (MSPE) of four estrogens in human serum and urine samples prior to HPLC-UV determination. The uniform spherical core-shell Fe 3 O 4 @CD-MONs was successfully regulated by altering the reactive monomers and solvents. The Fe 3 O 4 @CD-MONs owned high specific surface area, good hydrophobicity, large superparamagnetism, and abundant extraction sites for estrogens. Under optimal conditions, the proposed MSPE-HPLC-UV method provided wide linearity range (2.0-400 μg L -1 ), low limits of detection (0.5-1.0 μg L -1 ), large enrichment factors (183-198), less adsorbent consumption (3 mg), short extraction time (3 min), and good stability and reusability (at least 8 cycles). The established method had also been successfully applied to the enrichment and detection of four estrogens in serum and urine samples with a recovery of 88.4-105.1 % and a relative standard deviation of 1.0-5.9 %. This work confirmed the feasibility of solvent and monomer regulation synthesis of Fe 3 O 4 @CD-MON composites, and revealed the great prospects of magnetic CD-MONs for efficient enrichment of trace estrogens in complex biological samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

Background: Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication., Methods: This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS)., Results: Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p < .001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r(73) = -0.32, p = .005). Higher testosterone predicted better cognitive functioning (working memory: β = 0.20, p = .007, verbal fluency: β = 0.30, p = .001) and lower symptom scores (total: β = -0.21, p = .001; negative: β = -0.24, p = .002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (β = -0.22, p < .001) and higher symptoms scores (β = 0.23, p = .010) in men with SSD., Conclusion: The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiol baseline - serum estradiol follow-up /study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m 2 , I 2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m 2 ; I 2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I 2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I 2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I 2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes. NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

Declines in estrogen levels occur in women transitioning to menopause. Estrogen hormones play important roles in multiple systems of the body, and estrogen loss is associated with a variety of symptoms that can decrease quality of life. The gut microbiota is involved in regulating endogenous estrogen levels. A portion of estrogen glucuronides can be reactivated in the gut by the microbial enzyme β-glucuronidase, and the resulting free estrogens can return to the bloodstream. Here, we carried out in vitro screening of β-glucuronidase activities for 84 strains belonging to 16 different species of lactic acid bacteria and bifidobacteria and found that one and three strains of Levilactobacillus brevis and Lacticasebacillus rhamnosus , respectively, can deconjugate estrogens. Among these strains, L. brevis KABP052 had the highest β-glucuronidase activity. Moreover, in an exploratory, randomized, double-blind, placebo-controlled trial, we demonstrated that serum estrogen levels in healthy peri- and postmenopausal women given a probiotic formula containing KABP052 were maintained over time, whereas levels significantly decreased in the group given a placebo. Significantly higher levels of estradiol (31.62 ± 7.97 pg/mL vs. 25.12 ± 8.17 pg/mL) and estrone (21.38 ± 8.57 pg/mL vs. 13.18 ± 8.77 pg/mL) were observed in the probiotic versus placebo group after 12 weeks of intervention. This clinical study demonstrated for the first time the estrogen modulation capacity of a probiotic formula containing a bacterial strain having β-glucuronidase activity in women during the menopausal transition and formed the basis for future investigations using probiotics in the menopausal population.

We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and progesterone/progestin are associated with functional performance changes. National Rugby League Indigenous Women's Academy athletes [n = 11 naturally menstruating (NM), n = 13 using HC] completed performance tests [countermovement jump (CMJ), squat jump (SJ), isometric mid-thigh pull, 20 m sprint, power pass and Stroop test] during three phases of a MC or three weeks of HC usage, confirmed through ovulation tests alongside serum estrogen and progesterone concentrations. MC phase or HC use did not influence jump height, peak force, sprint time, distance thrown or Stroop effect. However, there were small variations in kinetic and kinematic CMJ/SJ outputs. NM athletes produced greater mean concentric power in MC phase four than one [+0.41 W·kg -1 (+16.8%), p = 0.021] during the CMJ, alongside greater impulse at 50 ms at phase one than four [+1.7 N·s (+4.7%), p = 0.031] during the SJ, without differences between tests for HC users. Among NM athletes, estradiol negatively correlated with mean velocity and power (r = -0.44 to -0.50, p < 0.047), progesterone positively correlated with contraction time (r = 0.45, p = 0.045), and both negatively correlated with the rate of force development and impulse (r = -0.45 to -0.64, p < 0.043) during the SJ. During the CMJ, estradiol positively correlated to 200 ms impulse (r = 0.45, p = 0.049) and progesterone to mean power (r = 0.51, p = 0.021). Evidence of changes in testing performance across a MC, or during active HC use, is insufficient to justify "phase-based testing"; however, kinetic or kinematic outputs may be altered in NM athletes., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Objective: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor., Methods: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods., Results: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05)., Conclusion: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Neuroendocrine tumors (NETs) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations. An extensive workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Immunohistochemical analyses revealed marked aromatase immunoactivity in the ovarian NET cells, while CYP17A1 and SF-1 were detected in the adjacent ovarian stromal cells but not the NET cells. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells. A retrospective search of electronic medical records revealed that 21% (14/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Together, these findings support the presence of a novel NET-associated hormonal syndrome., Competing Interests: Conflict of interest: M.L.F.v.V., E.M.R., L.J.H., and H.S. have no potential conflict of interest. M.C.F.M. has received a travel fee from Ipsen. J.H. has received speaker or consultancy fees from Novartis, Ipsen, and Serb. W.W.d.H. has received travel or speaker fees from Novartis, Ipsen, and Advanced Accelerator Applications, research funds from Ipsen, and is on the Advisory Boards of Novartis and of Ipsen., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background: Reports suggested that hormone replacement therapy decreased the incidence of squamous cell carcinoma (SCC) of the oral cavity., Aim: The aim of this study was to analyze and quantify the serum 17β-estradiol (E2) level by chemiluminescence immunoassay in four groups, Group I (control group with no habit of tobacco and areca), Group II (control group with a habit of tobacco and areca), Group III (potentially malignant disorder-leukoplakia), and Group IV (oral squamous cell carcinoma (OSCC)). It was the first study to evaluate E2 in four study groups with and without the habit of tobacco., Method: The serum analysis was carried out in Cobas e411 analyzer by electrochemiluminescence immunoassay analysis., Results: As per the Kruskal--Wallis test, statistically significant rise in estradiol levels in Group IV as in comparison to Group III as compared with Groups II and I., Conclusion: This study proved that irrespective of the gender bias, the female sex hormone, estradiol levels were significantly raised in OSCC patients. This study suggests that E2 may play a vital role in determining the patient prognosis in OSCC with tobacco habit. The confounding results of this preliminary study opened up new advents emphasizing the role of E2 in OSCC. The role of E2 in estrogen receptor regulation can also be a subject of study for targeted therapies in improving the patient's prognosis., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Purpose: The aromatase inhibitor letrozole and the aromatase inactivator exemestane are two of the most pivotal cancer drugs used for endocrine treatment of ER-positive breast cancer in all phases of the disease. Although both drugs inhibit CYP19 (aromatase) and have been used for decades, a direct head-to-head, intra-patient-cross-over comparison of their ability to decrease estrogen synthesis in vivo is still lacking., Methods: Postmenopausal breast cancer patients suitable for neoadjuvant endocrine therapy were randomized to receive either letrozole (2.5 mg o.d.) or exemestane (25 mg o.d.) for an initial treatment period, followed by a second treatment period on the alternative drug (intra-patient cross-over study design). Serum levels of estrone (E1), estradiol (E2), letrozole, exemestane, and 17-hydroxyexemestane were quantified simultaneously using a novel, ultrasensitive LC-MS/MS method established in our laboratory., Results: Complete sets of serum samples (baseline and during treatment with letrozole or exemestane) were available from 79 patients, including 40 patients starting with letrozole (cohort 1) and 39 with exemestane (cohort 2). Mean serum estrone and estradiol levels in cohort 1 were 174 pmol/L and 46.4 pmol/L at baseline, respectively. Treatment with letrozole suppressed serum E1 and E2 to a mean value of 0.2 pmol/L and 0.4 pmol/L (P < 0.001). After the cross-over to exemestane, mean serum levels of E1 and E2 increased to 1.4 pmol/L and 0.7 pmol/L, respectively. In cohort 2, baseline mean serum levels of E1 and E2 were 159 and 32.5 pmol/L, respectively. Treatment with exemestane decreased these values to 1.8 pmol/L for E1 and 0.6 pmol/L for E2 (P < 0.001). Following cross-over to letrozole, mean serum levels of E1 and E2 were significantly further reduced to 0.1 pmol/L and 0.4 pmol/L, respectively. Serum drug levels were monitored in all patients throughout the entire treatment and confirmed adherence to the protocol and drug concentrations within the therapeutic range for all patients. Additionally, Ki-67 values decreased significantly during treatment with both aromatase inhibitors, showing a trend toward a stronger suppression in obese women., Conclusion: To the best of our knowledge, we present here for the first time a comprehensive and direct head-to-head, intra-patient-cross-over comparison of the aromatase inhibitor letrozole and the aromatase inactivator exemestane concerning their ability to suppress serum estrogen levels in vivo. All in all, our results clearly demonstrate that letrozole therapy results in a more profound suppression of serum E1 and E2 levels compared to exemestane., (© 2024. The Author(s).)

Purpose: Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability., Methods: We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included., Results: Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported., Conclusions: Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays., (© 2024. The Author(s).)

Objectives: Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV., Design: Longitudinal and cross-sectional studies nested in the Women's Interagency HIV Study., Methods: Intestinal fatty acid binding protein, lipopolysaccharide binding protein, and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (∼6 measures per woman over ∼13 years). A separate cross-sectional analysis was conducted among 72 postmenopausal women with HIV with these biomarkers and serum estrogens., Results: Women in the longitudinal analysis were a median age of 43 years at baseline. In piecewise, linear, mixed-effects models with cutpoints 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]: 38 [12 to 64] ng/mL/yr, P = 0.004), followed by a decrease posttransition (-46 [-75 to -18], P = 0.001), with the piecewise model providing a better fit than a linear model (P = 0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses, among women with HIV, free estradiol inversely correlated with sCD14 levels (r = -0.26, P = 0.03). Lipopolysaccharide binding protein and intestinal fatty acid binding protein levels did not appear related to the menopausal transition and estrogen levels., Conclusions: Women with HIV may experience heightened innate immune activation during menopause, possibly related to the depletion of estrogens., Competing Interests: P.C.T. investigator initiated grants from Merck unrelated to this manuscript. All other authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females., Objective: To determine the effects of exercise on sex steroid hormones in eumenorrheic females., Methods: This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone., Results: Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I 2  = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I 2  = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I 2  = 94%)]., Conclusion: A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals., Trial Registration Number: The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767., (© 2024. The Author(s).)

Background: This study aimed to investigate the association between sex hormones and the risk of pulmonary fibrosis by conducting a meta-analysis of previously published studies., Methods: We executed a comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases to locate pertinent studies published up to April 2024. We included studies that reported the association between sex hormones and the risk of pulmonary fibrosis. Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model., Results: A total of 10 articles, encompassing 1371 patients, were finally incorporated in this meta-analysis. Based on the evaluation of the included studies, it was observed that the levels of dehydroepiandrosterone sulfate (DHEA-S) (pooled SMD: -0.72, 95% CI: -1.21 to -0.24, p  < 0.001), testosterone (pooled SMD: -1.25, CI: -2.39 and -0.11, p  < 0.001) and estrogen (pooled SMD: -0.56, 95% CI: -0.96 to -0.15, p  < 0.001) were significantly lower in patients with pulmonary fibrosis, whereas the levels of luteinizing hormone (LH) remained unaffected. Publication bias was ruled out through funnel plots., Conclusion: This meta-analysis indicates that reduced levels of DHEA-S, testosterone, estrogen may serve as potential risk factors for pulmonary fibrosis. There is a pressing need for additional studies to confirm this association and explore the underlying biological mechanisms. Clinicians should recognize the potential influence of sex hormones in the etiology of pulmonary fibrosis and consider this aspect during the patient management process.

Objective: To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population., Materials and Methods: We 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., Result: A 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 = .039). No association was noted between serum estrogen levels and SUI or MUI., Conclusion: Our 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important., (© 2024 The Author(s). Reproduction in Domestic Animals published by Wiley‐VCH GmbH.)

In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability-as measured by Oswestry Head and Neck Pain Scale and social isolation-as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen., Methods: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years., Results: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT., Conclusion: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol., (© 2024. The Author(s).)

Abstract: This cross-sectional observational study examined associations among symptom burden, lifetime duration of estrogen exposure, and serum antimüllerian hormone (AMH) levels among women living with HIV (n = 98) using bivariate bias-corrected Pearson correlations and multiple correspondence analyses. The mostly Black (85.6%) sample of women, with a mean age of 50 years (SD 12.6 years), exhibited no significant reproductive history factors and symptom burden interrelationships or significant associations between lifetime duration of estrogen exposure and symptoms. Predictably, serum AMH levels were lower among older women; however, less predictable were its significant relationships with months living with HIV (r = -0.362), months on ART (r = -0.270), and CD4+ T-cell nadir (r = 0.347). Symptom-symptom relationships support a fatigue, pain, sleep, anxiety, and depression symptom cluster. The hypotheses were not supported by cross-sectional observation. Further studies should explore variation in relationships between HIV, estrogen exposure, ovarian reserve, and AMH levels over time., (Copyright © 2024 Association of Nurses in AIDS Care.)

Estrogens, acting through their receptors (ERα and ERβ), regulate cell turnover in the pituitary gland, influencing cell proliferation and apoptosis across various species. However, their role in pituitary processes in seasonally reproducing animals remains poorly understood. This study aims to investigate the influence of estrogens, through the expression of their specific receptors, on the apoptosis of PD cells in relation to sexual maturity, the reproductive cycle, and pregnancy in a seasonal reproductive rodent (Lagostomus maximus maximus). ERα and caspase-3-cleaved (CASP3c) immunoreactive (-ir) cells were identified through immunohistochemistry. Apoptotic cells were detected using the TUNEL technique, with quantitative analysis facilitated by image analysis software, alongside measurement of serum estradiol levels using radioimmunoassay The immunostaining pattern for ERα included nuclear (ERαn) and cytoplasmic (ERαc) staining. In male viscachas, ERα expression significantly increases from immature to adult animals, correlating with the rise in serum estradiol levels and a decrease in the percentage of apoptotic cells. During the gonadal regression period in adult males, a decrease in the number of ER-ir cells and serum levels of estradiol corresponds with an increase in the number of apoptotic cells. In females, serum levels of estradiol peaked during mid-pregnancy, coinciding with a significant decrease in the number of apoptotic cells in the PD. Simultaneously, the percentage of ERαn-ir cells reaches its maximum value during late pregnancy, indicating the need to maintain the protective action of this gonadal hormone throughout the extensive pregnancy in these rodents. Regional ERα receptor expression and apoptotic cells appear to be associated with distinct PD cell populations and their hormonal responses. Finally, elevated estradiol levels coincide with diminished apoptotic cells in the male reproductive cycle and during pregnancy, suggesting an antiapoptotic role of estradiol in this species., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fabian Heber Mohamed reports financial support was provided by National University of San Luis. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background and Objectives : The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-β-1, and leukotriene C4 (LTC4). Materials and Methods : The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg -1 ) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-β-1, and LTC4. Results : Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions : Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.

Objective: Anterior cruciate ligament (ACL) tears are exceedingly common among the athletic population and are seen with higher incidence in females. Observational studies have noted peak ACL tear rates in the luteal phase of the menstrual cycle, a time in which the hormone relaxin peaks in serum concentration., Methods: A systematic review of the literature was performed. Inclusion criteria specified all prospective and retrospective studies which included the role of relaxin in the pathogenesis of ACL tears., Results: Six studies met inclusion criteria yielding 189 subjects from clinical studies and 51 in vitro samples. Included studies found that ACL samples exhibit selective relaxin binding. When pre-treated with estrogen prior to relaxin exposure, female ACL tissue samples exhibit increased expression of collagen degrading receptors., Conclusion: Relaxin displays binding specificity to the female ACL and increased serum concentrations are correlated with increased ACL tear rates in female athletes. Further research is needed in this area., Level of Evidence: V., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is associated with sexual dysfunction and hypogonadism. Androgens are associated with sexual function in healthy men, but the role of estrogens is less well-known, and the association of these sex steroids with sexual function during AHSCT has not been characterized., Objectives: The purpose of this study was to determine the predictive value of sex hormones before and acutely after AHSCT on sexual function recovery., Materials and Methods: We examined sex hormones and self-reported sexual function before (PRE) and 1-month post-AHSCT (MONTH1; n = 19), and sexual function again 1-year post-AHSCT in men (YEAR1; n = 15)., Results: Sexual function decreased from PRE to MONTH1 (p ≤ 0.05) with no differences between PRE and YEAR1. Erectile dysfunction was prevalent at PRE (68.4%) and increased at MONTH1 (100%; p ≤ 0.05) but was not different between PRE and YEAR1 (60.0%). From PRE to MONTH1, total testosterone (TT), dihydrotestosterone (DHT), follicle-stimulating hormone, and sex-hormone-binding globulin (SHBG) increased (p ≤ 0.02) while estradiol (p ≤ 0.026) and estrone decreased (p ≤ 0.001). MONTH1 TT and DHT were associated with sexual function at MONTH1, while PRE SHBG, MONTH1 estradiol, and change in estrone predicted sexual function at YEAR1., Discussion: Sexual dysfunction is very prevalent prior to AHSCT and is transiently and severely worsened acutely after. AHSCT induces acute decreases in total and free estrogens, with SHBG increases leading to increases in total androgens, without changes in free androgens., Conclusion: Androgens and estrogens are both adversely affected by AHSCT but may predict sexual dysfunction in this population. This supports the premise that estrogen impacts sexual function independent from androgens and that steroid hormones are associated with acute changes in sexual function in this setting. Larger, controlled trials with long-term sex hormone assessment will need to confirm the association between early changes in estrogens and long-term sexual function recovery., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: Gestagens are the most widely used therapy in anestrus type II. The aim of this research is to evaluate the effectiveness of the vaginal progesterone inserts therapy in anestrus type II in cows., Methods: The study was conducted on 33 cows. Progesterone (PR) and estrogen (ER) receptors expression in endometrium was assessed on a molecular level based on mRNA tissue expression. Additionally, blood 17ß-estradiol and progesterone levels were evaluated., Results: A decrease in mRNA expression of A and B PR and ER α was noted in treated and untreated animals. In the treated group, an increase of ERß mRNA expression was observed, while a decreased was found in untreated animals. There was increased PR, ERα and ß expression in endometrial tissue in treated cows, and decreased expression of these factors in untreated cows. In the treated group, recurrence of ovarian cyclicity was noted in 52% of animals and pregnancy was obtained in 34.8% of them, while in the untreated group, recurrence did not occur. In the control group, spontaneous recurrence of ovarian cyclicity was not observed. An increase of PR expression was correlated with increased proliferation of endometrial cells., Conclusions: It seems likely that the endometrium is well developed and ready for placentation after removing the exogenous source of progesterone and preventing the recurrence of cyclicity of ovaries.

Ethnopharmacological Relevance: Saffron petal has traditionally been used to treat a variety of diseases, such as gynecological disease such as primary dysmenorrhea and premenstrual tension. Polycystic Ovary Syndrome (PCOS) is a form of gynecological disease that causes amenorrhea, infertility, menopausal and urogenital disorders. This disease may be treated with saffron petals., Aim of the Study: In this study, the effects of saffron petal extract (SPE) and saffron petal anthocyanins (SPA) on ovarian hormones, steroidogenic enzymes, ovarian dysfunction, regulation of anti-inflammatory genes, and antioxidant factors in female PCOS mice were studied., Methods and Results: The PCOS mouse model was induced by testosterone enanthate (TE), and an in vivo evaluation of whether the dietary consumption of SPE and SPA improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH), testosterone, and estrogen levels increased in PCOS mice, but decreased following SPE and SPA treatment. In the PCOS mice, the reduced follicular-stimulating hormone (FSH) progesterone levels were restored to that of normal controls with SPE and SPA treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1), inflammatory markers (TNFα, IL1ß, IL6 and IL18), inflammatory-related factors (NF-κB, NF-κB p65, IκB) and antioxidant enzymes (GPx, SOD, CAT, GST, and GSH) changed under the PCOS condition. Moreover, they were regulated by SPE and SPA treatment in PCOS mice ovaries. The reproductive tissues of TE induced PCOS mice were restored into estrogenic conditions from androgen environments. The study of antioxidant activity of SPE and SPA using FRAP and DPPH tests showed high antioxidant activity., Conclusion: These results suggest that SPE and SPA ameliorates symptoms of PCOS by improving dysregulation of ovarian steroids, steroidogenic, antioxidant enzymes and inflammatory markers in PCOS mice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As a frequently occurring infectious disease mainly caused by Candida albicans, vulvovaginal candidosis (VVC) affects more than 100 million women worldwide every year. Multiple factors that influence C. albicans colonisation have been linked to the incidence of VVC, including high levels of circulating oestrogen due to pregnancy, the use of oral contraceptives, and hormone replacement therapy. This review provides an overview of the current understanding of the mechanism(s) by which oestrogen contributes to VVC, which might provide meaningful guidance to the prevention and treatment of this disease., (© 2021 Wiley-VCH GmbH.)

Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on the cerebrovascular system in humans remains largely unknown. To address this, we used a multi-modal magnetic resonance imaging (MRI) approach to investigate the link between serum hormones in the follicular phase and luteal phase of the menstrual cycle (MC) with measures of cerebrovascular function (cerebral blood flow [CBF]) and structure (intracranial artery diameter). Fourteen naturally cycling women were recruited and assessed at two-time points of their MC. CBF was derived from pseudo-continuous arterial spin labeling while diameters of the internal carotid and basilar artery was assessed using time of flight magnetic resonance angiography, blood samples were performed after the MRI. Results show that PROG and EST had opposing and spatially distinct effects on CBF: PROG correlated negatively with CBF in anterior brain regions (r = -.86, p < .01), while EST correlations were positive, yet weak and most prominent in posterior areas (r = .78, p < .01). No significant correlations between either hormone or intracranial artery diameter were observed. These results show that EST and PROG have opposing and regionally distinct effects on CBF and that this relationship is likely not due to interactions with large intracranial arteries. Considering that CBF in healthy women appears tightly linked to their current hormonal state, future studies should consider assessing MC-related hormone fluctuations in the design of functional MRI studies in this population., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In humans, females process a sound's harmonics more robustly than males. As estrogen regulates auditory plasticity in a sex-specific manner in seasonally breeding animals, estrogen signaling is one hypothesized mechanism for this difference in humans. To investigate whether sex differences in harmonic encoding vary similarly across the reproductive cycle of mammals, we recorded frequency-following responses (FFRs) to a complex sound in male and female rats. Female FFRs were collected during both low and high levels of circulating estrogen during the estrous cycle. Overall, female rodents had larger harmonic encoding than male rodents, and greater harmonic strength was seen during periods of greater estrogen production in the females. These results argue that hormonal differences, specifically estrogen, underlie sex differences in harmonic encoding in rodents and suggest that a similar mechanism may underlie differences seen in humans., (© 2021. The Author(s).)

Purpose: This study aimed to identify the effects of early follicular (EF) and midfollicular (MF) menstrual phases on body composition, resting metabolic rate (RMR), and respiratory quotient (RQ) assessment accuracy to identify an optimal testing period., Methods: Body composition was obtained from a four-compartment (4C) criterion model (fat mass (FM), fat-free mass, body fat percent, and dual-energy x-ray absorptiometry (DXA; FM, lean mass (LM), trunk FM, and trunk LM) in 19 eumenorrheic females (mean ± SD: age, 21.3 ± 3.1 yr, body mass index, 23.6 ± 1.8 kg·m-2). RMR (kcal·d-1) and RQ (a.u.) were measured via indirect calorimetry for 25 min. Body composition, RMR, and RQ were measured during the EF and MF phases. Dependent-samples t-tests were used to compare outcomes between EF and MF., Results: 4C outcomes were similar between phases (P > 0.05). During EF, the following 4C components were significantly greater (P < 0.05): body volume (mean difference (MD) ± SD, 0.70 ± 1.05 L), extracellular fluid (MD ± SD, 0.27 ± 0.51 L), and body mass (MD ± SD, 0.56 ± 0.80 kg). DXA-measured LM, body fat percent, trunk LM, and trunk FM were similar (P > 0.05); however, DXA FM was significantly greater during EF (MD ± SD, 0.29 ± 0.40 kg; P = 0.005), yet within measurement error of the device. Although RMR was not significantly different between phases (MD ± SD, 6.0 ± 190.93 kcal·d-1; P > 0.05), RQ was significantly higher during EF (mean ± SD, 0.03 ± 0.06 a.u.; P = 0.029) compared with MF., Conclusions: Body composition from 4C and DXA do not seem to be affected beyond measurement error as a result of compartmental changes from the menstrual cycle. During MF, women oxidized more fat as demonstrated by a lower RQ. Researchers should aim to be more inclusive and schedule testing for females within 11-12 d from the onset of menstruation., (Copyright © 2021 by the American College of Sports Medicine.)

Purpose: Does an association exist between serum progesterone and estradiol levels and live birth rates in artificial cycle frozen embryo transfer (AC-FET)?, Methods: Retrospective cohort study was based on prospectively collected data at a university-affiliated fertility center. Included were all cycles using an artificial endometrial preparation with estradiol hemihydrate (Estrofem, 2 mg/8 h) and vaginal progesterone (Endometrin 100 mg/8 h), autologous oocytes, and cleavage stage embryo transfers. Serum progesterone and estradiol levels were measured 14 days after FET. A total of 921 cycles in 568 patients from to December 2010 to June 2019 were investigated. Live birth was the primary outcome measure., Results: Significant association was found between live birth and progesterone as well as estradiol levels (progesterone 14.65 vs 11.62 ng/ml, p = 0.001; estradiol 355.12 vs 287.67 pg/ml, p = 0.001). A significant difference in live birth rate was found below and above the median progesterone level (10.9 ng/ml, p = 0.007). Lower estradiol level was significantly associated with lower live birth rate (< 188.2 pg/ml 8.3%, > 263.1 pg/ml 16%, p = 0.02)., Conclusions: Serum progesterone and estradiol levels impact live birth rate in AC-FET., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the menopausal transition may be different depending on the menopausal stage. The aim of this study was to determine the changes in circulating androstenediol during the menopausal transition in Japanese women and the associations of androstenediol with estrogen, androgen and cortisol for each stage of the menopausal transition. We divided the 104 subjects into 6 stages by menstrual regularity and follicle-stimulating hormone level: mid reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause and early postmenopause. Levels of dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and cortisol were measured. Serum androstenediol concentration was measured by using liquid chromatography mass spectrometry. There were no significant differences in androstenediol levels among the 6 stages. Levels of DHEA-S and testosterone showed significant and positive correlations with androstenediol in all stages. Estradiol levels showed negative correlations with androstenediol levels in the late menopausal transition and very early postmenopause (r=-0.452, p = 0.052 and r=-0.617, p = 0.006, respectively). Cortisol levels showed significant and positive correlations with androstenediol levels in the mid and late reproductive stages (r = 0.719, p = 0.003 and r = 0.808, p < 0.001, respectively).The associations of androstenediol with estradiol and cortisol were different depending on the stage of the menopausal transition. Androstenediol may play a compensatory role for estrogen deficiency from late menopausal transition to very early postmenopause., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The toxicity of certain novel perfluoroalkyl substances (PFCs) has attracted increasing attention. However, the toxic effects of sodium p-perfluorous nonenoxybenzene sulfonate (OBS) on the endocrine system have not been elucidated. In this study, OBS was added to the drinking water during the pregnancy and lactation of the healthy female mice at dietary levels of 0.0 mg/L (CON), 0.5 mg/L (OBS-L), and 5.0 mg/L (OBS-H). OBS exposure during the pregnancy and lactation resulted in the presence of OBS residues in the placenta and fetus. We also analyzed physiological and biochemical parameters and gene expression levels in mice of the F0 and F1 generations after maternal OBS exposure. The total serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly increased in female mice of the F0 generation. The androgen levels in the serum and the ovarian mRNA levels of androgen receptor (AR) also tended to increase after maternal OBS exposure in the F0 generation mice. Moreover, maternal OBS exposure altered the mRNA expression of endocrine-related genes in male mice of F1 generation. Notably, the serum TC and LDL-C levels were significantly increased in 8-weeks-old male mice of the F1 generation, and the serum high-density lipoprotein cholesterol (HDL-C) levels were decreased in 24-week-old male mice of the F1 generation. These results indicated that maternal OBS exposure can interfere with endocrine homeostasis in the F0 and F1 generations. Therefore, exposure to OBS during pregnancy and lactation has the potential toxic effects on the dams and male offspring, which cannot be overlooked.

Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results., Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided., Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log 2 1-unit increment   =   1.17 [95% confidence interval   =   1.00 to 1.38]; odds ratio quartile4-quartile1   =   1.33 [95% confidence interval   =   0.89 to 1.97], P trend   =   .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk., Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women., (© The Author(s) 2021. Published by Oxford University Press.)