bluuebunny/crossref_metadata_2025_split huggingface dataset:
7789 PCOS and probiotics - a randomized controlled trial with a comparison to metformin
Authors: Obermayer-Pietsch B M , Valentin B , Luegger B , Regina R , Haudum C W , Tandl V 
Published: October 2024

Abstract
Disclosure: B.M. Obermayer-Pietsch: None. B. Valentin: None. B. Luegger: None. R. Regina: None. C.W. Haudum: None. V. Tandl: None.
Polycystic ovary syndrome (PCOS) has a complex association not only with gonadal hormones, but also with insulin resistance and the gut – showing a decreased alpha diversity of the microbiome in PCOS women. Based on our previous investigations, we conducted a randomized controlled trial (RCT) using probiotics (OMNi-BiOTiC®, Institut Allergosan) and placebo daily, compared to a metformin group over 6 months. In this RCT, we included 112 women with PCOS, defined by Rotterdam criteria. Clinical and biochemical characterisation covered medical history with cycle abnormalities, Ferriman–Gallwey (FG) Score and anthropometric data. Hormonal profiles included gonadal hormones with a focus on androgens and AMH. Oral glucose tolerance tests (oGTT) with parallel insulin/c-peptide determinations and stool sampling for microbiome determination at every visit were done. Study participants were randomized 2:1 for probiotics/placebo or metformin (Glucophage®, Merck) and further 1:1 between probiotics and placebo for 6 months followed by a voluntary 6 months period on probiotics only. NGS for microbiome profiles was carried out. 93 PCOS women completed the study, 19 drop-outs for various reasons including 6 pregnancies were recorded (5 in the probiotic/placebo group, 1 in the metformin group). Participants were 27±5 years old, obesity with a BMI &gt;30 was found in 35% of them. Initial cycle duration ranged from 22 to 200 days, 18% had amenorrhoea. Hirsutism was present with a mean FG score of 12,7±7,71. Mean levels (±standard deviation, reference range, no units depicted) for total testosterone were 0,38±0,15 (0,14-0,77), SHBG 54,1±29,0 (19–117), free testosterone 3,2±3,1 (0,45-2,19) and AMH 8,9±4,8 (0,17-7,37). Initial oGTTs showed insulin resistance prevalent in 43%, with an overall reduction to 36% at visit 2. Weight loss over 6 months was documented in 37%, cycle abnormalities decreased overall to 14%. Group comparisons and microbiome characterisation are ongoing. No serious adverse reactions related to the study medication were recorded. All intervention products were well tolerated in our PCOS study cohort. Based on the intended cycle normalisation, 6 pregnancies were recorded. Metabolic changes were seen both in the probiotic/placebo and in the metformin groups, with fewer changes in the placebo group despite nutritional counselling. Microbiome changes were recorded in both intervention groups.
Presentation: 6/3/2024
9221 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study
Authors: Yahyavi Sam Kafai , Selmer Christian , Torp-Pedersen Christian , Juul Anders , Jensen Martin Blomberg 
Published: October 2024

Abstract
Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility.
Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women.
Presentation: 6/3/2024
8384 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study
Authors: Yahyavi Sam Kafai , Selmer Christian , Torp-Pedersen Christian , Juul Anders , Jensen Martin Blomberg 
Published: October 2024

Abstract
Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility.
Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects &gt; 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women.
Presentation: 6/3/2024
9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study
Authors: Ogoniak Lynn , Sandmann Sarah , Varghese Julian , Busch Alexander S 
Published: October 2024

Abstract
Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None.
Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes.
Presentation: 6/2/2024
8429 Serotonin Receptor Antagonist Alleviates Vascular Defects Produced by Selective Serotonin Reuptake Inhibitor Treatment During Gestation
Authors: Agnew L P , Domingues R , Weichmann A , Hernandez L L 
Published: October 2024

Abstract
Disclosure: L.P. Agnew: None. R. Domingues: None. A. Weichmann: None. L.L. Hernandez: None.
Maternal mental health is critical for both mother and infant and often antidepressant therapy outweighs the potential risks of selective serotonin reuptake inhibitor (SSRI) treatment; however, SSRI use is associated with adverse neonatal outcomes. Preliminary work in our laboratory revealed placental apoptosis in pregnant dams treated with fluoxetine (FLX) and dams genetically deficient for the serotonin transporter gene. We hypothesize that SSRIs decrease placental blood flow, causing apoptosis and organ death via signaling through the serotonin 2A/2C receptors. Pregnant female C57BL6 mice were randomized to be treated daily, via I.P. injection, from E10-17.5 with saline (CON; n=6), 2 mg/kg FLX (n=5), or 2 mg/kg ketanserin plus 2 mg/kg FLX (n=5). On E17.5, using high-resolution ultrasound imaging, we identified the uterine artery, individual umbilical cords, and placental disc blood vessels. We calculated blood pressure, blood volume, blood flow rate, and heart rate in the uterine artery, umbilical cord, and placental disc. FLX (decreased blood volume in the uterine artery compared to ketanserin plus FLX (48.42 ± 18.26, 116.54 ± 45.25; p=0.0077), and decreased average (89.38 ± 31.50) and peak (130.36 ± 39.05) blood velocity in the uterine artery compared to ketanserin plus FLX average (162.76 ± 68.46; p=0.0322) and peak (236.77 ± 92.43; p=0.0242) blood velocity. FLX decreased average (0.04 + 0.02) and peak (0.07 ± 0.04) blood pressure in the uterine artery compared to ketanserin and FLX treated animals average (0.12 ± 0.10; p=0.0634) and peak (0.25 ± 0.19; p=0.0412) blood pressure. Ketanserin plus FLX (391 ± 38.29) decreased heart rate (BPM) in the placental disc compared to untreated controls (450.67 ± 26.08; p=0.0128). In the umbilical cord, ketanserin plus FLX (393 ± 28.25) decreased BPM compared to CON (450.17 ± 29.44; p=0.0078) and compared to FLX treatment alone (437.20 ± 17.28; p=0.0450). FLX treatment of dams during pregnancy reduces blood flow volume, heart rate, and blood flow velocity to the placenta via the uterine artery. The use of ketanserin, an inhibitor of serotonin receptor 2A/2C signaling, in combination with FLX, reduced the effects of FLX on the uterine artery. These data suggest that treatment with ketanserin could be utilized to alleviate the reproductive side effects of antidepressant usage for pregnant mothers while allowing the mother to remain on antidepressants. Future research should further investigate the effects of SSRI and ketanserin on blood flow to the fetus through the umbilical cord.
Presentation: 6/2/2024
9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis
Authors: Osmancevic Amar , Allison Matthew , Miljkovic Iva , Vella Chantal , Ouyang Pamela , Trimpou Penelope , Daka Bledar 
Published: October 2024

Abstract
Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None.
Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, & B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution.
Presentation: 6/2/2024
7896 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis
Authors: Osmancevic Amar , Allison Matthew , Miljkovic Iva , Vella Chantal , Ouyang Pamela , Trimpou Penelope , Daka Bledar 
Published: October 2024

Abstract
Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None.
Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, & B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution.
Presentation: 6/2/2024
6432 Enriching Testicular Organoid Aggregates to Promote Germ Cell Homing
Authors: Patel A , Printy O O , Joswiak C , Laronda M M 
Published: October 2024

Abstract
Disclosure: A. Patel: None. O.O. Printy: None. C. Joswiak: None. M.M. Laronda: None.
The long-term effects of life-saving chemotherapy treatments, such as an increased risk of infertility, are of concern to the growing number of childhood cancer survivors. De novo testicular morphogenesis seeks to generate testicular organoids that are structurally and functionally similar to the native testis. These organoids serve as a tool for investigating patient-specific models for restoring spermatogenesis for prepubertal cancer patients. Our lab has previously developed testicular organoids containing tubule-like structures (TLS) resembling the native seminiferous tubules as assessed by immunohistochemistry of testicular cell-type markers for Leydig cells (HSD3B2), peritubular myoid cells (ACTA1), Sertoli cells (SOX9), germ cells (DDX4), and spermatogonial stem cells (SSCs) (SALL4). Internal architecture demonstrated semi-continuous ring-like structures composed of ACTA1-positive cells encapsulating a population of SOX9-positive cells with HSD3B2-positive cells clustering near the periphery of the organoids. However, organoids lacked native germ cell populations. We hypothesized that murine testicular organoids would merge to form elongated TLS, within which exogenous SSCs would home to existing Sertoli cell niches, when cultured within structures designed from the appropriate dimensions and materials. Organoids were generated from testicular tissue isolated from 5 days-post-partum (dpp) CD1 mice using cell-seeding densities and microenvironmental conditions previously established by our lab. To promote aggregate formation, 48-hour-old organoids were transferred to trough-shaped structures formed from 2% agarose using 3D printed silicone molds. Separately, SSCs were isolated from 5 dpp tdTomato+ mice via magnetic-activated cell sorting of THY1+ cells. Organoids and aggregates were enriched with SSCs by three methods: (1) enrichment of cell suspension during organoid formation, (2) enrichment of culture during aggregate formation, and (3) injection of SSCs into aggregate using 20 µm glass pipette. Organoids transferred to agarose troughs on day 2 of culture merged to form aggregates by day 5 and continued to display dynamic architecture, shortening in length and increasing in width over time. Aggregates were more elongated in shape when cultured in narrow troughs less than 700µm in width. Observations thus far indicate that attempts to inject aggregates resulted in penetrance and inclusion of the SSC suspension; additionally, tdTomato+ cells were visualized within injected aggregates on day 17 of culture. Research is ongoing to define where exogenous SSCs take up residence, how long they survive, and if they proliferate over time within the testicular aggregates. This research expands upon foundational work establishing testicular organoids as an approach to in vitro spermatogenesis with clinical applications in fertility restoration.
Presentation: 6/2/2024
7828 First Trimester Serum 11-Deoxycorticosterone Predicts Extreme Premature Childbirth
Authors: Ronde Salminen Emma K , Schoenmakers Sam , van Zelst Bertrand D , van den Berg Sjoerd A A 
Published: October 2024

Abstract
Disclosure: E.K. Ronde Salminen: None. S. Schoenmakers: None. B.D. van Zelst: None. S.A. van den Berg: None.
Background: Preterm birth is the leading cause of perinatal mortality and morbidity worldwide. Unfortunately, the prediction of preterm birth remains challenging, causing unnecessary hospital admittance and overexposure to medication. Studies have shown that metabolites of progesterone can influence uterine contractility[1] and serum levels of 11-deoxycorticosterone have been shown to correlate with an increased risk of preterm birth before 32 weeks of gestation2. The aim of this prospective study was to determine whether first trimester measurement of the progesterone metabolites 11-deoxycorticosterone (11-DOC) and 16-alpha hydroxyprogesterone (16-OHP) could be used as a predictive marker for preterm birth. Methods and results: A cohort of 386 pregnant women were included at 12 weeks of gestation between 2014-2016. Their obstetric histories and comorbidities were noted and their plasma was frozen. Of these women, n=26 delivered prior to 32 weeks of gestation and n=286 delivered at term. 11-DOC and 16-OHP were determined using LC-MS/MS. Mann-Whitney U test was used to statistically analyze differences between the groups. There was a highly significant difference in the level of 11-DOC between women delivering prior to 32 weeks of gestation in comparison to women delivering after 37 weeks of gestation (p=0.007). 16-OHP levels tended to be different between the two groups, but this did not reach statistical significance (p=0.062). No difference was found in the ratio 16-alpha hydroxyprogesterone/11-deoxycorticosterone between the two groups (p=0.916). Conclusion: Plasma levels of progesterone metabolites collected late in the first trimester of pregnancy predicts preterm birth prior to 32 weeks of pregnancy. References: 1.Patil AS, Swamy GK, Murtha AP et al, Progesterone metabolites produced by cytochrome P450 3A modulate uterine contractility in a murine model, Reprod Sci, 2015 Dec 22(12):1577-1586 2.Patil AS, Gaikwad NW, Grotegut CA et al, Alterations in endogenous progesterone metabolism associated with spontaneous very preterm delivery, Hum Reprod Open, 2020 Apr 6;2020(2):hoaa007
Presentation: 6/1/2024