bluuebunny/crossref_metadata_2025_split huggingface dataset:
8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study
Authors: Ogoniak L , Sandmann S , Varghese J , Busch A 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
7467 Supplement Use Among Transgender Patients: Case Reports and Literature Review
Authors: Cunningham H , Jones Q , Kelley C 
Published: October 2024

Abstract
Disclosure: H. Cunningham: None. Q. Jones: None. C. Kelley: None.
The barriers to initiating gender affirming medical treatment are innumerable and increasing in the wake of wide-sweeping anti-trans legislation, leading many transgender individuals to utilize more accessible means of transitioning. We provide examples of patient-initiated supplement use at a gender medicine clinic in the Southeast. We describe a 60-year-old transgender woman who was unable to establish care due to lack of affirming providers in her region and insurance approval delays. She began taking Pueraria mirifica, along with saw palmetto and fenugreek, for feminization. Subsequently, her breast size increased from an A to B cup, and she noticed fat redistribution to her hips. When finally seen one year later, labs demonstrated suppressed luteinizing and follicle stimulating hormones and increased sex hormone binding globulin, with an associated decrease in estradiol and testosterone levels. Cessation of supplements resulted in lab normalization. Our second case describes masculinizing effects, including voice deepening, experienced by a transgender man using a supplement that contained "orchic extract.” Supplements used for gender affirmation can also have more adverse effects, including polycythemia in the setting of trenbolone, an illicit steroidogenic performance enhancing supplement used for masculinization by some patients assigned female at birth. Patients without access to gender affirming hormones through a medical provider, or who do not feel comfortable accessing health care, may be more likely to use supplements purchased online without a prescription. Considering this, we must create more safe spaces for gender affirming care and ask all transgender patients about supplement use. Providers should consider supplement use as a possible explanation for unexpected lab results. The literature on supplement use for gender-affirming effects is sparse; this presentation provides a summary of and contributes to the current literature on this topic.
Presentation: 6/2/2024
7310 System-level Analysis in Polycystic Ovary Syndrome on a Panel of Genetically Diverse Strains of Mice
Authors: Velez Leandro Martin , Johnson Casey , Tamburrini Ian , Zhou Mingqi , Viesi Carlos , Ujagar Naveena , Ashbrook David , Nelson Marin , Senior Alistair , James David , Williams Robert , Nicholas Dequina , Seldin Marcus 
Published: October 2024

Abstract
Disclosure: L.M. Velez: None. C. Johnson: None. I. Tamburrini: None. M. Zhou: None. C. Viesi: None. N. Ujagar: None. D. Ashbrook: None. M. Nelson: None. A. Senior: None. D. James: None. R. Williams: None. D. Nicholas: None. M. Seldin: None.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, with a prevalence of ∼4-20% in women of reproductive age. The diagnosis of the syndrome generally occurs when the patient consults for fertility issues and is only based on a reproductive criterion, which includes (1) hyperandrogenism, (2) oligo-anovulation, and (3) polycystic ovary morphology. However, the overlap of PCOS with cardiometabolic diseases is significant. To put in numbers; up to 75% of PCOS women present some degree of insulin insensitivity, 38-88% present obesity or overweight, 20-50% develop type 2 diabetes by age 40, and PCOS women are at increased risk of cardiovascular disease. Despite these facts, shared reproductive/metabolic mechanisms are largely underexplored. Moreover, studies addressing the genetic architecture of PCOS are missing. Here, we induced a PCOS-like condition in 25 recombinant and classical inbred female strains and matched placebo controls over 6 weeks. Comprehensive in vivo and terminal reproductive/metabolic analyses were performed, as well as ovary and adipose RNA-Seq. These strains varied in PCOS response in a number of key metabolic and reproductive traits, including circulating hormone levels, glucose metabolism, and cardiac function. We applied a linear mixed-effects model to estimate heritability, and genetic (h2), PCOS, and gene-by-PCOS interactions. High h2 was observed for lean and fat mass, glucose, and AUC, whereas PCOS effects were high for the BW change, testosterone, and AUC. Substantial gene-by-PCOS interactions were found for reproductive hormones. Undirected network construction and centrality estimates showed that the reproductive hormones LH and LH/FSH ratio were the strongest central traits connecting metabolic phenotypes. We also showed select strains represent subtypes of human PCOS-metabolism interaction with varied susceptibilities to disease in a PCOS setting. Ovarian RNA-seq analysis of PCOS DEGs showed strong enrichments with human disease settings such as hyperandrogenism, inflammation, and pregnancy hypertension. Similar analyses in GWAT RNA-seq showed enrichments in weight gain, liposarcoma, inflammation, and reproductive diseases were at the top, with adipose genes connecting these diseases and potentially involved with PCOS. In conclusion, we established a PCOS model to study relevant mechanisms intersecting reproduction with metabolism in the context of genetic variation.
Presentation: 6/2/2024
7426 Tamoxifen-Induced Ovarian Hyperstimulation in a Pre-Menopausal Patient with Breast Cancer History: Spontaneous Resolution with Conservative Management
Authors: Gondi S , Contento M , Leiter A 
Published: October 2024

Abstract
Disclosure: S. Gondi: None. M. Contento: None. A. Leiter: None.
Background: Tamoxifen is a selective estrogen receptor modulator (SERM) that competitively binds to estrogen receptors (ER) on tumors and inhibits the effect of estrogen, which is used in the treatment and prevention of ER-positive breast cancer. Tamoxifen therapy has been reported to increase serum estrogens and cause ovarian hyperstimulation in premenopausal women, but knowledge on how to manage these conditions is limited. Clinical Case: A 36-year-old pre-menopausal female with history of malignant neoplasm of the right breast (ER positive) who completed neoadjuvant chemotherapy, lumpectomy, and radiation, on tamoxifen for seven years presented with new-onset oligomenorrhea. Laboratory testing done by the patient’s gynecologist revealed total estrogen 2,723 pg/mL (reference range [RR] 34-501), testosterone 132 ng/dL (RR 8-60), anti-Mullerian hormone 12.7 ng/mL (RR for age 0.66-8.75), ovulation-phase follicle stimulating hormone 11.5 mIU/mL (RR 4.7-21.5) and luteinizing hormone (LH) 63.3 mIU/mL (RR 14-95.6). Further workup revealed that ovarian tumor markers alpha-fetoprotein and serum human chorionic gonadotropin and other labs including dehydroepiandrosterone sulfate, progesterone 17-OH, lactate dehydrogenase, prolactin, and thyroid stimulating hormone were normal. Transvaginal ultrasound (TVUS) showed a new 2.8 x 1.9 x 2.3 cm complex left ovarian cyst, which, along with the elevated estrogen level, was concerning for ovarian hyperstimulation. Treatment with LH-releasing hormone (LHRH) agonists, surgical consultation, and discontinuation of tamoxifen were offered as potential management strategies, but the patient opted for observation and continued tamoxifen. Two months later, estradiol was 989 pg/mL (RR 85-498), and then three months later decreased to 152 pg/mL with repeat TVUS showing resolution of the left ovarian cyst. The patient’s oligomenorrhea resolved with resumption of regular menstrual cycles. Conclusion: While it is well-known that tamoxifen causes elevated serum estrogen levels and can lead to ovarian hyperstimulation, there is limited research on the management of these side effects. Treatment strategies in past cases have included oophorectomy or medical management with LHRH agonists or gonadotropin-RH agonists. However, this case demonstrates that a tamoxifen-induced ovarian cyst and high estrogen levels can resolve on its own with continued tamoxifen treatment. Conservative management with monitoring via imaging and repeat estrogen levels may be sufficient in management of pre-menopausal women with tamoxifen-induced ovarian hyperstimulation.
Presentation: 6/1/2024
7953 Testosterone II (TSTII) Immunoassay Meets the CDC HoSt Certification Requirements for a Fourth Consecutive Year
Authors: Nissen K N , Parker N , Samantha P , Rhea-McManus J M , Shalhoub V , Freeman J 
Published: October 2024

Abstract
Disclosure: K.N. Nissen: Employee; Self; Siemens Healthineers. N. Parker: Employee; Self; Siemens Healthineers. P. Samantha: Employee; Self; Siemens Healthineers. J.M. Rhea-McManus: Employee; Self; Siemens Healthineers. V. Shalhoub: Employee; Self; Siemens Healthineers. J. Freeman: Employee; Self; Siemens Healthineers.
Background: The Atellica® IM and ADVIA Centaur® Testosterone II (TSTII) assay is enrolled in the CDC Hormone Standardization (CDC HoST) Certification Program, which is traceable to the primary testosterone Standard National Measurement Institute (NMI) M914. Certification is a yearlong process of 40 blinded samples from the CDC, 10 to be tested each quarter. If 4 consecutive quarters meet the bias acceptance criteria of ± 6.4%, CDC certification is achieved. The TSTII assay is standardized using internal standards made from United States Pharmacopea (USP)-grade testosterone. Standards are traceable to ID-LC-MS/MS by method comparison using CDC samples; ID-LC-MS/MS is traceable to the primary testosterone standard NMI M914. Methods: Initially, to standardize the assay, approximately 120 samples were obtained from CDC with CDC HoST ID-LC-MS dose values to value assign master curve standards. Multiple ADVIA Centaur TSTII reagent lots were tested with the CDC patient samples. Internal master curve standards were assayed as unknowns and dose values assigned using the RLU (system generated units–Relative Light Units) to CDC ID-LC-MS dose relationship. From 2019 to 2023, after standard value assignment, at least 179 individual patient samples from the CDC with blinded amounts of testosterone have been tested across all platforms. Each quarter, 10 blinded samples were tested in duplicate over 2 days. Results were analyzed by the CDC according to CLSI EP9-A2 for bias. Results: Correlation between the CDC assigned values and the Atellica IM, ADVIA Centaur, and ADVIA Centaur CP TSTII assay results was strong across all quarterly blind trials from 2019 to 2023 combined—Atellica IM intercept = +0.5 ng/dL, slope = 1.03, r = 0.990, n = 180, Bland Altman mean bias was 4.55%; ADVIA Centaur intercept = +0.3 ng/dL, slope = 1.04, r = 0.993, n = 179, mean bias was -0.27%; ADVIA Centaur CP intercept = +0.9 ng/dL, slope = 1.07, r = 0.993, n = 180, mean bias was 1.26%. The TSTII assay bias on all systems was consistently &lt;6.4%. This enabled the TSTII assays to be CDC certified for a fourth consecutive year. Conclusions: The TSTII assay has consistently achieved CDC certification from 2019 to 2023. Siemens Healthineers is the only testosterone immunoassay manufacturer to be currently certified and has achieved certification for four consecutive years.
Presentation: 6/1/2024
6816 The Estrogen Environment Characteristic of Endometriotic Lesion May Attenuate the Receptor γ-Mediated Antiproliferative Activity of Retinoids
Authors: Izawa M , Azuma Y , Taniguchi F 
Published: October 2024

Abstract
Disclosure: M. Izawa: None. Y. Azuma: None. F. Taniguchi: None.
Background: Endometriosis has been accepted as an estrogen-dependent disease, and the estrogen environment in endometriotic lesions has been proposed as a major background of the pathophysiology. Although the hormonal therapy targeting the reduction of estrogen has been employed to reduce endometriosis-associated symptoms, the limitation of therapy has been well recognized. How to overcome the limitation remains an urgent subject to be explored. [Objective:]We focused on retinoids, which have been known to induce an antiproliferative activity in tumors. Based on the retinoic acid receptor (RAR) expression profile in endometriotic lesions, we evaluated the antiproliferative activity of retinoids using endometriotic cells. Finally, we examined the effect of estrogen on antiproliferative activity. Methods: Endometriotic tissue and cells: Institutional Review Boards approved this project. The chocolate cyst lining in the ovaries of patients with endometriosis was the source of endometriotic tissue. Stromal cells collected from endometriotic tissues were used as endometriotic cells. RAR expression: RNAs were prepared from endometriotic tissues and cells, and single-stranded cDNAs were subjected to RT-PCR. Primers were designed using the UCSF genome browser. Protein expression was examined by Western blotting. Cell proliferation assay: Cells were treated with all-trans retinoic acid (ATRA), selective RAR modulators (sRARMs), BMS753, CD2314 and CD437, RARγ antagonist MM11253 and 17β-estradiol (E2). Viable cells were estimated using WST-8 assay. RNA-seq analysis: Cells were treated with retinoids and E2. RNA samples were used for polyA+ selected library and the strand-specific RNA-seq. Differentially expressed genes with p-values &lt; 0.05 and log2 fold changes &gt; 1 were extracted as responsive genes. Results: RAR expression: Transcripts of wild-type RARα, RARβ, and RARγ were demonstrated in arbitrary 10 regions of patient tissue, and in endometriotic cells. The expression of these RARs was almost at a comparable level. Effect of retinoids and/or estrogen on cell proliferation: Cell proliferation rate was significantly decreased in the presence of ATRA. Among sRARMs tested, only CD437 reduced the cell proliferation. The antiproliferative activity of ATRA was attenuated either in the presence of MM11253 or E2, respectively. ATRA- and/or E2-responsive gene expressions To explore gene expressions in response to retinoids and E2, RNA-seq analysis was performed. The results suggest the diversity of ATRA- and E2-responsive genes in endometriotic lesions.[Conclusion:]Endometriotic cell proliferation was significantly suppressed in response to retinoids through RARγ. The observation that the antiproliferative activity was attenuated in the presence of E2 suggests a suppressive environment against the activity of retinois in endometriotic legions.
Presentation: 6/2/2024
5178 TNFα-dependent altered miRNA expression regulates endometrial stromal cell proliferation
Authors: Chowdhury I , Banerjee S , Xu W , Driss A , Nezhat C , Sidell N , Taylor R N , Thompson W E 
Published: October 2024

Abstract
Disclosure: I. Chowdhury: None. S. Banerjee: None. W. Xu: None. A. Driss: None. C. Nezhat: None. N. Sidell: None. R.N. Taylor: None. W.E. Thompson: None.
Abstract: Aberrant upregulation of cytokines, including tumor necrosis factor α (TNFα) and activation of nuclear factor κB (NF-κB) with disbalance of microRNAs (miRNAs) are often found in endometrium of endometriosis subjects, which causes directly or indirectly pelvic inflammation, pain, and infertility, Although, the pathophysiology of endometriosis is not clearly established yet, inflammation is an essential feature. MicroRNAs are emerging as potential regulatory factors in cellular processes such as cell growth, survival, migration, and invasion. In the current study, we examined the direct effects of exogenous recombinant TNFα dependent regulation of miRNAs involved in proliferation in primary cultures of normal endometrial stromal cells (NESC) and compared with the untreated cells derived from endometriosis-ESC (EESC). NanoString nCounter-based assays and quantitative real-time polymerase chain reaction (RT-PCR) were used to identify and validate differentially expressed miRNAs linked to cell proliferation in EESC compared to NESC and TNFα treated NESCs. The expression level of miRNAs linked to cell cycle was downregulated significantly in EESCs compared to NESCs. Interestingly, a dose and time-dependent exogenous TNFα treatment in NESCs showed a similar cell cycle regulator miRNAs expression pattern with EESCs. In further studies, protein analysis by Western Blots of selective cell cycle regulators such as PCNA, Ki67, CDK2, CDK4, CDK6, p21, and p27, and cell proliferation assay demonstrated an inverse correlation between cell cycle regulators and miRNA expression pattern both in EESC and TNFα treated NESCs. These findings suggest that TNFα dependent dysregulation of miRNAs in EESCs may promote proliferation of endometriosis. Further research is needed to investigate the detailed mechanisms by which TNFα regulates miRNA expression and determine these findings' potential therapeutic implications. Acknowledgments: This study was supported in part by National Institutes of Health Grants 1SC3 GM113751, 1SC1 GM130544, U01 HD66439, 1R01HD057235, U54 CA118948, HD41749, S21MD000101, and G12-RR03034. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Grant #C06 RR18386 from NIH/NCRR.
Presentation: 6/2/2024
12545 Transgender Healthcare Online Curriculum: A Partnership Between An Academic Medical Center And Corrections Facility
Authors: Lamos Elizabeth , Malek Rana 
Published: October 2024

Abstract
Disclosure: E. Lamos: None. R. Malek: None.
Introduction: The World Professional Association for Transgender Health Standards of Care (WPATH SOC-8) states that all recommendations be applied equally to individuals living in institutions​, including those incarcerated. Studies suggest correctional staff have little training in transgender care.​ To demonstrate a partnership between an academic medical center and a corrections facility and increase knowledge and comfort in transgender healthcare, academic faculty developed an online curriculum as an educational opportunity for state corrections facility staff and clinicians. Methods: There were 6 modules: Overview of Transgender Competent Care, Health Vulnerabilities, Creating an Inclusive Environment, Feminizing and Masculinizing Hormone Treatment, and Preventative Care of the Transgender Individual (Image). The Short Course (first 3 modules) was for staff or clinicians not providing hormone-affirming care and the Full Course (all 6 modules) for clinicians who provide hormone-affirming care. Each module included embedded knowledge assessments and post-module action items. An anonymous pre and post curriculum survey assessed module effectiveness. The project was considered non-human subject research by the Institutional Review Board. Result analysis used the Fisher Exact Test and unpaired t test. Results: 44 corrections staff and clinicians participated (2022-2023) with a 32% post survey response rate. 57% indicated zero prior hours of transgender education with 59% feeling somewhat or extremely comfortable with transgender healthcare. Most were interested in learning about transgender healthcare (Table 1). Participants had a statistical improvement in knowledge and their access to resources were good or excellent after completion (p &lt;0.05, both) (Table 2). Also, for the Short Course, comfort in recognizing barriers to care significantly improved (p&lt;0.05), 100% agreed both with the importance of what they were asked to learn and that knowledge and skills increased. Domains of comfort with transgender healthcare did not statistically change for participants of the Full Course. Participants positively reflected on curriculum content and bias discussion. Full Course respondents requested more therapeutics information. Inclusive interactions were the most frequent practice improvement strategy. Conclusion: This curriculum increased knowledge and improved resources for those providing healthcare to incarcerated transgender patients. The curriculum was inclusive of many diverse types of learner and allowed learners to choose the course that aligned with their clinical role. It meets WPATH SOC-8 recommendations that corrections staff and clinicians receive training in transgender care.​ It highlights the collaboration between an academic medical center and corrections facility, meeting the academic mission to serve marginalized groups.
Presentation: 6/1/2024