bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Androgen Insensitivity and Decreased Bone Mineral Density
Authors: Bauer Elizabeth M , Hoang Thanh Duc 
Published: May 2021

Abstract
Background: Complete androgen insensitivity syndrome (CAIS) is a rare disorder of sex development and primary amenorrhea results in an XY karyotype but female phenotype. Patients with this syndrome have lower bone mineral density (BMD) when compared to age matched controls.
Clinical Case: A 44-year-old phenotypic woman with a history of complete androgen insensitivity syndrome presented for follow-up. She was previously on hormone replacement therapy (HRT) at various doses from the age of 12 until her early 30s when her therapy became sporadic. At age 40, she was prescribed transdermal estrogen therapy but discontinued soon after a dermatologic reaction and had not been on any form of hormone replacement since that time. Past medical history was significant for karyotype 46 XY, osteochondritis dissecans of right ankle and bilateral orchiectomy at age 4. She was single with one adopted child. Physical examination showed a height 75 inches, weight 244 lbs and a normal heart, lung, and abdominal examinations. Laboratory results showed estradiol 12.3pg/mL(7.63-42.6), total testosterone 12.0 ng/dL(7-40), FSH 109.6 mIU/mL(25.8-134.8), LH 42.49 mIU/mL(7.7-58.5), anti-mullerian hormone &lt; 0.015 ng/mL (0.26-5.81), inhibin B &lt;7.0 pg/mL(&lt;17), androstenedione 48 ng/dL(41-262), dihydrotestosterone 2.7 ng/dL(4-22) and dehydroepiandrosterone sulfate 209 ng/dL(31-701). A baseline DXA showed low bone density for age with T-score (Z-score) of -2.0 (-1.6) lumbar-spine; -1.6 (-1.2) femoral neck, -1.1 (-0.8) total hip and -2.5 (-2.0) forearm.
Discussion:CAIS is caused by a mutation in the androgen receptor (AR) located on the X-chromosome causing complete unresponsiveness to androgen hormone. Karyotype is XY but feminization occurs due to aromatization of androgen to estrogen. Gonadectomy for testicular malignancy prevention is controversial as testicular tumors in CAIS is generally low and gonadal resection subjects individuals to lifelong hormone replacement. These patients also have lower BMD when compared to female or male age matched controls. This is even more apparent in those with removed gonads. Low BMD is exacerbated by poor compliance, inadequate dose or inappropriate HRT. Whether or not fracture risk is higher has yet to be elucidated. Currently, there is no guideline on how to manage low BMD including osteoporosis in this patient population. It is important to counsel patients with CAIS on BMD loss and to ensure optimization of factors that affect bone health including compliance with HRT, vitamin D/calcium intake and exercise.
The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or the United States Government.
“It Wasn’t for the Sake of Me and My Mental Health”: Transgender People’s Perspective on the Role of Mental Health Providers in Initiating Gender-Affirming Hormones - a Qualitative Study
Authors: Maksutova Mariam , Wu Justine P , Indig Gnendy , Moravek Molly Bennette , Popoff Elliot , Trammell Racquelle , Ballard Jesse , Stroumsa Daphna 
Published: May 2021

Abstract
Introduction: Hormone therapy can be an essential part of medical transition for some transgender people. Despite ongoing debate on the role of mental health providers in the initiation of gender-affirming hormones, little evidence exists to guide the discussion. We seek to elucidate the patient perspective on the feasibility, utility, risks, and benefits of mandatory mental health evaluation (MHE) prior to hormone initiation.
Methods: We conducted semi-structured interviews with individuals who have initiated gender-affirming hormone therapy (n=21). We purposively sampled respondents to include those who indicated that they were required to have mental health evaluation prior to hormone initiation, and those who did not. A transgender advisory board helped develop the semi-structured interview guide. Interviews were transcribed verbatim and coded using emergent and a priori codes.
Results: The majority of respondents saw the requirement for MHE prior to hormone initiation as distinct from, and often discordant with, their mental health care. We identified the following roles of mental health care as seen by patients: 1) General psychosocial support; 2) Identity formation: therapy as a safe space to explore gender and self; and 3) Logistics: assistance navigating the healthcare system. Themes that emerged regarding the MHE requirement included 1) Access: for some, the MHE requirement delayed access to gender-affirming care; 2) “pathologizing my existence”: the effects of having one’s identity result in a diagnosis of mental disorder; and 3) “auditioning” for care: fear of being denied care if one does not present with a stereotypical transgender narrative. Many participants drew direct connections between the MHE requirement and negative effects on their mental health and the patient/provider relationship, while concurrently identifying mental health care as essential for wellbeing.
Conclusion: While mental health care is appreciated, many transgender people see the universal MHE requirements as having significant negative implications on access, safety, and on even on their mental health. Guidelines should explicitly account for and mitigate the structural barriers preventing transgender individuals from accessing medical and mental health care.
A Cross Sectional Analysis of the Prevalence of Co-Morbidities in Older Transgender Individuals Receiving Hormone Affirming Therapy in Comparison With the General Population
Authors: Breda Ido , Yaish Iris , Sofer Yael , Tordjman Karen Michele , Greenman Yona 
Published: May 2021

Abstract
Background: Transgender individuals feel an incongruity between the assigned gender at birth and their gender identity. Because the prevalence of cardiovascular risk factors and morbidity associated with cross-sex hormonal therapy is not well established, particularly in the older transgender population, we set out to compare it to that of the general population. Methods: Data were collected from medical records of transgender patients treated in the Endocrine Institute at the Tel Aviv-Sourasky Medical Center until October 2018. Data from the Israel National Health Survey INHIS-3 2013-2015 were used as reference. Results: 104 (75 transgender women and 29 transgender men) patients over 35 y were identified. The median follow up time was 3 y (1-6.1). Transgender women had a high standardized prevalence rate (SPR) of overweight, smoking and engaging in physical exercise, but not of dyslipidemia compared with cisgender men and women. The SPR for overweight was high in transgender males compared with cisgender men and women. The SPR for smoking and dyslipidemia was high in transgender men compared with cisgender women but not men. Depression and anxiety were markedly increased in transgender women compared with cisgender men [SPR 5.5 (95% CI 3.3-8.5), p&lt;0.001] and women [SPR 2.8 (95% CI 1.7-4.3), p&lt;0.001] in the control population. The SPR of hypertension, diabetes and cerebrovascular disease was not elevated among transgender patients. Conclusions: The prevalence of cardiovascular risk factors but not cardiovascular morbidity was higher in the transgender patients compared with the general population. Further studies including a larger population and a longer follow up time are needed to better assess the impact of a high prevalence of risk factors on cardiovascular morbidity on the long run.
Achieving Physiologic 17-ẞ-Estradiol Levels in Transgender Females on Estradiol Transdermal Patches and Optimal Dosing
Authors: Trovato Alexa , Leinung Matthew C , Joseph Jalaja , Nguyen Son 
Published: May 2021

Abstract
Purpose: Gender dysphoria is defined as a significant incongruence between an individual’s experienced gender and the gender assigned at birth, leading to persistent distress. Hormone therapy and gender affirmation surgery improve gender dysphoria by mitigating or completely removing undesirable primary/secondary sexual characteristics which would better align with one’s physical and psychological features. Maintaining cross-sex hormone levels in the physiologic range for the preferred gender is the basis of transgender hormonal therapy. For trans females (MTF), estradiol is most commonly administered orally, and studies have shown this route is often successful in achieving therapeutic hormone levels. However, there is wide individual variability in the dose response to oral estradiol, and approximately 25% of patients will not reach therapeutic goal on maximum oral estradiol. Furthermore, high dose oral estrogen has been associated with increased thrombotic risk, especially in older individuals. The efficacy or optimal dose of adding or switching to the transdermal route is not known. We investigated the efficacy of estradiol transdermal patches and the optimal dose to reach therapeutic goal. Methods: A chart review was conducted of all MTF patients who were treated with estradiol transdermal patches in our transgender clinic from 2006 through 2020. We looked at the success of achieving physiologic serum 17-β-estradiol levels (with and without antiandrogens spironolactone and finasteride) on various doses of estradiol transdermal patches. Target serum level for estradiol &gt;100 pg/mL is recommended (but may be lower in certain clinical circumstances). Results: 371 MTF patients were identified, 41 received an estradiol transdermal patch. Of these 41 patients, 16 of them were placed on a transdermal patch due to failure to achieve target 17-β-estradiol levels on maximal oral therapy. We found that 9 of these 16 patients achieved goal estrogen levels, as well as one patient very near goal. Of the 7 who did not reach goal, only 2 were on patch doses &gt;60 mcg/day. The majority who reached goal serum estradiol levels were taking a dose of 100 mcg/daily. When considering all MTF patients on the highest dose (100 mcg) of transdermal estrogen, 11 of 18 attained goal level, as well as one just under goal. Of the 41 MTF patients taking a transdermal patch, only 6 of them had serum estrogen levels lowered from being at goal on oral therapy. Thirteen patients had their estrogen levels improve to reach goal when placed on patch (4 as add-on therapy). Conclusions: Our study supports the findings that using an estradiol transdermal patch can help MTF patients achieve goal 17-β-estradiol levels. This delivery method can be useful for patients unable to reach goal on oral agents and for patients at higher thrombotic risk. The highest dose patch available is often needed to achieve therapeutic goal.
International Clinical Practice Guidelines for Gender Minority/Trans People: Systematic Review & Quality Assessment. How Does the Endocrine Society Fare?
Authors: Bewley Susan , Dahlen Sara , Connolly Dean , Arif Isra , Junejo Muhammad , Catherine Meads 
Published: May 2021

Abstract
Aim: High quality care depends on evidence being used in clinical practice guidelines (CPGs) & processes to create recommendations. This study identified & critically appraised published international CPGs regarding health care of gender minority/ trans people. Methods: Prospectively registered systematic review(1); searched 6 databases & 6 CPG websites & approached international key opinion leaders; quality assessment using AGREE II, Appraisal of Guidelines for Research & Evaluation tool(2); & stakeholder domain prioritization. CPGs relating to gender minority/ trans adults &/or children were included, with any health-related intervention connected to their care & no exclusions for comorbidities except differences in sex development. Outcome measures: number & quality of relevant international CPGs, information on estimated changes in mortality or quality of life (QoL), recommendation consistency across CPGs & appraisal of key messages for patients. Results: A 2017 Endocrine Society Guideline(3) was one of 12 international CPGs found. Five higher-quality CPGs focused on HIV & other blood-borne infections (overall assessment scores 69-94%). Six lower-quality CPGs concerned transition-specific interventions (overall assessment scores 11-56%). None dealt with primary care, mental health, or longer-term medical issues. Sparse information on estimated changes in mortality & QoL was conflicting. None provided key messages for patients. Endocrine Society was ranked 6th by overall assessment score (56%), the highest of CPGs addressing transition-related care. Domain scores were; scope & purpose 65%, stakeholder involvement 40%, rigour of development 41%, clarity & presentation 73%, applicability 29%, editorial independence 65%. Conclusion: Future iterations of the Endocrine Society CPG might be strengthened by referencing AGREE II, greater use of systematic reviews, considering applicability, independent external review, encouraging stakeholder participation & producing patient facing material. Lack of primary research into gender minority/trans health was noted & ought to be addressed.
References: 1. PROSPERO CRD42019154361, 2. AGREE Next Steps Consortium (2017) The AGREE II Instrument [Electronic version]. http://www.agreetrust.org, 3. Hembree WC, Cohen-Kettenis PT, Gooren L, et al (2017) Endocrine treatment of gender-dysphoric/ gender-incongruent persons: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 102:3869-3903
Magnetic Resonance Spectroscopy in Gender Dysphoria
Authors: Collet Sarah Marie , Bhaduri Sourav , Kiyar Meltem , Mueller Sven , T’sjoen Guy G 
Published: May 2021

Abstract
Background: Much research has been conducted on sexual dimorphisms of the human brain to determine whether and to what extent a brain gender exists. Consequently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain phenotype in people with gender dysphoria (GD). However, to date, brain sexual dimorphisms at the metabolite level in transgender people have not been explored using magnetic resonance spectroscopy (1H-MRS). Methods: In this study, 29 transgender men, 30 cisgender men and 35 cisgender women underwent 1H-MRS at 3 Tesla MRI to characterize common brain metabolites. Specifically, absolute levels of N –acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate (Glu), myo-inositol (mI) and their respective ratios were assessed in two brain regions, i.e. the amygdala-anterior hippocampus and the lateral parietal cortex. Influences of nicotine consumption, physical activity, education and psychopathology were considered. Results: The results indicated a sex-assigned at birth pattern for choline and glutamate ratios in the amygdala-anterior hippocampus of trans men. In the lateral parietal cortex cis men and cis women differed in the majority of metabolites (i.e. mI; Cr; NAA/Cr; Cho/Cr; mI/Cr; NAA/mI). Moreover, except for mI, trans men did not differ from either cisgender group, showing a pattern subtly moving towards the experienced gender identity. Post-hoc, careful exploration of the age of onset of GD in transgender men demonstrated the possibility of a developmental trend in absolute NAA levels, as a measure of neuronal function. Conclusion: We found sex-typical 1H-MRS spectra and they appear to be brain region specific. While the brain metabolite levels in trans men mostly resembled that of cis women, interesting findings such as modulation by age of onset warrant future enquiry to address potential neurobiological underpinnings of GD.
Understanding, Communication and Concerns Around Sexual Development Differences by Patients’ Perspectives
Authors: Lousada Lia Mesquita , Domenice Sorahia , Costa Elaine Maria Frade , Bachega Tania A , Batista Rafael Loch , Fontenele Eveline Gadelha Pereira , Mendonca Berenice Bilharinho 
Published: May 2021

Abstract
Introduction: The approach to Differences of Sexual Development (DSD) patients is complex. It involves discussion on karyotype, gonads, genital phenotypes, hormonal treatment, genitoplasty, sexual activity and fertility. A satisfactory understanding by the patients optimize the follow up and the acceptance of the condition. Objective/Methods: To analyze the understanding of DSD patients about their condition, the doubts and concerns, the barriers to communication and repercussion in gender, sexual orientation and relationships in a cohort of patients followed at a reference center, through a semi directed interview. Results: 57 patients were interviewed. The mean ages were 36.5y. Around 90% of all patients concluded at least the high school. Only 50% of all patients knew the condition’s name and how they were affected by it. Still 92% knew the treatment. 63% of the patients presented doubts, mainly related to diagnosis. The median level of satisfaction about the condition understanding (on a scale from 1 to 5) was 4. Most of the patients were first informed by doctors (65%) or mothers (27%). The mean age of diagnostic disclosure was 13 y among patients with atypical genitalia. However, 67% of them preferred be first informed in childhood. Around communication, 60% of them reported no dialogue at home about the condition, 82% feel uncomfortable in talking to other people and 57% experienced negative comments related to DSD. Only four 46,XY DSD presented gender dysphoria: 3 with partial gonadal dysgenesis (who were admitted at the reference service after genitoplasty) and one 5-α-reductase 2 deficiency. About affective relationships, 42% of the patients were single and 70% had already experienced sexual activity. The mean age at first sexual activity was 22y. 72% considered that condition influences negatively on relationships because the stigma, the genitalia appearance, the insecurity in sexual intercourse and fertility. The concern related to stigma was higher among patients with atypical genitalia. The patients’ self-evaluation (scale from 0 to 10) about their condition understanding improved after the interview: 6 to 8.9 (p&lt;0.01). Conclusion: There is lack of knowledge about DSD among patients even treated in a referral center. The atypical genitalia arouses curiosity and stigma. Educational acts for patients, health team and community are needed to make DSD conditions popular, to improve the understanding and communication and to decrease the stigma.
AR Is Not an Independent Marker for TNBC: The Lesson We Learn From Two PDX Models
Authors: Wang Xiaoqiang , Petrossian Karineh , Huang Miao-Juei , Saeki Kohei , Kanaya Noriko , Chang Gregory , George Somlo , Chen Shiuan 
Published: May 2021

Abstract
Extensive efforts, through cell line-based models, have been made to characterize the androgen receptor (AR) signaling pathway in triple-negative breast cancer (TNBC). However, these efforts have not yet reached a consensus with regards to the mechanism of AR in TNBC. On the other hand, patient-derived xenografts (PDXs) are generally considered more appropriate than cell line-based models for recapitulating the structural and molecular features of a patient’s tumor, but only a few have been reported to be AR-positive TNBC. In our study, we identified and molecularly characterized two new, AR-positive TNBC PDX models and assessed the impacts of AR agonist (DHT) and antagonist (enzalutamide) on tumor growth and gene expression profiles by utilizing immunohistochemistry (IHC), western blots, and RNA-Seq and TNBC subtyping analyses. Two PDX models, termed TN1 and TN2, were derived from two grade 3 TNBC tumors, each containing 1~5% of AR positive tumor cells. DHT activated AR in both PDX tumors by increasing AR nuclear localization and protein levels. However, the endpoint tumor volume of DHT-treated TN1 was 3-folds smaller than that of non-treated TN1 tumors. Conversely, the endpoint tumor volume of DHT-treated TN2 was 2-folds larger than that of non-treated TN2. Moreover, enzalutamide failed to antagonize DHT-induced tumor growth in TN2. The RNA-Seq analyses revealed that DHT suppressed gene expression in TN1 (961 down-regulated genes versus 149 up-regulated genes), while the DHT promoted gene expression in TN2 (673 up-regulated genes versus192 down-regulated genes). TNBC subtyping analyses based on RNA-Seq data predicted distinct molecular subtypes of TN1 and TN2: TN1 correlated to a basal-like 1 (BL1) subtype, and TN2 correlated to a basal-like 2 (BL2) subtype. These analyses suggest that TN1 and TN2, which both express functional AR, are two molecularly distinct PDX models that expand our current knowledge of AR-positive TNBC. Our results do not support that AR is a suitable therapeutic target in TNBC. To our best knowledge, the molecular mechanisms of AR in TNBC are equivocal and should be evaluated using clinically relevant models, considering both the heterogeneous expression of AR in TNBC and the general complexities of AR signaling.
Investigating the Role of Farnesoid X Receptor in Heme Biosynthesis and Ductular Reaction
Authors: Dean Angela E , Jungwirth Emilian , Panzitt Katrin , Wagner Martin , Anakk Sayeepriyadarshini 
Published: May 2021

Abstract
Bile acids (BAs) have gained traction not just as emulsifiers of fat, but also as hormones. Nuclear receptor Farnesoid X receptor (FXR) is the master regulator of BAs and can also control glucose and lipid metabolism. We examined if FXR contributed towards heme biosynthesis and induction of a ductular reaction. Male and female whole body Fxr knockout (FxrKO) mice, as well as liver- and intestine-specific knockouts (LFxrKO and IFxrKO, respectively) were treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC, a ferrochelatase inhibitor) for two weeks. At the end of the two weeks, mice were fasted for four hours and euthanized. All groups of mice had lost a similar percentage of body weight when fed the DDC diet. However, female FxrKO mice had significantly increased liver to body weight ratio, while male FxrKO mice had significantly decreased liver to body weight ratio when fed the DDC diet compared with their wild type counterparts. Serum liver injury markers were analyzed and liver histology and changes in genes involved in the heme biosynthesis pathway were examined. Both male and female whole body FxrKO livers had decreased ductular reaction with minimal bile plugs (porphyrin accumulation) compared with their wild type counterparts. LFxrKO mice mimicked diminished ductular reaction, while IFxrKO mice exhibited severe ductular reaction similar to that of wild type mice, indicating that the ductular reaction is dependent on hepatic FXR. ChIP-Seq for FXR revealed binding peaks in the heme biosynthesis genes, Alas1, Alad, Uros, and Fech, suggesting that FXR may act as a transcription factor for these genes. Further investigation revealed that Pbgd gene expression was increased, while Fech gene expression was decreased in female FxrKO mice compared to wild type mice. In male mice, Pbgd, Uros, Urod, and Cpox gene expression was increased in the absence of Fxr. In conclusion, Fxr is necessary to mount a ductular reaction and plays a key role in heme biosynthesis in the liver.