Moving toward targeted eating disorder care for transgender, non-binary, and gender expansive patients in the United States.

OBJECTIVE: Literature suggests that transgender, non-binary, and/or gender expansive (TNG) people are more likely than cisgender peers to experience eating disorders (EDs) and engage in dangerous weight control behaviors. TNG individuals with EDs are dramatically higher risk for self-harm behaviors, suicidal ideation, and suicidal behaviors than cisgender peers with EDs or TNG peers without EDs, and often engage in ED symptoms/behaviors to alleviate gender dysphoria. Yet, no treatment paradigms have yet been adapted for TNG-specific ED care. This qualitative study aims to identify stakeholder needs from such care to inform future clinical interventions. METHODS: We elicited patient (n = 12) and mental health clinician (n = 9) stakeholder needs and preferences regarding TNG-specific ED care. Semi-structured interview guides informed by the Consolidated Framework for Implementation Research (CFIR) and a behavioral insights framework, EAST, were developed to ensure uniform inclusion and sequencing of topics and allow for valid comparison across interviews. Using a rapid analysis procedure, we produced a descriptive analysis for each group identifying challenges of and opportunities in providing ED care for TNG adults. RESULTS: Stakeholders expressed needs and preferences for TNG-specific treatment including that it be: (1) TNG-affirming, weight-inclusive, trauma-informed, and anti-racist; (2) delivered by an interdisciplinary team, including gender-affirming care clinicians; (3) focused on parsing gender dysphoria from other body image concerns, building distress tolerance, and working toward gender euphoria (rather than body acceptance). DISCUSSION: Future work is needed exploring ED care delivery models that integrate gender-affirming care services with mental health care. Such models may improve TNG access to ED treatment and recovery. PUBLIC SIGNIFICANCE: Transgender, non-binary, and/or gender expansive (TNG) experience disproportionately high rates of eating disorders and have unique barriers to accessing care. In individual interviews, TNG adults with eating disorders and mental health clinicians who provide psychotherapy for eating disorders voiced desire for greater availability of TNG-affirming, weight-inclusive eating disorder care, integrated with other gender-affirming care services. This informs future research developing eating disorder care for TNG individuals.

Women, opioid use and addiction.

In the midst of the current coronavirus pandemic, the United States continues to struggle with an ongoing opioid epidemic, initially fueled by widespread prescribing of opioid medications during the 1990s. The primary reason for prescribing opioids is to treat pain. Women have more acute and chronic pain and have been prescribed these drugs in significantly greater numbers than men. Comparison of women and men with chronic pain also shows that women receive the majority of prescription opioids, and the use of these prescribed medications became the major pathway to misuse and addiction for women. Yet, recognition of the extent of women's exposure to opioids and the attendant consequences has been limited. Attempts to stem the overall tide of the epidemic focused on reducing the availability of prescription opioids. However, as these medications became more difficult to obtain and treatment opportunities were limited, many turned to other synthetic opioids, such as heroin and fentanyl. Thus, the public health crisis of opioid addiction has endured. This paper highlights the importance of understanding differences among women and men in opioid use and its biological and psychosocial effects to advance the gender-based treatment approaches and effective public health policy.

Adipocyte alterations in endometriosis: reduced numbers of stem cells and microRNA induced alterations in adipocyte metabolic gene expression.

BACKGROUND: Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5-10% of reproductive-aged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. Previously, we identified microRNAs that are differentially expressed in endometriosis and altered in the serum of women with the disease. Here we explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number. METHODS: Primary adipocyte cells cultured from 20 patients with and without endometriosis were transfected with mimics and inhibitors of microRNAs 342-3p or Let 7b-5p to model the status of these microRNAs in endometriosis. RNA was extracted for gene expression analysis by qRT-PCR. PCNA expression was used as a marker of adipocyte proliferation. Endometriosis was induced experimentally in 9-week old female C57BL/6 mice and after 10 months fat tissue was harvested from both the subcutaneous (inguinal) and visceral (mesenteric) tissue. Adipose-derived mesenchymal stem cells in fat tissue were characterized in both endometriosis and non-endometriosis mice by FACS analysis. RESULTS: Gene expression analysis showed that endometriosis altered the expression of Cebpa, Cebpb, Ppar-γ, leptin, adiponectin, IL-6, and HSL, which are involved in driving brown adipocyte differentiation, appetite, insulin sensitivity and fat metabolism. Each gene was regulated by an alteration in microRNA expression known to occur in endometriosis. Analysis of the stem cell content of adipose tissue in a mouse model of endometriosis demonstrated a reduced number of adipocyte stem cells. CONCLUSIONS: We demonstrate that microRNAs Let-7b and miR-342-3p affected metabolic gene expression significantly in adipocytes of women with endometriosis. Similarly, there is a reduction in the adipose stem cell population in a mouse model of endometriosis. Taken together these data suggest that endometriosis alters BMI in part through an effect on adipocytes and fat metabolism.

A time to be born: Variation in the hour of birth in a rural population of Northern Argentina.

OBJECTIVES: The present study aimed at investigating the timing of birth across the day in a rural population of indigenous and nonindigenous women in the province of Formosa, Argentina in order to explore the variation in patterns in a non-Western setting. MATERIALS AND METHODS: This study utilized birth record data transcribed from delivery room records at a rural hospital in the province of Formosa, northern Argentina. The sample included data for Criollo, Wichí, and Toba/Qom women (n = 2421). Statistical analysis was conducted using directional statistics to identify a mean sample direction. Chi-square tests for homogeneity were also used to test for statistical significant differences between hours of the day. RESULTS: The mean sample direction was 81.04°, which equates to 5:24 AM when calculated as time on a 24-hr clock. Chi-squared analyses showed a statistically significant peak in births between 12:00 and 4:00 AM. Birth counts generally declined throughout the day until a statistically significant trough around 5:00 PM. DISCUSSION: This pattern may be associated with the circadian rhythms of hormone release, particularly melatonin, on a proximate level. At the ultimate level, giving birth in the early hours of the morning may have been selected to time births when the mother could benefit from the predator protection and support provided by her social group as well as increased mother-infant bonding from a more peaceful environment.

Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency.

Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice.

The gynecological disease endometriosis is characterized by the deposition and proliferation of endometrial cells outside the uterus and clinically is linked to low body mass index (BMI). Gene expression in the liver of these women has not been reported. We hypothesized that endometriosis may impact hepatic gene expression, promoting a low BMI. To determine the effect of endometriosis on liver gene expression, we induced endometriosis in female mice by suturing donor mouse endometrium into the peritoneal cavity and measuring the weight of these mice. Dual-energy X-ray absorptiometry (DEXA) scanning of these mice showed lower body weight and lower total body fat than controls. Microarray analysis identified 26 genes differentially regulated in the livers of mice with endometriosis. Six of 26 genes were involved in metabolism. Four of six genes were upregulated and were related to weight loss, whereas two genes were downregulated and linked to obesity. Expression levels of Cyp2r1, Fabp4, Mrc1, and Rock2 were increased, whereas Igfbp1 and Mmd2 expression levels were decreased. Lep and Pparg, key metabolic genes in the pathways of the six genes identified from the microarray, were also upregulated. This dysregulation was specific to metabolic pathways. Here we demonstrate that endometriosis causes reduced body weight and body fat and disrupts expression of liver genes. We suggest that altered metabolism mediated by the liver contributes to the clinically observed low BMI that is characteristic of women with endometriosis. These findings reveal the systemic and multiorgan nature of endometriosis.

The Transgender and Gender Diverse and Attention Deficit Hyperactivity Disorder Nexus: A Systematic Review.

Introduction: Prior work suggests an increased prevalence of Attention Deficit Hyperactivity Disorder (ADHD) among transgender and/or gender diverse (TGD) individuals. This systematic review summarizes primary literature on TGD/ADHD experience. Methods: Texts from databases, reference lists, and referral were screened per PRISMA guidelines, with author consensus. Results: Since 2014, 17 articles have been published on the TGD/ADHD nexus. Gender-affirming care specialists authored 65%. 71% reported prevalence, per medical records. Only case reports discussed implications. None avoided deficit-framing, nor included explicit TGD/ADHD authorship. Conclusions: The paucity of literature and lack of explicit TGD/ADHD community involvement are striking; each warrants increased attention.

A formative evaluation to inform integration of psychiatric care with other gender-affirming care.

BACKGROUND: Transgender, non-binary, and/or gender expansive (TNG) individuals experience disproportionately high rates of mental illness and unique barriers to accessing psychiatric care. Integrating TNG-specific psychiatric care with other physical health services may improve engagement, but little published literature describes patient and clinician perspectives on such models of care. Here we present a formative evaluation aiming to inform future projects integrating psychiatric care with physical health care for TNG individuals. METHODS: In this qualitative pre-implementation study, semi-structured interview guides were developed informed by the Consolidated Framework for Implementation Research to ensure uniform inclusion and sequencing of topics and allow for valid comparison across interviews. We elicited TNG patient (n = 11) and gender-affirming care clinician (n = 10) needs and preferences regarding integrating psychiatric care with other gender-affirming clinical services. We conducted a rapid analysis procedure, yielding a descriptive analysis for each participant group, identifying challenges of and opportunities in offering integrated gender-affirming psychiatric care. RESULTS: Participants unanimously preferred integrating psychiatry within primary care instead of siloed service models. All participants preferred that patients have access to direct psychiatry appointments (rather than psychiatrist consultation with care team only) and all gender-affirming care clinicians wanted increased access to psychiatric consultations. The need for flexible, tailored care was emphasized. Facilitators identified included taking insurance, telehealth, clinician TNG-competence, and protecting time for clinicians to collaborate and obtain consultation. CONCLUSIONS: This health equity pre-implementation project engaged TNG patients and gender-affirming care clinicians to inform future research exploring integration of mental health care with primary care for the TNG community and suggests utility of such a model of care.

Accuracy of automated analyzers for the estimation of CSF cell counts: A systematic review and meta-analysis.

This systematic review evaluates the evidence for accuracy of automated analyzers that estimate cerebrospinal fluid (CSF) white blood cell counts (WBC) compared to manual microscopy. Inclusion criteria of original research articles included human subjects, English language, and manual microscopy comparator. PUBMED, EMBASE and Cochrane Review databases were searched through 2019 and QUADAS-2 Tool was used for assessment of bias. Data were pooled and analyzed by comparison method, using random effects estimation. Among 652 titles, 554 abstracts screened, 104 full-text review, 111 comparisons from 41 studies were included. Pooled estimates of sensitivity and specificity (n = 7) were 95% (95%-CI 93%-97%) and 84% (95%-CI: 64%-96%), respectively. Pooled R2 estimates (n = 29) were 0.95 (95%-CI: 0.95-0.96); Pooled spearman rho correlation (n = 27) estimates were 0.95 (95% CI 0.95-0.96). Among those comparisons using Bland-Altman analysis (n = 11) pooled mean difference was estimated at 0.98 (95% CI-0.54-2.5). Among comparisons using Passing-Bablok regressions (n = 14) the pooled slope was estimated to be 1.05 (95% CI 1.03-1.07). Q tests of homogeneity were all significant with the exception of the Bland-Altman comparisons (I2 10%, p value 0.35). There is good overall accuracy for CSF WBC by automated hematologic analyzers. These findings are limited by the small sample sizes and inconsistent validation methodology in the reviewed studies.

"Coming Home to My Body": A Qualitative Exploration of Gender-Affirming Care-Seeking and Mental Health.

Among transgender, non-binary, and/or gender expansive (TNG) persons, interest in medical and/or surgical forms of gender affirmation is heterogenous, as is access to those forms of medically necessary health care. Yet, the literature characterizing TNG persons' interest in medical and/or surgical gender-affirming care, barriers to accessing that care, and how societal narratives and expectations impact TNG individuals' self-image and mental health, as well as their personal choices regarding gender-affirming care remains sparse. Here we present qualitative research exploring TNG participants' interest in gender-affirming care and how such interventions impact identity formation. We conducted loosely structured interviews with a convenience sample of 54 TNG persons in the U.S. and Canada from Facebook pages used to recruit TNG research participants. One-hour interviews were conducted by an openly TNG researcher; participants were compensated. The most frequently sought gender-affirming care was hormone therapy, followed by chest ("top") surgery, genital ("bottom") surgery, electrolysis, breast augmentation, hysterectomy, and voice training. Less commonly desired interventions included fertility preservation, facial feminization/masculinization, and vocal surgery. Participants described four main categories of access barriers: financial (e.g., cost of medical/surgical care, inadequate insurance), logistical (e.g., no local providers, gatekeeping policies around body size and mental health, pandemic-related delays), personal fears about sub-optimal outcomes (e.g., complications, loss of sensation, undesired aesthetic and/or functional results), and societal discrimination (e.g., familial rejection, job loss, safety concerns). Participants reported primarily seeking this healthcare for social legibility, alleviating dysphoria/pursuing euphoria, and/or gender exploration. All who sought gender-affirming care reported improved mental health-including depression, anxiety, dissociation, and eating disorders-and social relationships, though many struggled to find TNG-competent mental health providers. This work provides key insights into how gender-affirming care can contribute to improving mental health for TNG communities, which will assist health providers in optimally treating TNG patients.

Psychopharmacological Considerations for Gender-Affirming Hormone Therapy.

ABSTRACT: The field of transgender health has grown exponentially since the early 2010s. While this increased visibility has not been without controversy, there is growing acknowledgement of the needs of transgender, nonbinary, and gender expansive (TNG) patients and the health disparities they experience compared to the cisgender population. There is also increased interest among clinicians and trainees in providing gender-affirming care in all medical specialties. This is particularly relevant in psychiatry as mental health disparities in TNG patients have been well-documented. TNG patients experience significant minority stress and higher rates of psychiatric illness, self-harm, suicidality, and psychiatric hospitalization compared to their cisgender peers. In this review, we will cover potential interactions and side effects relevant to psychiatric medication management for the three most common medication classes prescribed as part of gender-affirming hormone therapy (GAHT): gonadotropin-releasing hormone receptor agonists, estradiol, and testosterone. Although no studies directly examining the efficacy of psychiatric medications or their interactions with GAHT for TNG patients have been published yet, we have synthesized the existing literature from both cisgender and TNG patients to shed light on health care disparities seen in TNG patients. Since clinicians' lack of comfort and familiarity with gender-affirming care contributes significantly to these disparities, we hope this narrative review will help psychiatric prescribers provide TNG patients with the same quality of care that cisgender patients receive.

Perspective on equitable translational studies and clinical support for an unbiased inclusion of the LGBTQIA2S+community.

Research regarding the mental health of the Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, 2 Spirit (LGBTQIA2S+) community has been historically biased by individual and structural homophobia, biphobia, and transphobia, resulting in research that does not represent the best quality science. Furthermore, much of this research does not serve the best interests or priorities of LGBTQIA2S + communities, despite significant mental health disparities and great need for quality mental health research and treatments in these populations. Here, we will highlight how bias has resulted in missed opportunities for advancing understanding of mental health within LGBTQIA2S + communities. We cite up-to-date research on mental health disparities facing the LGBTQIA2S + community and targeted treatment strategies, as well as guidance from health care professionals. Importantly, research is discussed from both preclinical and clinical perspectives, providing common language and research priorities from a translational perspective. Given the rising tide of anti-transgender sentiment among certain political factions, we further emphasize and discuss the impact of historical and present day ciscentrism and structural transphobia in transgender mental health research, from both clinical and translational perspectives, with suggestions for future directions to improve the quality of this field. Finally, we address current best practices for treatment of mental health issues in this community. This approach provides an opportunity to dispel myths regarding the LGBTQIA2S + community as well as inform the scientific community of best practices to work with this community in an equitable manner. Thus, our approach ties preclinical and clinical research within the LGBTQIA2S + community.

Using Animal Models for Gender-Affirming Hormone Therapy.

We have recently proposed experimental design guidelines and areas of study for preclinical rodent models of gender-affirming hormone therapy in neuroscience. These guidelines also apply to any field subject to the influences of gonadal steroid hormones, including metabolism and growth, cancer, and physiology. This perspective briefly describes our suggestions for these fields. Studying the effects of exogenous steroid hormones will have translational benefits for the community. We also discuss the need for equitable practices for cisgender scientists who wish to implement these guidelines and engage with the community. It is necessary that community-informed practices are implemented in preclinical research to maximize the benefit to transgender, nonbinary, and/or gender diverse (TNG) healthcare, which is currently in jeopardy in the United States, Europe, and across the globe.

Centering the Needs of Transgender, Nonbinary, and Gender-Diverse Populations in Neuroendocrine Models of Gender-Affirming Hormone Therapy.

Most studies attempting to address the health care needs of the millions of transgender, nonbinary, and/or gender-diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations. Research into the effects of exogenous hormones such as estradiol, testosterone, and progesterone has a direct translational benefit for TNG individuals on gender-affirming hormone therapies (GAHTs). Despite this potential, endocrinological health care for TNG individuals remains largely unimproved. Here, we outline important areas of translational research that could address the unique health care needs of TNG individuals on GAHT. We highlight key biomedical questions regarding GAHT that can be investigated using animal models. We discuss how contemporary research fails to address the needs of GAHT users and identify equitable practices for cisgender scientists engaging with this work. We conclude that if necessary and important steps are taken to address these issues, translational research on GAHTs will greatly benefit the health care outcomes of TNG people.

Evaluating Medical Students' Views of the Complexity of Sexual Minority Patients and Implications for Care.

Purpose: Sexual and gender minority (SGM) people experience many health care disparities. We aimed to determine if medical students viewed sexual minority patients (lesbian, gay, or bisexual [LGB] men/women) as more complex than heterosexual patients, even when presenting with the same symptoms, and whether this perceived complexity affected confidence caring for LGB patients. Methods: A fictional patient with an upper respiratory infection was presented with systematic variation of the patient's sexual orientation across six experimental conditions in an online, vignette-based experimental study. Participants rated their perception of the medical, therapeutic, and social complexity of the patient, and completed a measure of stigma toward SGM people. Finally, participants indicated their confidence caring for the presented patient. Results: Overall, 665 students participated. Participants viewed the LGB patients as more complex across all domains, relative to heterosexual patients. Perceived medical and social complexity predicted lower confidence caring for the patient. Participants reported lower confidence caring for gay male patients with indirect effects of medical and social complexity. LGB identity was broadly and indirectly associated with lower confidence through social complexity. Conclusion: Our results suggest students view LGB patients as more complex compared with heterosexual patients. Medical education programs must provide training about the effects of social biases on clinical judgments and care for LGB patients, as well as build skills to ensure confidence caring for LGB patients.

Transgender data collection in the electronic health record: Current concepts and issues.

There are over 1 million transgender people living in the United States, and 33% report negative experiences with a healthcare provider, many of which are connected to data representation in electronic health records (EHRs). We present recommendations and common pitfalls involving sex- and gender-related data collection in EHRs. Our recommendations leverage the needs of patients, medical providers, and researchers to optimize both individual patient experiences and the efficacy and reproducibility of EHR population-based studies. We also briefly discuss adequate additions to the EHR considering name and pronoun usage. We add the disclaimer that these questions are more complex than commonly assumed. We conclude that collaborations between local transgender and gender-diverse persons and medical providers as well as open inclusion of transgender and gender-diverse individuals on terminology and standards boards is crucial to shifting the paradigm in transgender and gender-diverse health.

Prevalence and minority-stress correlates of past 12-month prescription drug misuse in a national sample of transgender and gender nonbinary adults: Results from the U.S. Transgender Survey.

BACKGROUND: Prescription drug (PD) misuse, particularly opioid misuse, is a major US public health concern. While transgender and gender nonbinary (TGNB) individuals experience numerous health disparities, including substance use disparities, little research has focused on PD misuse in this population. METHODS: Data for this secondary analysis come from the US Transgender Survey (N = 26,689). First, we examined bivariate differences in past 12-month PD misuse among binary transgender women, binary transgender men, nonbinary individuals assigned-female-at-birth (AFAB), and nonbinary individuals assigned-male-at-birth (AMAB). We then used multivariable logistic regression (separately based on sex-assigned-at-birth) to examine the relationship between gender-identity related discrimination and PD misuse. RESULTS: PD misuse was significantly more common among binary transgender men (17.3 %), nonbinary AFAB individuals (18.7 %), and nonbinary AMAB individuals (18.0 %); compared to binary transgender women (13.5 %). In multivariable analyses, nonbinary identity was associated with higher odds of PD misuse among TGNB AFAB individuals (OR = 1.121; 95 %CI 1.021-1.232) and AMAB individuals (OR = 1.315; 95 % CI 1.133-1.527). Controlling for overall health status and psychological distress, public accommodations discrimination was associated with PD misuse among TGNB AMAB individuals (OR = 1.578, 95 %CI 1.354-1.839). Among both groups, healthcare discrimination was associated with PD misuse (AFAB OR = 1.388, 95 %CI 1.255-1.534; AMAB OR = 1.227, 95 %CI 1.073-1.404). CONCLUSION: In this national sample of TGNB individuals, nonbinary individuals were at greater risk for PD misuse than binary individuals, possibly due to less societal affirmation. Similar to other TGNB health disparities, discrimination based on gender identity/expression was associated with PD misuse. This highlights the importance of interventions to reduce discrimination against TGNB individuals.