Combating Scientific Disinformation on Gender-Affirming Care.

Scientific disinformation is false and misleading information that is used intentionally by legal and political actors to sway public opinion and oppose facts. In recent years, disinformation has become a tool for authorities to limit gender-affirming health care (GAC) for transgender and gender-expansive youth who experience gender dysphoria. Existing modes of expert intervention in health policy may not be sufficient to match the pace of these quickly unfolding health care bans. A cross-disciplinary team of academics in medicine, psychology, and law assembled to challenge scientific disinformation on GAC with 2 rapid-response rebuttal reports. Reports were produced in 3 to 10 weeks after the passage of GAC bans in Texas, Alabama, and Florida in 2022. They were posted online to facilitate dissemination and engage litigators, judges, policy experts, advocates, parents, and others. The team's efforts complemented public statements by medical societies and lawsuits brought by national LGBTQ litigators. The team's reports were cited in legal challenges to GAC bans in Texas, Alabama, and Florida. The team also filed amicus briefs for direct consideration by the courts and public comments to health care agencies in Florida. The reports received coverage in local and national media outlets in broadcast and print media. This advocacy case study describes the process used to challenge disinformation about GAC with rapid-response rebuttal reports, as well as the impact of this work and associated challenges. In an increasingly polarized political climate, this process may be adapted to other areas of health policy in which scientific disinformation takes root.

Sporadic pituitary adenoma with somatic double-hit loss of MEN1.

PURPOSE: Pituitary adenomas commonly arise in patients with MEN1 syndrome, an autosomal dominant condition predisposing to neuroendocrine tumor formation, and typically diagnosed in patients with a relevant family cancer history. In these patients with existing germline loss of MEN1 on one allele, somatic loss of the second MEN1 allele leads to complete loss of the MEN1 protein, menin, and subsequent tumor formation. METHODS: Whole exome sequencing was performed on the tumor and matching blood under an institutional board approved protocol. DNA extraction and analysis was conducted according to previously described methods. RESULTS: We describe a 23 year-old patient with no significant past medical history or relevant family history who underwent surgical resection of a symptomatic and medically resistant prolactinoma. Whole exome sequencing of tumor and blood samples revealed somatic loss of MEN1 at both alleles, suggesting a double hit mechanism, with no underlying germline MEN1 mutation. CONCLUSION: To our knowledge, this is the first case of pituitary adenoma to arise from somatic loss of MEN1 and in the absence of an underlying germline MEN1 mutation.

Primary Ovarian Insufficiency in the Prepubertal Adolescent: A Case Report.

Although there are many etiologies for delayed puberty in adolescent-aged girls, the pediatric provider should consider primary ovarian insufficiency if estradiol remains undetectable despite elevated levels of gonadotropins. Adolescent girls with this diagnosis will need holistic care from their primary care provider, focusing on both their medical and psychosocial needs. The following case study describes a 14-year-old girl who was referred to pediatric endocrinology for delayed puberty, in the setting of increased gonadotropins and undetectable estradiol. The differential diagnosis, evaluation, and management of primary ovarian insufficiency are reviewed as well as potential long-term health considerations.

Trends in the "Off-Label" Use of GnRH Agonists Among Pediatric Patients in the United States.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) agonists are FDA approved for the treatment of precocious puberty. The therapy consists of histrelin acetate (Supprelin), a surgically implanted device, or Lupron injections. In recent years, the use of these agents has been extended to include the off-label treatment of children with normally timed puberty. Trends in the off-label use of GnRH agonists in children across the U.S. have not been previously described in the literature. METHODS: We analyzed data on the use of Supprelin and Lupron reported to the Pediatric Health Information System (PHIS) from 2013 to 2016 to determine the trends in both the FDA-approved and off-label uses of these medications. RESULTS: We identified a stable cohort of 39 children's hospitals administering GnRH agonist therapies from 2013 to 2016. During this period, the annual number of children treated with these medications for precocious puberty increased modestly, from 283 to 303; meanwhile, the fraction of children receiving therapy for an off-label indication more than doubled, from 12% (39 of 322 total patients) to 29% (125 of 428 total patients). Privately insured patients were more likely to be treated for an off-label indication (13%; 119 out of 883 patients) than Medicaid patients (8%; 58 out of 706 patients; χ2[1] = 10.97, P = .00093). CONCLUSION: From 2013 to 2016, the proportion of children treated with GnRH agonists for an off-label indication notably increased. The number of children treated for precocious puberty modestly increased. Private insurance coverage was associated with higher rates of off-label use.

Trends in the use of puberty blockers among transgender children in the United States.

BACKGROUND: The objective of the study was to identify national trends in the utilization of histrelin acetate implants among transgender children in the United States. METHODS: We analyzed demographic, diagnostic and treatment data from 2004 to 2016 on the use of histrelin acetate reported to the Pediatric Health Information System (PHIS) to determine the temporal trends in its use for transgender-related billing diagnoses, e.g. "gender identity disorder". Demographic and payer status data on this patient population were also collected. RESULTS: Between 2004 and 2016, the annual number of implants placed for a transgender-related diagnosis increased from 0 to 63. The average age for placement was 14 years. Compared to natal females, natal males were more likely to receive implants (57 vs. 46) and more likely to have implants placed at an older age (62% of natal males vs. 50% of natal females were ≥;13 years; p<0.04). The majority of children were White non-Hispanic (White: 60, minority: 21). When compared to the distribution of patients treated for precocious puberty (White: 1428, minority: 1421), White non-Hispanic patients were more likely to be treated with a histrelin acetate implant for a transgender-related diagnosis than minority patients (p<0.001). This disparity was present even among minority patients with commercial insurance (p<0.001). CONCLUSIONS: Utilization of histrelin acetate implants among transgender children has increased dramatically. Compared to natal females, natal males are more likely to receive implants and also more likely to receive implants at an older age. Treated transgender patients are more likely to be White when compared to the larger cohort of patients being treated with histrelin acetate for central precocious puberty (CPP), thus identifying a potential racial disparity in access to medically appropriate transgender care.

Knowledge and attitudes toward transgender health.

BACKGROUND: Hormonal interventions for transgender adolescents have become increasingly common; however, there is a paucity of research on medical student knowledge of, and attitudes toward, these interventions following didactic instruction. Furthermore, no studies have examined whether students can be aware of the literature on the mental health benefits of these treatments yet continue to find them unethical. METHODS: An anonymous online survey was administered to students, from first to fourth year (n = 407), who had received one or two lectures on the treatment of youths with gender dysphoria (GD). RESULTS: Surveys were completed by 162 respondents (40%). A majority was able to correctly answer questions regarding psychiatric co-morbidities, diagnostic criteria, hormonal interventions, long-term benefits of interventions and terminology. There was some evidence that precision in the use of terminology waned over time. Many were unclear on the role of puberty blockers and the time requirement for a diagnosis of GD. A minority (14%) reported a belief that hormonal therapy is unethical, although these same individuals recognised that these treatments have mental health benefits. DISCUSSION: Our results have implications for future instruction, including: the need to teach pharmacological and diagnostic issues more deliberately; providing refresher training on terminology; and relying on interactive discussion or patient visits, rather than didactic lectures alone, for ethically charged medical topics. Similar levels of knowledge among students who believe that hormonal therapy is ethical and unethical may indicate that imparting didactic knowledge about therapeutic benefits alone may not be sufficient to affect attitudes regarding endocrine care for transgender youth. Hormonal interventions for transgender adolescents have become increasingly common.

Development of the Yale Gender Center: An Early Progress Report.

As the need for comprehensive, affirmative health care for transgender and gender nonconforming youth has increased in recent years, clinical practice has struggled to catch up with evolving standards of care. The Yale Gender Center is an example of an interdisciplinary model of care that addresses not only clinical needs, but also ancillary needs for patients and training opportunities for students across several health disciplines. In this article, we discuss our clinical and training models, lessons learned, and our proposed directions to expand care. It is our hope to not only offer a model for interdisciplinary care among other health care centers, but to be able to learn from missteps and potentially collaborate with other centers in the future.