Gender-affirming Therapy Research Articles

The metabolic effects of hormonal treatment in transgender males: Safety of the testosterone gender-affirming therapy.

Gender dysphoria is characterised by a sense of distress because of discordance between the self-perception of gender identity and the assigned sex. Hormonal treatment of transgender males uses testosterone to induce and preserve masculinisation. The study investigated the safety of testosterone therapy in transgender males. The present study used a retrospective file review of transgender male subjects who were treated with testosterone (initially transdermal testosterone gel and subsequently parenteral testosterone undecanoate) for at least 18 months and had subsequently achieved a serum testosterone level within the normal range of cisgender male counterparts. Changes in somatometric data and blood biomarkers were investigated. The mean testosterone serum levels after approximately 18 months of treatment were about 545 ng/dL (SD ± 94 ng/dL). There was a statistically significant rise in body mass index (𝜒d = +1.23 kg/m2) with a reduction in blood glucose (𝜒d = -5.33 mg/dL) as well as statistically significant increases in aspartate transaminase (𝜒d = +4.3 U/L), haemoglobin (𝜒d = +1.72 g/dL), and haematocrit (𝜒d = +4.76%). In contrast, there were no significant changes in the lipidaemic profile of the subjects. Treatment with testosterone is routinely used for the promotion of virilising physical changes in transgender males. However, the likelihood of adverse effects of continuous treatment is still unclear. This study contributed to the notion that achieving testosterone levels within the target range is a prerequisite for the safety of the gender-affirming treatment.

17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.

Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender-affirming therapy can also increase cis- and trans-females' risk for future CVD, respectively. The microvasculature is a unique vascular bed that when dysfunctional can independently predict future adverse cardiac events; however, studies on the influence of estrogen on human microvessels are limited. Here, we show that isolated human arterioles from females across the life span maintain nitric oxide (NO)-mediated dilation to flow, whereas chronic (16-20 h) exposure to exogenous (100 nM) 17β-estradiol promotes microvascular endothelial dysfunction in vessels from adult females of <40 and ≥40 yr of age. The damaging effect of estrogen was more dramatic in arterioles from biological males, as they exhibited both endothelial and smooth muscle dysfunction. Furthermore, females of <40 yr have greater endothelial expression of estrogen receptor-β (ER-β) and G protein-coupled estrogen receptor (GPER) compared with females of ≥40 yr and males. Estrogen receptor-α (ER-α), the prominent receptor associated with protective effects of estrogen, was identified within the adventitia as opposed to the endothelium across all groups. To our knowledge, this is the first study to report the detrimental effects of estrogen on the human microvasculature and highlights differences in estrogen receptor expression.NEW & NOTEWORTHY Microvascular dysfunction is an independent predictor of adverse cardiac events; however, the effect of estrogen on the human microcirculation represents a critical knowledge gap. To our knowledge, this is the first study to report sex-specific detrimental effects of chronic estrogen on human microvascular reactivity. These findings may offer insight into the increased CVD risk associated with estrogen use in both cis- and trans-females.

Fertility preservation options for transgender and nonbinary individuals.

Transgender and nonbinary individuals are historically underserved by healthcare systems. A crucial area for improvement is fertility preservation counseling and service delivery, as gender-affirming hormone therapy and gender-affirming surgery may negatively affect future fertility. The methods available for fertility preservation depend on the patient's pubertal status and utilization of gender-affirming therapies, and counseling and delivery of these services are complex and require a multidisciplinary approach. Further research is needed to identify pertinent stakeholders in managing the care of these patients, as well as to better understand the optimal frameworks for delivering integrated and comprehensive care to this patient population. Fertility preservation is an active and exciting area of scientific discovery and offers a wealth of opportunities to improve the care of transgender and nonbinary individuals.

Gender Diversity Cultural Responsiveness Education in Speech-Language Pathology Graduate Programs: A Pilot Survey

Purpose: Gender-affirming voice therapy aims to align a person’s voice and communication with their gender identity. Historically, transgender and gender-nonconforming (TGNC) individuals have been marginalized and continue to face significant healthcare disparities. The goal of this research was to examine the self-perceived preparedness of recent speech-language pathology (SLP) graduates for working with TGNC clients. A survey was developed to include both multiple choice and open-ended questions. Topics included graduate-level training on working with TGNC individuals, perceived preparedness to work with this client population, educational resources sought by respondents, and suggested improvements for SLP graduate programs. Thirty recent (since 2016) SLP graduates completed the survey anonymously. Although a majority (83%) of respondents reported that working with TGNC clients was addressed in their graduate education, 66% of respondents felt that instruction time spent on this topic was insufficient or slightly insufficient. Those who had clinical experiences with TGNC clients, or who learned from the perspectives of the TGNC community (e.g., from a guest speaker or video), reported that their graduate education better prepared them to work with TGNC clients. One of the most common recommendations to improve graduate education was to invite TGNC speakers to share their experiences. The majority of respondents identified a need for improvement of gender diversity education in SLP graduate programs. Further research is needed to determine the efficacy of different curricula in increasing the knowledge and skills of SLP graduates specific to TGNC clients to ensure clinical competency and equitable care.

Chest mass in a transgender man after top surgery

A 37-year-old transgender man presented to the outpatient Breast Care Clinic at the Medical College of Wisconsin (WI, USA) for evaluation of a new left chest mass in April, 2022, which he had noticed 1 month earlier. The mass was painless, and he had no other symptoms. His previous surgical history was notable in that he had undergone chest masculinisation surgery, colloquially called top surgery, 5 years earlier and was on gender-affirming testosterone therapy for the past 10 years. His family history was significant for a mother who had passed away from breast cancer in her 20s and a sister who was recently diagnosed with breast cancer at age 39 years.

Book Review of A Clinician's Guide to Gender Actualization: An Approach to Gender Affirming Therapy by Caitlin Yilmazer

Book Review of A Clinician's Guide to Gender Actualization: An Approach to Gender Affirming Therapy by Caitlin Yilmazer

Factors Related to Treatment Attendance for Patients Seeking Gender-Affirming Voice Therapy.

The purpose of this study was to investigate factors related to treatment attendance for patients seeking gender-affirming voice therapy (GAVT). We completed retrospective chart reviews of 50 patients (43 transgender women, three transgender men, four nonbinary patients; aged 18-67 years, M = 34.92 years, SD = 12.32 years) referred for GAVT at a Midwest outpatient center from 2016 to 2021. Data extraction included patient demographics, therapy visit specifics (e.g., number of sessions attended, treatment completion status, and in-person vs. virtual visits) and treatment timing (in relation to the onset of the COVID-19 pandemic), and psychosocial and socioeconomic information. There was no impact of treatment-timing relative to the onset of the pandemic on any attendance measure; however, patients were 1.9 times more likely to complete therapy with each virtual telehealth session attended. Individual factors of outside social support and hormone replacement therapy were positively related to the number of therapy sessions attended, whereas insurance provider and employment status were related to therapy completion. Telehealth attendance during the COVID-19 pandemic was positively associated with GAVT completion. Future research should investigate psychosocial and socioeconomic factors to understand how to identify patients at risk for poor treatment adherence and facilitate access to clinical care.

Moving toward standardization: physician reporting of sleep studies.

Lastra AC, Ingram D, Park J, etal. Moving toward standardization: physician reporting of sleep studies. J Clin Sleep Med. 2023;19(3):595-603.

2080. Differences in Hormonal Measures Among Transgender Individuals Assigned Male at Birth Switching from Tenofovir Disoproxil Fumarate/Emtricitabine to Tenofovir Alafenamide/Emtricitabine for Pre-Exposure Prophylaxis

Abstract Background There are concerns among transgender (TG) individuals about the effect of changing pre-exposure prophylaxis (PrEP) products on hormone concentrations. The objective of this study was to compare hormone concentrations among TG individuals assigned male at birth (AMAB) who switched from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) for PrEP. Methods An observational cohort study was performed among a subset of TG individuals AMAB enrolled in a clinical trial evaluating TAF/FTC for PrEP. Inclusion criteria for this study were ≥18 years old, TG identity, HIV negative, use of both TDF/FTC and TAF/FTC for ≥12 weeks, and availability of stored blood samples for hormone measurement while on both medications. Estradiol, testosterone (total and free) and sex hormone binding globulin were quantified at two time points: once while on ≥12 weeks of TDF/FTC and after ≥12 weeks on F/TAF. Median hormone concentrations were compared using related-samples Wilcoxon Signed Rank Test. Results Thirty participants met inclusion criteria with mean age of 35.9 ± standard deviation 9.7 years. There were 20 (67%) participants who identified as TG female. The remaining identified as gender non-conforming. Most participants self-identified as either Caucasian (40%), Hispanic or Latino/a/x (33%), Black (13.3%) or Asian (13.3%). Gender affirming therapy was used by 20 (67%) participants. The median (interquartile range, IQR) duration of TDF/FTC use before switching to TAF/FTC was 48 (15 – 60) weeks. Hormone values during TDF/FTC and TAF/FTC by use of gender affirming therapy is displayed in the Figure. Hormonal Values Before and After Switching PrEP Products, by Use of Gender Affirming Therapy Conclusion Switching to TAF-based PrEP was not associated with significant changes in hormone values among TG individuals AMAB. Disclosures Nimish Patel, PharmD, PhD, Gilead: Grant/Research Support Jill Blumenthal, MD, Gilead: Grant/Research Support Sheldon Morris, MD, Gilead: Grant/Research Support.

Healthcare Professionals' Conflicts When Treating Transgender Youth: Is It Necessary to Prioritize Protection Over Respect?

Increasingly, transgender minors are seeking medical care such as puberty-suppressing or gender-affirming hormone therapies. Yet, whether these interventions should be performed at all is highly controversial. Some healthcare practitioners oppose irreversible interventions, considering it their duty to protect children from harm. Others view minors, like adults, as transgender individuals who must be protected from discrimination. The underlying ethical question is presented as a problem of priority. Is it primarily relevant that minors are involved? Or should decision makers focus on the fact that they treat transgender individuals? The paper explores the relevance for medical practice. We provide results of an interview study with German healthcare professionals. We discuss the general question whether prioritization among different group memberships of the same person is ethically defensible. We conclude that priority conflicts between group memberships of the same person can be deceptive and should be addressed by an intersectional approach. Eventually, we discuss practical implications.

PSAT121 Treatment considerations in a patient with Turner syndrome and Gender Incongruence

Abstract Background Gender incongruence has not been described in Turner Syndrome (TS) patients. Estrogen replacement for ovarian failure has been an integral part of the management of TS to improve body composition, lipid profile and bone mineral density. There is limited data supporting testosterone supplementation in patients with TS. We present a transgender male patient with TS (mosaicism 45X/46XX) who underwent affirming therapy with testosterone. Clinical Case 12 years 6 month old adoptive Vietnamese assigned female at birth presented to Endocrine clinic for short stature. At that time patient had spontaneous menarche at age 11 years and menorrhagia with irregular menses. Further evaluation showed a karyotype consistent with TS and a FISH study that did not reveal Y chromosome material. Patient's skeletal age was 13 years 9 months (based on female Greulich and Pyle standards), growth hormone therapy could not be completed. Patient was started on oral estrogen + progesterone treatment to regulate menses. Cardiovascular evaluation including EKG and Echocardiogram showed mild aortic root dilation and prolonged QTc. BMI was &amp;gt;99th percentile. Lab studies including thyroid, lipid panel, glucose, HbA1c, liver and kidney functions were normal. At the follow up visit at age 14, patient identified as being masculine with a desire to have a broader chest and phallus, and distress regarding gender identity which reportedly had been present for 3 years. He met with our gender health team including reproductive endocrinologist for consideration of reproductive function and fertility options, he decided not to pursue these options. Testosterone treatment was initiated using the endocrine society protocol at age 15 years 2 months after extensive counseling and confirmation of gender incongruence by two specialists. Cardiac MRI was obtained at baseline and repeated at 1 year after treatment with no changes to the underlying aortic dilation. Lab studies were repeated every 6 months and remained normal. Hemoglobin was high normal at 16. Follow up visits completed every 3-4 months showed normal vital signs, increased BMI which was reflective also of muscular changes associated with testosterone treatment and overall satisfaction with the lack of menses and masculine changes. He completed 'top surgery' at age 16 years 3 months and currently at age 18 started college having successfully transitioned socially as well as physically. Conclusions This case emphasizes the importance of personalized treatment of patients with TS who present with gender incongruence. While testosterone treatment in TS (outside of a small study looking at low dose oral testosterone) patients is not well studies, a thorough risk and benefits discussion with the patient and collaboration with a variety of providers including mental health providers, reproductive endocrinologist and cardiologist remain important as gender affirming therapy is lifesaving for individuals who may have already overcome a lifetime of challenges. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Serum oestradiol levels and risk of adverse cardiovascular events associated with gender-affirming oestrogen therapy: a protocol for a systematic review and meta-analysis

IntroductionThe use of gender-affirming oestrogen therapy (GAOT) is an integral part of the gender-affirming transition process for transgender women (assigned male at birth who identify as women) and gender-diverse individuals....

PMON192 Impact of Gender-Affirming Care Learning Module on Medical Students’ Knowledge and Self-Efficacy

Abstract While evidence supports the need for increased provider education on gender-affirming care, few medical curricula address the healthcare needs of transgender and non-binary (TGNB) patients. To bridge this knowledge gap, we developed an online learning module to educate medical students (MS) in the care of this underserved population. The module included topics such as TGNB health disparities, gender dysphoria, and gender-affirming therapy. We hypothesized that learners would possess greater knowledge and self-efficacy following completion of the module. A cohort of 272 first- (MS1) and second-year medical students (MS2) from a single institution received protected time during their academic training to complete the mandatory online module (total duration: 60 minutes). Of those, 90 learners consented to participate in our IRB approved study and completed pre- and post-module surveys. Surveys assessed the impact of the educational module on self-reported knowledge and self-efficacy pertaining to learning objectives. Most participants self-identified as cisgender (97%), while 40% of those who chose to answer reported being part of LGBTQIA+ community. Baseline knowledge scores ranged from 7 (not knowledgeable) to 35 (knowledgeable). Following completion of the module, the median knowledge score significantly increased by 9 points (23 to 32; p&amp;lt;0.0001). At baseline, self-efficacy scores ranged from 9 (not confident) to 45 (confident) and similarly increased by 9 points (31 to 40; p&amp;lt;0.0001). Feedback from participants indicated that the module was well-received. Our data showed that an online educational module on gender-affirming care was successful in increasing knowledge and self-efficacy in surveyed MS1 and MS2 at our institution. Education of healthcare providers is a key step towards improving care for TGNB patients. Therefore, more institutions should adopt formal curricula for MS on gender-affirming care to mitigate health disparities in this vulnerable population. Similar modules could be adapted to educate already practicing clinicians and support staff to ensure a more gender-inclusive healthcare environment. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Managing Dermatologic Effects of Gender-Affirming Therapy in Transgender Adolescents.

Transgender adolescents seek gender-affirming medical care to address gender identity and incongruence. Improved understanding of the dermatologic impact of gender-affirming medical care such as pubertal suppression, hormone therapy, and surgeries can enhance patient outcome. Pubertal suppression treats dysphoria associated with development of secondary sex characteristics, including androgen-driven acne. Gender-affirming hormone therapy influences acne and hair development in transgender adolescents. Dermatologists can help manage skin effects associated with chest binding and gender-affirming hormone therapy and surgery. Provision of patient-centered gender-affirming care in dermatologic and multidisciplinary settings is essential to improve skin and overall outcomes of gender-affirming therapy.

S2989 Excessive Hormonal Therapy in a Male Transitioning to a Female Causing Cirrhosis

Introduction: High doses of progestins/estrogens can cause elevated liver enzymes, serum aminotransferase elevations with no changes in alkaline phosphatase or bilirubin, 1 to 2 weeks after treatment. These side effects are usually transient and resolve with dose modification or discontinuation. We present a unique case where a male in-transition to female was found to be cirrhotic from hormonal dose therapy. Gastroenterologists should be aware of the importance of starting hormonal therapy in the transgender process as exogenous estrogen therapy may lead to underlying liver disease. Case Description/Methods: This is a 63 year male on hormone replacement therapy who presented to the hospital for evaluation of hyperlipidemia, hypertension, diabetes, and gender dysmorphia with concerns of questionable abdominal pain and early findings of cirrhosis. During evaluation, he complained of abdominal pain, jaundice, and dark urine. His LFTs were unremarkable prior to the visit. Upon inquiry of a prior history of fatty liver disease, he admitted not following up with his doctor. The patient then described how he had recently begun hormonal therapy to transition to a female. He reported first starting on an estrogen patch with a transition to estradiol 2mg daily. He denied having a prior history of alcohol abuse or other risk factors of cirrhosis. His liver function tests were noted to be T. Bili of 6.3, D. Bili of 3.2, ALK phos of 263, AST of 51, ALT of 176 and lipase of 100. Given his elevated LFTs an ultrasound and MRCP were performed which showed cirrhosis with portal hypertension and cholelithiasis. He did not have any synthetic liver dysfunction. Upon discontinuation of his estradiol his LFTS resolved back to baseline after five days. Discussion: Gastroenterologists should be aware of gender-affirming hormonal therapies in the transgender population as they can lead to long term sequale such as developing cirrhosis. Evidence in the literature is sparse with no consensus on the long term effects of high dose hormone therapy. Further studies should focus on the risk factors of starting hormonal therapy using demographic characteristics, BMI, and alcohol use as further parameters for gauging cirrhosis. We present the case of a 63-old trans-female patient whose hormone therapy can be associated directly with liver cirrhosis.

Central Feminization of Obese Male Mice Reduces Metabolic Syndrome.

Metabolic syndrome encompasses a spectrum of conditions that increases the risk for cardiovascular and metabolic diseases. It is widely accepted that the sex hormone estrogen plays a protective metabolic role in premenopausal women, in part through central nervous system (CNS) mechanisms. However, most work to date has focused on the loss of estrogen in females (e.g., menopause). Interestingly, transgender individuals receiving feminizing gender affirming therapy (i.e., estrogen) are relatively protected from metabolic syndrome conditions, pointing to a role for CNS estrogen in the development of metabolic syndrome in men. Here, we show that estrogen signaling in the brain protects males from metabolic syndrome and obesity related complications. First, short-term CNS specific supplementation of low-dose 17-β-estradiol in diet-induced obese male mice resulted in a significant reduction in body weight in parallel with a decrease in food intake without alterations in energy expenditure. In conjunction, central supplementation of estrogen reduced visceral adiposity, including epididymal and abdominal regions, with slighter decreases in subcutaneous inguinal and thermogenic brown adipose tissue. Furthermore, central estrogen administration reduced the liver manifestation of metabolic syndrome including hepatomegaly and hepatic steatosis. Collectively, these findings indicate that a lack of estrogen action in the brain may predispose males to metabolic syndrome pathogenesis.

Fertility Preservation and Reproductive Potential in Transgender and Gender Fluid Population

The gender diverse and transgender community is a minor patient group that is encountered with increasing frequency in the clinical setting, attributed to the improved awareness and access to medical facilities. Partial impairment to permanent elimination of fertility potential and outcomes depending on the treatment modality usually is a result of gender-affirming therapy, which includes both hormone therapy and surgical intervention. Although seldom conducted in the clinical field, transgender patients should be counseled on their fertility preservation options prior to medical and surgical gender transition. There is relatively limited data and clinical information regarding fertility preservation for transgender individuals. Current treatment regimens are based on protocols from fertility preservation after oncological treatments. Major barriers for the transgender population exist due to the lack of information provided and clinical narrative that is not familiar to the physician or health care provider, although there are various options for fertility preservation. A deeper understanding of this clinical agenda and the mandatory processes will ultimately result in a much more comprehensive and specific care for transgender individuals who are in great need for fertility counseling or treatment options that concern fertility preservation. In this review, current clinical approaches will be summarized and fertility preservation options along with ongoing and future clinical trials in fertility preservation for transgender individuals will be thoroughly reviewed.

Gender-affirming estrogen therapy route of administration and cardiovascular risk: a systematic review and narrative synthesis.

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET.NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals.

P17-29 Development of innovative rodent models to mimic gender-affirming hormone therapies for hazard identification of transgender people: preliminary data

P17-29 Development of innovative rodent models to mimic gender-affirming hormone therapies for hazard identification of transgender people: preliminary data

32559 Risk of hidradenitis suppurativa and hyperhidrosis in transgender patients on hormone therapy compared with cisgender patients

Background: Gender-affirming hormone therapies (GAHT) are known to affect pilosebaceous units and sweat production, but the risk of hidradenitis suppurativa (HS) and hyperhidrosis in the transgender/gender diverse (TGD) populations has not yet been studied.