Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial.

Background: A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing. Objective: To evaluate 1 month and 6 months testosterone suppression <50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT. Methods: This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL. Results: Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group. Conclusion: Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.

Co-occurring psychiatric disorders in young people with eating disorders: An multi-state and real-time analysis of real-world administrative data.

OBJECTIVE: We aimed to use real-world data to characterize the burden of psychiatric comorbidities in young people with eating disorders (EDs) relative to peers without EDs. METHOD: This retrospective cohort study used a large federated multi-national network of real-time electronic health records. Our cohort consisted of 124,575 people (14,524 people receiving their index, first-ever, ED diagnosis, compared to 110,051 peers without EDs initiating antidepressants). After 1:1 propensity score matching of the two cohorts by pre-existing demographic and clinical characteristics, we used multivariable logistic regression to compute the adjusted odds ratio (aOR) of psychiatric diagnoses arising in the year following the index event (either first ED diagnosis or first antidepressant script). RESULTS: Over 50% of people with EDs had prior psychiatric diagnoses in the year preceding the index EDs diagnosis, with mood disorders, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), specific phobia (SP), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) being the most common. Adjusted analyses showed higher odds for mood disorders (aOR = 1.20 [95% CI = 1.14-1.26]), GAD (aOR = 1.28 [1.21-1.35]), PTSD (aOR = 1.29 [1.18-1.40]), and SP (aOR = 1.45 [1.31-1.60]) in the EDs cohort compared to antidepressant-initiating peers without EDs, although rates of ADHD and ASD were similar in both cohorts. CONCLUSION: This large-scale real-time analysis of administrative data illustrates a high burden of co-occurring psychiatric disorders in people with EDs.

Quantifying Nipple-Areolar Complex Shape and Location After Transmasculine Top Surgery: A Study of Postoperative Photographs Posted on Social Media and Surgeons' Professional Websites.

Purpose: The transgender community utilizes online platforms to view and share postoperative masculinizing top surgery photographs. However, the quantitative and qualitative nature of these photographs is unknown. We aimed to conduct an analysis of postoperative online photographs for nipple-areolar complex (NAC) shape and location, and compare social media platforms to World Professional Association for Transgender Health (WPATH) surgeons' websites and published cis-male chest proportions. Methods: In a cross-sectional analysis (April to May 2019), social media (Instagram and Reddit) and WPATH surgeon website postoperative top surgery photographs were analyzed. Areola height (AH):areola width (AW), NAC horizontal (inter-nipple distance [IND]:chest width [CW]) and vertical placement (sternal notch to nipple line [SN-NL]:sternal notch to umbilicus [SN-U]), and vertical scar placement (sternal notch to scar line [SN-SL]:SN-U) ratios were assessed on MATLAB. Data were compared to published cis-male proportions. Photograph skin color, soft tissue redundancy, and scar location were also analyzed. Results: We analyzed 304 social media and 192 surgeons' website photographs qualitatively, and 139 social media and 189 surgeons' photographs quantitatively. Means (standard deviation) for postoperative photographs were AH:AW 1.12±0.24, IND:CW 0.68±0.07, SN-NL:SN-U 0.37±0.06. Most ratios significantly differed from published cis-male ratios (p<0.001). Photographs from WPATH surgeons' websites differed from social media platforms in SN-NL:SN-U and SN-SL:SN-U (p<0.001), and in scar location and soft tissue redundancy (p=0.012). Conclusion: Postoperative top surgery photographs on online platforms showed more vertically oval, caudally positioned, and in many cases wider-spaced NACs than cis-male proportions. Our study highlights variability in results of masculinizing top surgery as it relates to an emerging source of information; online photographs.

Effectiveness and Safety of Different Estradiol Regimens in Transgender Women (TREAT Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Current guidelines for gender-affirming hormone therapy (GAHT) for transgender women are mostly based on clinical experience from experts in the field and treatments used on postmenopausal women. While care is currently provided with the best available evidence, there is a critical gap in knowledge about the safest and most effective estradiol routes of administration for GAHT in transgender women; this statement is supported by the World Professional Association for Transgender Health on their Standards of Care for the Health of Transgender and Gender Diverse People, version 8. Furthermore, the reported rates of cardiometabolic adverse events in transgender women highlight the importance of investigating changes in lipoproteins, glucose, and insulin sensitivity, among other markers while receiving GAHT. OBJECTIVE: This study aims to evaluate the degree of testosterone suppression achieved at 1, 6, and 12 months in treatment-naive transgender women when randomized to GAHT with estradiol and spironolactone as antiandrogens. As a secondary aim, this study will assess the treatment effect on metabolic and coagulation factors from baseline to 6 and 12 months after initiating GAHT. METHODS: This is a prospective pilot, open-label, randomized clinical trial conducted at an adult transgender clinic in a tertiary medical center. The 3 treatment arms include once-daily sublingual 17-ß estradiol, twice-daily sublingual 17-ß estradiol, and transdermal 17-ß estradiol. All participants received spironolactone as an antiandrogen. Transgender women aged 18 to 45 years who are being evaluated for the initiation of GAHT with 17-ß estradiol and did not have a history of coagulopathy, cigarette smoking, liver disease, dyslipidemia requiring treatment, or use of gonadotropin-releasing hormone agonist were eligible to enroll. The main outcome is the total testosterone suppression at 1 and 6 months after the initiation of GAHT, and the secondary outcome is to assess treatment effect in a lipid panel; homeostatic model assessment for insulin resistance; coagulation factors II, IX, and XI; Von Willebrand factor; activated protein C resistance; protein C; and protein S at baseline, 6 months, and 12 months after therapy is initiated. RESULTS: This study was funded in March 2022, and enrollment concluded in August 2022. It was concluded in July 2023, and currently, the results are being analyzed for publication. CONCLUSIONS: The Transgender Estradiol Affirming Therapy (TREAT) study offers a rigorous and reproducible approach to answer important questions regarding GAHT in transgender women, specifically, the most effective 17-ß estradiol regimen to suppress testosterone levels to 50 ng/dL, as currently recommended. TRIAL REGISTRATION: ClinicalTrials.gov NCT05010707; https://clinicaltrials.gov/study/NCT05010707. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53092.

Clinician and Consumer Perspectives on Gender-Affirming Voice Services.

INTRODUCTION: A significant portion of the transgender, nonbinary, and gender-expansive community experiences gender-related voice issues. However, barriers exist to accessing gender-affirming voice care, and most existing voice research does not include the gender-nonbinary population. Our study aimed to examine transgender, nonbinary, and gender-expansive consumer/potential consumer (hereafter referred to as consumer) engagement and compare/contrast consumer and speech-language pathologist perspectives on gender-affirming voice services. A secondary aim was to assess possible voice impairments in transgender, nonbinary, and gender-expansive individuals. METHODS: Two surveys were distributed via listservs for SLPs and flyers and social media posts for consumers. Surveys included items regarding experience with and accessibility of gender-affirming voice services and clinician competence. Consumers and clinicians answered the same questions from their respective positions. Consumers additionally completed the Voice Handicap Index-10 (VHI-10). RESULTS: Forty-eight consumer and 54 clinician responses were collected. Twenty (41.7%) consumers were trans women, 15 (31.2%) were trans men, 12 (25%) were gender-nonbinary, and one (2.1%) was gender fluid. VHI-10 responses were in the abnormal range for 61.4% of consumers, and 68.8% indicated desire to receive gender-affirming voice services, including 58.3% of gender-nonbinary respondents. However, only 6.25% of consumers considered themselves as having a voice disorder and 29.2% reported that their voice impairs communication. In contrast, 24.1% of clinicians felt consumers seeking gender-affirming voice services have a voice disorder and 51.2% felt they have an impaired communication ability. Consumers indicated positive perceptions of voice services/providers but reported a variety of barriers to access. SLPs indicated mixed confidence in accessibility of services. Both groups perceived an affordability barrier. CONCLUSIONS: This study demonstrates the desire and need for gender-affirming voice services and is the first to our knowledge to explicitly include gender-nonbinary individuals' perspectives on them. Understanding how consumer and clinician perspectives differ can help focus provider efforts in improving experiences with, access to, and visibility of gender-affirming voice services.

Withdrawal method inquiries and user experiences: An analysis of content posted on 4 gendered forums on Reddit.

OBJECTIVES: Limited research and guidance on the use of "withdrawal" or coitus interruptus for contraception lead to inconsistent or even inaccurate physician recommendations regarding its use. Consequently, patients rely on online communities to learn about this commonly used contraceptive method. To identify knowledge gaps and concerns between men and women, as well as explore how they use withdrawal, we examined withdrawal-related posts on the popular internet discussion forum, Reddit. STUDY DESIGN: To explore gendered variations in withdrawal-related Reddit posts, we extracted posts from the gendered forums: "TwoXChromosomes," "Askwomen," "Askmen," and "OneY" between 2010 and 2019 that contained the search terms: "coitus interruptus," "withdrawal," "pull out," "preejaculate," or "precum." We developed an initial codebook with expected codes and augmented it with emerging findings from a random sampling of 10% of posts. We revised iteratively for interrater agreement, after which researchers coded the remaining posts independently. RESULTS: Of 269 withdrawal-related queries, 19% were submitted by men; 81% referenced the contributor's own withdrawal use. Salient domains included: concerns about pregnancy risk (59%), how to effectively use withdrawal (13%), benefits/pleasure from using withdrawal (12%), impact on personal life/relationship (9%), and problems encountered, inclusive of consent (7%). Posts to female-focused forums more frequently inquired about pregnancy risk, while those on male forums more frequently inquired about withdrawal-related logistics (p < 0.001); domains were not associated with contributor gender. CONCLUSION: Withdrawal-related queries within this Reddit sample are frequently posted by women, the majority of whom want to understand their risk of pregnancy with withdrawal. Research operationalizing withdrawal and more accurately estimating withdrawal-related pregnancy risk is warranted. IMPLICATIONS: Reddit users discuss their personal experiences with withdrawal as contraception, as well as seek advice regarding its use from the online community. Pregnancy risk, logistics of use, and ongoing stigma are salient topics. Further research on pregnancy risk, operationalizing success, and approaches for discussing this behavioral method is warranted.

Getting to the Bottom of Patient Experiences with Genital Gender Affirmation Surgery: A Qualitative Analysis of Online Reviews.

BACKGROUND: Patients undergoing gender-affirming surgery seek information from online sources including online reviews written by peers. We aimed to conduct a qualitative analysis of the information discussed in online reviews related to genital gender-affirming surgery and evaluate the topics driving positive/negative reviews. METHODS: Reviews for genital gender-affirming surgery (vaginoplasty, metoidioplasty, and phalloplasty) were identified on three popular review platforms: Google, Yelp, and RealSelf. Content was analyzed line by line using a conventional inductive content analysis to identify recurring themes. Individual statements were marked as either having a positive or negative sentiment. Median rating was calculated and compared across platforms (max score 5). Associations between theme/subthemes and sentiment were also analyzed using Chi-squared test. RESULTS: A total of 129 reviews were analyzed and 433 codes were identified, the majority of which were positive (n=372; 85.9%). Three overarching themes described factors important to patient experience: surgeon medical, surgeon non-medical, and non-surgeon; with surgeon medical being the most popular. Fifteen subthemes comprised these themes, the most popular being interactions with supporting staff, surgeon bedside manner, and overall postoperative result. There was no difference in median review ratings between platforms (5 across all platforms; p=0.452). There was no association between sentiment and themes or subthemes (p=0.187 and p=0.578, respectively). CONCLUSIONS: This study is the first to analyze online reviews of genital gender-affirming surgery. The majority of patients gave positive ratings and the qualitative content had mostly positive sentiment. Salient themes not only include surgeon medical care and outcome, but other nonsurgical elements that formulate the patient's experience as a whole. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of Vitamin B12 Injection on the Vocal Performance of Professional Singers: A Randomized, Double-blind, Placebo-Controlled, Crossover Trial.

Importance: One-third of singers and vocal professionals report experiencing a benefit from empirical vitamin B12 injections for improvement of mild singing-related symptoms (eg, reduced stamina, vocal fatigue, and effort). However, there is no objective evidence to support or refute these claims. Objective: To assess the presence and magnitude of the effect of empirical vitamin B12 injection on the vocal performance of singers. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled, crossover trial was conducted from November 7, 2017, to November 30, 2018, at an academic voice center among 20 active adult singers without dysphonia but with mild vocal symptoms. Individuals with known or suspected vitamin B12 deficiency or active or recent vitamin B12 treatment were excluded. Analysis was on a per-protocol basis. Interventions: Participants were randomized to receive an intramuscular (deltoid) injection of either vitamin B12 (1000 µg of cyanocobalmin) or placebo (0.9% sodium chloride). After a washout period of at least 4 weeks, participants were crossed over to receive the opposite injection. Both the investigators and participants were blinded to the order of injections. Main Outcomes and Measures: The participants completed the Singing Voice Handicap Index-10 (SVHI-10), the Voice Fatigue Index (VFI), and the Evaluation of the Ability to Sing Easily (EASE) before each injection and at intervals of 1 hour, 3 hours, 24 hours, 72 hours, and 1 week after the injection. The primary time point assessment was 72 hours after injection, and the SVHI-10 score was the primary outcome measure. Results: Twenty singers (10 men; median age, 22 years [range, 19-42 years]) were enrolled. The improvements after either placebo or vitamin B12 injections were comparable to each other. At 72 hours after the vitamin B12 injection, the median difference in the SVHI-10 score was 1 (95% CI, -1 to 2) compared with 3 (95% CI, 0-4) after placebo. The median difference between differences at 72 hours between placebo and vitamin B12 injections were 1.5 (95% CI, -2 to 5) for the SVHI-10, 1 (95% CI, -9 to 9) for the VFI, and -1 (95% CI, -3 to 2) for the EASE. The improvements after both injections failed to reach the estimated minimal clinically important difference. Of the 20 participants, 4 (20%) reached the estimated minimal clinically important difference in their SVHI-10 score after 72 hours for both vitamin B12 and placebo injections. Conclusions and Relevance: This randomized, double-blind, placebo-controlled, crossover trial found that after empirical vitamin B12 injection to improve mild voice-related symptoms, the improvement in self-reported voice measures in singers shows no meaningful difference compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03437824.