Initiation Of Gender-affirming Hormone Therapy Research Articles

A Qualitative Study of Transgender and Nonbinary Perspectives Regarding the Desired Properties of a Peer Support Intervention for the Initiation of Gender-Affirming Hormone Therapy [ID 2683451

INTRODUCTION: Transgender and nonbinary (TNB) people experience significant mental health disparities and challenges accessing gender-affirming care. Peer support interventions have been shown to improve mental health in other populations and contexts but have not been uniquely tailored to the initiation of gender-affirming hormones. This study aims to identify the desired properties of a peer support intervention for TNB people initiating gender-affirming hormones. METHODS: We conducted semistructured interviews with TNB adults who had initiated or attempted to initiate gender-affirming hormones (IRB: HUM00203630: approved/exempt; gender-affirmation: off-label). Participants were selected by snowball and purposive sampling methods. Interview questions focused on the participants' experiences with peer support and their vision for ideal peer support while initiating hormones. Interviews were transcribed and analyzed using reflective thematic analysis with inductive and deductive coding. A TNB community advisory board collaborated in the study design and interviews were conducted by TNB research team members. RESULTS: The ages of the participants ranged from 20 to 52 years (mean=32); 8/18 identified as men or trans men; 4/18 identified as nonbinary; 3/18 identified as women or trans women; 3/18 identified as genderqueer or genderfluid; 10/18 identified as a person of color. Themes include the importance of 1) trans community knowledge in guiding hormone therapy decisions, 2) having support structures attend to intersectional identities, and 3) recognizing barriers to peer engagement, including anxieties about fitting in and internalized transphobia. CONCLUSION: Centering TNB voices is essential in designing a peer support intervention for hormone initiation. Our participants offered nuanced approaches for how to share information about hormones, attend to intersectional identities, and navigate barriers to peer engagement.

Inflammation as a Potential Mechanism Contributing to Sexual Functioning Following Initiation of Gender-Affirming Hormone Therapy

Inflammation as a Potential Mechanism Contributing to Sexual Functioning Following Initiation of Gender-Affirming Hormone Therapy

Effects of progesterone on gender affirmation outcomes as part of feminizing hormone therapy

BackgroundThe use of progesterone as a component of feminizing gender-affirming hormone therapy (GAHT) is controversial; however, use in transgender women continues owing to anecdotal reports of benefit. ObjectivesThis study aimed to provide quantifiable outcomes data regarding the use of progesterone in transgender women by comparing groups from this population who use feminizing GAHT with and without progesterone. MethodsThis retrospective cohort study captured data from transgender female patients seen at the Summa PRIDE Clinic between September 2019 and December 2021. Data were extracted from chart documentation for patients who were prescribed feminizing GAHT, with and without progesterone, for at least 6 months during the study window. Outcomes included satisfaction with breast development, satisfaction with libido, mental health trends, and weight change at 0, 6, and 9 months from initiation of GAHT. ResultsA total of 88 charts were reviewed (59 in the standard group, 29 in the progesterone group). The progesterone group had statistically significant improvements in satisfaction with breast development at 6 months (53.8% vs. 19.6%; P = 0.004) and 9 months (71.4% vs. 20.8%; P = 0.003). The progesterone group had more patients at goal testosterone levels < 55 ng/dL at 6 months (47.6% vs. 33%) and 9 months (50% vs. 24.4%), but these were not statistically different. The progesterone group was also more likely to show improved provider-documented mental health at 6 months (70.6% vs. 28.2%; P = 0.009); however, the difference was not statistically significant at 9 months. There were no differences between groups for weight change and patient satisfaction with libido. ConclusionThe addition of progesterone to standard feminizing GAHT was associated with greater satisfaction with breast development and improved patient mental health within 6 months compared with standard GAHT regimens alone in this patient population. Progesterone’s impact on libido, testosterone suppression, and weight were nonsignificant.

Testosterone administration affects 1H-MRS metabolite spectra in transgender men

BackgroundRecently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain endophenotype in people with gender dysphoria (GD). However, despite mounting neuroimaging work, brain gender differences and effects of gender-affirming hormone therapy (GAHT) at the metabolite level remain understudied. MethodsThirty-one transgender men (TM) before and after testosterone administration (7.7 months ± 3.5 months), relative to 30 cisgender men (CM) and 35 cisgender women (CW) underwent magnetic resonance spectroscopy (1H-MRS) at two time points. Two brain regions were assessed, i.e. the lateral parietal cortex and the amygdala/anterior hippocampus. Associated metabolites that were measured include N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamate and glutamine (Glx), myo-inositol (mI), glycine (Gly) and their respective ratios. ResultsA critical time by group interaction revealed an effect of GAHT in the lateral parietal cortex of TM. MI+Gly/Cr ratios decreased upon initiation of GAHT. In addition, NAA/Cr and Cho/Cr ratios were lower in CW when compared to CM in the lateral parietal cortex. Glx levels and Glx/Cr ratios in TM differed from those in CW in the amygdala/anterior hippocampus. Interestingly, pubertal age of onset of gender dysphoria (i.e. GD) in TM differentially affected testosterone-mediated effects on Cr concentration and NAA/Cr ratios when compared to childhood and adult GD onset in the amygdala/anterior hippocampus. ConclusionThis 1H-MRS study demonstrated that testosterone administration shifts mI+Gly/Cr ratios in the parietal cortex. In the amygdala/anterior hippocampus, modulation of metabolite concentrations by age of onset of GD is suggestive for a possible developmental trend.

Minimal change in minority stress after a 6 month follow up in a transgender population

Gender minority individuals experience higher degrees of mental health conditions compared to cisgenders persons. In recent years, extensive literature suggests minority stress factors contribute to these mental health problems in transgender/gender-nonconforming individuals. In this study, minority stress was surveyed by means of a battery of 10 self-report questionnaires. We aimed to assess whether experienced minority stress decreases in transgender men (TM) and transgender women (TW) upon initiation of gender affirming hormone therapy (GAHT) and to identify hormonal correlations. The Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), Resilience Scale (RS-nl), Stigma Consciousness Questionnaire (SCQ), Everyday Discrimination Scale (EDS), Beck Suicidality Scale (BSS), Emotion Regulation Questionnaire (ERQ), Social Desirability Scale (SDC) and Suicidal Attempts/Thoughts (SAT) were prospectively assessed in 57 TM and 40 TW at initiation of GAHT and after 6 months of follow up. Estrogens (orally or transdermally) plus anti-androgens (cyproterone acetate) were administered in TW and intramuscular long-acting testosterone undecanoate in TM. All data was analysed prospectively. Correlations with sex steroid levels were investigated. A prospective decrease in total scores for STATE (p=0.021) and TRAIT (p<0.001) Anxiety Inventory after 6 months of GAHT was found. Although BDI-II scores also decreased, a significant result was not demonstrated (p=0.051). A correlation was found between PSS scores and testosterone in TM (ρ=0.327, p=0.045). In TW, correlations with estradiol were found for STAI State (ρ=0.746), STAI Trait (ρ=0.810), BSS (ρ=0.783), PSS (ρ=0.688), RS-nl (ρ=-0.480), SAT (ρ=0.565) and EDS (ρ=0.542) (all p<0.05). No other effects or correlations were found. Small changes in a battery of mental health related questionnaires were assessed after a short (6 months) period of GAHT, stressing the need for longer follow up and continued research on the effect of GAHT on minority stress in transgender persons. No conflict of interest to report.

The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function: A Systematic Review and Meta-Analysis.

Gender-affirming hormone therapy modifies body composition and lean muscle mass in transgender persons. We sought to characterize the change in serum creatinine, other kidney function biomarkers, and GFR in transgender persons initiating masculinizing and feminizing gender-affirming hormone therapy. We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to September 16, 2020 for randomized controlled trials, observational studies, and case series that evaluated the change in serum creatinine, other kidney function biomarkers, and GFR before and after the initiation of gender-affirming hormone therapy in adult transgender persons. Two reviewers independently screened and abstracted data, and disagreements were resolved by a third reviewer. A random effects meta-analysis was performed to determine the change in outcomes over follow-up of 3, 6, and 12 months. Of the 4758 eligible studies, 26 met the inclusion criteria, including nine studies that recruited 488 transgender men and 593 women in which data were meta-analyzed. There was heterogeneity in study design, populations, gender-affirming hormone therapy routes, and dosing. At 12 months after initiating gender-affirming hormone therapy, serum creatinine increased by 0.15 mg/dl (95% confidence interval, 0.00 to 0.29) in 370 transgender men and decreased by -0.05 mg/dl (95% confidence interval, -0.16 to 0.05) in 361 transgender women. No study reported the effect of gender-affirming hormone therapy on albuminuria, proteinuria, cystatin C, or measured GFR. Gender-affirming hormone therapy increases serum creatinine in transgender men and does not affect serum creatinine in transgender women. The effect on gender-affirming hormone therapy on other kidney function biomarkers and measured GFR is unknown. Change in Kidney Function Biomarkers in Transgender Persons on Gender Affirmation Hormone Therapy-A Systematic Review and Meta-Analysis, CRD42020214248.

Hypertension in transgender individuals.

Although there has been a dramatic increase in visibility and recognition of transgender and gender-diverse populations, remarkably little has been published on prevalence rates of hypertension within these populations. In addition to summarizing the limited data on prevalence rates, this review compares the prevalence rates with those of cisgender populations and explores whether gender-affirming hormone therapy affects blood pressure and hypertension rates. The studies show that hypertension affects a significant proportion of transgender and gender-diverse people and support the practice of routinely monitoring blood pressure in transgender and gender-diverse people, especially after the initiation of gender-affirming hormone therapy. The two largest studies both found that estrogen plus an antiandrogen was associated with a decrease in systolic blood pressure and that testosterone was associated with an increase in systolic blood pressure.

Cardiovascular outcomes in transgender individuals in Sweden after initiation of gender-affirming hormone therapy.

We compared the incidence of cardiovascular disease (CVD) in transgender participants with a diagnosis of gender dysphoria (GD) with and without gender-affirming hormone therapy (GAHT) to the incidence observed in the general population. The population-based cohort included all individuals >10 years in Sweden linked to Swedish nationwide healthcare Registers (2006-16). Two comparator groups without GD/GAHT were matched (1:10) on age, county of residence, and on male and female birth-assigned sex, respectively. Cox proportional models provided hazard ratios (HRs) and 95% confidence intervals (CI) for CVD outcomes. Among 1779 transgender individuals [48% birth-assigned males (AMAB), 52% birth-assigned females (AFAB)], 18 developed CVD, most of which were conduction disorders. The incidence of CVD for AFAB individuals with GD was 3.7 per 1000 person-years (95% CI: 1.4-10.0). Assigned male at birth individuals with GD had an incidence of CVD event of 7.1 per 1000 person-years (95% CI: 4.2-12.0). The risk of CVD event was 2.4 times higher in AMAB individuals (HR: 2.4, 95% CI: 1.3-4.2) compared with cisgender women, and 1.7 higher compared with cisgender men (HR: 1.7, 95% CI: 1.0-2.9). Analysis limited to transgender individuals without GAHT yielded similar results to those with GAHT treatment. The incidence of CVD among GD/GAHT individuals was low, although increased compared with matched individuals without GD and similar to the incidence among GD/no GAHT individuals, thus not lending support for a causal relationship between treatment and CVD outcomes. Larger studies with longer follow-up are needed to verify these findings, as well as possible effect modification by comorbidity.

Breaking Down Barriers to Reproductive Care for Transgender People

There are an estimated 1.4 million transgender adults in the United States, representing 0.6% of the population.1 Transgender and gender diverse (TGD) individuals have gender identities that differ from their recorded sex at birth, and medical/surgical interventions are often pursued to better align these. Gender-affirming medical therapy, including pubertal suppression and initiation of gender-affirming hormone therapy (GAHT), improves quality of life and psychological outcomes.2,3

The Effect of Gender-Affirming Hormone Therapy on Serum Creatinine in Transgender Individuals

ObjectiveTo describe the changes in serum creatinine (Cr) levels after the initiation of gender-affirming hormone therapy (GAHT) in transgender individuals to better understand the expected changes and interpretation of laboratory values in this population. MethodsA retrospective chart review of all adult transgender patients initiated on GAHT at Mayo Clinic from January 2011 to October 2019 was completed. Laboratory values were obtained prior to initiating GAHT and at 3, 6, and 12 months after initiating GAHT. Baseline Cr values were compared with Cr values at 3, 6, and 12 months after initiating GAHT in transgender men (TM) on testosterone and transgender women (TW) on estradiol and antiandrogens. ResultsA total of 84 TW (median age of 30 years) and 24 TM (median age of 23 years) were included for analysis. Following a matched pair analysis of TW, Cr values were found to be significantly decreased by −0.03 at 3 months (P = .04), −0.10 at 6 months (P < .01), and −0.07 at 12 months (P < .01) compared with baseline values. Following a matched pair analysis of TM, Cr values were found to be significantly increased, on average, by 0.14 at 3 months (P = .04), 0.21 at 6 months (P = .016), and 0.15 at 12 months (P = .003) compared with baseline values. ConclusionIn TW and TM, a change in Cr level was seen as early as 3 months toward their affirmed gender after initiating GAHT. Clinicians can use Cr levels established at 6 months as new baseline values, as these changes continue to persist up to 12 months.

Effect on Kidney Function During Gender Affirming Hormonal Treatment in Transgender Individuals

Background: Accurate interpretation of laboratory values with sex-specific reference ranges presents a challenge in transgender individuals on gender affirming hormone therapy (GAHT). Creatinine (Cr), the most common marker used for kidney function, varies significantly with body mass and composition. Both Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations account for sex in estimating glomerular filtration rate. GAHT can effect Cr values in 2 potential ways: 1) by causing changes in muscle mass and body fat redistribution as early as 3 months after GAHT initiation and 2) by direct effects of sex hormones on kidney function. Previous studies have shown Cr values approaching affirmed gender identity as early as 6 months when on GAHT without mention of sex steroid levels. In this study we sought to describe the changes in serum Cr after initiation of GAHT in an effort to better understand expected changes and interpretation of lab data in TG individuals. Methods: A retrospective chart analysis on all adult TG patients initiated on GAHT at our institution from January 2011 to 2020 was completed. We reviewed demographics, baseline health information, body mass index, and lab values including Cr, sex hormone levels, A1C, and fasting blood glucose. Lab values were obtained prior to GAHT, at the start of GAHT, at 3, 6, and 12 months after GAHT. Matched pair testing was conducted with sex steroid levels and Cr values in transgender men (TM) on testosterone and transgender women (TW) on estradiol in order to compare the median pre GAHT Cr to median Cr levels at 3, 6, and 12 months. Results: 84 TW with a median age of 30 and 24 TM with a median age of 23 were included for analysis. TW and TM had a low rate of existing kidney disease (4.9%, 0%), diabetes mellitus (4.8%, 0%), and hypertension (10.8%, 4.5%) respectively. TW on GAHT achieved a goal estradiol level (≥100 pg/ml) at a rate of 37.3%, 51.7%, and 71.1% and suppressed testosterone to a goal level (<60ng/ml) at a rate of 44.4%, 54.7%, and 76.5% at 3, 6, and 12 months respectively. There was no significant change in Cr values at 3 months, but significantly decreased on average by -0.07 (p<0.001) at 6 months, and by -0.09 (p<0.001) at 12 months. TM on GAHT achieved a goal testosterone level (≥240 ng/dl) at a rate of64.3%, 80.0%, and 72.3% at 3, 6, and 12 months respectively. Cr values increased significantly on average by 0.14 (p=0.036) at 3 months, by 0.21 (p=0.004) at 6 months, and by 0.15 (p=0.003) at 12 months. Conclusions: In TW on GAHT, clinicians can consider using affirmed gender Cr reference ranges as early as 6 months. Similarly in TM on GAHT, affirmed gender Cr reference ranges can be used as early at 3 months. It remains to be seen whether changes in Cr levels reflect changes in sex steroid levels or sex steroid direct effects. Additionally, research is needed to determine if change in Cr levels reflect true changes in GFR.

Blood Pressure Effects of Gender-Affirming Hormone Therapy in Transgender and Gender-Diverse Adults.

[Figure: see text].

Abstract 13215: Gender-affirming Hormones Are Associated With Increased Risk of QT Prolongation in Transgender Females

Introduction: Women have a longer QT interval than men. This sex-specific difference is attributed to hormones associated with the biological female sex. Male-to-female transgender individuals often take antiandrogens such as spironolactone or goserelin in addition to estrogens to suppress testosterone effects while increasing feminine features. Effects of gender-affirming hormone therapy (GHT) on the QT interval in these individuals remains to be elucidated. Hypothesis: We assessed the hypothesis that the use of GHT is associated with an increased risk for QT interval prolongation in transgender females. Methods: We identified 46 transgender females through a search of the electronic medical records of a Veterans Administration hospital in Northern Nevada. Patients with a diagnosis of congenital long QT syndrome were excluded. Of these, 13 patients had ECGs before and after initiation of GHT and were included. We adapted the Tisdale score using the auto-calculated corrected QT interval (QTc) to estimate the risk of QT prolongation. Age, QTc, and Tisdale scores before and after GHT initiation were compared using the Wilcoxon signed-rank test. All tests were performed as two-tailed at a 5% level of significance. Results: All 13 study patients were taking estrogens. Of these, 3 (23.1%) were taking goserelin and 9 (69.2%) were taking spironolactone. Mean ± SEM age at ECG acquisition was 45.0 ± 4.4 and 47.7 ± 4.7 years before and after the initiation of GHT respectively. Mean ± SEM QTc after initiation of GHT was significantly higher compared to the baseline (467.5 ± 12.8 ms vs. 428.2 ± 7.1 ms) (Figure 1A). The average baseline Tisdale score was significantly smaller on follow-up (1-point vs. 3 points) (Figure 1B). Conclusions: GHT appears to be associated with increased QTc in transgender women. This needs to be interpreted with caution owing to the very small sample size in this study. Further studies to investigate the strength of this association, if it exists, are warranted.

Effects of gender affirming hormone therapy on body mass index in transgender individuals: A longitudinal cohort study

IntroductionMany transgender people take hormone therapy to affirm their gender identity. One potential long-term consequence of gender affirming hormone therapy is increased body mass index (BMI), which may be associated with metabolic syndrome, cardiovascular disease and higher mortality. Only a few published studies explored changes in BMI in transgender people taking gender affirming hormone therapy (GAHT). ObjectiveTo examine the changes in BMI longitudinally in response to GAHT in transgender women and men. MethodsWe conducted a retrospective cohort study of transgender individuals who received GAHT from the endocrinology clinic between January 1, 2000 and September 6, 2018. Subjects who sought GAHT were included if they had two separate measurements of BMI and were excluded if they had a BMI greater than 35 kg/m2 or were missing demographic data at entry. We used a linear mixed model to analyze the longitudinal change in BMI. ResultsThere were a total of 227 subjects included in this cohort. Among subjects already on GAHT, transgender women were receiving GAHT longer than transgender men (6.59 ± 9.35 vs 3.67 ± 3.43 years, p-value = 0.04). Over the period of 7 years, there was a significant increase in BMI in transwomen who newly initiated GAHT (p-value 0.004). There were no changes in BMI in transgender men and women already on GAHT or in transgender men who newly initiated GAHT in the study. ConclusionWe conclude that BMI significantly increases in transwomen but not in transmen after initiation of GAHT in a single center based in the United States. In transwomen and transmen, BMI appears to be stable following 3 to 6 years of GAHT. Future investigations should examine the causes for increased BMI in transgender women including type of GAHT, diet and lifestyle, and association with risk of metabolic syndrome and cardiovascular disease.

Baseline Mental Health and Psychosocial Functioning of Transgender Adolescents Seeking Gender-Affirming Hormone Therapy.

Research suggests that adolescents seeking gender-affirming hormone therapy experience elevated rates of depression, anxiety, and difficulties with peer relationships. Less is known regarding more specific aspects of mental health and psychosocial functioning. Furthermore, few studies have explored variations in mental health and psychosocial functioning by age, gender, degree of physical dysphoria, and informant type (adolescent, mother, and father). Participants are adolescents (n = 149) and parents/guardians (n = 247) who presented to a multidisciplinary gender clinic in Dallas, TX for an initial assessment before initiation of gender-affirming hormone therapy. Adolescents completed the Youth Self-Report (YSR) and the Body Image Scale (a measure of physical dysphoria), and parents/guardians completed the Child Behavior Checklist (CBCL). Approximately half of participants reported clinically significant difficulties with internalizing symptoms and psychosocial functioning (particularly engagement in activities), with approximately one-third indicating significant difficulties with depression, anxiety, obsessive compulsive, and posttraumatic stress symptoms. Parents reported fewer symptoms than adolescents across several subscales, but differences were generally small. By contrast, gender differences were found across all internalizing subscales and were generally large. Age and body dissatisfaction were not independently associated with broadband measures but, in combination with gender, were strongly associated with variance in YSR and CBCL reports of internalizing symptoms. Elevated rates of depression, anxiety, and competency difficulties were broadly consistent with the previous literature and demonstrate the need for investment in the clinical training and infrastructure to provide comprehensive care to this population. Differences in mental health and psychosocial functioning by gender and clinic location appear to be less straightforward.

Bone Health in the Transgender Population.

It is well known that sex steroids, particularly estrogen, play a crucial role in the attainment and maintenance of peak bone density in all people. Transgender (trans) women have been frequently observed to have low bone density prior to initiation of gender-affirming hormone therapy, while trans men generally do not. With pharmacologic estrogen, many studies show improving bone density in trans women. With pharmacologic testosterone, bone density in trans men remains largely unchanged although androgens have indirect effects on bone health via changes in fat and lean mass. Much remains unknown about best practices to optimize bone health, interpret DXA scans and assess fracture risk in trans adults.