Gender-affirming Hormone Treatment Research Articles

Mental Health and Endocrine Telemedicine Consultations in Transgender Subjects During the COVID-19 Outbreak in Italy: A Cross-Sectional Web-Based Survey

Transgender people are a vulnerable group with a higher incidence of mental health issues and, during the COVID-19 outbreak, they may have faced psychological, physical and social obstacles. To evaluate the impact of the pandemic and the access to health care services during the COVID-19 pandemic on the mental health of the transgender people living in Italy. An anonymous web-based survey was conducted among transgender people living in Italy. The survey consisted of 41 questions (to address socio-demographic and COVID-19 related variables, general health problems and trans-related health issues) and three validated questionnaires (the Impact of Event Scale [IES], the Beck Depression Inventory [BDI-II] and the SF-12. In total 108 respondents were included in the analysis, of these 73.1% were transmen and 26.9% transwomen. The mean age was 34.3 ± 11.7 years with 88.9% undergoing gender affirming hormonal treatment (GAHT). Of these respondents 55.6% were not working during the COVID-19 pandemic, mainly because they lost their jobs due to the lockdown (30.5%) or because they were otherwise unemployed (25.0%). Only four subjects were quarantined at home because of a positive COVID-19 swab. The mean total IES score was 21.1 ± 14.9 with 24.1% of subjects scoring over the cut-off score of 26 thereby suggesting a moderate-to-severe impact of the pandemic event. Mean BDI score was 8.6 ± 8.4. SF-12 total mean score was 96.1 ± 11.9 with a Mental Component Summary (MCS) score of 42.8 ± 9.1. Access to endocrinological consultations for hormonal prescription via telemedicine services was associated with better IES total scores (P=.01). Our results highlight the impact of the pandemic on the mental health of this particular population and how telemedicine services may serve to mitigate negative psychological effects. Internet-based surveys may select a group of people not necessary representative of the whole population. The self-reporting bias should also be considered. Those who responded to our survey were mainly from northern Italy were COVID-19 has had a greater impact. Vulnerable groups such as the transgender population should receive more consideration also during pandemic events and their access to health services especially for endocrine and mental health care should be improved. A nationwide plan for the extended use of telemedicine should be established with targeted intervention to reduce psychological distress. Gava G, Fisher AD, Alvisi S, etal. Mental Health and Endocrine Telemedicine Consultations in Transgender Subjects During the COVID-19 Outbreak in Italy: A Cross-Sectional Web-Based Survey. J Sex Med 2021;18:900-907.

Genetycznie obciążony transseksualny mężczyzna w trakcie korekty płci z dwoma pierwotnymi nowotworami – opis przypadku

Transgender is defined as an incongruence between the assigned at birth sex and an experienced gender identity. The biological sex is neither familiar nor acceptable to transgender people. Gender-affirming hormone treatment (GHT) is a multidisciplinary approach aiming to develop and maintain physical characteristics of the desirable sex. The influence of exogenous hormones on the cancer pathogenesis and development is a subject of ceaseless studies and observations. However incomplete statistical and epidemiological data hamper deducing about the risk of cancer among these people. The article describes a case of a transgender female-to-male (FtM) patient during gender transition with two primary neoplasms (endometrial cancer and colon cancer) as well as Lynch syndrome and von Recklinghausen’s disease confirmed by next-generation sequencing (NGS).

Adolescent Transgender Females Present Impaired Semen Quality That Is Suitable for Intracytoplasmic Sperm Injection Even Before Initiating Gender-Affirming Hormone Treatment

The present study aimed to determine the semen quality and cryopreservation outcomes among adolescent transgender females at the time of fertility preservation (FP) before initiating gender-affirming hormone (GAH) treatment. This retrospective cohort study included 26 adolescent transgender females who underwent FP in our Fertility Institute between 06/2013 and 10/2020. Pre-freezing semen parameters were compared to WHO 2010 reference values. Post-thaw semen parameters were used to determine the adequate assisted reproductive technology (ART). A multivariate linear regression analysis was performed to assess the impact of medical and lifestyle factors on semen quality. The mean age at which adolescent transgender females underwent FP was 16.2 ± 1.38 years. The median values of all semen parameters in our study group were significantly lower compared to the WHO data, including volume (1.46 mL vs 3.2 mL, respectively, P = 0.001 ), sperm concentration (28 × 106/mL vs 64 × 106/mL, P < 0.001), total sperm number (28.2 × 106 vs 196 × 106, P < 0.001), total motility (51.6% vs 62%, P < 0.001), and normal morphology (2% vs 14%, P < 0.001). The frequency of semen abnormalities was teratozoospermia 72%, hypospermia 52%, oligozoospermia 28%, and azoospermia 4%. The median post-thaw total motile count was 0.17 × 106/vial, and the quality was adequate only for ICSI in 87.7% of the thawed semen samples. No correlation was found between selected medical and lifestyle factors and poor semen parameters. Semen quality is strongly reduced among adolescent transgender females before hormone therapy and their stored sperm samples are suitable for intracytoplasmic sperm injection (ICSI) rather than conventional IVF/intrauterine insemination (IUI).

Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI)

BackgroundCardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown. AimTo evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT. MethodsIn a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate. Main Outcome MeasureChanges in CV risk factors and 30-year Framingham CVD risk during GAHT. Clinical ImplicationsIn transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk. Strengths & LimitationsThe strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT. ResultsIn transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes – such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time. ConclusionsOur findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk.Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;18:821–829.

Gender-affirming hormone treatment causes changes in gender phenotype in a 12-lead electrocardiogram

Men and women have specific patterns in an electrocardiogram (ECG) differentiated by J-point elevation and ST-segment angle. Although gender-affirming hormone treatment is one of the treatments for gender dysphoria, its influence on an ECG has not been clarified yet. The purpose of this study was to investigate ECG changes induced by gender-affirming hormone treatment. The study population consisted of 29 transgender males and 8 transgender females and 37 age- and sex-matched cisgender females and males. Male pattern was defined as J-point elevation > 0.1 mV and ST-segment angle > 20° in precordial leads. In the comparison between 29 transgender males and cisgender females, the prevalence of the male pattern (89.7% vs 6.9%; P < .001), prevalence of the early repolarization pattern (51.7% vs 17.2%; P = .01), J-point elevation (leads V1-V6), T-wave amplitudes (leads V1-V6), QRS amplitudes (leads II, III, V1-V6), and P-wave amplitudes (leads V1-V3) were significantly higher in transgender males. The prevalence of the male pattern was lower in transgender females than in cisgender males (25.0% vs 87.5%; P= .04). In the analysis of transgender males for whom ECGs were available before and after gender-affirming hormone treatment (n = 13), J-point elevation and T-wave amplitudes significantly increased after gender-affirming hormone treatment, leading to a higher prevalence of the male pattern (23.1% vs 92.3%; P < .001). The prevalence of the early repolarization pattern and QRS amplitudes also significantly increased after the treatment, but the augmentation of P-wave amplitudes was modest. Gender-affirming hormone treatment for gender dysphoria is accompanied by a change in ECG phenotype toward affirming gender, in which change in androgen level may be involved.

Individual Treatment Progress Predicts Satisfaction With Transition-Related Care for Youth With Gender Dysphoria: A Prospective Clinical Cohort Study

BackgroundThe number of adolescents presenting with gender dysphoria (GD) in healthcare services has increased significantly, yet specialized services offering transition-related care (TRC) for trans youth is lacking. AimTo investigate satisfaction with TRC, regret, and reasons for (dis)satisfaction with transition-related medical interventions (TRMIs) in trans adolescents who had presented to the Hamburg Gender Identity Service for children and adolescents (Hamburg GIS). MethodsData were collected from a clinical cohort sample of 75 adolescents and young adults diagnosed with GD (81% assigned female at birth) aged 11 to 21 years (M = 17.4) at baseline and follow-up (on a spectrum of ongoing care, on average 2 years after initial consultation). To determine progress of the youth's medical transitions, an individual treatment progress score (ITPS) was calculated based on number of desired vs received TRMIs. OutcomesMain outcome measures were satisfaction with TRC at the time of follow-up, ITPS, social support, reasons for regret and termination of TRC, and (dis)satisfaction with TRMIs. ResultsParticipants underwent different stages of TRMIs, such as gender-affirming hormone treatment or surgeries, and showed overall high satisfaction with TRC received at the Hamburg GIS. Regression analysis indicated that a higher ITPS (an advanced transition treatment stage) was predictive of higher satisfaction with TRC. Sex assigned at birth, age, and time since initial consultation at the clinic showed no significant effects for satisfaction with TRC, while degree of social support showed a trend. No adolescents regretted undergoing treatment at follow-up. Additional analysis of free-text answers highlighted satisfaction mostly with the physical results of TRMI. Clinical ImplicationsBecause youth were more satisfied with TRC when their individual transition (ITPS) was more progressed, treatment should start in a timely manner to avoid distress from puberty or long waiting lists. Strengths and LimitationsThis study is one of the first to report on treatment satisfaction among youth with GD from Europe. The ITPS allowed for a more detailed evaluation of TRMI wishes and experiences in relation to satisfaction with TRC and may close a gap in research on these treatments in adolescent populations. However, all participants were from the same clinic, and strict treatment eligibility criteria may have excluded certain trans adolescents from the study. Low identification rates with non-binary identities prevented comparisons between non-binary and binary genders. ConclusionThe study highlights the role of TRMI and individual treatment or transition progress for youth's overall high satisfaction with TRC received at the Hamburg GIS.Nieder TO, Mayer TK, Hinz S, et al. Individual Treatment Progress Predicts Satisfaction With Transition-Related Care for Adolescents With Gender Dysphoria: A Prospective Clinical Cohort Study. J Sex Med 2020;XX:XXX–XXX.

Research gaps in medical treatment of transgender/nonbinary people.

With the growing number of transgender and gender-nonbinary individuals who are becoming visible, it is clear that there is a need to develop a rigorous evidence base to inform care practice. Transgender health research is often limited to HIV/AIDS or mental health research and is typically subsumed in larger studies with general LGBTQ focus. Although the number of knowledgeable health care providers remains modest, the model for the medical approach to transgender health is shifting owing to growing social awareness and an appreciation of a biological component. Gender-affirming medicine facilitates aligning the body of the transgender person with the gender identity; typical treatment regimens include hormone therapy and/or surgical interventions. While broadly safe, hormone treatments require some monitoring for safety. Exogenous estrogens are associated with a dose-dependent increase in venous thromboembolic risk, and androgens stimulate erythropoiesis. The degree to which progressing gender-affirming hormone treatment changes cancer risk, cardiac heart disease risk, and/or bone health remains unknown. Guidelines referencing the potential exacerbation of cancer, heart disease, or other disease risk often rely on physiology models, because conclusive clinical data do not exist. Dedicated research infrastructure and funding are needed to address the knowledge gap in the field.

Physical and Psychological Effects of Gender-Affirming Hormonal Treatment Using Intramuscular Testosterone Enanthate in Japanese Transgender Men.

IntroductionThe evidence on gender-affirming hormonal treatment (HT) for transgender persons is still insufficient.AimTo characterize the physical and psychological effects of HT using testosterone enanthate in transgender men, and to validate the safety of this treatment.MethodsA total of 85 Japanese transgender men who were followed up for at least 1 year at our gender clinic from 2004 to 2017 were included in this study. All self-reported effects that they recognized and regularly acquired laboratory data were investigated after initiation of HT.Main Outcome MeasureHT mainly using testosterone enanthate 250 mg every 2 weeks caused the most desired physical effects to appear promptly and effectively, whereas small but not negligible numbers of undesired physical and psychological effects were also confirmed.ResultsThe initial dose of testosterone enanthate was 250 mg for 72 (84.7%) subjects, and the injection interval was maintained every 2 weeks for 70 (82.3%). Most physical effects appeared within 6 months. A deepened voice (87.1%), cessation of menses (78.8%), acne (69.4%), and facial (52.9%)/body (37.6%) hair growth occurred within 3 months. Although recognition of psychological effects was rare, emotional instability (9.4%) and increased libido (7.1%) appeared in the relatively early phase after beginning HT. The mean values for red blood cells, hemoglobin, uric acid, and alkaline phosphatase were significantly increased for 2 year. During the observation period, there were no life-threatening adverse effects in any subjects.ConclusionThe present HT strategy is effective and safe for Japanese transgender men.The information from self-reported effects and objective data from blood tests can help both physicians and transgender men to understand testosterone HT.Kirisawa T, Ichihara K, Sakai Y, et al. Physical and Psychological Effects of Gender-Affirming Hormonal Treatment Using Intramuscular Testosterone Enanthate in Japanese Transgender Men. Sex Med 2021;9:100306.

Positive and Negative Affect Changes during Gender-Affirming Hormonal Treatment: Results from the European Network for the Investigation of Gender Incongruence (ENIGI).

Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirming care. Prospective changes in affect can influence QoL. We aim to assess the impact of initiating gender-affirming hormonal treatment (HT) on affect. In the European Network for the Investigation of Gender Incongruence (ENIGI) study, we prospectively collected data of 873 participants (451 transwomen (TW) and 422 transmen (TM)). At baseline, psychological questionnaires including the Positive and Negative Affect Schedule (PANAS) were administered. The PANAS, levels of sex steroids and physical changes were registered at each follow-up visit during a 3-year follow-up period, starting at the initiation of hormonal therapy. Data were analyzed cross-sectionally and prospectively. Over the first three months, we observed a decline in positive affect (PA) in both TM and TW. Thereafter, PA reached a steady state in TW, whereas in TM there was also a second decline at 18 months. In both TM and TW there was no persisting difference comparing baseline to the 36-months results. Concerning negative affect (NA), we observed a decline during the first year in TM, which sustained during the second year and was not different anymore at 36 months compared to baseline. In TW though, we did not find any change of NA during the entire follow-up. Even if some of these results show significant differences, they should be considered with caution, since there was no control group and the absolute differences are small. No association between affect and the level of sex steroids was observed. Baseline QoL and psychological burden are related to affect independently from gender but are not necessarily good predictors of the evolution of one’s affect during the gender-affirming process. Further research is necessary to investigate these preliminary results.

Hyperprolactinemia and association with prolactinoma in transwomen receiving gender affirming hormone treatment.

Approximately 0.6% of the adult population identifies as transgender. Gender affirming hormone treatment (GAHT) is required by many to develop physical and psychological characteristics that align with their gender identity. Once started, GAHT is continued lifelong and at higher doses than conventionally used in the management of cis-gendered women. Hyperprolactinemia and pituitary lactotroph adenomas are a potential consequence of GAHT. Case series of three transfeminine women with hyperprolactinemia during gender affirming hormone treatment. We report two new cases of prolactinoma and one new case of marked hyperprolactinemia without pituitary adenoma associated with GAHT in transwomen at different stages of hormonal transition. Novel aspects of our case series include the first report of a prolactinoma in a transwoman associated with spironolactone and the alternate progestin medroxyprogesterone acetate and documentation of the transient changes in prolactin from baseline (prior to feminizing hormones) in two transwomen which demonstrate that marked hyperprolactinemia develops early in the course of GAHT. Transgender women receiving GAHT may be at increased risk for prolactinoma. As the number of transwomen seeking GAHT continues to increase, hyperprolactinemia and GAHT-associated prolactinoma may become an increasingly important component of endocrine practice. Screening of prolactin levels in transwomen receiving GAHT could potentially prevent morbidity related to hyperprolactinemia and allow for early detection of prolactin secreting pituitary adenomas.

Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty.

ABSTRACTBone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender‐affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people, no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin‐releasing hormone agonist (GnRHa) and GAH before achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip structure analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual‐energy X‐ray absorptiometry scans performed at the start of GnRHa and GAH treatments, and after ≥2 years of GAH treatment. Mixed‐model analyses were performed to study differences over time. Data were visually compared with reference values of the general population. A total of 322 participants were included, of whom 106 were trans women and 216 trans men. In both trans women and trans men, participants resembled the reference curve for SPW and ED of the experienced gender but only when GnRHa was started during early puberty. Those who started during mid and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one's life span. Therefore, this study adds insights into sex‐specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population. © 2021 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Sustained Breast Development and Breast Anthropometric Changes in 3 Years of Gender-Affirming Hormone Treatment.

Breast development is important for most trans women. An important limitation of current breast development measurement methods is that these do not allow for 3D volume analyses. To examine breast development and change in anthropometry during the first 3 years of gender-affirming hormone treatment using 3D imaging. Associations with clinical or laboratory parameters and satisfaction with the gained breast development were also studied. Prospective cohort study. Specialized tertiary gender identity clinic in Amsterdam, the Netherlands. Participants were 69 adult trans women with a median age of 26 years (interquartile range, 21-38). Gender-affirming hormone treatment. Volumetric and anthropometric breast development and satisfaction. Breast volume increased by 72 cc (95% confidence interval [CI], 48-97) to 100 cc (standard deviation 48). This resulted in a cup-size <A-cup in 71% of the participants. Although the change in breast-chest difference plateaued after approximately 9 months, sustained increase in breast volume was observed during the 3-year observation period. Sternal notch to nipple distance increased by 1.3 cm (95% CI, 0.9-1.7) and internipple distance increased by 1.0 cm (95% CI, 0.4-1.5). At least 58% of trans women were satisfied with the gained breast size. Sustained breast growth and development during hormone treatment was observed during the full 3-year observation period. The breasts of trans women are positioned more laterally and caudally on the chest compared with cis women. Although modest breast volumes were observed, breast development was satisfactory to most trans women.

Zürcher Sprechstunde für Jugendliche mit Genderdysphorie – erste Verlaufsergebnisse

The Zurich Specialist Clinic for Adolescent with Gender Dysphoria - Preliminary Follow-up Results The specialist clinic for children and adolescents with gender dysphoria (GD) of the Psychiatric University Hospital of Zurich shows an increasing number of referrals since its foundation in 2009. Since 2014 we started an observational study including adolescents aged 13 years and older. At the time of the first appointment (T0) N = 77 participants completed a battery of questionnaires assessing demographic factors, general psychopathology, quality of life as well as gender identity, social transitioning and GD treatment modalities. Few of the adolescents were socially transitioned and had hormone therapy but 77.9 % wished to get hormone therapy. Follow up assessment T1 was performed after at least one year of treatment in our specialist clinic. 51 adolescents completed an online follow-up examination including the same questionnaires and baseline parameters as well as a scale measuring treatment satisfaction. At T0, 77.3 % of the adolescents scored in the clinical range of the Youth Self Report (YSR) total score, which did not decrease significantly until T1 in our preliminary follow up sample. Puberty blocking before T0 correlated negatively with the YSR score, indicating less psychopathology in treated patients. Preliminary longitudinal analysis suggests that social transitioning influences quality of life (Kidscreen subscale autonomy and parental relationship). At T1, 52 % of the adolescents were socially transitioned in all contexts and 70 % received gender affirming hormonal treatment. Gender identity changed between T0 and T1 in about 18 % of the cases. Treatment satisfaction in most cases was high.

Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.

ContextHormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual.ObjectiveTo describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones.DesignObservational prospective study.Subjects51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups.Main Outcome MeasuresBone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers.ResultsAt the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment.ConclusionsBMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

Gender-affirming therapy linked to mental health.

Aldridge, Z. et al. Long-term effect of gender-affirming hormone treatment on depression and anxiety symptoms in transgender people: a prospective cohort study. Andrology https://doi.org/10.1111/andr.12884 (2020) Article PubMed Google Scholar To, M. et al. Visual conformity with affirmed gender or “passing”: its distribution and association with depression and anxiety in a cohort of transgender people. J. Sex. Med. https://doi.org/10.1016/j.jsxm.2020.07.019 (2020) Article PubMed Google Scholar Holmberg, M., Arver, S. & Dhejne, C. Supporting sexuality and improving sexual function in transgender persons. Nat. Rev. Urol. 16, 121–139 (2019) CAS Article Google Scholar Download references Nature Reviews Urology Caroline Barranco You can also search for this author in PubMed Google Scholar Correspondence to Caroline Barranco. Reprints and Permissions Barranco, C. Gender-affirming therapy linked to mental health. Nat Rev Urol (2020). https://doi.org/10.1038/s41585-020-00377-6 Download citation Published: 10 September 2020 DOI: https://doi.org/10.1038/s41585-020-00377-6

Long-term effect of gender-affirming hormone treatment on depression and anxiety symptoms in transgender people: A prospective cohort study.

Cross-sectional studies show that transgender people are more likely than cisgender people to experience depression and anxiety before gender-affirming hormone treatment (GAHT). However, the effect of GAHT on mental health in transgender people, and the role of other factors that may have a predictive effect, is poorly explored. Using a longitudinal methodology, this study investigated the effect of 18-month GAHT on depression and anxiety symptomatology and the predictors on mental health outcomes in a large population of transgender people. Participants (n=178) completed a socio-demographic questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Scale of Perceived Social Support (MSPSS) and the Autism Spectrum Quotient-Short Version (AQ-Short) at pre-assessment (T0) and at 18months after initiation of GAHT (T1). From T0 to T1, symptomatology was significantly decreased for depression (P<.001) and non-significantly reduced for anxiety (P=.37). Scores on the MSPSS predicted reduction in depression, while scores on the AQ-Short predicted reduction in anxiety. GAHT reduces symptoms of depression which are predicted by having higher levels of social support. Although anxiety symptoms also reduce, the changes are not significant and high levels of anxiety still remain post-GAHT. These results highlight the important mental health benefits of GAHT. Support services (professional, third sector or peer support) aiming at increasing social support for transgender individuals should be made available.

The Desire and Status of Gender-Affirming Hormone Therapy and Surgery in Transgender Men and Women in China: A National Population Study

BackgroundGender-affirming hormone therapy and surgery are important medically necessary approaches to transgender care. However, few related data exist in China. AimTo understand the desire and access of transgender cares in the Chinese transgender men and women population. MethodsA cross-sectional self-selecting survey targeting the Chinese transgender population was conducted in 2017 using a snowball sampling method. Participants completed an online questionnaire anonymously. Gender identity was verified by specifically designed questions. Data analysis of this study was performed in 2019. OutcomesThe main outcome was the status of receiving transgender medical care, including the desire vs actual state of receiving gender-affirming hormone treatment and gender-affirmation surgery, methods of accessing hormonal therapy and surgery, and risky behaviors associated with obtaining treatments. ResultsOf the total 2060 valid questionnaires, there were 1,304 transgender individuals (626 transgender men and 678 transgender women), with a median age of 22 (interquartile range, 19–26) years. Among them, 1,036 (79.4%) expressed desires for hormonal therapy, but of 1,036, 741 (71.5%) considered it difficult to obtain medications from doctors. Of 1,036 individuals, 275 (26.5%) and 172 (16.6%) had thoughts or behaviors of self-injury, respectively, when lacking access to hormone therapy. Of 1,036 individuals, 602 (58.1%) had used hormones. Of those 602 hormone users, 407 (67.6%) had ever obtained medications from informal drug dealers, and 372 (61.8%) of them did not perform regular monitoring. 868 of 1,303 (66.6%) participants had received or wanted to undergo gender-affirming surgeries, but 710 of 868 (81.8%) considered the surgery resources not adequate or very scarce. Clinical ImplicationsThe transgender medical resources in China are scarce, and many transgender individuals have engaged in high-risk activities to access care. Strengths & LimitationsThis is the first study to focus on the current status of gender-affirming hormone therapy and surgery in the Chinese transgender population, providing valuable and real-world data for understanding the need for transgender health care in China. But, the online questionnaire could not provide the prevalence and other epidemiologic information about transgender individuals in China, and the survey did not address specific medication regimens, dosages, sex hormone levels, and specific hormone therapy–related or surgery-related adverse events. ConclusionSignificant improvement in access to gender-affirming medical and surgery care is needed in China.Liu Y, Xin Y, Qi J, et al. The Desire and Status of Gender-Affirming Hormone Therapy and Surgery in Transgender Men and Women in China: A National Population Study. J Sex Med 2020;17:2291–2298.

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

BackgroundBrain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor α (ESR1) is one of the implicated genes. AimTo analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. MethodsWe carried out a prospective study of the CpG methylation profile of RIII (−1,188 to −790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain reactions were sequenced. The analysis of 671 bisulfite sequences was carried out with the QUMA (QUantification tool for Methylation Analysis) program. OutcomesThe main outcome of this study was RIII analysis using bisulfite genomic sequencing. ResultsWe found sex differences in RIII methylation profiles in cisgender and transgender populations. Cismen showed a higher methylation degree than ciswomen at CpG sites 297, 306, 509, and at the total fragment (P ≤ .003, P ≤ .026, P ≤ .001, P ≤ .006). Transmen showed a lower methylation level than trans women at sites 306, 372, and at the total fragment (P ≤ .0001, P ≤ .018, P ≤ .0107). Before the hormone treatment, transmen showed the lowest methylation level with respect to cisgender and transgender populations, whereas transwomen reached an intermediate methylation level between both the cisgender groups. After the hormone treatment, transmen showed a statistically significant methylation increase, whereas transwomen showed a non-significant methylation decrease. After the hormone treatment, the RIII methylation differences between transmen and transwomen disappeared, and both transgender groups reached an intermediate methylation level between both the cisgender groups. Clinical ImplicationsClinical implications in the hormonal treatment of trans people. Strengths & LimitationsIncreasing the number of regions analyzed in the ESR1 promoter and increasing the number of tissues analyzed would provide a better understanding of the variation in the methylation pattern. ConclusionsOur data showed sex differences in RIII methylation patterns in cisgender and transgender populations before the hormone treatment. Furthermore, before the hormone treatment, transwomen and transmen showed a characteristic methylation profile, different from both the cisgender groups. But the hormonal treatment modified RIII methylation in trans populations, which are now more similar to their gender. Therefore, our results suggest that the methylation of RIII could be involved in gender dysphoria.Fernández R, Ramírez K, Gómez-Gil E, et al. Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen. J Sex Med 2020;17:1795–1806.

Impaired semen quality in trans women: prevalence and determinants.

STUDY QUESTIONWhat is the semen quality in trans women at time of fertility preservation, prior to the start of gender-affirming hormone treatment?SUMMARY ANSWERBefore the start of gender-affirming hormone treatment, semen quality in trans women was already strongly decreased compared to the general population.WHAT IS KNOWN ALREADYHormone treatment for -trans women (birth-assigned males, female gender identity) consists of anti-androgens combined with estrogens in order to achieve feminization and it is accompanied by a loss of reproductive capability. Trans women can opt for semen cryopreservation prior to their medical transition to retain the possibility to parent genetically related offspring. Post-thaw semen parameters determine which ART can be used. Knowledge of semen quality and the factors negatively influencing semen parameters in trans women are important to improve semen quality before fertility preservation.STUDY DESIGN, SIZE, DURATIONA retrospective cohort study was performed between 1972 and 2017. In total, 260 trans women were included for this study. Due to the study design, there was no loss to follow-up or attrition.PARTICIPANTS/MATERIALS, SETTING, METHODSWe studied the quality of the preserved semen in trans women, prior to their medical transition, who visited our gender clinic. Semen parameters were collected, as well as data on age, alcohol consumption, smoking, cannabis use, BMI, previous use of estrogens or anti-androgens and endocrine laboratory results. Semen parameters were categorized using reference values for human semen of the World Health Organization (WHO) and compared with data from the general population. Logistic regression analyses were performed to analyze the extent to which factors known to have a negative impact on semen quality in the general population explained the impaired semen quality in the cohort.MAIN RESULTS AND THE ROLE OF CHANCEThe cohort consisted of 260 trans women between the age of 16 and 52 years. Semen quality in trans women was significantly decreased compared to WHO data from the general population. In total, 21 trans women had an azoospermia and median semen parameters for the remaining trans women and the general population, respectively, were as follows: volume 2.7 and 3.2 ml (P < 0.05), sperm concentration 40 and 64 million/ml (P < 0.05), total sperm number 103 and 196 million (P < 0.05) and progressive motility 41% and 57% (P < 0.05). Smoking (odds ratio (OR) 2.35 (95% CI 1.06–5.21)) and a higher age at time of fertility preservation (OR 1.04 (95% CI 1.00–1.08)) were found to correlate with an impaired progressive motility. Twelve trans women reported to have used anti-androgens and estrogens, and all had discontinued for at least 3 months prior to the first attempt for semen cryopreservation. No correlation was found between previous gender-affirming hormone use and decreased semen parameters. The median post-thaw total motile sperm count was 1.0 million per vial (interquartile range 0.1–3.1) and in only 26.4% of thawed semen samples was the quality adequate for a minimally invasive IUI.LIMITATIONS, REASONS FOR CAUTIONLimitations include the retrospective design and insufficient data on transgender-specific factors, such as bringing the testes into the inguinal position (tucking), wearing tight underwear and low masturbation frequency.WIDER IMPLICATIONS OF THE FINDINGSSemen quality in trans women was decreased compared to the general population, which could not be explained by known risk factors, such as BMI, alcohol consumption, cannabis use, gender-affirming hormone use or abnormal endocrine laboratory results. Although a negative impact of smoking was observed, it was insufficient to explain the overall decreased semen quality in this cohort. Since low pre-freeze semen quality results in an even lower post-thaw semen quality, the majority of trans women and their female partner or surrogate may need an invasive and burdensome treatment to establish a pregnancy.STUDY FUNDING/COMPETING INTEREST(S)For this study, no external funding was obtained and there were no competing interests.TRIAL REGISTRATION NUMBERNA.

Thyroplasty Type III to Lower the Vocal Pitch in Trans Men.

About 20% of trans men do not achieve cisgender male frequencies (F0≤131 Hz) after gender-affirming hormone treatment (GAHT) with testosterone. The surgical procedure Isshiki thyroplasty type III (TPIII) is described to lower F0, but data on this technique in trans men are lacking. In this study, 8 trans men, unsatisfied with their voice after a minimum of 12 months of GAHT, underwent TPIII to lower F0 at the Department of Head and Neck Surgery at Ghent University Hospital. TPIII was performed by 1 surgeon using the same method each time. Pre- and postoperatively, an acoustic evaluation of the voice took place. The F0 dropped significantly from the preoperative mean of (154.60 ± 12.29) Hz to the postoperative mean of (105.37 ± 10.52) Hz (t = 9.821, P < .001). TPIII is an effective method for lowering the F0 in trans men who are not satisfied with their voice after long-term GAHT.