Brain connectivity dynamics in cisgender and transmen people with gender incongruence before gender affirmative hormone treatment.

Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self.

Medicolegal issues surrounding legal sex designations.

The medical profession is deeply involved in designating and amending the sex designations on legal records that themselves are not used clinically. The assumptions inherent in the current legal sex designation system and the criteria for amending such are being reexamined. The harms of the current legal sex designation system, especially for transgender people, have become increasingly recognized. Consequently, the appropriateness of the health care professional's participation in recording legal sex designations has been called into question. Herein, we describe the medicolegal challenges surrounding legal sex designations and their potential solutions.

Ovarian, breast, and metabolic changes induced by androgen treatment in transgender men.

Gender-affirming hormone therapy (GAHT) is often provided to transgender people. In this review of the literature, the current knowledge of ovarian, breast, and metabolic changes (body composition, insulin resistance, bone density, cardiovascular risk factors such as lipids, blood pressure, and hematocrit) observed following GAHT in adult transgender men is discussed. A body of literature concurs to describe that long-term androgen therapy in transgender men exerts atrophic effects on the breast. There is currently no evidence of an increased risk of breast cancer. Long-term testosterone treatment induces ovarian effects that become visible after 6 months of therapy. These changes consist of both macroscopic and microscopic alterations of ovarian morphology that mimic the typical ovarian aspect encountered in women with polycystic ovary syndrome but without an effect on antral follicle count. Metabolic effects of long-term androgen treatment in transgender men put them at par with cisgender men in terms of lipid profile, insulin resistance, and overall mortality. Body composition changes as desired after testosterone administration in most transgender men, and insulin resistance decreases with virilization. There are no detrimental effects on bone mineral density. Cardiometabolic risk and morbidity data are currently reassuring, even if certain studies show conflicting results. An increase in blood pressure and a decrease in high-density lipoprotein cholesterol have been reported as risk factors, whereas polycythemia is rare and treatable. Most available data are observational and based on biochemical markers instead of the more direct measures of cardiovascular damage. An explanation for these observed changes is mostly lacking. Psychological stress and lifestyle factors are often forgotten in a much needed integrated approach.

The uterus in transgender men.

Transgender men experience a disharmony between their birth sex and their intimate sense of gender belonging. Gender-affirming hormone therapy and gender-affirming surgery (GAS) are often inherently part of the gender-affirming process. In this context, we should ask whether it is better to keep or remove the uterus. Keeping the uterus and ovaries avoids a surgical procedure and a pubic scar. Furthermore, it preserves fertility and the possibility of carrying a baby. On the other hand, keeping the uterus is often psychologically unbearable for transgender men and the long-term effects of androgens on the uterus and ovaries remain uncertain. Conversely, hysterectomy and oophorectomy are part of the GAS process. New mini-invasive surgery procedures for hysterectomies decrease the risks and limit the likelihood of scars to a minimum. In practice, the data suggest that very few transgender men carry a pregnancy and/or use their oocytes after gender-reaffirming treatment. Clinicians should counsel their transgender men patients about the definitive infertility consequences of hysterectomy and oophorectomy and discuss all fertility preservation options before undertaking GAS. Individualized approaches must be preferred to systematic procedures regarding the personal decision to keep or not keep the uterus and ovaries.

Transgender men: clinical care and implications in reproductive medicine: introduction.

Gender dysphoria, a discrepancy between gender identity and genetically determined sex, is encountered in approximately 0.5% of people uniformly across the world. In the case of transgender men, formerly called female-to-male transsexuals, the available gender-affirming measures, hormone therapy and possible surgical procedures, are multiple and discussed in detail in this series of articles.

Masculinizing gender-affirming surgery for trans men and non-binary individuals: what you should know.

Gender dysphoria, the discordance between one's gender identity and anatomy, affects nearly 25 million people worldwide, and the prevalence of transgender and non-binary identities is increasing because of greater acceptance and awareness. Because of the improved accessibility to gender-affirming surgery (GAS), many providers will care for patients during and after gender transition. For trans men (female-to-male), GAS represents a combination of procedures rather than a single surgery. The particular combination of masculinizing procedures is chosen on the basis of informed patient-provider discussions regarding the patient's goals and anatomy and implemented through a multidisciplinary team approach. In this review, we describe the common procedures comprising masculinizing GAS to improve delivery of specialized care for this patient population.

Reproductive functions and fertility preservation in transgender women: a French case series.

RESEARCH QUESTION: The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed by gender-affirming surgery involving bilateral orchiectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender women mainly relies on sperm cryopreservation. There are few studies on this subject, and the sample sizes are small, and so it difficult to know whether fertility preservation procedures are feasible and effective in trans women. DESIGN: This retrospective study reports the management of fertility preservation in transgender women referred to the study centre for sperm cryopreservation, and the semen parameters of trans women were compared with those of sperm donors. RESULTS: Ninety-six per cent of transgender women who had not started treatment benefitted from sperm cryopreservation, compared with 80% of those who attempted a therapeutic window and 50% of those receiving hormonal treatment at the time of sperm collection. No major impairment of semen parameters was observed in transgender women who had not started GAHT compared with sperm donors. However, even though the frequency of oligozoospermia was no different, two transgender women presented azoospermia. Some transgender women who had started GAHT could benefit from sperm freezing. None of them were treated with gonadotrophin-releasing hormone (GnRH) analogues. CONCLUSIONS: Parenthood strategies for transgender people have long been ignored, but this is an important issue to consider, especially because medical treatments and surgeries may be undertaken in adolescents or very young adults. Fertility preservation should ideally be offered prior to initiation of GAHT.

Low feasibility of in vitro matured oocytes originating from cumulus complexes found during ovarian tissue preparation at the moment of gender confirmation surgery and during testosterone treatment for fertility preservation in transgender men.

OBJECTIVE: To study the feasibility of in vitro maturation of ovarian tissue oocytes for fertility preservation in transgender men on testosterone treatment. DESIGN: Cross-sectional study SETTING: University hospital PATIENT(S): Eighty-three transgender men enrolled from November 2015 to January 2019 INTERVENTION(S): In vitro maturation of cumulus-oocyte complexes (COCs) harvested at the time of gender confirmation surgery, and fertilization through intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): In vitro maturation, fertilization, and blastulation rates; comparison of morphokinetics with vitrified-warmed oocytes; and analysis of the genetic profiles of embryos. SECONDARY OUTCOMES: association between serum hormone levels; COCs' morphologic characteristics, and vitrification rate. RESULT(S): All participants were on testosterone treatment for a median of 83 (64[Quartile 1]; 113.2[Quartile 2]) weeks. A total of 1,903 COCs (mean per participant, 23 ± 15.8) were collected. The in vitro maturation rate was 23.8%, vitrification rate was 21.5%, and survival rate after warming was 72.6% (n = 151). Intracytoplasmic sperm injection was performed in 139 oocytes. The rate of normal fertilized oocytes was 34.5%, and 25 (52.1%) embryos reached day 3. One blastocyst was achieved on day 5. Aberrant cleavage patterns and early embryo arrest were observed in 22 (45.8%) and 44 (91.7%) zygotes, respectively. Compared with vitrified-warmed donor oocytes, a delay was observed in pronuclei disappearance, t2 (time to reach 2 cell stage) timings, and CC1 (the duration of the 1st cell cycle) and SS3 (synchronization of cleavage pattern (calculated as t8-t5) time intervals. A normal genetic pattern was seen in 42% embryos. The proportion of vitrified oocytes was negatively associated with progesterone (odds ratio, 0.76) and positively associated with antimüllerian hormone serum levels (odds ratio, 1.23). The highest vitrification rate was achieved by the morphologic characteristic 344 at day 0 and by 433 at day 2. CONCLUSION(S): Ovarian tissue oocytes matured in vitro show low developmental capacity in transgender men, when collected under testosterone treatment.

Sperm quality in transgender women before or after gender affirming hormone therapy-A prospective cohort study.

BACKGROUND: Due to recent changes in the legal framework, access to fertility preservation (FP) for transgender individuals has opened up in several countries. In Sweden and the Nordic countries, fertility preservation for medical reasons is fully reimbursed as part of the established tax-funded healthcare services. As this issue is relatively new, procedures for FP have seldom been reported in the transgender patient population. The very limited literature has indicated that transgender women may have poorer sperm quality than cisgender men when assessing samples aimed at semen banking. OBJECTIVES: To assess sperm quality parameters of semen samples provided for FP by transgender women before or after gender affirming hormone therapy (GAHT), and to compare sperm quality with a reference population of unscreened men defined by the World Health Organization (WHO). Additionally, we aimed to describe referral patterns over calendar time and estimate time from referral to semen cryopreservation. MATERIAL AND METHODS: Prospective cohort study of 212 transgender women referred for FP to the Reproductive Medicine Clinic of Karolinska University Hospital, Sweden, between 2013 and 2018. Among 177 individuals that provided semen samples for cryopreservation, 16 had previously received GAHT. RESULTS: Individuals with previous GAHT presented with significantly lower total sperm count than individuals without GAHT (p = 0.002). However, higher proportions of sperm abnormalities were also noted among individuals who had not undergone previous GAHT, compared to the WHO reference population (p < 0.001). Referrals of transgender women for FP increased over time. The median time from referral to semen cryopreservation was 27 days. CONCLUSIONS: A high occurrence of sperm abnormalities was found in transgender women, especially among individuals who had previously received GAHT. The results underline the importance of thoroughly discussing parenthood options and FP with patients early after diagnosis and referring the patients for semen banking preferably before starting GAHT.

Desarrollo y validación de la versión abreviada del Transsexual Voice Questionnaire for Male-to-Female Transsexuals en español / Development and validation of the Spanish abbreviated version of the Transsexual Voice Questionnaire for Male-to-Female Transsexuals

OBJETIVO: El objetivo de este estudio es crear y validar un cuestionario abreviado de la versión española del Transsexual Voice Questionnaire for Male-to-Female Transsexuals (VeTVQMtF). METODOLOGÍA: El estudio fue dirigido por 2 hospitales de referencia para la feminización quirúrgica de la voz y por un departamento universitario de psicología y rehabilitación vocal, todos ellos en España. MATERIAL Y MÉTODOS: Se realizó un estudio prospectivo de 51 mujeres transexuales a las que se les intervino de feminización quirúrgica de la voz entre enero 2017 y diciembre 2018. La VeTVQMtF fue rellenada por las mujeres transexuales antes y después de la cirugía y los 10 ítems de este cuestionario que más variaron fueron seleccionados por un grupo de expertos en feminización de la voz, para desarrollar la versión abreviada de la VeTVQMtF (VeTVQMtF-10). Se estudió la correlación entre la puntuación total y la puntuación de cada ítem en la VeTVQMtF y en la VeTVQMtF-10. Se analizó la consistencia interna de la VeTVQMtF-10. RESULTADOS: Se encontró una buena correlación entre los 2 cuestionarios (coeficiente de Pearson > 0,90), una buena correlación entre la puntuación total y la puntuación de cada ítem de la VeTVQMtF-10 y una correlación negativa entre la de la VeTVQMtF y la frecuencia fundamental de la voz tras la cirugía. El alfa Cronbach fue de 0,79. CONCLUSIÓN: La VeTVQMtF-10 es una versión abreviada válida de la VeTVQMtF y podría usarse para valorar la calidad de vida relacionada con la voz en mujeres transexuales en el idioma español

OBJECTIVE: The aim of this study was to create and validate an abbreviated version of the Spanish Transsexual Voice Questionnaire for Male-to-Female Transsexuals (SvTVQMtF). SETTING: The study was conducted by two referral hospitals for voice feminization surgery and by a university department of psychology and speech therapy, all in Spain. Subjects and methods: We prospectively studied 51 male-to-female transsexuals who underwent voice feminization surgery between January 2017 and December 2018. The SvTVQMtF was completed before and after surgery, and the 10 items with the greatest variation were selected by clinical consensus of an expert panel to develop the short version of the SvTVQMtF (SvTVQMtF-10). The correlation between the total score and the score for each item on the SvTVQMtF and the SvTVQMtF-10 was studied. The internal consistency of the SvTVQMtF-10 was analysed. RESULTS: Good correlation (Pearson coefficient above .90) was found between the two questionnaires. A significant correlation was found between the total SvTVQMtF-10 score and the score for each item. A significant negative correlation was found between the SvTVQMtF and fundamental frequency after voice feminization surgery. Cronbach's Alpha was .79. CONCLUSION: The SvTVQMtF-10 is a valid short version of the SvTVQMtF and can be used to quantify voice-related quality of life in MtF transsexuals

Efficacy of Sex Steroid Therapy Without Progestin or GnRH Agonist for Gonadal Suppression in Adult Transgender Patients.

CONTEXT: Testosterone (T) or estradiol (E2) are administered to suppress gonadal function in female-to-male (FTM) and male-to-female (MTF) transgender patients. How often sex steroids cause adequate suppression without GnRH agonist (GnRHa) or progestin therapy has not been reported. OBJECTIVES: (1) To determine how often T and E2 therapy alone can effectively suppress gonadal function in MTF and FTM transgender patients, and (2) to determine the frequency and range of serum E2 levels above the normal male range in FTM patients receiving T therapy. DESIGN: Retrospective cohort study. SETTING: Outpatient reproductive endocrinology clinic at an academic medical center. PATIENTS: A total of 65 FTM and 33 MTF patients were included who were > 18 years of age and not receiving progestin or GnRHa therapy. INTERVENTION: Female-to-male patients were receiving T through injections or gel. Male-to-female patients were receiving oral or subcutaneous E2. MAIN OUTCOME MEASUREMENTS: In FTM patients the indicator of ovary suppression was amenorrhea. In MTF patients, the indicator of testes suppression was T levels <50 ng/dL. RESULTS: Median serum total T level for FTM patients was 712 ng/dL (range, 370-1164 ng/dL). On T therapy alone, 90.8% of patients achieved amenorrhea and 49.2% of patients had serum E2 levels above the normal range for women. For MTF patients, the median serum E2 level was 129.2 pg/mL (range, 75-197 pg/mL). On E2 therapy alone, 84.8% of MTF patients had adequate suppression of testicular function. CONCLUSIONS: Testosterone and E2 therapy are usually effective without progestin or GnRHa therapy to suppress gonadal function in transgender patients. Progestin and/or GnRHa therapy should only be initiated in those patients who do not have adequate gonadal suppression on optimized doses of T or E2 alone.

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

CONTEXT: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. OBJECTIVE: To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. DESIGN: Observational prospective study. SUBJECTS: 51 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 MEASURES: Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. RESULTS: At 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. CONCLUSIONS: BMAD 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.

Transgender Men and the Gynecologist.

Recently, greater attention has been paid to the care of gender dysphoric and gender incongruent individuals. Gynecologists may be called upon to care for individuals who were assigned female at birth throughout or following social, medical, or surgical gender transition. Thus, gynecologists need to be aware of language regarding sex and gender, treatment typically used for the care of gender dysphoric or incongruent individuals, and aspects of well gynecologic care necessary for these individuals. This review highlights these aspects of care for transgender males to aid the general gynecologist in the care and treatment of these individuals.

Transwomen and bone mineral density: a cross-sectional study in Brazilian population.

OBJECTIVES: Transgender individuals submitted to hormone or surgical treatment may have alterations in their bone metabolism as these elements are important players in bone remodeling. We aimed to study bone mineral density (BMD) and body composition in transwomen undergoing cross-sex hormonal treatment (CSHT) from Brazil for over 3 years, comparing them with female and male controls. METHODS: 93 individuals (31 transwomen, 31 females and 31 males paired for age and body mass index) were studied for bone mass, and body composition by densitometry (by DXA). Epidemiological and clinical data were collected through direct questioning. RESULTS: Low bone mass (T score ≤2) was found in 12.9% of transwomen; in 3.2% of females and 3.3% of males. Transwomen individuals had lower spine Z score (0.26 ± 1.42 vs 0.50 ± 1.19) and femur Z score (-0.41 ± 0.95 vs 0.29 ± 1.04) than females. They had lower total femur Z score than males (-0.41 ± 0.95 vs 0.20 ± 0.83). Lean mass values correlated positively with total femur BMD (ρ = 0.40; 95% confidence interval = 0.009-0.68; p = 0.04) and BMD in femoral neck (ρ = 0.48; 95% confidence interval = 0.11-0.74; p = 0.01) but neither the type of therapy received nor the time that they were used, impacted bone mass. CONCLUSION: Low BMD is found frequently in transwomen and it is correlated with lean body mass. ADVANCES IN KNOWLEDGE: There are few studies of the effects of hormone therapy on the bones and muscles of transwomen. This study demonstrated that significant changes occur, and that the population studied needs greater care in musculoskeletal health.

Valuing the Vulnerable - The Important Role of Transgender Communities in Biomedical Research.

Every cell has a genetic sex that is determined at the time of fertilization. However, the natal sex of cells may not match the hormonal environment in which they reside in transgender individuals. This discordance provides a unique opportunity to study the short- and long-term effects across a range of cellular functions, health conditions, physiologic processes and psychosocial outcomes to the benefit of transgender and cisgender communities. While there is a growing body of knowledge as the literature on sex differences in virtually every organ system accumulates, there remains a paucity of data on the effect of cross hormonal therapy on cellular function in transgender individuals. Beyond cellular function, the effect of cross hormonal therapy on neuroanatomy, the interpretation of neuropsychological assessments or even the effect of daily stressors of stigma and discrimination on long-term neurocognitive function remain unclear. In 2011 the Institute of Medicine indicated that transgender adults were an understudied population and in critical need of more biomedical and population health research, yet the experience of stigma, discrimination, microaggressions, limited access to culturally competent care continue to make this an unfulfilled mandate. In addition to using a life course perspective, it is essential to identify research gaps and formulate a responsive research agenda while maintaining scientific rigor and respectful involvement of the population under study. None of this, however, will enhance the participation of transgender communities in biomedical research until the transgender and biomedical research communities can engage in open, respectful and bidirectional dialogue. From respectful, sensitive and appropriate health care to culturally competent research engagement from study inception to data dissemination, transgender communities can make an important and valuable contribution to biomedical research. Inclusion of their voices at all levels, including investigators from transgender communities, are essential to advance this much overdue scientific agenda. Transgender, cisgender and the biomedical research communities will all benefit from a more inclusive and expansive research agenda.

Validation of the German Version of the Transsexual Voice Questionnaire for Male-to-Female Transsexuals.

OBJECTIVE: The purpose of this study was to examine the psychometric properties of the German translation of the Transsexual Voice Questionnaire for Male-to-Female Transsexuals (TVQMtF), an instrument assessing the voice-related quality of life (VrQoL) in trans women. STUDY DESIGN: This is a cross-sectional study. METHOD: The conducted online survey contained the TVQMtF as well as a generic measurement of VrQoL (Voice Handicap Index) and items on transition. Data of 127 trans women were analyzed computing coefficients of reliability and convergent validity. Additionally, confirmatory factor analysis and model modification were performed. RESULTS: Analyses revealed excellent internal consistency (α = 0.97), split-half reliability (rSB = 0.95) and good convergent validity. Significant associations were found between the total scores of the German TVQMtF and the Voice Handicap Index (r = 0.88; P < 0.001) as well as the vocal self-perception (r = -0.57; P < 0.001). An acceptable model with a two-factor structure including 22 of the 30 items was found. CONCLUSIONS: The TVQMtF is the first German reliable and valid measurement of VrQoL for trans women. Therefore, its utilization can be recommended for clinical and research purposes in the fields of voice therapy and surgery.