Neural and Hormonal Correlates of Sexual Arousal in Transgender Persons.

BACKGROUND: Whereas mounting work has begun to document the neural correlates underlying sexual arousal (SA) in humans, the associations between gender identity and the brain correlates of SA as well as their hormonal contributions remain unknown. AIM: This study investigated neural activation to sexual arousal in transgender and cisgender persons. METHODS: 20 transgender men and 19 transgender women (TW) already living in their identified gender were compared to 21 cisgender men (CM) and 19 cisgender women. Participants viewed erotic and neutral video clips while undergoing 3 Tesla magnetic resonance imaging. OUTCOMES: Group-specific brain activation, brain functional connectivity, and brain-hormone associations within the neurophenomenological model of sexual arousal (Stoleru et al, 2012). RESULTS: Consistent with the model, participants activated most of its components. However, between-group differences were mostly showing larger activation for CM relative to any of the other 3 groups. Moreover, functional connectivity analyses (psychophysiological interactions) indicated unique patterns for CM, cisgender women, and TW in how different components of SA communicated with one another. Finally, androgens in transgender men and estrogens in TW correlated negatively with parietal cortex and primary (sensori-) motor regions, respectively, while CM showed positive correlations of androgens with parietal cortex, somatosensory regions, and the insula. CLINICAL IMPLICATIONS: Data provide information on neurobiological changes in sexual arousal during treatment with gender-affirming hormone therapy. STRENGTHS & LIMITATIONS: Although a limitation is the lack of pretreatment data, the present study provides comprehensive information including brain activation, functional connectivity, and hormonal associations in a large sample. CONCLUSIONS: The results highlight a complex picture of the neural correlates of SA in gender identity and sex assigned at birth. Mueller SC, Wierckx K, T'Sjoen G. Neural and Hormonal Correlates of Sexual Arousal in Transgender Persons. J Sex Med 2020;17:2495-2507.

Neural correlates of ostracism in transgender persons living according to their gender identity: a potential risk marker for psychopathology?

BACKGROUND: Stigmatization in society carries a high risk for development of psychopathology. Transgender persons are at particularly high risk for such stigmatization and social rejection by others. However, the neural correlates of ostracism in this group have not been captured. METHOD: Twenty transgender men (TM, female-to-male) and 19 transgender women (TW, male-to-female) already living in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW) completed a cyberball task assessing both exclusion and re-inclusion during functional magnetic resonance imaging (fMRI). RESULTS: During psychosocial stress between-group differences were found in the dorsal and ventral anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG relative to CM and TW. During re-inclusion, transgender persons showed greater ventral ACC activity relative to CW, possibly indicating persistent feelings of exclusion. Functional connectivity analyses supported these findings but showed a particularly altered functional connectivity between ACC and lateral prefrontal cortex in TM, which may suggest reduced emotional regulation to the ostracism experience in this group. Depressive symptoms or hormonal levels were not associated with these findings. CONCLUSION: The results bear implications for the role of social exclusion in development of mental health problems in socially marginalized groups.

A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Sex Hormone Therapy.

BACKGROUND: To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of long-term cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. METHODS: Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were presence of psychiatric or neurological disorders. RESULTS: The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and a smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. CONCLUSIONS: Neuroanatomical differences were region specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy.

Prevalence of Gender Nonconformity in Flanders, Belgium.

Gender nonconformity refers to the extent to which a person's gender identity, gender role and/or gender expression differs from the cultural norms prescribed for people of a particular sex, within a certain society and era. Most data on gender nonconformity focus on the prevalence of gender dysphoria (which also includes a distress factor) or on the number of legal sex changes. However, not every gender nonconforming individual experiences distress or applies for treatment. Population-based research on the broad spectrum of gender nonconformity is scarce and more information on the variance outside the gender binary is needed. This study aimed to examine the prevalence of gender incongruence (identifying stronger with the other sex than with the sex assigned at birth) and gender ambivalence (identifying equally with the other sex as with the sex assigned at birth) based on two population-based surveys, one of 1,832 Flemish persons and one of 2,472 sexual minority individuals in Flanders. In the general population, gender ambivalence was present in 2.2 % of male and 1.9 % of female participants, whereas gender incongruence was found in 0.7 % of men and 0.6 % of women. In sexual minority individuals, the prevalence of gender ambivalence and gender incongruence was 1.8 and 0.9 % in men and 4.1 and 2.1 % in women, respectively. With a current Flemish population of about 6 million, our results indicate a total of between 17,150 and 17,665 gender incongruent men and between 14,473 and 15,221 gender incongruent women in Flanders.

Clinical review: Breast development in trans women receiving cross-sex hormones.

INTRODUCTION: In trans women (male-to-female transsexual persons), cross-sex hormone therapy is administered to induce feminization. Breast development is an important part of feminization for most trans women. AIM: The aim of this study is to assess the effect of cross-sex hormone therapy on breast development in adult trans women. Additionally, we aimed to investigate the benefit or harm of administration of progestogens on breast development. METHODS: A review of the literature in Embase, Medline, The Cochrane Library, PsycINFO databases, PubMed, and Web of Knowledge until January 2014. MAIN OUTCOME MEASURES: Effects of cross-sex hormone therapy and progestogens on breast development in trans women. RESULTS: Only few studies with low quality of evidence addressed these topics. The available evidence suggests that breast development is insufficient for the majority of trans women and that type and dosage of hormonal therapy seem not to have an important role on final breast size. CONCLUSIONS: Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions.

Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence.

INTRODUCTION: Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities. AIM: The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons). METHODS: This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 µg/24 hours transdermal 17-ß estradiol. MAIN OUTCOME MEASURES: Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined. RESULTS: No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P ≤ 0.01). Testosterone therapy increased acne scores, facial and body hair, and prevalence of androgenetic alopecia. Waist-hip ratio, muscle mass, triglycerides, total cholesterol (C), and LDL-C increased, whereas total body fat mass and HDL-C decreased. Three trans women experienced transient elevation of liver enzymes. A significant increase in breast tenderness, hot flashes, emotionality, and low sex drive was observed (all P ≤ 0.02). Fasting insulin, total body fat mass, and prolactin levels increased, and waist-hip ratio, lean mass, total C, and LDL-C decreased. CONCLUSIONS: Current treatment modalities were effective and carried a low risk for side effects and adverse events at short-time follow-up.

Short- and long-term clinical skin effects of testosterone treatment in trans men.

INTRODUCTION: Our knowledge concerning the effects of testosterone (T) therapy on the skin of trans men (female-to-male transsexuals) is scarce. AIM: The aim of this study was to evaluate the short- and long-term clinical effects of T treatment on the skin of trans men. METHODS: We conducted a prospective intervention study in 20 hormone naive trans men and a cross-sectional study in 50 trans men with an average of 10 years on T therapy. MAIN OUTCOME MEASURES: Acne lesions were assessed using the Gradual Acne Grading Scale, hair patterns using the Ferriman and Gallwey classification (F&G), and androgenetic alopecia using the Norwood Hamilton Scale. RESULTS: T treatment increased facial and body hair growth. The F&G score increased progressively from a median value of 0.5 at baseline to a value of 12 after 12 months of T administration. After long-term T treatment, all but one trans man achieved an F&G score indicative of hirsutism in women, with a median value of 24. Only one trans man acquired mild frontotemporal hair loss during the first year of T treatment, whereas 32.7% of trans men had mild frontotemporal hair loss and 31% had moderate to severe androgenetic alopecia after long-term T therapy. The presence and severity of acne increased during the first year of T therapy, and peaked at 6 months. After long-term T treatment, most participants had no or mild acne lesions (93.9%). Dermatological outcome was not demonstrably related to individual serum T or dihydrotestosterone levels. CONCLUSIONS: T treatment increased facial and body hair in a time-dependent manner. The prevalence and severity of acne in the majority of trans men peaked 6 months after beginning T therapy. Severe skin problems were absent after short- and long-term T treatment.

Sexual desire in trans persons: associations with sex reassignment treatment.

INTRODUCTION: Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons. AIM: This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons. METHODS: A cross-sectional single specialized center study including 214 trans women (male-to-female trans persons) and 138 trans men (female-to-male trans persons). MAIN OUTCOME MEASURES: Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction. RESULTS: In retrospect, 62.4% of trans women reported a decrease in sexual desire after SRT. Seventy-three percent of trans women never or rarely experienced spontaneous and responsive sexual desire. A third reported associated personal or relational distress resulting in a prevalence of HSDD of 22%. Respondents who had undergone vaginoplasty experienced more spontaneous sexual desire compared with those who planned this surgery but had not yet undergone it (P = 0.03). In retrospect, the majority of trans men (71.0%) reported an increase in sexual desire after SRT. Thirty percent of trans men never or rarely felt sexual desire; 39.7% from time to time, and 30.6% often or always. Five percent of trans men met the criteria for HSDD. Trans men who were less satisfied with the phalloplasty had a higher prevalence of HSDD (P = 0.02). Trans persons who were more satisfied with the hormonal therapy had a lower prevalence of HSDD (P = 0.02). CONCLUSION: HSDD was more prevalent in trans women compared with trans men. The majority of trans women reported a decrease in sexual desire after SRT, whereas the opposite was observed in trans men. Our results show a significant sexual impact of surgical interventions and both hormonal and surgical treatment satisfaction on the sexual desire in trans persons.

Bilateral non-arteritic ischemic optic neuropathy in a transsexual woman using excessive estrogen dosage.

We present a case report on a 53-year-old transsexual woman who developed acute painless vision loss in both eyes during cross-sex hormone treatment. After 10 months of cross-sex hormone treatment, she experienced total vision loss of the right eye and, 6 months later, vision loss to 20/63 in the left eye. After a full ophthalmic exam, bilateral sequential non-arteritic ischemic optic neuropathy (NA-ION) was diagnosed. Extensive etiological work-up revealed no cardiac abnormalities or inherited blood-clotting disorders. A manifest self-administered overdose of transdermal estrogen treatment with serum estradiol levels of 5,765 pg/ml was possibly related to the sequential bilateral NA-ION resulting in nearly total vision loss in this transsexual woman.

Long-term evaluation of donor-site morbidity after radial forearm flap phalloplasty for transsexual men.

INTRODUCTION: Phalloplasty using the radial forearm flap is currently the most frequently used technique to create the neophallus in transsexual men (formerly described as female-to-male transsexual persons). Although it is considered the gold standard, its main disadvantage is the eventual donor-site morbidity in a young, healthy patient population. AIM: The study aims to examine the long-term effects of radial forearm flap phalloplasty in transsexual men and to evaluate aesthetic outcome, scar acceptance, bone health, and daily functioning. MAIN OUTCOME MEASURES: Scars were evaluated with the patient and observer scar assessment scale, the Vancouver Scar Scale, and self-reported satisfaction. Bone health was assessed using dual X-ray absorptiometry and peripheral quantitative computed tomography, and daily functioning using a physical activity questionnaire (Baecke). These measurements were compared with 44 age-matched control women. METHODS: This is a cross-sectional study of 44 transsexual, a median of 7 years after radial forearm flap phalloplasty, recruited from the Center for Sexology and Gender Problems at the Ghent University Hospital, Belgium. RESULTS: We observed no functional limitations on daily life activities, a pain-free and rather aesthetic scar, and unaffected bone health a median of 7 years after radial foreram flap phalloplasty. Over 75% of transsexual men were either satisfied or neutral with the appearance of the scar. CONCLUSIONS: Transsexual men, despite scarring the forearm, consider the radial forearm flap phalloplasty as worthwhile.

The Belgian Diabetes in Pregnancy Follow-Up Study (BEDIP-FUS): A Multi-Centric Prospective Cohort Study on the Long-Term Metabolic Risk across Different Degrees of Gestational Glucose Intolerance: Methodology and Design.

The Belgian Diabetes in Pregnancy follow-up study (BEDIP-FUS) aims to investigate the impact of body mass index (BMI), adiposity and different degrees of glucose intolerance on the metabolic profile and future risk for type 2 diabetes (T2D) in women and offspring five years after delivery in the BEDIP study. The BEDIP study was a prospective cohort study to evaluate different screening strategies for gestational diabetes (GDM) based on the 2013 WHO criteria. The aim of the BEDIP-FUS is to recruit 375 women-offspring pairs, stratified according to three different subgroups based on the antenatal result of the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during the BEDIP pregnancy. The follow-up visit consists of a 75 g OGTT, anthropometric measurements and questionnaires for the mothers, and a fasting blood sample with anthropometric measurements for the child. Primary outcome for the mother is glucose intolerance defined by the American Diabetes Association criteria and for the offspring the BMI z-score. Recruitment began in January 2021. The BEDIP-FUS study will help to better individualize follow-up in women with different degrees of hyperglycemia in pregnancy and their offspring.

Reproductive wish in transsexual men.

BACKGROUND: Hormonal therapy and sex reassignment surgery (SRS) in transsexual persons lead to an irreversible loss of their reproductive potential. The current and future technologies could create the possibility for female-to-male transsexual persons (transsexual men) to have genetically related children. However, little is known about this topic. The aim of this study is to provide information on the reproductive wishes of transsexual men after SRS. METHODS A self-constructed questionnaire was presented to 50 transsexual men in a single-center study. RESULTS: The majority (64%) of transsexual men were currently involved in a relationship. Eleven participants (22.0%) reported having children. For eight participants, their female partner was inseminated with donor sperm, whereas three participants gave birth before hormonal therapy and SRS. At the time of interview, more than half of the participants desired to have children (54%). There were 18 participants (37.5%) who reported that they had considered freezing their germ cells, if this technique would have been available previously. Participants without children at the time of investigation expressed this desire more often than participants with children (χ²; test: P= 0.006). CONCLUSIONS: Our data reveal that the majority of transsexual men desire to have children. Therefore, more attention should be paid to this topic during the diagnostic phase of transition and to the consequences for genetic parenthood after starting sex reassignment therapy.

Long-term evaluation of cross-sex hormone treatment in transsexual persons.

INTRODUCTION: Long-term effects and side effects of cross-sex hormone treatment in transsexual persons are not well known. AIM: The aim of this study is to describe the effects and side effects of cross-sex hormone therapy in both transsexual men and women. MAIN OUTCOME MEASURES: Hormone levels were measured by immunoassays. Physical health was assessed by physical examination and questionnaires on general health and specific side effects, areal bone parameters by dual energy X-ray absorptiometry. METHODS: Single center cross-sectional study in 100 transsexual persons post-sex reassignment surgery and on average 10 years on cross-sex hormone therapy. RESULTS: Transsexual men did not experience important side effects such as cardiovascular events, hormone-related cancers, or osteoporosis. In contrast, a quarter of the transsexual women had osteoporosis at the lumbar spine and radius. Moreover, 6% of transsexual women experienced a thromboembolic event and another 6% experienced other cardiovascular problems after on average 11.3 hormone treatment years. None of the transsexual women experienced a hormone-related cancer during treatment. CONCLUSION: Cross-sex hormone treatment appears to be safe in transsexual men. On the other hand, a substantial number of transsexual women suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management.

Quality of life and sexual health after sex reassignment surgery in transsexual men.

INTRODUCTION: Although sexual health after genital surgery is an important outcome factor for many transsexual persons, little attention has been attributed to this subject. AIMS: To provide data on quality of life and sexual health after sex reassignment surgery (SRS) in transsexual men. METHODS: A single-center, cross-sectional study in 49 transsexual men (mean age 37 years) after long-term testosterone therapy and on average 8 years after SRS. Ninety-four percent of the participants had phalloplasty. MAIN OUTCOME MEASURES: Self-reported physical and mental health using the Dutch version of the Short Form-36 Health Survey; sexual functioning before and after SRS using a newly constructed specific questionnaire. RESULTS: Compared with a Dutch reference population of community-dwelling men, transsexual men scored well on self-perceived physical and mental health. The majority reported having been sexually active before hormone treatment, with more than a quarter having been vaginally penetrated frequently before starting hormone therapy. There was a tendency toward less vaginal involvement during hormone therapy and before SRS. Most participants reported an increase in frequency of masturbation, sexual arousal, and ability to achieve orgasm after testosterone treatment and SRS. Almost all participants were able to achieve orgasm during masturbation and sexual intercourse, and the majority reported a change in orgasmic feelings toward a more powerful and shorter orgasm. Surgical satisfaction was high, despite a relatively high complication rate. CONCLUSION: Results of the current study indicate transsexual men generally have a good quality of life and experience satisfactory sexual function after SRS.

Value and pitfalls in iodine fortification and supplementation in the 21st century.

Although the number of iodine-deficient countries has been reduced by almost 50 % over the last decade, it still remains a frequently misunderstood health problem. The most devastating effects of iodine deficiency occur during fetal development and childhood, periods in which sufficient iodine delivery remains critical. Besides the determination of thyroid size, the concentration of urinary iodine, serum thyroid-stimulating hormone and serum thyroglobulin are useful biomarkers to assess iodine status. Severe iodine deficiency is associated with neurological complications, cretinism, endemic goitre development, hypothyroidism, decreased fertility and increased infant mortality. The recommended iodine supplementation strategies are based on correction of iodine deficiency, close monitoring and evaluation of iodine administration, cooperation of the salt industry, training of local health care professionals and education of the population. Besides the multiple beneficial effects of supplementation, we present in this review a critical look at the possible side effects.

Ten years of fertility treatment experience and reproductive options in transgender men.

BACKGROUND: Up to 2018, the Belgian law stated that transgender people who wanted to change their legal sex had to undergo physical gender affirming treatment. This included gonadectomy to a medically possible and justified extent, which entailed that they had to accept the fact that they could no longer reproduce. However, research has shown that many transgender people desire to have children. AIMS: (1) to describe a cohort of transgender men and their respective cisgender female partners, to share our experiences with their request for donor conception, and to evaluate their disclosure intentions to the child, (2) to explore how the couples approach current and future reproductive options. METHODS: This mixed method study presents data from a retrospective analysis of patient records and from a qualitative interview study. The couples were selected from the group of transgender men who - together with their respective cisgender female partners - applied for sperm donation at Ghent University Hospital between 2002 and 2012. RESULTS: Forty-seven transgender men with a cisgender female partner requested treatment with anonymous donor sperm for a first child as a couple. Forty-one requests were accepted for treatment. We found that most couples requesting treatment intended to disclose the use of donor sperm to their future child (n = 34) while 24 couples were planning to inform the child about the parent's transgender identity. The six couples we interviewed saw donor conception as the preferred route to become parents. Adoption was seen as less obvious. The couples' attitudes toward stem cell-derived gametes reflected the significance of the genetic link with the child for both parents. DISCUSSION: Not all participants in our study were aware of their reproductive options. To be able to make a well-informed decision, transgender people should be counseled about all options at the time of transition.

Adrenal insufficiency, be aware of drug interactions!

SUMMARY: A 42-year-old man with complaints of muscle soreness and an increased pigmentation of the skin was referred because of a suspicion of adrenal insufficiency. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency (PAI) and treatment with hydrocortisone and fludrocortisone was initiated. An etiological workup, including an assessment for anti-adrenal antibodies, very long-chain fatty acids, 17-OH progesterone levels and catecholamine secretion, showed no abnormalities. 18Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands and bilateral presence of an adrenal nodule, with 18fluorodeoxyglucose accumulation. A positive tuberculin test and positive family history of tuberculosis were found, and tuberculostatic drugs were initiated. During the treatment with the tuberculostatic drugs the patient again developed complaints of adrenal insufficiency, due to insufficient dosage of hydrocortisone because of increased metabolism of hydrocortisone. LEARNING POINTS: Shrinkage of the adrenal nodules following tuberculostatic treatment supports adrenal tuberculosis being the common aetiology. The tuberculostatic drug rifampicin is a CYP3A4 inducer, increasing the metabolism of hydrocortisone. Increase the hydrocortisone dosage upon initiation of rifampicin in case of (adrenal) tuberculosis. A notification on the Addison's emergency pass could be considered to heighten physician's and patients awareness of hydrocortisone drug interactions.

Circulating androgens correlate with resting-state MRI in transgender men.

Despite mounting evidence regarding the underlying neurobiology in transgender persons, information regarding resting-state activity, particularly after hormonal treatment, is lacking. The present study examined differences between transgender persons on long-term cross-sex hormone therapy and comparisons on two measures of local functional connectivity, intensity of spontaneous resting-state activity (low frequency fluctuations, LFF) and local synchronization of specific brain areas (regional homogeneity, ReHo). Nineteen transgender women (TW, male-to-female), 19 transgender men (TM, female-to-male), 21 non-transgender men (NTM) and 20 non-transgender women (NTW) underwent a resting-state MRI scan. The results showed differences between transgender persons and non-transgender comparisons on both LFF and ReHo measures in the frontal cortex, medial temporal lobe, and cerebellum. More interestingly, circulating androgens correlated for TM in the cerebellum and regions of the frontal cortex, an effect that was associated with treatment duration in the cerebellum. By comparison, no associations were found for TW with estrogens. These data provide first evidence for a potential masculinization of local functional connectivity in hormonally-treated transgender men.