Psychosocial Functioning in Transgender Youth after 2 Years of Hormones.

BACKGROUND: Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol). METHODS: We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children's Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome. RESULTS: A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants. CONCLUSIONS: In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

[Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria]. / Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie.

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.

Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.

OBJECTIVES: The phase 2 MANTA and MANTA-RAy studies aimed to determine if the oral Janus kinase 1 preferential inhibitor filgotinib affects semen parameters and sex hormones in men with inflammatory diseases. METHODS: MANTA (NCT03201445) and MANTA-RAy (NCT03926195) included men (21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases (rheumatoid arthritis, spondyloarthritis or psoriatic arthritis), respectively. Eligible participants had semen parameters in the normal range per the WHO definition. In each study, participants were randomised 1:1 to receive once-daily, double-blind filgotinib 200 mg or placebo for 13 weeks for pooled analysis of the primary endpoint (proportion of participants with a ≥50% decrease from baseline in sperm concentration at week 13). Participants who met the primary endpoint were monitored over an additional 52 weeks for 'reversibility'. Secondary endpoints included change from baseline to week 13 in: sperm concentration, total motility, normal morphology, total count and ejaculate volume. Sex hormones (luteinising hormone, follicle stimulating hormone, inhibin B and total testosterone) and reversibility were exploratory endpoints. RESULTS: Across both studies, 631 patients were screened, and 248 were randomised to filgotinib 200 mg or placebo. Baseline demographics and characteristics were similar within indications between treatment groups. Numerically similar proportions of filgotinib-treated versus placebo-treated patients met the primary endpoint (8/120 (6.7%) vs 10/120 (8.3%)), Δ-1.7% (95% CI -9.3% to 5.8%)). There were no clinically relevant changes from baseline to week 13 in semen parameters or sex hormones, or patterns of reversibility between treatment groups. Filgotinib was well tolerated, with no new safety events. CONCLUSIONS: Results suggest that once daily filgotinib 200 mg for 13 weeks has no measurable impact on semen parameters or sex hormones in men with active IBD or inflammatory rheumatic diseases.

Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on seizure frequency of postmenopausal women with epilepsy-A systematic review.

BACKGROUND AND PURPOSE: Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE. METHODS: PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool. RESULTS: Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results. CONCLUSIONS: There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population.

Hormonothérapie injectable et réduction des risques : pratiques, difficultés, santé des personnes trans en France.

INTRODUCTION: Hormone therapy (HT) adherence practices among trans people are poorly studied. For a large proportion of these people, HT is administered parenterally. The unavailability of certain treatments in France, combined with poor institutional care, keeps injectors away from the health care system and encourages potentially risky injection practices. Following a significant increase in the number of trans people in its active list, the association Safe, coordinator of the remote harm reduction system in France, conducted a cross-sectional descriptive study from December 2020 to February 2021 using an anonymous self-administered online questionnaire. PURPOSE OF RESEARCH: The objective is to better understand the profile of trans people who inject their HT and their injection practices. RESULTS: We observed that a significant proportion of trans injectors do not benefit from professional support, either to obtain treatment or to carry out the injection. This situation can lead to certain misuses of medical supplies, such as needle sharing or reuse, which present significant health risks. This is especially true for injectors whose treatment is not legally available and who obtain it through parallel markets. This study also underlines the importance of self-support associations to accompany transition. CONCLUSIONS: We therefore propose that a harm reduction policy adapted to the practices of trans people be implemented in order to better support this population and avoid the emergence of major health problems such as HIV infection.

Effect of Mirena intrauterine device combined with GNRH-A on endometriosis, sex hormone level and carbohydrate antigen 125.

To investigate the clinical value of Mirena (levonorgestrel intrauterine sustained release system) combined with gonadotropin-releasing hormone agonist (GnRH-a) in patients with endometriosis, 80 patients with endometriosis (March 2019 ~ March 2020) were selected as the research object. According to the "random number table method", they were divided into the control group (treated with GnRH-a) and the observation group (treated with Mirena IUD combined with GnRH-a), with 40 cases included in each group. The total clinical efficacy, sex hormone level, carbohydrate antigen 125 (CA125) level, degree of pain and recurrence rate indexes were compared between the two groups. Results showed that the total effective rate of 92.50% in the observation group was higher than 75.00% in the control group (P < 0.05). Intercourse pain of dysmenorrhea and sexual intercourse pain (VAS) in the two groups were compared before treatment. After treatment, the VAS scores in the two groups decreased, and the VAS scores in the observation group were lower than those in the control group (P<0.05). The levels of E2, FSH, LH and CA125 in the observation group were lower than in the control group (P<0.05). The recurrence rate of 5.00% in the observation group was lower than 20.00% in the control group (P<0.05). In conclusion, Mirena IUD combined with GnRH-a can improve the clinical efficacy of endometriosis, improve ovarian function, effectively regulate serum factors, further alleviate the symptoms of sexual intercourse pain and dysmenorrhea, control the risk of postoperative recurrence and achieve an ideal therapeutic effect.

SIGIS-SIAMS-SIE position statement of gender affirming hormonal treatment in transgender and non-binary people.

PURPOSE: Gender Incongruence (GI) is a marked and persistent incongruence between an individual's experienced and the assigned gender at birth. In the recent years, there has been a considerable evolution and change in attitude as regards to gender nonconforming people. METHODS: According to the Italian Society of Gender, Identity and Health (SIGIS), the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE) rules, a team of experts on the topic has been nominated by a SIGIS-SIAMS-SIE Guideline Board on the basis of their recognized clinical and research expertise in the field, and coordinated by a senior author, has prepared this Position statement. Later on, the present manuscript has been submitted to the Journal of Endocrinological Investigation for the normal process of international peer reviewing after a first internal revision process made by the SIGIS-SIAMS-SIE Guideline Board. RESULTS: In the present document by the SIGIS-SIAMS-SIE group, we propose experts opinions concerning the psychological functioning, gender affirming hormonal treatment, safety concerns, emerging issues in transgender healthcare (sexual health, fertility issues, elderly trans people), and an Italian law overview aimed to improve gender non-conforming people care. CONCLUSION: In this Position statement, we propose experts opinions concerning the psychological functioning of transgender people, the gender-affirming hormonal treatment (full/partial masculinization in assigned female at birth trans people, full/partial feminization and de-masculinization in assigned male at birth trans people), the emerging issues in transgender health care aimed to improve patient care. We have also included an overview of Italian law about gender affirming surgery and registry rectification.

Sex and Gender Considerations in Episodic Migraine.

PURPOSE OF REVIEW: We seek to update readers on recent advances in our understanding of sex and gender in episodic migraine with a two part series. In part 1, we examine migraine epidemiology in the context of sex and gender, differences in symptomatology, and the influence of sex hormones on migraine pathophysiology (including CGRP). In part 2, we focus on practical clinical considerations for sex and gender in episodic migraine by addressing menstrual migraine and the controversial topic of hormone-containing therapies. We make note of data applicable to gender minority populations, when available, and summarize knowledge on gender affirming hormone therapy and migraine management in transgender individuals. Finally, we briefly address health disparities, socioeconomic considerations, and research bias. RECENT FINDINGS: Migraine is known to be more prevalent, frequent, and disabling in women. There are also differences in migraine co-morbidities and symptomatology. For instance, women are likely to experience more migraine associated symptoms such as nausea, photophobia, and phonophobia. Migraine pathophysiology is influenced by sex hormones, e.g., estrogen withdrawal as a known trigger for migraine. Other hormones such as progesterone and testosterone are less well studied. Relationships between CGRP (the target of new acute and preventive migraine treatments) and sex hormones have been established with both animal and human model studies. The natural course of migraine throughout the lifetime suggests a contribution from hormonal changes, from puberty to pregnancy to menopause/post-menopause. Treatment of menstrual migraine and the use of hormone-containing therapies remains controversial. Re-evaluation of the data reveals that stroke risk is an estrogen dose- and aura frequency-dependent phenomenon. There are limited data on episodic migraine in gender minorities. Gender affirming hormone therapy may be associated with a change in migraine and unique risks (including ischemic stroke with high dose estrogen). There are key differences in migraine epidemiology and symptomatology, thought to be driven at least in part by sex hormones which influence migraine pathophysiology and the natural course of migraine throughout the lifetime. More effective and specific treatments for menstrual migraine are needed. A careful examination of the data on estrogen and stroke risk suggests a nuanced approach to the issue of estrogen-containing contraception and hormone replacement therapy is warranted. Our understanding of sex and gender is evolving, with limited but growing research on the relationship between gender affirming therapy and migraine, and treatment considerations for transgender people with migraine.

[Adverse effects of opioids, antidepressants and anticonvulsants on sex hormones : Often unnoticed but clinically relevant]. / Unerwünschte Wirkungen von Opioiden, Antidepressiva und Antikonvulsiva auf Sexualhormone : Häufig unbeachtet, aber klinisch relevant.

Androgen insufficiency under treatment with opioids, antidepressants and anticonvulsants in chronic pain diseases is a side effect with a high prevalence. It can lead to clinical metabolic alterations, adynamia, stress intolerance, anemia or osteoporosis and has a significant impact on the quality of life. Opioids, antidepressants and anticonvulsants affect the hypothalamic-pituitary-gonadal axis of sex hormones. A urologist, andrologist or endocrinologist should be involved in the treatment at an early stage. The recommendation of a differential therapeutic selection of certain substances is only indicative and does not meet evidential criteria. The indications for androgen substitution must be individualized and in consideration of the risk-benefit profile. Awareness of this side effect of an otherwise lege artis medicinal pain therapy must be sharpened and compulsory included in the differential diagnostic considerations.

GPER (GPR30): A Nongenomic Receptor (GPCR) for Steroid Hormones with Implications for Cardiovascular Disease and Cancer.

Although the rapid effects of steroids, such as estrogen and aldosterone, were postulated originally to be nongenomic, it is now appreciated that activation of such signaling pathways via a steroid-acting G protein-coupled receptor, the G protein estrogen receptor (GPER), has important transcription-dependent outcomes in the regulation of cell growth and programmed cell death secondary to GPER-regulated second-messenger pathways. GPER is expressed ubiquitously and has diverse biological effects, including regulation of endocrine, immune, neuronal, and cardiovascular functions. Perhaps the most biologically important consequences of GPER activation are the regulation of cell growth, migration, and apoptotic cell death. These cell growth regulatory effects, important in cancer biology, are also relevant in the regulation of cardiac and vascular hypertrophy and in the response to ischemia. This review provides a summary of relevant findings of the impact of GPER regulation by either estradiol or aldosterone in in vitro model systems and extends those findings to in vivo studies of direct clinical relevance for development of GPER-directed agents for treatment of cancer and cardiovascular diseases associated with cellular proliferation.

Probing the Impact of Gender-Affirming Hormone Treatment on Odor Perception.

Evidence suggests that women outperform men in core aspects of odor perception, and sex hormones may play a significant role in moderating this effect. The gender-affirming treatment (GAT) of transgender persons constitutes a powerful natural experiment to study the psychological and behavioral effects of high dosages of cross-sex hormone applications. Therefore, our aim was to investigate the effects of GAT on odor perception in a sample of 131 participants including female and male controls, as well as transmen and transwomen over their first 4 months of gender transition. The Sniffin' Sticks test battery was used to measure odor detection, discrimination, and identification at baseline, as well as 1 and 4 months after the start of GAT. Plasma levels of estradiol, testosterone, and sex hormone-binding globulin were analyzed for each assessment point. Results revealed no significant change of olfactory performance in the two transgender groups compared with female and male controls. There was no significant difference between groups at baseline or any other time point. Neither biological sex, nor gender identity had an influence on odor perception. Moreover, there was no significant correlation between sex hormones and odor perception and between GAT-induced changes in sex hormones and changes in odor perception. Our results indicate that the effects of sex hormones on olfactory performance are subtle, if present at all. However, our results do not preclude hormonal effects on odors not included in the Sniffin' Sticks test battery, such as body odors or odors associated with sex.

Adverse events associated with gender affirming vaginoplasty surgery.

BACKGROUND: There is an abundance of reports on the surgical techniques for vaginoplasty surgery. However, careful review reveals a paucity of evidence-based data in addition to few reports on outcomes related to all of the varying techniques. OBJECTIVE: This study aimed to describe the perioperative adverse events related to vaginoplasty surgery for transgender women and to determine a threshold case number needed to reduce adverse events. STUDY DESIGN: This was a retrospective study of all women who underwent vaginoplasty surgery for gender affirmation at a tertiary care center. All cases were performed by a single board-certified female pelvic medicine and reconstructive surgery specialist. Women were included if 6-month outcomes were available. Once patients were identified, perioperative data were collected. Comparisons of adverse events and perioperative outcomes were made between varying threshold case numbers to determine the case number needed to significantly reduce adverse events. An a priori review of the literature was done to determine the incidence of commonly reported adverse events, and these incidences were used as a frame of reference to determine a threshold case number needed to replicate these reported incidence rates. Once this threshold was determined, outcomes were compared between cases performed before and after this threshold. RESULTS: Between December 2015 and March 2019, 76 vaginoplasty surgeries were performed. Six-month outcomes data were available for all patients. Mean age and body mass index of all patients were 41 (±17) years and 27.3 (±5.1) kg/m2, respectively. Median (range) time on hormone therapy preceding surgery was 36 (12-360) months, and 7.9% (6) of patients had undergone previous orchiectomy. Of the patients, 83.4% (71) underwent full-depth vaginoplasty, whereas the remaining patients underwent a zero-depth procedure. Median (range) surgical time was 210 (138-362) minutes. Median (range) follow-up for all patients was 12.5 (6-50) months. The incidence of any intraoperative adverse event was 2.6% (95% confidence interval, 1.8-4.1) for all patients, whereas the incidence of any immediate (<30 days) and delayed (>30 days and <6 months) postoperative event was 19% (95% confidence interval, 16.4-22.2) and 25% (95% confidence interval, 22.4-28.4), respectively. Performance of 50 cases was identified to be a threshold that reduced adverse events in both clinically and statistically significant ways. Cases performed after the first 50 cases had lower surgical times (187 (138-224) vs 240 (162-362) minutes, P<.0001), a lower incidence of delayed postoperative adverse events (15.4% vs 36%, P=.007), including a lower incidence of urinary stream abnormalities, introital stenosis, and the need for revision surgery. The incidence of intraoperative and immediate adverse events was not different between the groups. CONCLUSION: The incidence of serious adverse events related to vaginoplasty surgery is low, whereas minor events are common. After a threshold of 50 vaginoplasty surgeries, these events were reduced, including the need for revision surgery.

Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood.

Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.

Sex hormone replacement therapy in periodontology-A systematic review.

OBJECTIVE: To analyse whether sex hormone replacement therapy (HRT) improves periodontal parameters and dental implants osseointegration in humans. MATERIALS AND METHODS: Electronic databases and hand searches were performed from June to August 2018 in SciELO, LILACS and PubMed/MEDLINE. Human observational and interventional studies that evaluated the following parameters were included: clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BOP), radiographic bone loss (RBL) or osseointegration. RESULTS: Initial search retrieved 1,282 non-duplicated articles. Fifteen studies were selected after inclusion criteria were applied. All studies were performed in postmenopausal women. Mean differences for PPD reduction ranged from 0.02 to 0.2 mm in HRT-positive patients; mean CAL gain -0.18 to 0.54 mm; mean RBL reduction -0.87 to 0.15 mm; and mean BOP reduction 9%-30.3%. Failure rate of dental implants increased -5.5% to 11.21% when HRT was used. CONCLUSIONS: Very low but consistent evidence suggests a reduction in BOP and no impact on RBL in postmenopausal women receiving HRT. There are inconsistent reports that suggest that HRT in postmenopausal women: (a) improves or does not impact PPD reduction and CAL gain; and (b) does not impact or increase implant loss. In summary, there is no evidence to support HRT prescription for either men or women for periodontal/implant placement purposes.

Drone Brood Homogenate as Natural Remedy for Treating Health Care Problem: A Scientific and Practical Approach.

Drone brood homogenate is a little-known bee product used in folk medicine to treat various health problems. It is a very nutritious milky substance with high content of nutrients: proteins, lipids, fatty acids, carbohydrates, vitamins (A, B, E and D), and minerals. Moreover, when collected on early stage of larvae development, it is, most of all, rich source of sex hormone (testosterone, progesterone and estradiol). Some beekeepers consider drone brood as a waste product, although in some countries they use it to fight Varroa. Meanwhile, in many scientific reports a curative effect of bee drone homogenate in treating urgent global health problems have been confirmed, including ovarian dysfunction in women and male infertility, thyroid and immunity disorders, as well as malnutrition in children. A few dietary supplements based on drone brood are available online. Many patents relating to drone brood-based dietary supplements have been filed in Russia, but their prevalence in EU countries is still limited. Further research is needed to fully recognize the pharmacological activity and increase the use of drone brood.

Cross sex hormone treatment is linked with a reversal of cerebral patterns associated with gender dysphoria to the baseline of cisgender controls.

Transgender persons experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), is frequently treated with cross-sex hormones. However, very little is known about how this treatment affects the brain of individuals with GD, nor do we know the neurobiology of GD. We recently suggested that disconnection of fronto-parietal networks involved in own-body self-referential processing could be a plausible mechanism, and that the anatomical correlate could be a thickening of the mesial prefrontal and precuneus cortex, which is unrelated to sex. Here, we investigate how cross-sex hormone treatment affects cerebral tissue in persons with GD, and how potential changes are related to self-body perception. Longitudinal MRI measurements of cortical thickness (Cth) were carried out in 40 transgender men (TrM), 24 transgender women (TrW) and 19 controls. Cth increased in the mesial temporal and insular cortices with testosterone treatment in TrM, whereas anti-androgen and oestrogen treatment in TrW caused widespread cortical thinning. However, after correction for treatment-related changes in total grey and white matter volumes (increase with testosterone; decrease with anti-androgen and oestrogen), significant Cth decreases were observed in the mesial prefrontal and parietal cortices, in both TrM and TrW (vs. controls) - regions showing greater pre-treatment Cth than in controls. The own body - self congruence ratings increased with treatment, and correlated with a left parietal cortical thinning. These data confirm our hypothesis that GD may be associated with specific anatomical features in own-body/self-processing circuits that reverse to the pattern of cisgender controls after cross-sex hormone treatment.

The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment.

Benign brain tumours may be hormone sensitive. To induce physical characteristics of the desired gender, transgender individuals often receive cross-sex hormone treatment, sometimes in higher doses than hypogonadal individuals. To date, long-term (side) effects of cross-sex hormone treatment are largely unknown. In the present retrospective chart study we aimed to compare the incidence of common benign brain tumours: meningiomas, pituitary adenomas (non-secretive and secretive), and vestibular schwannomas in transgender individuals receiving cross-sex hormone treatment, with those reported in general Dutch or European populations. This study was performed at the VU University Medical Centre in the Netherlands and consisted of 2555 transwomen (median age at start of cross-sex hormone treatment: 31 years, interquartile range 23-41) and 1373 transmen (median age 23 years, interquartile range 18-31) who were followed for 23 935 and 11 212 person-years, respectively. For each separate brain tumour, standardized incidence ratios with 95% confidence intervals were calculated. In transwomen (male sex assigned at birth, female gender identity), eight meningiomas, one non-secretive pituitary adenoma, nine prolactinomas, and two vestibular schwannomas occurred. The incidence of meningiomas was higher in transwomen than in a general European female population (standardized incidence ratio 4.1, 95% confidence interval 1.9-7.7) and male population (11.9, 5.5-22.7). Similar to meningiomas, prolactinomas occurred more often in transwomen compared to general Dutch females (4.3, 2.1-7.9) and males (26.5, 12.9-48.6). Noteworthy, most transwomen had received orchiectomy but still used the progestogenic anti-androgen cyproterone acetate at time of diagnosis. In transmen (female sex assigned at birth, male gender identity), two cases of somatotrophinomas were observed, which was higher than expected based on the reported incidence rate in a general European population (incidence rate females = incidence rate males; standardized incidence ratio 22.2, 3.7-73.4). Based on our results we conclude that cross-sex hormone treatment is associated with a higher risk of meningiomas and prolactinomas in transwomen, which may be linked to cyproterone acetate usage, and somatotrophinomas in transmen. Because these conditions are quite rare, performing regular screenings for such tumours (e.g. regular prolactin measurements for identifying prolactinomas) seems not necessary.

Fertility preservation options for transgender and gender-nonconforming individuals.

PURPOSE OF REVIEW: To provide an overview of the current state of knowledge of fertility risks of gender-affirming therapy, review fertility preservation options for transgender individuals and ways to minimize gender dysphoria during fertility treatment, and identify gaps in knowledge. RECENT FINDINGS: Recent studies have corroborated older data that gender-affirming hormone therapy creates histopathological changes in the gonads; however, the newer data suggests that some function of the gametes may be preserved. One study in transgender men reported successful in-vitro maturation of testosterone-exposed oocytes with normal spindle structures, and recent studies in transgender women reveal early spermatogenesis in estradiol-exposed testes and some recovery of semen parameters following cessation of hormones. Particular attention has recently been given to fertility preservation in transgender adolescents, revealing unmet informational needs in this population and very few are actually pursuing fertility preservation, even with counseling. SUMMARY: There is currently a paucity of data on the fertility effects of gender-affirming hormones, necessitating fertility preservation counseling prior to initiation of therapy. Several modifications can be made to fertility preservation protocols and procedures to decrease gender dysphoria or distress in transgender individuals, but outcome data is still lacking. Achieving high-quality data collection will likely require cooperation across multiple institutions.

Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study.

Background: Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use. Objective: To examine the incidence of these events in a cohort of transgender persons. Design: Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment. Setting: Kaiser Permanente in Georgia and northern and southern California. Patients: 2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women. Measurements: VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts. Results: Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants. Limitation: Inability to determine which transgender members received hormones elsewhere. Conclusion: The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen. Primary Funding Source: Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Gender-Affirming Hormone Use in Transgender Individuals: Impact on Behavioral Health and Cognition.

PURPOSE OF REVIEW: With increasing numbers of transgender and gender non-binary individuals presenting for care, knowing how to elucidate the mental health and cognitive outcomes of gender-affirming hormone therapy (GAHT) is necessary. This article reviews the present literature covering GAHT effects on mood, behavioral health, and cognition in these individuals and offers research priorities to address knowledge gaps. RECENT FINDINGS: Although there are some conflicting data, GAHT overwhelmingly seems to have positive psychological effects in both adolescents and adults. Research tends to support that GAHT reduces symptoms of anxiety and depression, lowers perceived and social distress, and improves quality of life and self-esteem in both male-to-female and female-to-male transgender individuals. Clinically, prescribing GAHT can help with gender dysphoria-related mental distress. Thus, timely hormonal intervention represents a crucial tool for improving behavioral wellness in transgender individuals, though effects on cognitive processes fundamental for daily living are unknown. Future research should prioritize better understanding of how GAHT may affect executive functioning.