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Physiologic Response to Gender-Affirming Hormones Among Transgender Youth
Abstract
Purpose:
The purpose of this study was to examine the physiologic impact of hormones on youth with gender dysphoria. These data represent follow-up data in youth ages 12-23 years over a two-year time period of hormone administration.
Methods:
This prospective, longitudinal study initially enrolled 101 youth with gender dysphoria at baseline from those presenting consecutively for care between February 2011 and June 2013. Physiologic data at baseline and follow-up were abstracted from medical charts. Data were analyzed by descriptive statistics.
Results:
Of the initial 101 participants, 59 youth had follow-up physiologic data collected between 21 and 31 months after initiation of hormones available for analysis. Metabolic parameters changes were not clinically significant, with the exception of sex steroid levels, intended to be the target of intervention.
Conclusions:
Although the impact of hormones on some historically concerning physiologic parameters, including lipids, potassium, hemoglobin, and prolactin, were statistically significant, clinical significance was not observed. Hormone levels physiologically concordant with gender of identity were achieved with feminizing and masculinizing medication regimens. Extensive and frequent laboratory examination in transgender adolescents may be unnecessary. The use of hormones in transgender youth appears to be safe over a treatment course of approximately two years.
... Testosterone leads to an increase of BMI SDS (82) whereas estradiol does not affect BMI SDS, fat or lean body mass percentage (90). Some studies found no change in blood pressure during testosterone or estradiol treatment (90, 92) but one study observed an increase in systolic blood pressure during testosterone treatment (93). Transgirls have an average adult height of +1.9 SDS. ...
... Mean HDL-cholesterol decreases and mean LDL-cholesterol increases during treatment with lynestrenol (82). Testosterone also induces a decrease of HDL-cholesterol (92,93). It is uncertain how this affects the risk of cardiovascular complications in the long term; few cardiovascular events and deaths have been reported in transgender males but available data are insufficient to draw any conclusions (96). ...
... Total cholesterol, HDL-cholesterol and triglycerides decrease during cyproterone acetate treatment (83). Some studies found no effect of estradiol on lipid levels (83, 92) but one study reported an increase in HDL-cholesterol (93). ...
Over the past 20 years, the care for transgender adolescents has developed throughout many countries following the "Dutch Approach" initiated in the 90's in pioneer countries as the Netherlands, United States and Canada, with increasing numbers of children and adolescents seeking care in transgender clinics. This medical approach has considerable positive impacts on the psychological outcomes of these adolescents and several studies have been recently published underlining the relative safety of such treatments. This paper reviews the current standards of care for transgender children and adolescents with particular emphasis on disparities among countries and short to medium-term outcomes. Finally it highlights ethical considerations regarding categorization of gender dysphoria, timing of treatment initiation, infertility, and how to deal with the long-term consequences.
... Testosterone leads to an increase of BMI SDS (82) whereas estradiol does not affect BMI SDS, fat or lean body mass percentage (90). Some studies found no change in blood pressure during testosterone or estradiol treatment (90, 92) but one study observed an increase in systolic blood pressure during testosterone treatment (93). Transgirls have an average adult height of +1.9 SDS. ...
... Mean HDL-cholesterol decreases and mean LDL-cholesterol increases during treatment with lynestrenol (82). Testosterone also induces a decrease of HDL-cholesterol (92,93). It is uncertain how this affects the risk of cardiovascular complications in the long term; few cardiovascular events and deaths have been reported in transgender males but available data are insufficient to draw any conclusions (96). ...
... Total cholesterol, HDL-cholesterol and triglycerides decrease during cyproterone acetate treatment (83). Some studies found no effect of estradiol on lipid levels (83, 92) but one study reported an increase in HDL-cholesterol (93). ...
... 72 Several other studies in transgender adolescent males have also showed a statistically significant increase in haemoglobin and haematocrit concentrations in response to testosterone therapy. 34,36,41 Importantly, no clinical complications were observed to warrant treatment discontinuation. In their trans gender adolescent male sample (n=25, mean age 17·4 years), Tack and colleagues 36 noted that haemoglobin and haematocrit concentration variables increased, but had stabilised at 6 months. ...
... 39 In a separate study that examined HDL over a 2 year period (in a different sample of transgender adolescent males using testosterone) the mean HDL reduction was clinically significant. 41 No changes in low-density lipoprotein (LDL) or triglycerides have been documented in the short term for transgender adolescent males, 36,39 although statistically significant increases in triglyceride concentrations were observed by Olson-Kennedy and colleagues 41 after 2 years of receiving testosterone. Overall, none of the studies reviewed showed significant changes in mean total cholesterol concentrations. ...
... 39 Changes in HbA 1c , glucose, or insulin have not been observed. 36,39,41 Evidence regarding alterations in the aforementioned variables in transgender adolescents is in accordance with findings from a study in transgender adult males, which found that exogenous testosterone did not alter metabolic variables associated with polycystic ovarian syndrome. 76 A retrospective pilot study 34 ...
The Endocrine Society Clinical Practice Guidelines on the treatment of gender incongruent people recommend the use of gender-affirming cross-sex hormone (CSH) interventions in transgender children and adolescents who request this treatment, who have undergone psychiatric assessment, and have maintained a persistent transgender identity. The intervention can help to affirm gender identity by inducing masculine or feminine physical characteristics that are congruent with an individual's gender expression, while aiming to improve mental health and quality-of-life outcomes. Some transgender individuals might also wish to access gender-affirming surgeries during adolescence; however, research to inform best clinical practice for surgeons and other medical professionals is scarce. This Review explores the available published evidence on gender-affirming CSH and surgical interventions in transgender children and adolescents, amalgamating findings on mental health outcomes, cognitive and physical effects, side-effects, and safety variables. The small amount of available data suggest that when clearly indicated in accordance with international guidelines, gender-affirming CSHs and chest wall masculinisation in transgender males are associated with improvements in mental health and quality of life. Evidence regarding surgical vaginoplasty in transgender females younger than age 18 years remains extremely scarce and conclusions cannot yet be drawn regarding its risks and benefits in this age group. Further research on an international scale is urgently warranted to clarify long-term outcomes on psychological functioning and safety.
... 72 Several other studies in transgender adolescent males have also showed a statistically significant increase in haemoglobin and haematocrit concentrations in response to testosterone therapy. 34,36,41 Importantly, no clinical complications were observed to warrant treatment discontinuation. In their trans gender adolescent male sample (n=25, mean age 17·4 years), Tack and colleagues 36 noted that haemoglobin and haematocrit concentration variables increased, but had stabilised at 6 months. ...
... 39 In a separate study that examined HDL over a 2 year period (in a different sample of transgender adolescent males using testosterone) the mean HDL reduction was clinically significant. 41 No changes in low-density lipoprotein (LDL) or triglycerides have been documented in the short term for transgender adolescent males, 36,39 although statistically significant increases in triglyceride concentrations were observed by Olson-Kennedy and colleagues 41 after 2 years of receiving testosterone. Overall, none of the studies reviewed showed significant changes in mean total cholesterol concentrations. ...
... 39 Changes in HbA 1c , glucose, or insulin have not been observed. 36,39,41 Evidence regarding alterations in the aforementioned variables in transgender adolescents is in accordance with findings from a study in transgender adult males, which found that exogenous testosterone did not alter metabolic variables associated with polycystic ovarian syndrome. 76 A retrospective pilot study 34 ...
... Reports on changes in BMI among the transgender population have been mixed. [44][45][46];. tThere were three studies showed an increase in BMI [10,43,47] and one study observedshows a decrease in BMI [48]. ...
... States were relatively small with cohort size of between 16 and 38 and short term had followup periods in the range of 6-35 months [10,[43][44][45][46][47][48]. Our study contributes a relatively large number of transgender individuals both already on hormone therapy and newly initiated on hormone therapy for a period up to 7 years.Our findings also differ from those published in Europe likely due to the differences in GAHT regimens. ...
... A higher baseline BMI in transgender women was related to a smaller increase in body fat and larger decrease in lean body mass[42]. In the United States, in transgender women, Ffour observational studies of transgender women in the US observed show no change in BMI[10,[43][44][45]. In transgender men, three studies show no change in BMI ...
Introduction
Many transgender people take hormone therapy to affirm their gender identity. One potential long-term consequence of gender affirming hormone therapy is increased body mass index (BMI), which may be associated with metabolic syndrome, cardiovascular disease and higher mortality. Only a few published studies explored changes in BMI in transgender people taking gender affirming hormone therapy (GAHT).
Objective
To examine the changes in BMI longitudinally in response to GAHT in transgender women and men.
Methods
We conducted a retrospective cohort study of transgender individuals who received GAHT from the endocrinology clinic between January 1, 2000 and September 6, 2018. Subjects who sought GAHT were included if they had two separate measurements of BMI and were excluded if they had a BMI greater than 35 kg/m² or were missing demographic data at entry. We used a linear mixed model to analyze the longitudinal change in BMI.
Results
There were a total of 227 subjects included in this cohort. Among subjects already on GAHT, transgender women were receiving GAHT longer than transgender men (6.59 ± 9.35 vs 3.67 ± 3.43 years, p-value = 0.04). Over the period of 7 years, there was a significant increase in BMI in transwomen who newly initiated GAHT (p-value 0.004). There were no changes in BMI in transgender men and women already on GAHT or in transgender men who newly initiated GAHT in the study.
Conclusion
We conclude that BMI significantly increases in transwomen but not in transmen after initiation of GAHT in a single center based in the United States. In transwomen and transmen, BMI appears to be stable following 3 to 6 years of GAHT. Future investigations should examine the causes for increased BMI in transgender women including type of GAHT, diet and lifestyle, and association with risk of metabolic syndrome and cardiovascular disease.
... Emi and colleagues 77 reported higher systolic, mean arterial, and diastolic blood pressure in TM on HT, compared with TM not on testosterone. One prospective study 56 observed an increase in systolic and diastolic blood pressure in adolescent TM after 2 years of HT. Two prospective studies 59,78 reported no change in systolic over diastolic blood pressure in adult TM after initiation of HT. ...
... Vita and colleagues 78 observed no change in total HDL and LDL cholesterol and triglycerides over 30 months of follow-up. Whereas some studies report no change in HDL levels in TM, 30,78 others reported a decrease in HDL levels in TM. 8,56,57,[62][63][64][65][66][67][68][69] Regarding LDL, 1 study observed an increase after 1 year of testosterone undecanoate therapy, 8 whereas 2 other studies 30,64 observed a decrease after 12 to 18 months of testosterone undecanoate. ...
... 79 Elements pointing toward increased atherogenicity in TM (increased triglyceride levels, decreased HDL2 and HDL3 levels), as well as elements pointing toward decreased atherogenicity (smaller LDL size with lower free cholesterol and phospholipid concentration, increased hepatic lipase activity and ApoC-II levels, reduced ApoA-I), have been reported. 61,69 Metabolic syndrome Most the studies on TM 8,31,56,67,74,80 reported no changes in insulin resistance in TM, although 2 studies 78,80 reported a decrease in fasting glucose levels after 3 to 30 months of testosterone therapy in TM. However, 1 study 8 reported a decrease in fasting insulin in TM after 1 year of testosterone therapy. ...
Prescribing gender-affirming hormonal therapy in transgender men (TM) not only induces desirable physical effects but also benefits mental health. In TM, testosterone therapy is aimed at achieving cisgender male serum testosterone to induce virilization. Testosterone therapy is safe on the short term and middle term if adequate endocrinological follow-up is provided. Transgender medicine is not a strong part of the medical curriculum, although a large number of transgender persons will search for some kind of gender-affirming care. Because hormonal therapy has beneficial effects, all endocrinologists or hormone-prescribing physicians should be able to provide gender-affirming hormonal care.
... 37 In adolescents, the use of testosterone similarly shows contradictory results. [40][41][42] Among women who are transgender receiving estrogen, 1 study found that compared to BMI-matched men and women who are cisgender, percent lean mass was lower and higher, respectively. 38 The effect of estrogen use on BMI among women who are transgender is unclear; European studies have shown an increase in BMI, [42][43][44][45][46] waist circumference, and weight, 44 whereas several US studies have not demonstrated an increase in BMI. ...
... 38 The effect of estrogen use on BMI among women who are transgender is unclear; European studies have shown an increase in BMI, [42][43][44][45][46] waist circumference, and weight, 44 whereas several US studies have not demonstrated an increase in BMI. 40,41,47 These results may be attributable to differences in duration of follow-up, and to differences in hormone prescription practices across regions, as well: cyproterone acetate and gonadotropin releasing hormone analogs are often used in Europe, whereas spironolactone is used in the United States for androgen blockade. ...
There is growing evidence that people who are transgender and gender diverse (TGD) are impacted by disparities across a variety of cardiovascular risk factors compared with their peers who are cisgender. Prior literature has characterized disparities in cardiovascular morbidity and mortality as a result of a higher prevalence of health risk behaviors. Mounting research has revealed that cardiovascular risk factors at the individual level likely do not fully account for increased risk in cardiovascular health disparities among people who are TGD. Excess cardiovascular morbidity and mortality is hypothesized to be driven in part by psychosocial stressors across the lifespan at multiple levels, including structural violence (eg, discrimination, affordable housing, access to health care). This American Heart Association scientific statement reviews the existing literature on the cardiovascular health of people who are TGD. When applicable, the effects of gender-affirming hormone use on individual cardiovascular risk factors are also reviewed. Informed by a conceptual model building on minority stress theory, this statement identifies research gaps and provides suggestions for improving cardiovascular research and clinical care for people who are TGD, including the role of resilience-promoting factors. Advancing the cardiovascular health of people who are TGD requires a multifaceted approach that integrates best practices into research, health promotion, and cardiovascular care for this understudied population.
... While a fair amount of extant literature supports the safety, positive impact, and importance of medical intervention for transgender adults, 11,12 only a handful of studies focused on the impact of hormonal intervention on youth with gender dysphoria, particularly minors. [13][14][15][16][17][18][19] As a result, there is lack of consensus among professionals around timing of initiation of medical interventions, as well as optimal dosing regimens. ...
... 23 Since this new recommendation, only a handful of studies have examined the physiologic impact of hormone use among younger adolescents. 13,14 In contrast, the safety and impact of genderaffirming hormones used in adult TGD patients undergoing medical transition have been written about comprehensively and have demonstrated that hormones are relatively safe and result in a low risk profile for patients. The potential sequelae of gender-affirming hormone use in adults have been outlined, including risk for thrombotic events and changes in blood pressure, hemoglobin and hormone levels, and lipid profiles. ...
Purpose: This article outlines the process of establishing the Trans Youth Care Research Network, composed of four academic clinics providing care for transgender and gender-diverse (TGD) youth. The Network was formed to design and implement research studies to better understand physiologic and psychosocial outcomes of gender-affirming medical care among TGD youth.
Methods: Formed in response to both the Institute of Medicine's report recommendation for an increase of data concerning sexual and gender minority populations and a transgender-specific NIH program announcement, The Center for Transyouth Health and Development at Children's Hospital Los Angeles, the Gender Management Service at Boston Children's Hospital, the Child and Adolescent Gender Center Clinic at Benioff Children's Hospital in San Francisco, and the Gender and Sex Development Program at Lurie Children's Hospital of Chicago established a collaborative research network that subsequently designed a longitudinal observational study of TGD youth undergoing medical interventions to address gender dysphoria.
Results: Two cohorts, youth starting puberty blockers and youth starting gender-affirming hormones, are participating. Psychosocial measures that span multiple domains of mental and behavioral health are collected from youth and parents. Physiologic data are abstracted from patient's charts. Baseline and follow-up data of this large cohort will be disseminated through conferences, abstracts, posters, and articles.
Conclusion: Since initiation of funding in 2015, a total of 497 participants have been enrolled in TYC across the four sites; gonadotropin releasing hormone analogs (GnRHa) cohort youth (n=93), GnRHa cohort parents (n=93), and gender affirming hormone cohort youth (n=311). As the network moves toward data dissemination, its lessons learned have helped strengthen the current study, as well as inform future endeavors in this field.
... [6][7][8] Current clinical practice guidelines recommend counseling transgender youth and families about potential cardiometabolic effects of testosterone. 5 However, recent studies demonstrate conflicting results on BMI changes and lipids after starting testosterone, [9][10][11][12][13] and it remains unknown whether these changes are solely influenced by testosterone exposure or whether differences in diet and physical activity in a population with a higher incidence of mental health disorders 14 also play a role. Furthermore, many studies have lacked a comparison group. ...
... 10 Likewise, Sequeira et al. found a significant rise in BMI after 6 months of testosterone therapy, although noted that this effect lost significance 12 months after initiation. 11 Olson-Kennedy et al. also found a significant decrease in HDL after starting testosterone in adolescent and young adult transgender males, although they noted an increase in triglycerides, 9 which were stable in our study. A more recent study also found a lower HDL, as well as higher aspartate transaminase level in transgender males taking testosterone as compared with cisgender females. ...
... Notwithstanding the foregoing, cross-sex hormonal therapy's impact on GD transgender youth has been investigated by only a small proportion of research. Jarin et al.'s (2017) retrospective study showed a minor impact of hormonal treatment on 116 adolescents of ages 14-25 years, reporting low level changes in physiological parameters 1 , without any known safety implications for at least two years following its administration (Olson-Kennedy, Okonta, Clark, & Belzer, 2018;Jarin et al., 2017). Henceforth, the plausibility of cross-sex hormonal therapy initiation/usefulness prior to the age of 16 remains controversial. ...
... The implementation of such fundamental aspects into biomedical treatment models may result in more robust, multidisciplinary interventions that are holistically efficient for GD individuals. The paradigm of emphasising more on biomedical and only partially on psychosocial perspectives should be revised and shifted towards achieving better efficiency of treatment options (Murshak, 2017). ...
Gender Dysphoria focuses on the psychological state at which individuals experience low levels of perceived satisfaction regarding their primary and secondary physiological traits, their biological gender, and their assigned societal gender roles. This condition primarily requires multidisciplinary and personalised treatment. Scientific evidence suggests that utilisation of gonadotropin-releasing hormone analogues, puberty blockers, and gender-affirming surgery may reduce distress, enhance mental health and quality of life, while diminishing Gender Dysphoria. However, some researchers contend that medical procedures pose adverse limitations since they may result in complications, feelings of frustration, and supplementary procedures undergone for aesthetic purposes. Moreover, individuals' age of readiness to pursue medical interventions and deal with additional issues such as post-surgery fertility and regret also need to be addressed. Conversely, psychotherapy and counselling intend to assist such individuals in accomplishing long-term relief relating to their gender identity, developing their interpersonal skills, and confronting Gender Dysphoria comorbidity. Yet, many psychotherapeutic schemes insufficiently address crucial facets of Gender Dysphoria, namely societal discrimination stemming from subsequent stigmatization, promotion of resilience among this highly marginalised population against unprecedented tribulation, and body dissatisfaction, thus not providing a complete relief of gender dysphoric feelings. Therefore, it is essential to appropriately address psychosocial functionality enhancement, integrate novel treatment propositions into a holistic therapeutic plan, and further develop/validate Gender Dysphoria metrics that can be universally accepted in order to prevent pathologisation of these individuals. It is also recommended that further qualitative data, needs assessments, and empirical studies be gathered, while carefully abiding by the necessary ethical considerations.
... Research, clinical, and media attention on medical care for trans youth has increased rapidly in recent years. A review of research on trans youth seeking medical care reveals several reviews of care models and practices (Edwards-Leeper & Spack, 2012;Khatchadourian, Amed, & Metzger, 2014;Olson, Forbes, & Belzer, 2011), clinical studies of a variety of mental and physical health characteristics of trans youth seeking care (Olson-Kennedy, Okonta, Clark, & Belzer, 2018), mental and physical health outcomes of hormone therapy (De Vries et al., 2014), examinations of health care providers' perspectives and concerns about offering trans youth care (Knight, Shoveller, Carson, & Contreras-Whitney, 2014;Vance, Halpern-Felsher, & Rosenthal, 2015), ethical approaches to the care of transgender youth (Clark, 2017), barriers to care for trans Gridley et al., 2016;Temple Newhook, Benson, Bridger, Crowther, & Sinnott, 2018a) and non-binary (Clark, Veale, Townsend, Frohard-Dourlent, & Saewyc, 2018) youth, and a community-based study of the future perspectives of trans youth and caregivers (Katz-Wise et al., 2017). An emergent body of research also focuses on the experiences of pre-pubescent gender diverse and trans children (Durwood, McLaughlin, & Olson, 2017;Olson, Durwood, DeMeules, & McLaughlin, 2016;Olson & G€ ulg€ oz, 2018;Temple Newhook et al., 2018b). ...
... Emerging research indicates that youth who are affirmed in their gender identities experience positive mental health outcomes equivalent to those of their cisgender peers (Durwood et al., 2017;Olson et al., 2016). Research from the United States and the Netherlands demonstrates that access to hormone blockers, hormone replacement therapy, and surgery, as needed, improves medium-and longterm health outcomes for transgender youth into adulthood (Chew, Anderson, Williams, May, & Pang, 2018;Cohen-Kettenis, Schagen, Steensma, de Vries, & Delemarre-van de Waal, 2011;De Vries et al., 2014;Olson-Kennedy et al., 2018). ...
Background: Canadian specialty clinics offering gender-affirming care to trans and gender diverse children and youth have observed a significant increase in referrals in recent years, but there is a lack of information about the experiences of young people receiving care. Furthermore, treatment protocols governing access to gender-affirming medical interventions remain a topic of debate.
Aims: This qualitative research aims to develop a deeper understanding of experiences of trans youth seeking and receiving gender-affirming care at Canadian specialty clinics, including their goals in accessing care, feelings about care and medical interventions they have undergone, and whether they have any regrets about these interventions.
Methods: The study uses an adapted Grounded Theory methodology from social determinants of health perspective. Thirty-five trans and gender diverse young people aged 9 to 17 years were recruited to participate in semi-structured interviews through the specialty clinics where they had received or were waiting for gender-affirming medical interventions such as puberty blockers, hormone therapy, and surgery.
Results: Young people felt positively overall about the care they had received and the medical interventions they had undergone, with many recounting an improvement in their well-being since starting care. Most commonly shared frustrations concerned delays in accessing interventions due to clinic waiting lists or treatment protocols. Some youth described unwanted medication side-effects and others said they had questioned their transition trajectory at certain moments in the past, but none regretted their choice to undergo the interventions.
Discussion: The results suggest that trans youth and gender diverse children are benefiting from medical gender-affirming care they receive at specialty clinics, providing valuable insight into their decision-making processes in seeking care and specific interventions. Providers might consider adjusting aspects of treatment protocols (such as age restrictions, puberty stage, or mental health assessments) or applying them on a more flexible, case-by-case basis to reduce barriers to access.
... In the UK cross-sex hormones are not available until the young person reaches the age of 16 years and surgery is not available until the age of 18 years (Gender Identity Development Service, GIDS, 2019) as will be discussed in Chapter Two. In contrast, in the USA children as young as 12 years old have been given cross-sex hormones (Olson-Kennedy, Okonta, Clark & Belzer, 2018) and young people under the age of 18 years have had surgical procedures (Milrod & Karasic, 2017) and this is likely to impact on their experiences. Therefore further UK studies are needed to better understand the experiences of transgender young people with regard to the contexts in which they live and study. ...
There has been a recent increase in the reported number of young people accessing specialist gender identity services. Transgender children and young people face a number of issues such as bullying and victimisation, academic difficulties and mental health needs. Their parents also face issues such as feelings of fear and loss, and judgement and hostility from others. Previous research has highlighted the importance of support for transgender young people and their parents, both at school and in the community. However, there is a lack of research in the United Kingdom which examines the perspectives of transgender young people and their parents to inform the work of Educational Psychologists. This study explored the experiences of transgender young people and their parents with regard to home, community and school. Semi-structured interviews were conducted with four secondary school age transgender young people and five mothers, four of whom were parents of the young people interviewed. Interpretative Phenomenological Analysis was used to inform the analysis of the interview data in order to gain an in-depth understanding of how the participants made sense of their experiences and the meaningfulness of these experiences. From the young people’s accounts, four superordinate themes were identified which related to understandings of gender, complexities of transitioning, experiences in school and support networks. Four superordinate themes were identified from the parents’ data, relating to understandings of gender, how they came to terms with their child being transgender, experiences with their child’s school and support networks. Implications for Educational Psychology policy and practice are discussed, including how Educational Psychologists might develop their work with transitioning young people and their parents.
... Previous clinical studies consistently reported significant increases in hematocrit and hemoglobin following initiation of testosterone therapy among TM patients; whereas feminizing hormone therapy was shown to have an opposite effect (15)(16)(17)(18)(19)(20)(21). On the other hand, relatively, limited data are available on the temporal trajectories of Hb and Hct changes among TM and TF subjects receiving HT relative to cisgender referent groups. ...
Context
The effect of gender affirming hormone therapy (HT) on erythropoiesis is an area of priority in transgender health research.
Objective
To compare changes in hematologic parameters and rates of erythrocytosis and anemia among transgender people to those of cisgender controls.
Design
Longitudinal observational study.
Participants and Setting
We compared 559 transfeminine and 424 transmasculine people enrolled in three integrated health care systems to matched cisgender referents.
Interventions and Outcome
HT receipt was ascertained from filled prescriptions. Hemoglobin and hematocrit levels were examined from first blood test to HT initiation, and from the start of HT to the most recent blood test. Rates of erythrocytosis and anemia in transgender participants and referents were compared by calculating adjusted hazard ratios and 95% confidence intervals (CI).
Results
In the transfeminine group, there was a downward trend for both hemoglobin and hematocrit. The corresponding changes in the transmasculine cohort were in the opposite direction. Transmasculine study participants experienced 7-fold higher rate (95% CI: 4.1-13.4) of erythrocytosis relative to matched cisgender males, and 83-fold higher rate (95% CI: 36.1-191.2) compared to cisgender females. The corresponding rates for anemia were elevated in transfeminine subjects, but primarily relative to cisgender males (hazard ratio 5.9; 95% CI: 4.6-7.5).
Conclusions
Our results support the previous recommendations that hematological parameters of transgender people receiving HT should be interpreted based on their affirmed gender, rather than their sex documented at birth. The clinical significance of erythrocytosis following testosterone therapy as well as anemia following feminizing HT requires further investigation.
... The rise in systolic blood pressure found during the first 6 months of testosterone treatment is similar to findings of some previous studies in adolescents and adults, although other studies found no changes in blood pressure. 10,11,22 The small change does not seem to be of clinical relevance, as systolic blood pressure after 6 months of testosterone was similar to pretreatment values. The significant decrease in BMD and BMD z-scores after initiation of GnRHa therapy is in line with previous findings. ...
Introduction
Current treatment guidelines for adolescents with gender dysphoria recommend therapy with gonadotropin-releasing hormone agonists (GnRHa) and testosterone in transgender males. However, most evidence on the safety and efficacy of testosterone is based on studies in adults.
Aim
This study aimed to investigate the efficacy and safety of testosterone treatment in transgender adolescents.
Methods
The study included 62 adolescents diagnosed with gender dysphoria who had started GnRHa treatment and had subsequently received testosterone treatment for more than 6 months.
Main Outcome Measure
Virilization, anthropometry, laboratory parameters, and bone mineral density (BMD) were analyzed.
Results
Adolescents were treated with testosterone for a median duration of 12 months. Voice deepening began within 3 months in 85% of adolescents. Increased hair growth was first reported on the extremities, followed by an increase of facial hair. Acne was most prevalent between 6 and 12 months of testosterone therapy. Most adolescents had already completed linear growth; body mass index and systolic blood pressure increased but diastolic blood pressure did not change. High-density lipoprotein (HDL) cholesterol and sex hormone binding globulin significantly decreased, but hematocrit, hemoglobin, prolactin, androstenedione, and dehydroepiandrosterone sulfate significantly increased, although not all changes were clinically significant. Other lipids and HbA1c did not change. Vitamin D deficiency was seen in 32–54% throughout treatment. BMD z-scores after 12 to 24 months of testosterone treatment remained below z-scores before the start of GnRHa treatment.
Clinical Implications
Adolescents need to be counseled about side effects with potential longer term implications such as increased hematocrit and decreased HDL cholesterol and decreased BMD z-scores. They should be advised on diet, including adequate calcium and vitamin D intake; physical exercise; and the use of tobacco and alcohol to avoid additional risk factors for cardiovascular disease and osteoporosis.
Strengths & Limitations
Strengths are the standardized treatment regimen and extensive set of safety parameters investigated. Limitations are the limited duration of follow-up and lack of a control group so some of the observed changes may be due to normal maturation rather than to treatment.
Conclusion
Testosterone effectively induced virilization beginning within 3 months in the majority of adolescents. Acne was a common side effect, but no short-term safety issues were observed. The increased hematocrit, decreased HDL cholesterol, and decreased BMD z-scores are in line with previous studies. Further follow-up studies will need to establish if the observed changes result in adverse outcomes in the long term.
Stoffers IE, de Vries MC, Hannema SE. Physical Changes, Laboratory Parameters, and Bone Mineral Density During Testosterone Treatment in Adolescents with Gender Dysphoria. J Sex Med 2019;16:1459–1468.
... Previous reports of interventions in several concomitant sex hormones only partly support our findings. Most report either unchanged (32)(33)(34)(35)(36) or decreasing (33,35,37), but never improving, insulin sensitivity after both feminization and masculinization, usually after short-term (1-4-week) interventions in small numbers of healthy men, but also after longer-term treatment (up to 1 year) in TW; most assessed static insulin sensitivity markers only. The one study similar to ours used state-of-the art dynamic testing (euglycemic-hyperinsulinemic clamp) but described worsening insulin sensitivity in both TM and TW (n 5 31) after 4 months of cross-sex hormone therapy (38). ...
Objective:
The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study.
Research design and methods:
Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated.
Results:
In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (-0.03 ± 0.01 kg; P < 0.01) increased. Fasting insulin (-1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (-1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP; -1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1; -0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] × min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] × min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg, P = 0.07) with decreasing FFM (-2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (-1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs 1,911 ± 162 [pmol/L] × min; P < 0.01), but fasting glucose (-0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L) and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] × min) remained unchanged.
Conclusions:
In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.
... We found a statistically significant elevation in serum prolactin at an E dosage of 6 mg but no change at other dosages. The literature is conflicting on this subject, with some studies suggesting elevated prolactin after feminizing estrogen therapy (31,32) and others showing a nonsignificant increase (33)(34)(35). It is likely that this measure is sensitive to statistical methodology because of interpatient variability. ...
Context
Medroxyprogesterone acetate (MPA) is a widely used progestin in feminizing hormone therapy. However, the side effects and hormonal changes elicited by this drug have never been investigated in the transgender population.
Objective
We evaluated the incidence of self-reported effects among transwomen using MPA, as well as this drug’s impact on hormonal and metabolic parameters.
Design, Setting, and Participants
We retrospectively collected data from 290 follow-up visits (FUVs) of transwomen treated at Rhode Island Hospital from January, 2011 to July, 2018 (mean duration of therapy 3.4±1.7 years). FUVs followed regimens of estradiol and spironolactone, with MPA (102) or without MPA (188).
Main Outcome Measures
We assessed the incidence of self-reported effects after MPA treatment. We also compared blood levels of estradiol, testosterone, and various laboratory parameters between MPA and non-MPA groups.
Results
Mean weighted estradiol level was 211±57 pg/ml after MPA treatment and 210±31 pg/ml otherwise; this difference was non-significant (T(274) = 0.143, p = 0.886). Mean weighted testosterone level was 79±18 ng/dl after MPA treatment and 215±29 ng/dl otherwise; testosterone levels were significantly lower in the MPA group (T(122) = 32.4, p < .001). There were minimal changes in other laboratory parameters. Of 39 patients receiving MPA, 26 reported improved breast development and 11 reported decreased facial hair. Five patients experienced mood swings on MPA.
Conclusions
In our cohort of transwomen, we found minimal side effects, unchanged estradiol levels, and a decline in testosterone associated with MPA--outcomes consistent with feminization. Prospective studies are needed to confirm our findings.
... However, supraphysiological doses of testosterone may induce insulin resistance in TM and cisgender women (75,93 ). Five prospective studies (64,72,74,75,81 ) observed no change in fasting glucose concentrations in TW, whereas 2 studies (74,75 ) observed an increase in insulin resistance markers. However, the available prospective studies on insulin resistance and metabolic risk in transgender people mainly report on short-term data, and it remains unsure whether the administration of testosterone may have effects on insulin sensitivity, as this has not been described in longer term studies. ...
Background:
Gender-affirming hormonal therapy consists of testosterone in transgender men and estrogens and antiandrogens in transgender women. Research has concluded that gender-affirming therapy generally leads to high satisfaction rates, increased quality of life, and higher psychological well-being. However, given the higher incidence of cardiometabolic morbidity and mortality in cisgender men compared with cisgender women, concerns about the cardiometabolic risk of androgen therapy have been raised.
Content:
A literature research was conducted on PubMed, Embase, and Scopus, searching for relevant articles on the effects of gender-affirming hormone therapy on cardiometabolic risk and thrombosis. After screening 734 abstracts, 77 full text articles were retained, of which 11 were review articles.
Summary:
Studies describing a higher risk for cardiometabolic and thromboembolic morbidity and/or mortality in transgender women (but not transgender men) mainly covered data on transgender women using the now obsolete ethinyl estradiol and, therefore, are no longer valid. Currently, most of the available literature on transgender people adhering to standard treatment regimens consists of retrospective cohort studies of insufficient follow-up duration. When assessing markers of cardiometabolic disease, the available literature is inconclusive, which may be ascribed to relatively short follow-up duration and small sample size. The importance of ongoing large-scale prospective studies/registries and of optimal management of conventional risk factors cannot be overemphasized.
... No records were identified through other resources. Following the screening of these records' titles and abstracts, 84 full text articles were assessed for eligibility; however, 70 articles were excluded due to not being original investigations, not assessing relevant outcomes, not obtaining pre-GHT outcome measurements [14] or including adolescent populations [15][16][17][18]. ...
Objectives:
Gender-affirming hormone therapy (GHT) is utilized by people who are transgender to align their secondary sex characteristics with their sex identity. Data relating to cardiovascular outcomes in this population are limited. We aimed to review the impact of GHT on the blood pressure (BP) of transgender individuals.
Methods:
We searched PubMed/MEDLINE, SCOPUS and Cochrane Library databases for articles published relating to the BP of transgender adults commencing GHT. Methodological quality was assessed via the 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group'.
Results:
Six hundred articles were screened, of which 14 studies were included in this systematic review encompassing 1309 individuals (∼50% transgender men and women) treated with GHT between 1989 and 2019. These articles were all pre-post observational studies without control groups. Mean ages ranged between 23.0-36.7 years (transgender men) and 25.2-34.8 years (transgender women). Interventions were diverse and included oral, transdermal and injectable hormonal preparations with 4 months to 5 years follow-up. Most studies in transgender men did not demonstrate a change in BP, whereas transgender women on GHT demonstrated an increase in SBP but not DBP. These studies were heterogenous with significant methodological limitations and only two were determined to have a good quality rating.
Conclusion:
There is currently insufficient data to advise the impact of GHT on BP in transgender individuals. Better quality research is essential to elucidate whether exogenous sex hormones modulate BP in transgender people and whether this putative alteration infers poorer cardiovascular outcomes.
... 10,11,20 In transgender male adolescents, studies have shown unchanged SBP and DBP after testosterone treatment in accordance with our study. 18,21 Limitations Our study has several limitations. It was retrospective in design, and it included a small number of patients, and an even smaller number of patients who received testosterone treatment. ...
Purpose:
We analyzed blood pressure (BP) changes in transgender male adolescents treated with gonadotropin-releasing hormone analogs (GnRHa) and after adding testosterone treatment.
Methods:
This was a retrospective pilot study. Outcome measures included systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding testosterone.
Results:
Fifteen transgender male adolescents received GnRHa. DBP percentiles increased significantly after GnRHa treatment (from 55.9% ± 26.4 to 73.6% ± 9.4, p = 0.019). BP levels did not meet criteria for hypertension. DBP percentiles were restored after adding testosterone.
Conclusion:
GnRHa may increase DBP in transgender male adolescents, and testosterone treatment may restore it. Further larger studies are indicated.
... In trans-men, the only findings were an increase in hemoglobin, hematocrit, and body mass index with lowering of high-density lipoprotein levels; in transwomen, only lower testosterone and alanine aminotransferase (ALT) were reported [15]. Olson-Kennedy et al., in their prospective study, found several statistically significant changes in mean values of physiological parameters over time but of no consequence to clinical safety concerns [16]. In both studies, the authors indicated that this cross-sex hormonal therapy is safe for transgender youth over a period of approximately two years. ...
Gender affirmation surgery remains one of the greatest challenges in transgender medicine. In recent years, there have been continuous discussions on bioethical aspects in the treatment of persons with gender dysphoria. Gender reassignment is a difficult process, including not only hormonal treatment with possible surgery but also social discrimination and stigma. There is a great variety between countries in specified tasks involved in gender reassignment, and a complex combination of medical treatment and legal paperwork is required in most cases. The most frequent bioethical questions in transgender medicine pertain to the optimal treatment of adolescents, sterilization as a requirement for legal recognition, role of fertility and parenthood, and regret after gender reassignment. We review the recent literature with respect to any new information on bioethical aspects related to medical treatment of people with gender dysphoria.
... relieving psychological suffering, development of secondary sex characteristics consistent with gender), the relatively low risks of associated harms in adults who access gender-affirming hormone therapy (e.g., thromboembolic disease, erythrocytosis), and the risks of withholding treatment (e.g., suicidality, harassment, violence, use of non-prescription hormones) (Coleman et al. 2012;de Vries et al. 2014;Hembree et al. 2017;Olson, Forbes, and Beltzer 2011;Rosenthal 2014;Shield 2007). While few prospective and longitudinal studies report on outcomes of gender-affirming hormone therapy initiated in adolescence, existing research indicates positive psychosocial outcomes (de Vries et al. 2014) and an absence of clinically significant physiologic outcomes (e.g., lipids, potassium, hemoglobin, prolactin) (Olson-Kennedy et al. 2018). Multiple longitudinal studies on long-term physiological and psychosocial outcomes are currently underway (Olson-Kennedy, Chan, Garofalo, et al. 2019a;Olson-Kennedy, Chan, Rosenthal, et al. 2019b;Trans Youth Can! 2018). ...
Inherent in providing healthcare for youth lie tensions among best interests, decision-making capacity, rights, and legal authority. Transgender (trans) youth experience barriers to needed gender-affirming care, often rooted in ethical and legal issues, such as healthcare provider concerns regarding youth capacity and rights to consent to hormone therapy. Even when decision-making capacity is present, youth may lack the legal authority to give consent. The aims of this paper are therefore to provide an empirical analysis of minor trans youth capacity to consent to hormone therapy and to address the normative question of whether there is ethical justification for granting trans youth the authority to consent to this care. Through qualitative content analysis of interviews with trans youth, parents, and healthcare providers, we found that trans youth demonstrated the understandings and abilities characteristic of the capacity to consent to hormone therapy and that they did consent to hormone therapy with positive outcomes. Employing deontological and consequentialist reasoning and drawing on a foundation of empirical evidence, human rights, and best interests we conclude that granting trans youth with decisional capacity both the right and the legal authority to consent to hormone therapy via the informed consent model of care is ethically justified.
... La testostérone induit une diminution du taux de HDL-cholestérol mais les études ne permettent pas de conclure sur une incidence sur le risque cardio-vasculaire [88,91]. Concernant l'estradiol, des études n'ont pas trouvé d'effet sur les taux de lipides [80,89] mais une étude rapporte une augmentation de l'HDL-cholestérol [90]. ...
Aujourd'hui, les progrès dans les biotechnologies et dans le champ de la médecine défient les lois de la biologie pour permettre à des hommes et des femmes transgenres d'advenir en tant que sujet et d'accéder à la parentalité. Ces avancées soulèvent dans de nombreux pays de vifs débats sociétaux, mais aussi de vraies questions éthiques l'enjeu majeur in fine étant pour la plupart des auteurs le bien-être des enfants à naître. Nous avons ainsi cherché à comparer le développement cognitif, la santé mentale, l'identité de genre, la qualité de vie et la dynamique familiale à l'aide d'instruments standardisés et de protocoles expérimentaux chez 32 enfants conçu·e·s par IAD en France dont le père est un homme transgenre et la mère une femme cisgenre (identifiée au genre féminin qui lui a été assigné à la naissance), la transition féminin vers masculin du père ayant eu lieu avant la conception. Nous avons constitué deux groupes témoins appariés pour l'âge, le sexe et la situation familiale : le premier composé d’enfants né·e·s de parents cisgenres hétérosexuels ayant eu recours à l’IAD pour concevoir, le second composé d’enfants conçu·e·s par rapport sexuel de parents hétérosexuels cisgenres.Nous n'avons trouvé aucune différence significative entre les groupes en ce qui concerne le développement cognitif, la santé mentale et l'identité de genre, ce qui signifie que ni la paternité transgenre ni l'utilisation des IAD n'ont eu d'impact sur ces caractéristiques. Les résultats de l'analyse descriptive ont montré un développement psycho-affectif positif. De plus, lorsque nous avons demandé à des groupe d’évaluateur·trice·s de différencier les dessins de famille du groupe d'enfants de pères trans’ de celleux qui étaient conçu·e·s par rapport sexuel de parents cisgenres, aucun n'a pu différencier ces groupes au-dessus des niveaux du hasard, ce qui signifie que ce que les enfants ont exprimé à travers le dessin de famille n'indiquait pas d’indices liés à la paternité transgenre. Cependant, lorsque nous avons étudié les émotions exprimées par les mères et les pères à partir d’un extrait de discours de 5 minutes (Five Minute Speech Sample), nous avons constaté que les émotions exprimées par les pères transgenres étaient plus intenses que celles des pères cisgenres qui ont conçu par rapport sexuel ou par IAD.Nous concluons que ces premières données empiriques sur le développement de l'enfant dans le contexte de la trans-parentalité sont rassurantes. Nous pensons que cette recherche améliorera également les soins aux couples transgenres et ceux de leurs enfants dans une société où les projections sociétales comme l'accès aux soins restent difficiles pour cette population. Cependant, des recherches transdisciplinaires complémentaires sont nécessaires, en particulier avec les adolescents, les jeunes adultes et en périnatalité.
... Current dosing protocols for pubertal induction for gender-affirming estradiol and testosterone administration are predominantly derived from experience with cis-gender hypogonadal patients and initial studies in adolescents support its safety. 3,[90][91][92][93][94] Pediatric endocrinologists previously manipulated height in cis-gender girls through administration of high-dose estrogen to attenuate adult height by accelerating epiphyseal fusion. [95][96][97] While this practice has fallen out of favor, this approach may still be practiced by some pediatric endocrinologists when desired by parents of children with severe intellectual disability. ...
The sexually dimorphic trait of height is one aspect of the experience of transgender and gender diverse (TGD) individuals that may influence their gender dysphoria and satisfaction with their transition. In this article, we have reviewed the current knowledge of the factors that contribute to one’s final adult height and how it might be affected in TGD youth who have not experienced their gonadal puberty in the setting of receiving gonadotropin‐releasing hormone analog (GnRHa) and gender‐affirming hormonal treatment. Additional research is needed to characterize the influence of growth and final adult height on the lived experience of TGD youth and adults and how to best assess their growth, predict their final adult height, and how medical transition can be potentially modified to help them meet their goals.
... Regarding cardiovascular health, while some studies have found that testosterone use may statistically increase some metabolic parameters, they have not been clinically significant; nonetheless, regular metabolic monitoring is warranted [66,67]. Regarding bone development, multiple recent studies have found that puberty blockers may initially decrease lumbar bone mineral density in transgender youth, though these may normalize later with hormone therapy [68,69]. ...
Purpose of Review
This paper reviews the evolving body of research on the mental health of transgender and gender diverse (TGD) youth. Minority stress experiences in families, schools, and the community impact the health and well-being of this population due to experiences of stigma, discrimination, and rejection. Poor healthcare access and outcomes may be compounded in youth with intersectional identities.
Recent Findings
There is increasing evidence that gender-affirming interventions improve mental health outcomes for TGD youth. TGD youth report worse mental health outcomes in invalidating school and family environments and improved outcomes in affirming climates. TGD youth experience significant healthcare disparities, and intersectional clinical approaches are needed to increase access to affirmative care.
Summary
Providers can best support TGD youth by considering ways they can affirm these youth in their healthcare settings, and helping them access support in schools, family systems, and communities. Understanding the intersection of multiple minority identities can help providers address potential barriers to care to mitigate the health disparities seen in this population.
... GAHT has been shown to be safe and have predictable effects on hormone levels in transgender youths (23). While an increased cancer risk with the use of hormone therapy is theoretically possible and plausible, there have been no well-designed studies published showing that long term use of GAHT or suppression of a patient's natal puberty increases cancer risk (24). ...
Over the last 50 years cancer mortality has decreased, the biggest contributor to this decrease has been the widespread adoption of cancer screening protocols. These guidelines are based on large population studies, which often do not capture the non-gender conforming portion of the population. The aim of this review is to cover current guidelines and practice patterns of cancer screening in transgender patients, and, where evidence-based data is lacking, to draw from cis-gender screening guidelines to suggest best-practice screening approaches for transgender patients. We performed a systematic search of PubMed, Google Scholar and Medline, using all iterations of the follow search terms: transgender, gender non-conforming, gender non-binary, cancer screening, breast cancer, ovarian cancer, uterine cancer, cervical cancer, prostate cancer, colorectal cancer, anal cancer, and all acceptable abbreviations. Given the limited amount of existing literature inclusion was broad. After eliminating duplicates and abstract, all queries yielded 85 unique publications. There are currently very few transgender specific cancer screening recommendations. All the guidelines discussed in this manuscript were designed for cis-gender patients and applied to the transgender community based on small case series. Currently, there is not sufficient to evidence to determine the long-term effects of gender-affirming hormone therapy on an individual's cancer risk. Established guidelines for cisgender individuals and can reasonably followed for transgender patients based on what organs remain in situ. In the future comprehensive cancer screening and prevention initiatives centered on relevant anatomy and high-risk behaviors specific for transgender men and women are needed.
... In our study, intramuscular and subcutaneous testosterone administration resulted in in the median serum total testosterone concentration of approximately 525 ng/dL. This level of serum total testosterone is consistent with levels found in other cohorts of trans men [13,14,16,17]. Pelusi et. ...
Objective: To examine the association of various gender affirmation hormone therapy (GAHT) regimens with blood hormone concentrations in transgender individuals.
Methods: This retrospective study included transgender persons receiving GAHT between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Non-parametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations.
Results: Overall 196 subjects (134 trans women, 62 trans men) with a total of 941 clinical visits were included into this study. Trans men receiving transdermal testosterone had a significantly lower median value of total serum testosterone when compared to those who were receiving injectable preparations (326.0 vs. 524.5 ng/dL respectively, p=0.018). Serum total estradiol concentrations of trans women was higher in those receiving intramuscular estrogen compared to those receiving oral and transdermal estrogen (366.0 vs. 102.0 vs. 70.8 pg/mL respectively, p<0.001). A dose dependent response in hormone levels was observed for oral estradiol (p<0.001) and injectable testosterone (p=0.018), but not for intramuscular estradiol and not for transdermal formulations. Older age and history of gonadectomy in both trans men and women were associated with significantly higher concentrations of serum gender-affirmed hormone.
Conclusion: In trans men, all routes and formulations of testosterone appear to be equally effective in achieving concentrations in the male range. Intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol whereas transdermal estradiol resulted in the lowest concentration. Dose was directly related to hormone levels for oral estradiol and injectable testosterone.
Abbreviations: TGGNB = Transgender and gender non-binary; GAHT = gender affirming hormone therapy, SD = standard deviation, BMI = body mass index, IQR = interquartile range, VTE = venous thromboembolism, HDL = high-density lipoprotein, TG = triglycerides, LDL = low-density lipoprotein, SHBG = sex hormone binding globulin.
Trans and non-binary youth (TNBY) face high levels of interpersonal and social adversity as well as disproportionate rates of mental health issues such as depression, self-harm and suicidal ideation. Among protective factors, context plays a key role. In addition to parental support, access to gender-affirming medical care begins to emerge as crucial for young people needed them. This paper compares, through thematic analysis, the experiences of TNBY with regard to access and experiences to care in Canada, Switzerland, England, and Australia. It identifies similarities and differences in barriers to access to care, as well as impacts of gender affirming care on young people and their well-being. The article concludes with a discussion on the importance of prompt and easier access to gender-affirming medical care, of training of professionals, and a hypothesis about the role of context in TNBY well-being.
Context:
The impact of gender-affirming hormone therapy (HT) on cardiometabolic parameters is largely unknown.
Objective:
The effects of 1 year of treatment with oral or transdermal administration of estrogen (plus cyproterone) and transdermal or IM application of testosterone on serum lipid levels and blood pressure (BP) were assessed in transgender persons.
Design and methods:
In this prospective, observational substudy of the European Network for the Investigation of Gender Incongruence, measurements were performed before and after 12 months of HT in 242 transwomen and 188 transmen from 2010 to 2017.
Results:
Mean values are reported. In transmen, HT increased diastolic BP (2.5%; 95% CI, 0.6 to 4.4) and levels of total cholesterol (TC; 4.1%; 95% CI, 1.5 to 6.6), low-density lipoprotein-cholesterol (LDL-C; 13.0%; 95% CI, 9.2 to 16.8), and triglycerides (36.9%; 95% CI, 29.8 to 44.1); high-density lipoprotein-cholesterol levels decreased (HDL-C; 10.8%; 95% CI, -14.0 to -7.6). In transwomen, HT slightly decreased BP (systolic BP, -2.6%, 95% CI, -4.2 to -1.0; diastolic BP, -2.2%, 95% CI, -4.0 to -0.4) and decreased levels of TC (-9.7%; 95% CI, -11.3 to -8.1), LDL-C (-6.0%; 95% CI, -8.6 to 3.6), HDL-C (-9.3%; 95% CI, -11.4 to -7.3), and triglycerides (-10.2%; 95% CI, -14.5 to -5.9).
Conclusion:
Unfavorable changes in lipid profile were observed in transmen; a favorable effect was noted in transwomen. HT effects on BP were negligible. Long-term studies are warranted to assess whether and to what extent HT in trans individuals results in a differential effect on cardiovascular disease outcomes.
Gender dysphoria can occur at any age, although young children often explore gender identity through dress-up and play at age 3. Youth experiencing gender incongruence need access to health care providers who are aware of medical interventions for gender reassignment and the importance of follow-up care. Nurse practitioners (NPs) need to be well versed on issues surrounding gender identity while providing culturally competent care. NPs must have a thorough understanding of treatment options for gender dysphoria, including pubertal blockade and cross-sex hormone therapy. NPs must consider possible implications of treatment delay in order to establish the most appropriate treatment plans.
Objectives:
We systemically reviewed the literature to assess how long-term testosterone suppressing gender-affirming hormone therapy influenced lean body mass (LBM), muscular area, muscular strength and haemoglobin (Hgb)/haematocrit (HCT).
Design:
Systematic review.
Data sources:
Four databases (BioMed Central, PubMed, Scopus and Web of Science) were searched in April 2020 for papers from 1999 to 2020.
Eligibility criteria for selecting studies:
Eligible studies were those that measured at least one of the variables of interest, included transwomen and were written in English.
Results:
Twenty-four studies were identified and reviewed. Transwomen experienced significant decreases in all parameters measured, with different time courses noted. After 4 months of hormone therapy, transwomen have Hgb/HCT levels equivalent to those of cisgender women. After 12 months of hormone therapy, significant decreases in measures of strength, LBM and muscle area are observed. The effects of longer duration therapy (36 months) in eliciting further decrements in these measures are unclear due to paucity of data. Notwithstanding, values for strength, LBM and muscle area in transwomen remain above those of cisgender women, even after 36 months of hormone therapy.
Conclusion:
In transwomen, hormone therapy rapidly reduces Hgb to levels seen in cisgender women. In contrast, hormone therapy decreases strength, LBM and muscle area, yet values remain above that observed in cisgender women, even after 36 months. These findings suggest that strength may be well preserved in transwomen during the first 3 years of hormone therapy.
Increasing numbers of transgender and gender diverse (TGD) youth are presenting for medical care, including seeking more information and access to services from gynecologic and reproductive health experts. Such experts are well positioned to provide affirming, comprehensive services, including education, hormonal interventions, menstrual management, contraception, and various gynecological procedures. Early medical guidance and support for the TGD community has been associated with long-term positive emotional and physical health outcomes. In this article medical interventions that reproductive health experts can offer to their TGD patients are discussed.
The term transgender youth commonly refers to those whose gender identity, or personal core sense of self as a particular gender, differs from their assigned sex at birth; this is often designated by what external genitalia are present. These youths are presenting to multidisciplinary clinics worldwide at exponentially higher rates than in decades past, and clinics themselves have grown in number to meet the specialized demands of these youth. Additionally, the scientific and medical community has moved towards understanding the construct of gender dimensionally (i.e., across a spectrum from male to female) as opposed to dichotomous or binary "male or female" categories. This is reflected in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM 5); in this publication, the diagnostic classification of gender dysphoria, GD, (which has two subtypes: childhood and adolescence/adulthood) provides a set of criteria that many transgender people meet. GD describes the affective distress that arises as a result of the incongruence between gender identity and sex anatomy. The DSM uses language to indicate that a person may identify as another gender instead of the other gender, which further captures the complexity of the human experience of gender. Also, research regarding how current adolescents are describing their identity development and experience along this spectrum within today's society is only now being addressed in the literature. Therefore, the clinical needs of the transgender population have outpaced medical training and scientific advancement, which has opened up gaps on how to define best practices. This article provides current concepts of evaluation and management for transgender persons with emphasis on hormonal therapy (i.e., puberty blockers and gender affirming hormone therapy). Other management issues are briefly considered including gender confirming surgery and changes in the face as well as voice.
Objective
The objective of this scoping review is to describe the extent, range, and nature of available literature examining nutrition-related intermediate and long-term health outcomes in individuals who are transgender. Specific sub-topics examined include 1) dietary intake, 2) nutrition-related health disparities, 3) validity and reliability of nutrition assessment methods, 4) the effects of nutrition interventions/exposures, and 5) hormone therapy.
Methods
A literature search was conducted using MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and other databases for peer-reviewed articles published from January 1999 until December 5, 2019 to identify studies addressing the research objective and meeting eligibility criteria. Conference abstracts and registered trials published or registered in the five years prior to the search were also included. Findings were reported in a study characteristics table, a bubble chart and heat maps.
Results
The search of the databases identified 5403 studies, including full peer-reviewed studies, systematic reviews, conference abstracts and registered trials. Following title/abstract screening, 189 studies were included in the narrative analysis. Ten studies reported dietary intake in transgender individuals, 64 studies reported nutrition-related health disparities in transgender compared to cisgender individuals, one study examined validity and reliability of nutrition assessment methods, two studies reported nutrition interventions, and 127 studies reported on the intermediate and health effects of hormone therapy.
Conclusion
Individuals who are transgender have unique nutrition needs, which may vary according to the stage and type of gender-affirmative therapy that they are undergoing. There is scant research examining effective nutrition therapy methods for nutrition professionals working with transgender individuals. More research is needed in order to inform evidence-based clinical practice guidelines for nutrition practitioners working with transgender individuals.
Suicide is a serious public health problem among adolescent and young adults. Indeed, 12.1% of adolescents contemplate suicide, 4.0% make a plan, and 4.1% make an attempt (Nock et al., 2013). LGBTQIA+ youth (i.e., lesbian, gay, bisexual, transgender, questioning/queer, intersex and/or asexual adolescents and young adults) are particularly vulnerable to suicide (CDC, 2016; Liu & Mustanksi, 2012; Peters et al., 2019). While many LGBTQIA+ youth are healthy and resilient (Ream & Savin-Williams, 2005) they often report higher rates of both suicidal ideation and behavior than their heterosexual (Haas et al., 2011) and cisgender (James et al., 2016) peers.
Objectives:
We characterized referral trends over time at a transgender clinic within an integrated health system in Northern California. We identified the transition-related requests of pediatric transgender and gender-nonconforming patients and evaluated differences in referrals by age group.
Methods:
Medical records were analyzed for all patients <18 years of age in the Kaiser Permanente Northern California health system who were referred to a specialty transgender clinic between February 2015 and June 2018. Trends in treatment demand, demographic data, service requests, and surgical history were abstracted from medical charts and analyzed by using descriptive statistics.
Results:
We identified 417 unique transgender and gender-nonconforming pediatric patients. The median age at time of referral was 15 years (range 3-17). Most (62%) identified on the masculine spectrum. Of the 203 patients with available ethnicity data, 68% were non-Hispanic. During the study period, the clinic received a total of 506 referrals with a significant increase over time (P < .001). Most referrals were for requests to start cross-sex hormones and/or blockers (34%), gender-affirming surgery (32%), and mental health (27%). Transition-related requests varied by age group: younger patients sought more mental health services, and older patients sought hormonal and surgical services. Eighty-nine patients underwent gender-affirming surgeries, mostly before age 18 and most frequently mastectomies (77%).
Conclusions:
The increase in referrals supports the need for expanded and accessible health care services for this population. The transition-related care of patients in this large sample varied by age group, underscoring the need for an individualized approach to gender-affirming care.
Although advances in our understanding of transgender/gender nonconforming youth have been achieved, gaps in knowledge remain. Compelling studies have emerged supporting the concept that gender identity is not simply a psychosocial construct, but likely reflects a complex interplay of biologic, environmental, and cultural factors. Replacement of the term gender identity disorder with gender dysphoria in the Diagnostic and Statistical Manual of Mental Disorders-V underscores that a transgender identity, in and of itself, is no longer considered pathologic. Thus clinical concern should focus on the gender dysphoria that may be present, along with concomitant mental health challenges. The first long-term study, based on current models of care, indicates that mental health comorbidities in gender dysphoric youth diminish or resolve when such individuals are provided with gender-affirming treatment, optimally delivered in a multidisciplinary setting. Further prospective, long-term outcome studies are needed to optimize care for transgender/gender nonconforming youth.
El objetivo de este trabajo consiste en examinar el desarrollo de la ciencia en torno a la disforia de género (DG) a través del marco analítico de la filosofía de la ciencia. En concreto, mi intención es estudiar qué factores han contribuido a la politización progresiva de la ciencia producida en este ámbito. Para ello utilizaré el modelo propuesto por la filósofa estadounidense Heather Douglas, para quien los valores no epistémicos sólo deben desempeñar un rol indirecto en los procesos de inferencia científica. Hablamos de ciencia politizada cuando dichos valores juegan un papel directo en el funcionamiento interno de la ciencia, siendo los únicos determinantes de la aceptación o el rechazo de hipótesis. Aplicando este modelo al caso específico de la tipología de la transexualidad de Blanchard, la disforia de género de inicio rápido (ROGD) y el tratamiento de niños y adolescentes con DG, trataré de demostrar que la ciencia en torno a la DG está politizada, de modo que son los valores no epistémicos de los profesionales e investigadores los que determinan qué ideas y procedimientos terapéuticos resultan aceptables. Todo ello tiene implicaciones para la disciplina en su conjunto y plantea importantes desafíos de cara al futuro.
A growing number of children and adolescents report having gender identities or expressions that differ from their birth‐assigned gender or from social and cultural gender norms. Some identify as transgender, whereas others consider themselves nonbinary or gender fluid. Nonbinary and gender fluid youth are distinct from transgender youth in that they typically report that their gender identity (i.e., their internal sense of gender) or their gender expression (i.e., their public presentation of their gender through appearance, dress, and behavior) fall outside the traditional male–female binary. For example, nonbinary youth may identify as both male and female or neither male nor female. In this article, I discuss what we know about nonbinary forms of gender identity and expression among children and adolescents, and how these experiences converge and diverge from binary forms of the transgender experience. I also identify the most important priorities for fostering well‐being among all youth.
Purpose:
The aim of the article was to understand adolescents' and parents' decision-making process related to gender-affirming hormone therapy (GAHT).
Methods:
We conducted qualitative semistructured interviews with transgender adolescents who began testosterone for GAHT in the prior year and the parents of such adolescents. Questions focused on decision-making roles, steps in the decision process, and factors considered in the decision. Participants used pie charts to describe the division of responsibility for the decision. All interviews were coded by at least two members of the research team with disagreements resolved through discussion. Thematic analysis was used to analyze the data.
Results:
Seventeen adolescents and 13 parents were interviewed (12 dyads). The process of deciding about GAHT involves a series of small conversations, typically with the adolescent advocating to start treatment and the parent feeling hesitant. In most cases, after seeking information from the Internet, healthcare providers and personal contacts move toward acceptance and agree to start treatment. Although adolescents have some short-term concerns, such as about needles, parents' concerns relate more to long-term risks. Ultimately, for both parents and adolescents, the benefits of treatment outweigh any concerns, and they are in agreement about the goals of personal confidence, comfort in one's body and happiness.
Conclusions:
To the extent that the decision about GAHT is a medical decision, the decision process is similar to others. However, decisions about GAHT are much more about gender identity than medical risks, suggesting that interventions based in a medical framework may not aid in supporting decision-making.
Objectives
To describe the extent, range and nature of literature examining the nutrition-related intermediate and long-term health outcomes in individuals who are transgender. Specific sub-topics include dietary intake, nutrition-related health disparities, validity and reliability of nutrition assessment methods, and the effects of nutrition interventions/exposures and hormone therapy.
Methods
A literature search was conducted of Medline, Embase, PsycINFO, CINAHL, Web of Science, and other databases from 1999 though 2019 to identify peer-reviewed articles published in English that addressed the research objective. Conference abstracts and registered trials were eligible if they were published in 2015 or later. Each title/abstract and eligible full-text article was screened by two reviewers and discrepancies were determined by consensus. Data was extracted by one reviewer and confirmed by a second reviewer.
Results
The literature search identified 3020 original studies, abstracts or registered trials, 424 full-text articles were reviewed for inclusion and 188 were included in qualitative analysis, including 17 systematic reviews. Populations examined included adults (n = 159), adolescents (n = 61) and children (n = 11). The vast majority of included articles examined the effects of hormone therapy on intermediate outcomes (n = 118) such as anthropometric, bone density and laboratory measures, or health outcomes (n = 18) such as cardiovascular disease events or quality of life. There was also considerable research examining the prevalence of health outcomes, such as eating disorders, malnutrition status, or diabetes, in transgender compared to cisgender populations. However, there was a paucity of data describing dietary intake (n = 10), validity and reliability of nutrition assessment methods (n = 1) or the effects of nutrition interventions on nutrition-related outcomes (n = 3) in transgender individuals. Nearly all evidence, except for three hormone trials, was observational in nature.
Conclusions
There is a need for research that examines medical nutrition therapy to promote health and prevent or treat adverse health outcomes that are prevalent in individuals who are transgender.
Funding Sources
Academy of Nutrition and Dietetics.
Background
Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy.
Methods
We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence.
Findings
We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas.
Interpretation
Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.
Gender affirming hormonal treatment (GAHT) in transgender men consists of testosterone treatment in different formulations. The main goal of testosterone treatment is to achieve cisgender male serum testosterone levels in order to induce virilization. The desired effects include increased facial and body hair, deepening of the voice, cessation of menses, fat redistribution and increased lean mass and strength, as well as improvement of psychological well-being. However, testosterone treatment may induce potential undesired effects and risks, such as acne, androgenetic alopecia, increase in systolic blood pressure, haematocrit and changes in lipid profile. GAHT in transgender men is considered safe on the short term and middle term, although several aspects, such as long-term cardiovascular and oncological safety, need to be adequately assessed in the future through long-term prospective studies.
Transgender and gender-diverse children and adolescents, that is, those children and adolescents whose gender identity does not match their sex assigned at birth, are presenting for gender-affirming care in ever-increasing numbers. Primary care providers play an important role in creating a gender-inclusive environment, referring for mental health support, and potentially initiating gender-affirming care. Gender-affirming care should be tailored to the desires and goals of each patient and may include support for social transition, pubertal blockade, and/or gender-affirming hormones. Referral to a pediatric endocrinologist is indicated for patients undergoing pubertal induction, patients with significant personal or family history of cardiovascular disease or thromboembolic disease, or patients with other significant medical history. Gender-affirming treatment should occur in the context of a multidisciplinary team of medical and mental health professionals comfortable counseling patients regarding the risks and benefits of treatment and regarding fertility preservation.
Transgender (trans) women (TW) were assigned male at birth but have a female gender identity or gender expression. The literature on management and health outcomes of TW has grown recently with more publication of research. This has coincided with increasing awareness of gender diversity as communities around the world identify and address health disparities among trans people. In this narrative review, we aim to comprehensively summarize health considerations for TW and identify TW-related research areas that will provide answers to remaining unknowns surrounding TW’s health. We cover up-to-date information on: (1) feminizing gender-affirming hormone therapy (GAHT); (2) benefits associated with GAHT, particularly quality of life, mental health, breast development and bone health; (3) potential risks associated with GAHT, including cardiovascular disease and infertility; and (4) other health considerations like HIV/AIDS, breast cancer, other tumours, voice therapy, dermatology, the brain and cognition, and aging. Although equally deserving of mention, feminizing gender-affirming surgery, paediatric and adolescent populations, and gender nonbinary individuals are beyond the scope of this review. While much of the data we discuss come from Europe, the creation of a United States transgender cohort has already contributed important retrospective data that are also summarized here. Much remains to be determined regarding health considerations for TW. Patients and providers will benefit from larger and longer prospective studies involving TW, particularly regarding the effects of aging, race and ethnicity, type of hormonal treatment (e.g. different oestrogens, anti-androgens) and routes of administration (e.g. oral, parenteral, transdermal) on all the topics we address.
Introduction: Some providers report concern for the safety of transgender hormone therapy (HT).
Methods: This is a systematic literature review of HT safety for transgender adults.
Results: Current literature suggests HT is safe when followed carefully for certain risks. The greatest health concern for HT in transgender women is venous thromboembolism. HT among transgender men appears to cause polycythemia. Both groups experienced elevated fasting glucose. There is no increase in cancer prevalence or mortality due to transgender HT.
Conclusion: Although current data support the safety of transgender HT with physician supervision, larger, long-term studies are needed in transgender medicine.
Gender-nonconforming youth are emerging at increasingly younger ages, and those experiencing gender dysphoria are seeking medical care at, or sometimes even before, the onset of puberty. Youth with gender dysphoria are at high risk for depression, anxiety, isolation, self-harm, and suicidality at the onset of a puberty that feels wrong. Medical providers would benefit from understanding interventions that help gender-nonconforming children and youth thrive. The use of gonadotropin-releasing hormone (GnRH) agonists to block the onset of an undesired puberty in youth with gender dysphoria is a relatively new practice, particularly in the United States. These medications shut down the hypothalamic-pituitary-gonadal axis (HPG), and the production of either testosterone or estrogen is temporarily halted. Puberty blocking allows a young person to explore gender and participate more fully in the mental health therapy process without being consumed by the fear of an impending developmental process that will result in the acquisition of undesired secondary sexual characteristics. GnRH agonists have been used safely for decades in children with other medical conditions, including central precocious puberty. Potential side effects of GnRH agonists include diminished bone density, injection site problems, emotional instability, and weight gain. Preliminary data have shown GnRH agonists to be very helpful in improving behavioral and overall functioning outcomes. Puberty suppression should ideally begin in the first stages of pubertal development and can be given via intramuscular or subcutaneous injections, or via an implant that is inserted in the upper arm. Monitoring to assure suppression of the HPG axis should occur regularly. Gender-nonconforming youth who remain gender dysphoric can go on to receive cross-sex hormones for phenotypic gender transition when they are older. GnRH agonists have changed the landscape of medical intervention for youth with gender dysphoria and are rapidly becoming the standard of practice. [Pediatr Ann. 2014; 43(6):e132-e137.].
Treatment outcome in transsexuals is expected to be more favourable when puberty is suppressed than when treatment is started after Tanner stage 4 or 5. In the Dutch protocol for the treatment of transsexual adolescents, candidates are considered eligible for the suppression of endogenous puberty when they fulfil the Diagnostic and Statistic Manual of Mental Disorders-IV-RT criteria for gender disorder, have suffered from lifelong extreme gender dysphoria, are psychologically stable and live in a supportive environment. Suppression of puberty should be considered as supporting the diagnostic procedure, but not as the ultimate treatment. If the patient, after extensive exploring of his/her sex reassignment (SR) wish, no longer pursues SR, pubertal suppression can be discontinued. Otherwise, cross-sex hormone treatment can be given at 16 years, if there are no contraindications. Treatment consists of a GnRH analogue (GnRHa) to suppress endogenous gonadal stimulation from B2-3 and G3-4, and prevents development of irreversible sex characteristics of the unwanted sex. From the age of 16 years, cross-sex steroid hormones are added to the GnRHa medication.
Preliminary findings suggest that a decrease in height velocity and bone maturation occurs. Body proportions, as measured by sitting height and sitting-height/height ratio, remains in the normal range. Total bone density remains in the same range during the years of puberty suppression, whereas it significantly increases on cross-sex steroid hormone treatment. GnRHa treatment appears to be an important contribution to the clinical management of gender identity disorder in transsexual adolescents.
Aim. Testosterone treatment is essential for the induction and maintenance of virilization of female-to-male transsexuals. This study tested the suitability of a novel testosterone preparation for this purpose.
Methods. Parenteral long-acting testosterone undecanoate (TU) was administered to 12 female-to-male transsexuals. Observations were made while subjects received treatment.
Main Outcome Measures. Virilization of female-to-male transsexuals and side effects of testosterone administration.
Results. The testosterone levels were largely identical to those in hypogonadal men receiving testosterone treatment with TU. There were no side effects. There was a small but significant decrease in plasma cholesterol and low-density lipoprotein, but plasma high-density lipoprotein did not change significantly. Both levels of hemoglobin and hematocrit rose upon administration but remained within the physiological range.
Conclusions. TU is suited for induction of virilization in female-to-male transsexuals without significant side effects. Jacobeit JW, Gooren LJ, and Schulte HM. Long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals. J Sex Med 2007;4:1479–1484.
Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones.
A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses.
In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population.
The increased mortality in hormone-treated MtF transsexuals was mainly due to non-hormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.
The aim was to formulate practice guidelines for endocrine treatment of transsexual persons.
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low.
Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines.
Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person's genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person's desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons.
We prospectively studied outcomes of sex reassignment, potential differences between subgroups of transsexuals, and predictors of treatment course and outcome.
Altogether 325 consecutive adolescent and adult applicants for sex reassignment participated: 222 started hormone treatment, 103 did not; 188 completed and 34 dropped out of treatment. Only data of the 162 adults were used to evaluate treatment. Results between subgroups were compared to determine post-operative differences. Adults and adolescents were included to study predictors of treatment course and outcome. Results were statistically analysed with logistic regression and multiple linear regression analyses.
After treatment the group was no longer gender dysphoric. The vast majority functioned quite well psychologically, socially and sexually. Two non-homosexual male-to-female transsexuals expressed regrets. Post-operatively, female-to-male and homosexual transsexuals functioned better in many respects than male-to-female and non-homosexual transsexuals. Eligibility for treatment was largely based upon gender dysphoria, psychological stability, and physical appearance. Male-to-female transsexuals with more psychopathology and cross-gender symptoms in childhood, yet less gender dysphoria at application, were more likely to drop out prematurely. Non-homosexual applicants with much psychopathology and body dissatisfaction reported the worst post-operative outcomes.
The results substantiate previous conclusions that sex reassignment is effective. Still, clinicians need to be alert for non-homosexual male-to-females with unfavourable psychological functioning and physical appearance and inconsistent gender dysphoria reports, as these are risk factors for dropping out and poor post-operative results. If they are considered eligible, they may require additional therapeutic guidance during or even after treatment.
Background and objectives:
The Endocrine Society states that adolescents with gender dysphoria may start cross-sex hormones. The goal of this study was to identify patterns in metabolic parameters in transgender adolescents receiving cross-sex hormones.
Methods:
Data from adolescents aged 14 to 25 years seen in 1 of 4 clinical sites between 2008 and 2014 were retrospectively analyzed. Subjects were divided into affirmed male (female-to-male) patients taking testosterone and affirmed female (male-to-female) patients taking estrogen. Previously recorded measurements of blood pressure, BMI, testosterone, estradiol, prolactin, lipids, electrolytes, liver function tests, hemoglobin/hematocrit, and hemoglobin A1c were reviewed. These values were obtained from before the start of therapy, at 1 to 3 months after initiation, at 4 to 6 months, and at 6 months and beyond. Repeated measures analysis of variance models were used to evaluate changes over time.
Results:
One hunderd and sixteen adolescents were included (72 female-to-male subjects and 44 male-to-female subjects). Of the 72 subjects taking testosterone, a significant increase in hemoglobin/hematocrit levels and BMI, as well as a decrease in high-density lipoprotein level, was recorded at each visit. No significant changes in any other parameter tested were found. Of the 44 subjects taking estrogen, no statistically significant changes were noted in the measured metabolic parameters.
Conclusions:
Testosterone use was associated with increased hemoglobin and hematocrit, increased BMI, and lowered high-density lipoprotein levels; estrogen was associated with lower testosterone and alanine aminotransferase levels. Otherwise, cross-sex hormone administration in adolescents was not associated with significant differences in the selected metabolic parameters over time.
The purpose of this study was to describe baseline characteristics of participants in a prospective observational study of transgender youth (aged 12-24 years) seeking care for gender dysphoria at a large, urban transgender youth clinic.
Eligible participants presented consecutively for care at between February 2011 and June 2013 and completed a computer-assisted survey at their initial study visit. Physiologic data were abstracted from medical charts. Data were analyzed by descriptive statistics, with limited comparisons between transmasculine and transfeminine participants.
A total of 101 youth were evaluated for physiologic parameters, 96 completed surveys assessing psychosocial parameters. About half (50.5%) of the youth were assigned a male sex at birth. Baseline physiologic values were within normal ranges for assigned sex at birth. Youth recognized gender incongruence at a mean age of 8.3 years (standard deviation = 4.5), yet disclosed to their family much later (mean = 17.1; standard deviation = 4.2). Gender dysphoria was high among all participants. Thirty-five percent of the participants reported depression symptoms in the clinical range. More than half of the youth reported having thought about suicide at least once in their lifetime, and nearly a third had made at least one attempt.
Baseline physiologic parameters were within normal ranges for assigned sex at birth. Transgender youth are aware of the incongruence between their internal gender identity and their assigned sex at early ages. Prevalence of depression and suicidality demonstrates that youth may benefit from timely and appropriate intervention. Evaluation of these youth over time will help determine the impact of medical intervention and mental health therapy.
Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Compelling studies have demonstrated that "gender identity"-a person's inner sense of self as male, female, or occasionally a category other than male or female-is not simply a psychosocial construct, but likely reflects a complex interplay of biologic, environmental, and cultural factors. An increasing number of pre-adolescents and adolescents, identifying as "transgender" (a transient or persistent identification with a gender different from their "natal gender"-i.e. the gender that is assumed based on the physical sex characteristics present at birth), are seeking medical services to enable the development of physical characteristics consistent with their affirmed gender. Such services, including use of agents to block endogenous puberty at Tanner stage 2 and subsequent use of cross-sex hormones, are based on longitudinal studies demonstrating that those individuals who were first identified as gender-dysphoric in early or middle childhood and still meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. Furthermore, onset of puberty in transgender youth is often accompanied by increased "gender dysphoria"-clinically significant distress related to the incongruence between one's affirmed gender and one's "assigned (or natal) gender". Studies have shown that such distress may be ameliorated by a "gender-affirming" model of care. While endocrinologists are familiar with concerns surrounding gender identity in patients with disorders of sex development (DSD), many providers are unfamiliar with the approach to the evaluation and management of transgender youth without a DSD. The goals of this article are to review studies that shed light on the biologic underpinnings of gender identity, the epidemiology and natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care. Prospective cohort studies focused on long-term safety and efficacy are needed to optimize medical and mental health care for transgender youth.
To describe patient characteristics at presentation, treatment, and response to treatment in youth with gender dysphoria.
A retrospective chart review of 84 youth with a diagnosis of gender dysphoria seen at BC Children's Hospital from 1998-2011.
Of the 84 patients, 45 (54%) identified as female-to-male (FtM), 37 (44%) as male-to-female (MtF), and 2 (2%) as natal males who were undecided. Median age of presentation was 16.9 years (range 11.4-19.8 years) and 16.6 years (range 12.3-22.5 years) for FtM and MtF youth, respectively. Gonadotropin-releasing hormone analog treatment was prescribed in 27 (32%) patients. One FtM patient developed sterile abscesses with leuprolide acetate; he was switched to triptorelin and tolerated this well. Cross-sex hormones were prescribed in 63 of 84 patients (39 FtM vs 24 MtF, P < .02). Median age at initiation of testosterone injections in FtM patients was 17.3 years (range 13.7-19.8 years); median age at initiation of estrogen therapy in MtF patients was 17.9 years (range 13.3-22.3 years). Three patients stopped cross-sex hormones temporarily due to psychiatric comorbidities (2 FtM) and distress over androgenic alopecia (1 FtM). No severe complications were noted in patients treated with testosterone or estrogen.
Treatment with gonadotropin-releasing hormone analog and/or cross-sex hormones, in collaboration with transgender-competent mental health professionals, is an intervention that appears to be appropriate in carefully selected youth with gender dysphoria. Long-term follow-up studies are needed to determine the safety of these treatments in this age group.
Administration of cross-sex hormones to male-to-female transsexual subjects, usually oestrogens + often anti-androgens, such as cyproterone acetate, carries a risk of venous thromboembolism (VTE). VTE usually occurs in the first year of oestrogen administration. Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer, but people who take hormones without medical supervision use often oral contraceptives containing ethinyl oestradiol, many times in overdose. Cessation of use of ethinyl oestradiol and peri-operative thrombosis prophylaxis for surgery have reduced prevalence rate of VTE. Other oral oestrogens should not be overdosed, and transdermal oestrogen is to be preferred. Thrombosis prophylaxis for surgery is mandatory. It seems advisable to stop hormone use at least 2 weeks before major surgery, to be resumed only after 3 weeks following full mobilisation.
To describe the patients with gender identity disorder referred to a pediatric medical center. We identify changes in patients after creation of the multidisciplinary Gender Management Service by expanding the Disorders of Sex Development clinic to include transgender patients.
Data gathered on 97 consecutive patients <21 years, with initial visits between January 1998 and February 2010, who fulfilled the following criteria: long-standing cross-gender behaviors, provided letters from current mental health professional, and parental support. Main descriptive measures included gender, age, Tanner stage, history of gender identity development, and psychiatric comorbidity.
Genotypic male:female ratio was 43:54 (0.8:1); there was a slight preponderance of female patients but not significant from 1:1. Age of presentation was 14.8 ± 3.4 years (mean ± SD) without sex difference (P = .11). Tanner stage at presentation was 4.1 ± 1.4 for genotypic female patients and 3.6 ± 1.5 for genotypic male patients (P = .02). Age at start of medical treatment was 15.6 ± 2.8 years. Forty-three patients (44.3%) presented with significant psychiatric history, including 20 reporting self-mutilation (20.6%) and suicide attempts (9.3%).
After establishment of a multidisciplinary gender clinic, the gender identity disorder population increased fourfold. Complex clinical presentations required additional mental health support as the patient population grew. Mean age and Tanner Stage were too advanced for pubertal suppressive therapy to be an affordable option for most patients. Two-thirds of patients were started on cross-sex hormone therapy. Greater awareness of the benefit of early medical intervention is needed. Psychological and physical effects of pubertal suppression and/or cross-sex hormones in our patients require further investigation.
PRL levels were evaluated during long-term treatment with cyproterone acetate 100 mg and ethinyloestradiol 100 micrograms/day orally or depot-oestrogens in 214 male-to-female transsexuals. PRL levels increased above normal in all subjects (normal less than 300 mU/l). In 46 (21.4%) subjects PRL levels rose to greater than 1000 mU/l. The incidence of PRL levels greater than 1000 mU/l was 3.7-7.2% per treatment year. Grossly elevated PRL levels were associated with high doses of oestrogens (P less than 0.05) and advanced age at the start of treatment (P less than 0.05). In 23 subjects PRL levels greater than 1000 mU/l decreased by more than 50% spontaneously (n = 5) or after dose reduction (n = 18). In five of the subgroup of 15 subjects with persistent PRL levels greater than 1000 mU/l enlargement of the pituitary gland was shown by CT-scanning. These data suggest that the lowest possible oestrogen dose and lifelong follow-up of hormone-treated male-to-female transsexuals is essential.
The aim of this study is to understand the relationship between polycystic ovary syndrome (PCOS), altered hormonal characteristics and insulin resistance in female-to-male (FTM) transsexual patients.
We studied 69 Japanese FTM cases, aged 17-47 years, who were seen in the Gender Identity Disorder Clinic of Sapporo Medical University Hospital between December 2003 and May 2006. The subjects had never received hormonal treatment or sex re-assignment surgery. Prior to treatment, they received physical examinations entailing measurement of anthropometric, metabolic and endocrine parameters, after which we compared the values obtained according to the presence or absence of PCOS and/or obesity. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR).
Of the 69 participating FTM cases, 40 (58.0%) were found to have PCOS. Of the 49 for whom HOMA-IR was calculated, 15 (30.6%) also showed insulin resistance, whereas of the 59 for whom adiponectin was measured, 18 (30.5%) showed hypoadiponectinaemia. Of 69 for whom androgens were measured, 29 (39.1%) showed hyperandrogenaemia. Insulin resistance was associated with obesity but not with PCOS. In contrast, hyperandrogenaemia was associated with both PCOS and obesity.
FTM transsexual patients have a high prevalence of PCOS and hyperandrogenaemia.
Transsexuals receive cross-sex hormone treatment. Its short-term use appears reasonably safe. Little is known about its long-term use. This report offers some perspectives.
The setting was a university hospital serving as the national referral center for The Netherlands (16 million people).
From the start of the gender clinic in 1975 up to 2006, 2236 male-to-female and 876 female-to-male transsexuals have received cross-sex hormone treatment. In principle, subjects are followed up lifelong.
Male-to-female transsexuals receive treatment with the antiandrogen cyproterone acetate 100 mg/d plus estrogens (previously 100 microg ethinyl estradiol, now 2-4 mg oral estradiol valerate/d or 100 microg transdermal estradiol/d). Female-to-male transsexuals receive parenteral testosterone esters 250 mg/2 wk. After 18-36 months, surgical sex reassignment including gonadectomy follows, inducing a profound hypogonadal state.
Outcome measures included morbidity and mortality data and data assessing risks of osteoporosis and cardiovascular disease.
Mortality was not higher than in a comparison group. Regarding morbidity, with ethinyl estradiol, there was a 6-8% incidence of venous thrombosis, which is no longer the case with use of other types of estrogens. Continuous use of cross-sex hormones is required to prevent osteoporosis. Androgen deprivation plus an estrogen milieu in male-to-female transsexuals has a larger deleterious effect on cardiovascular risk factors than inducing an androgenic milieu in female-to-male transsexuals, but there is so far no elevated cardiovascular morbidity/mortality. Low numbers of endocrine-related cancers have been observed in male-to-female transsexuals.
Cross-sex hormone treatment of transsexuals seems acceptably safe over the short and medium term, but solid clinical data are lacking.