In 2020 I summarised the then published research on puberty blockers in a blog. That blog post remains a comprehensive overview of the pre 2020 literature, with relevance to discussions today.

There has been a significant body of research on puberty blockers published since that 2020 blog, that I will summarise and keep updated here. I’ve been meaning to update that blog, 4 years later. I was given encouragement by the latest overstep by the Charity Commission.

Yesterday the UK Charity Commission insisted that UK Charities revise their communication on puberty blockers with due regard for the findings of the Cass Review. This Charity Commission recommendation is problematic for two major reasons. Firstly, the Cass Review was heavily biased, an exemplar of prejudice impacting on healthcare policy, and has been widely condemned by trans communities, by healthcare experts worldwide and by academic researchers. The Charity Commission has no business stepping into this realm of academic criticism, and should not be preventing UK charities from highlighting the areas where the Cass Review deviated, for ideological reasons, from the evidence base. UK charities should not be coerced by the Charity Commission to endorse and disseminate medical advice they know to be deeply flawed. (Ruth Pearce has also done a blog on the Charity Commission’s latest advice to UK charities).

Secondly, regardless of any view on the reliability of the Cass Review, the Cass Review presents a snapshot of scientific evidence review at one point in time. The Cass Review drew upon a systematic review that looked at evidence published before April 2022 (and omitted some evidence published before that). The Cass Review was very clear that the science and evidence base underpinning trans youth healthcare is evolving and growing, and that approaches need to be atuned to new evidence as it is published. Science does not stand still. We need to continue to track and report on new evidence as it becomes available. Charities and others advising and supporting trans youth need to ensure they are representing current literature and current knowledge on puberty blockers, including considering the numerous peer reviewed academic studies published since April 2022.

This blog summarises all the literature published on puberty blockers since my last blog (written in early 2020). Many of the more recent of these articles were not considered by the Cass Review. The Cass Review examined articles published before April 2022 – articles published since that date are starred to highlight the evolving evidence base in this field.  

(note: The April 2022 cut-off date was used variably by the Cass Review. April 2022 was stated as the cut-off date for inclusion of studies in the York systematic literature review – however the Cass Review did include more recent studies that were critical or ambivalent about gender affirmative care, whilst ignoring more recent studies that presented positive findings on gender affirmative care).

On effectiveness

Mejia-Otero et al. (2021) “Effectiveness of Puberty Suppression with Gonadotropin-Releasing Hormone Agonists in Transgender Youth”. Found that puberty blockers were effective at blocking puberty, and as effective in trans youth as in cis youth with precocious puberty.

On mental health

*Chen et al. (not yet published). This study was presented at WPATH 2024. It highlighted the different mental health trajectories of trans youth. It emphasised that for trans youth with childhood support, family support, affirmation, low levels of gender minority stress, they have good mental health from childhood, and that good mental health is maintained through puberty blocker and gender affirming hormone treatment. For these youth, puberty blocker treatment would not lead to an improvement in mental health but a retention and protection of that good mental health. This is a very important distinction and highlights that looking for ‘mental health improvements’ is the wrong metric for this cohort. Similarly it highlighted a group with persistent mental health challenges, throughout gender affirming treatment. It concluded that gender affirmative healthcare is an important component of healthcare, but not expected to eradicate mental health challenges, especially for trans youth facing hostility, hate and persecution, and for youth with co-existing challenges linked to elevated rates of mental health. Overall, amongst youth receiving gender affirming healthcare, good mental health was more likely in trans youth with less loneliness, less gender minority stress, higher parental acceptance and higher emotional support.

* Kuper et al. (not yet published). This study was presented at WPATH 2024. It examined the outcomes for trans youth receiving testosterone and oestrogen. It noted that large improvements in body dissatisfaction were seen as the primary goal of treatment. This is an important clarification of a key goal of gender affirming care. It noted modest improvements in mental health and quality of life, which were also impacted by gender minority stress. They noted that this sample is in Texas where there are very significant socio-political stressors and state persecution, which is likely impacting on mental health measures. This study again emphasises that mental health does not operate in a vacuum, and that looking for improvements in mental health may be an unhelpful metric in a context where trans youth face severe and chronic stressors.

 *McGregor et al. (2024) “Association of Pubertal Blockade at Tanner 2/3 With Psychosocial Benefits in Transgender and Gender Diverse Youth at Hormone Readiness Assessment”. It compared 40 trans adolescents receiving blocker at tanner 2 or 3 to 398 trans adolescents who had not accessed a puberty blocker. It found those who accessed a puberty blocker had lower anxiety, less depression, less stress, and were significantly less likely to report any suicidal thoughts.

*Horton (2022) [My article] “Experiences of Puberty and Puberty Blockers: Insights From Trans Children, Trans Adolescents, and Their Parents”. Three major themes are presented, relating to pre-pubertal anxiety; difficulties accessing blockers; and, for a minority who were on blockers, experiences of relief and frustration. It highlighted the increase of anxiety in the years before puberty, and the role of confidence that puberty blockers would be available in assuaging that anxiety. This is one of the only pieces of modern research that actually centres trans children’s voices and perspectives on puberty blockers.

Chen et. al (2021) “Psychosocial Characteristics of Transgender Youth Seeking Gender-Affirming Medical Treatment: Baseline Findings from the TYC Study”. It compared the well-being of 95 trans adolescents just before accessing puberty blockers (mean age 11) to the well-being of 316 trans adolescents just before accessing HRT (mean age 16). A vast majority (93%) of the youth just about to start HRT had not been able to access puberty blockers. This study compared the two groups. Amongst the group about to access puberty blockers 28% showed depression, 22% anxiety, 23% lifetime suicidal ideation and 7.9% a past suicide attempt. Amongst the group about to access HRT group, the vast majority of whom had not been able to access puberty blockers 51% showed depression, 57% anxiety, 66% suicidal ideation and 24% a past suicide attempt. The study may indicate a decline in well-being over adolescence for trans youth who are not able to access affirmative healthcare, pointing to possible benefits of accessing gender-affirming treatment earlier in life. 

*Tordoff et al. (2022) “Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care”. The study looked at 104 trans youths. It found that receipt of gender-affirming care, including puberty blockers and gender-affirming hormones, was associated with 60% lower odds of moderate or severe depression and 73% lower odds of suicidality over a 12-month follow-up. Given this population’s high rates of adverse mental health outcomes, these data suggest that access to pharmacological interventions may be associated with improved mental health among TNB youths over a short period.

Wittlin et al. (2024) “Mental Health during Medical Transition in a US and Canadian Sample of Early Socially Transitioned Transgender Youth“. Looked at anxiety and depressive symptoms among transgender youth at 3 stages: before youth had begun puberty blockers; after they had begun blockers; and after they had begun hormone therapy, comparing them to samples of cis youth. In this sample of transgender youth who sought and received gender-affirming medical care, participants experienced stable and relatively low levels of psychological distress across stages of medical transition and across time. There was one exception: transgender girls showed increased, followed by decreased, parent-reported depressive symptoms over time. In contrast, cisgender girls showed increases in internalizing symptomatology (with the exception of parent-reported anxiety) as they got older, and cisgender boys showed decreased self-reported anxiety and increased, followed by decreased, parent-reported depressive symptoms. By mid-adolescence, levels of anxiety and depressive symptoms among transgender girls and transgender boys generally fell between those of cisgender girls and cisgender boys.

On quality of life & well-being

Fontanari et al. (2020) “Gender Affirmation Is Associated with Transgender and Gender Nonbinary Youth Mental Health Improvement”. Survey of 350 Brazilian trans youth. Having accessed multiple steps of gender affirmation (social, legal, and medical/surgical) was associated with fewer symptoms of depression and less anxiety. Furthermore, engaging in gender affirmation processes helped youth to develop a sense of pride and positivity about their gender identity and a feeling of being socially accepted.

Carmichael et al. (2021) “Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK”. Research of 44 trans youth. Overall patient experience of changes on GnRHa treatment was positive. It identified no changes in psychological function. Bone mass density was as expected.

Becker-Helby et al. (2020) “Psychosocial health in adolescents and young adults with gender dysphoria before and after gender-affirming medical interventions: a descriptive study from the Hamburg Gender Identity Service”. Followed 75 German trans youth from baseline through to 2 years later. 21 had no medical interventions. 11 had puberty suppression only. 32 had gender affirming hormones only. 11 had gender affirming hormones and surgery, predominantly mastectomy. At baseline all groups had high anxiety and low quality of life scores. For the puberty suppression group, quality of life measures at follow up after 2 years matched German healthy norms. Clinicians’ ratings of global functioning (CGAS) indicated good functioning levels at follow-up. Rates of anxiety and depression were still elevated.

*Horton (2022) [My article] ““I Didn’t Want Him to Disappear” Parental Decision-Making on Access to Puberty Blockers for Trans Early Adolescents”. This looked at how 30 parents of trans children navigate decisions about puberty blockers, and what factors those parents see as important for their children’s health and well-being. Parents regarded puberty blockers as protective of short and long term mental health. They felt puberty blockers enabled and sustained adolescent well-being and quality of life, enabling trans youth to focus on education, socialising, friendships, enjoying their adolescence. Parents expressed frustration at an excessively onerous process for providing consent, in particular the practice of asking adolescents at the point of accessing puberty blockers to consider the impacts of other medical interventions like HRT and surgery. Parents felt the process of taking consent should acknowledge that taking puberty blockers for a trans adolescent is not a more significant decision than a decision to proceed through endogenous puberty. Parents expressed dismay at the way in which evidence of safety and effectiveness for cis youth was disregarded (the same drugs do not work differently in trans youth). Parents also commented on they fact that they would never engage in a Randomised Control Trial of puberty blockers, highlighting significant practical and ethical flaws.

Impact on bodies and future surgery

Van de Grift et al. (2021) “Timing of Puberty Suppression and Surgical Options for Transgender Youth”. Looked at the impact of puberty blocking medication for trans people who later pursue surgical transition. They found that trans masculine adolescents receiving early puberty blockers were less likely to need chest surgery. Trans feminine adolescents receiving early puberty blockers were more likely to require a different type of bottom surgery to trans feminine adolescents who had not received early puberty blockers.

*Boogers et al. 2023 “Time Course of Body Composition Changes in Transgender Adolescents During Puberty Suppression and Sex Hormone Treatment”. Study compared trans girls on puberty blockers to cis boys and trans boys on puberty blockers to cis girls. Trans girls experienced ongoing lean mass decrease and fat mass increase compared to cis boys during 3 years of PS while in trans boys smaller changes compared to cis girls were observed that stabilized after 1 year.

On body image and body satisfaction

‘Bodily satisfaction’ or ‘appearance congruence’ are recognised as a critical outcome or benefit of access to puberty blockers.

*Chen et al. (2023) “Psychosocial Functioning in Transgender Youth after 2 Years of Hormones”. It monitored the impact of 2 years of HRT on 315 trans adolescents (mean age 16). During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The authors note that two trans youth died by suicide during the study period.

Kuper et al. (2021) “Body Dissatisfaction and Mental Health Outcomes of Youth on Gender-Affirming Hormone Therapy”. This study was not specifically on puberty blockers. But highlights that bodily satisfaction is a key measure that is changed through gender affirming hormones.

Grannis et al. (2021) “Testosterone treatment, internalizing symptoms, and body image dissatisfaction in transgender boys”. This study was not specifically on puberty blockers. It examined the well-being and bodily satisfaction of trans boys who had not received puberty blockers, comparing those who accessed Testosterone to those who had not yet accessed Testosterone. Those who had been through puberty without puberty blockers had high bodily dissatisfaction, anxiety and depression. Those on testosterone had reduced bodily dissatisfaction, with lower depression and suicidality. Group differences on depression and suicidality were directly associated with body image dissatisfaction

Articles on the rates of satisfaction with treatment and rates of continuation of gender affirming healthcare after puberty blockers

*Van der Loos et al. (2022) “Continuation of gender-affirming hormones in transgender people starting puberty suppression in adolescence: a cohort study in the Netherlands”. 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0–16·3) years for people assigned male at birth and 16·0 (14·1–16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9–24·8) years for people assigned male at birth and 19·2 (17·8–22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones. Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment.

*Cavve et al. (2024) “Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort”. From those seen at this Australian clinic between 2014 and 2020, 1% of trans adolescents accessing medical treatment including puberty blockers later reidentified with their assigned sex when followed up in 2022.

*Van der Loos et al. (2023) “Children and adolescents in the Amsterdam Cohort of Gender Dysphoria: trends in diagnostic- and treatment trajectories during the first 20 years of the Dutch Protocol”. This Study looked at the pathways of children who received puberty blockers over a 20 year period. Of all 266 AMAB who started GnRHa at our center, 9 (3.4%) discontinued treatment. Six (2.3%) ceased treatment because of abating GD. In 2 AMAB (0.8%), GnRHa treatment ended due to psychological or social issues hindering transition. In 1 individual (0.4%), GnRHa was discontinued due to compliance issues. Of all 616 AFAB, 5 (0.8%) broke off GnRHa. In 3 (0.5%), remission of GD led to discontinuation. In 2 (0.3%), GnRHa was suspended due to compliance issues. Of 707 eligible VUmc participants using GnRHa, 93% subsequently started GAH. The majority of people who had not yet started GAH did so for protocol reasons respectively. They were either too young or had not used GnRHa for the required amount of time.

*Masic et al. (2022) “Trajectories of transgender adolescents referred for endocrine intervention in England”. Not very informative.

*Butler et al. (2022) “Discharge outcome analysis of 1089 transgender young people referred to paediatric endocrine clinics in England 2008–2021”. Looked at pathways of those who had accessed endocrine services. 999/1089 (91.7%) continued identifying as gender variant. 90/1089 ceased identifying as gender variant. 58/1089 (5.3%) stopped treatment either with the gonadotropin releasing hormone analogue (GnRHa) or gender-affirming hormones (GAH) and reverted to their birth gender: <16 years (20/217; 9.2%); ≥16 years (38/872; 4.4%). Subdividing further, 16/217 (7.4%) <16 years ceased GnRHa and 4/217 (1.8%) after GAH. Of those ≥16 years, 33/872 (3.8%) ceased GnRHa and 5/872 (0.6%) GAH. At discharge, 91.7% continued as transgender or gender variant, 86.8% sought ongoing care through NHS GICs. 2.9% ceased identifying as transgender after an initial consultation prior to any endocrine intervention and 5.3% stopped treatment either with GnRHa or GAH, a higher proportion in the <16 year compared with the ≥16 year groups. 

On impact of puberty blockers on future sexual functioning

Van der Meulen et al. (2024) “Timing of puberty suppression in transgender adolescents and sexual functioning after vaginoplasty“. Looked at 37 transfeminine individuals treated with a gonadotropin-releasing hormone agonist (puberty suppression), estrogen, and vaginoplasty (penile inversion technique or intestinal vaginoplasty) in the Netherlands, between 2000 and 2016. Experiences regarding sexual functioning and difficulties were assessed with a self-developed questionnaire ~1.5 years after genital gender-affirming surgery and compared between early (Tanner stage G2-3) and late (Tanner stage G4-5) treatment with puberty suppression. Following surgery, 91% of transfeminine individuals was able to experience sexual desire, 86% experienced arousal, and 78% could attain an orgasm. Seventy-five percent of transfeminine individuals who had not experienced an orgasm pre-surgery were able to experience one post-surgery. Of all participants, 62% reported having tried penile-vaginal intercourse post-surgery. The majority reported the presence of one or multiple sexual challenges. There were no significant differences in postoperative sexual function or sexual difficulties between groups treated with early versus late puberty suppression. This study found that post-vaginoplasty transfeminine individuals after both early and late suppression of puberty have the ability to experience sexual desire and arousal, and to achieve orgasms. Outcomes are comparable to previous findings in those who started treatment in adulthood.

Articles examining how puberty blockers impact on other aspects of health

Strang et al. (2021) “Transgender Youth Executive Functioning: Relationships with Anxiety Symptoms, Autism Spectrum Disorder, and Gender-Affirming Medical Treatment Status”. The study looked at executive functioning in 124 trans youth. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Autism, anxiety and depression were all associated with lower executive function. Those on just puberty blockers for a year or less saw no impact on executive function. Being on puberty blockers without HRT for more than a year was slightly associated with low executive function. Being on gender-affirming hormones was associated with better executive function. It noted that experiences of stress, rejection and gender minority stress are likely to negatively impact on executive function.

*Valentine et al. (2022) “Multicenter Analysis of Cardiometabolic-related Diagnoses in Transgender and Gender-Diverse Youth: A PEDSnet Study” The study found that GnRHa were not associated with greater odds of cardiometabolic-related diagnoses.

Perl et al. (2021) “Blood pressure dynamics after pubertal suppression with gonadotropin-releasing hormone analogs followed by estradiol treatment in transgender female adolescents: a pilot study”. This research found that being on puberty blockers for trans feminine adolescents did not impact on blood pressure.

Perl et al. (2021) “Blood Pressure Dynamics After Pubertal Suppression with Gonadotropin-Releasing Hormone Analogs Followed by Testosterone Treatment in Transgender Male Adolescents: A Pilot Study”. This research found that being on puberty blockers for trans masculine adolescents had some impact on blood pressure, with this effect disappearing when on testosterone.

Russel et al. (2020) “A Longitudinal Study of Features Associated with Autism Spectrum in Clinic Referred, Gender Diverse Adolescents Accessing Puberty Suppression Treatment”. The research found that for autistic trans youth, being on puberty blockers did not affect their social responsiveness. (?)

Articles related to bone health

*Van der Loos et al. (2023) “Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones”. This looked at people average age 28, who had been on affirming hormones for an average of 11-12 years, having started affirming hormones at 16, after previously being on puberty blockers from tanner 2-3. Trans girls had lower bone mass than cis boys before the start of puberty blocker treatment. The study provided evidence that bone mineral accrual is temporarily suspended by the use of puberty suppression but, due to an increase during GAH treatment, BMD catches up with pretreatment levels at long-term follow-up, except for the lumbar spine in individuals assigned male at birth. The study concluded that treatment with a GnRH agonist followed by long-term gender-affirming hormones is safe regarding bone health in transgender persons receiving testosterone, but bone health in transgender persons receiving estrogen requires extra attention and further study.  Estrogen treatment should be optimized and lifestyle counseling provided to maximize bone development in individuals assigned male at birth. [Note this is yet another study inappropriately using Z scores compared to assigned sex which other lit (see earlier blog) has found are not the most useful way of studying bone density for this population]. Whilst this article predominantly compares trans people to the bone density of their assigned sex, when comparing trans people to their affirmed sex it notes “At follow-up, when participants were in their late 20s (around 28 years), the majority had z scores within the normal range when using reference data of the affirmed gender”.

Navabi et al. (2021) “Pubertal Suppression, Bone Mass, and Body Composition in Youth With Gender Dysphoria”. Found that reduced bone density of trans adolescents on puberty blockers was related to insufficient Vitamin D. Found that trans adolescents on puberty blockers need to take vitamin D. (This is standard healthcare). 

*Bachrach et al. (2023) “Bone Health Among Transgender Youth: What Is a Clinician to Do?” provides advice for clinicians on how to advise trans youth and families on managing bone health relating to puberty blockers.  

Articles related to research ethics on puberty blockers

*Ashley et al. (2023) “Randomized-controlled trials are methodologically inappropriate in adolescent transgender healthcare”. Outlines why RCTs are inappropriate, unpractical and unethical for puberty blockers.

*Moscati et al. (2023) “Trans* identity does not limit children’s capacity: Gillick competence applies to decisions concerning access to puberty blockers too!”. Outlines why being trans does not override important medical ethical principles of decision making.  

Articles related to height

Schulmeister et al. (2021) “Growth in transgender/gender-diverse youth in the first year of treatment with gonadotropin-releasing hormone agonists”. It looked at impact on rates of growth in height. It followed 55 trans adolescents who started blockers at average age 11, 62% at tanner 2 and 29% at tanner 3.  Pre-pubertal cis children grow at average 6.1 cm a year (range 4.3 – 6.5). Trans children who started puberty blockers at tanner II grew at a median of 5.3cm a year (range 4.1 – 5.6cm). Trans children who started puberty blockers at tanner III grew a median of 4.4cm a year (range 3.3 – 6.0cm). These rates are slightly lower rates of height growth than pre-pubertal youth. Trans children who started puberty blockers at tanner IV grew a median of 1.6cm a year (range 1.5 – 2.9cm), at a lower rate of height growth than pre-pubertal youth. In summary, trans adolescents on puberty blockers at tanner 2 and 3 continue to grow in height at similar rates to pre-pubertal children. Trans adolescents on puberty blockers at tanner 4 grow in height at slower rates. More information on the timing of affirmative healthcare and impacts on height will be valuable for those who desire a height in ranges typical for cis men and women.

*Boogers et al. (2023) “Transgender Girls Grow Tall: Adult Height Is Unaffected by GnRH Analogue and Estradiol Treatment”. This study looked at how gender affirming healthcare affects the height of trans girls. In the Dutch population, cis men reach a mean adult height of 183.8 cm, which is more than 13 cm taller than cis women (170.7 cm)  This study looked at 161 trans girls who started puberty blockers before age 16 and started oestrogen at an average age of 15 or 16 years old. The cohort were at different tanner stages when starting blockers (Tanner 2 – 5). The mean duration of puberty suppression 2.4 years. Individuals had an average growth velocity of 5.3 cm/year in the first year of treatment. This decreased to 3.5 cm/year in the second year.  When starting oestrogen at 15 or 16 they were either treated with estradiol at a regular dose (2 mg), with high growth-reductive doses of estradiol (6 mg) or with ethinyl estradiol (EE, 100-200 µg).

Growth velocity and bone maturation decreased during GnRHa, but increased during GAHT. Adult height after regular-dose treatment was 180.4 ± 5.6 cm.  Growth velocity in the first year of GAHT was 2.8 cm/year, which decreased to 1.4 cm/year in the second year. From the start of GAHT, height increased by 5.9 cm to an adult height of 180.4cm.

The high dose estradiol group mostly had 1.5 years on regular dose before moving to high dose. Compared to regular-dose treatment, this group reduced adult height by 0.9 cm (179.5cm).

The EE group reduced adult height by 3 cm (177.4cm). High-dose EE resulted in greater reduction of adult height than high-dose estradiol, but this needs to be weighed against possible adverse effects.

Individuals who started affirming hormones at a lower bone age reached an adult height that was 1.6 cm/year lower than those who started hormones at a higher bone age.

Potentially earlier initiation of estradiol in transgender girls (before age 15-16) might result in shorter adult height.

Willemsen et al. (2023) “Just as Tall on Testosterone; a Neutral to Positive Effect on Adult Height of GnRHa and Testosterone in Trans Boys”. This study looked at 146 transgender boys treated with GnRH analogues and testosterone who reached adult height. Adult height was on average 172.0cm. Trans boys who started pubertal suppression at a young bone age were significantly taller. PS and GAHT do not have a negative impact on adult height in transgender boys and might even lead to a slightly taller adult height, especially in those who start at a younger age.

*Ciancia et al. (2023) “Early puberty suppression and gender-affirming hormones do not alter final height in transgender adolescents”. This study found that trans boys and trans girls height aligned with cis peers of their assigned gender rather than affirmed gender, with puberty suppression and gender affirming hormones not impacting on height. This study was for trans boys starting puberty suppression at average age 12, and trans girls starting puberty suppression at average age 13 (I couldn’t see the age of starting affirming hormones as I can’t access the full article).

Science does not stand still. We need to ensure we are up to date with the latest research in this field. Charities and those supporting trans children and young people need to keep informed about the latest evidence, and ensure the most accurate, up to date, and comprehensive evidence is made widely available, for informed decision making.

On the 3^rd full day of WPATH 2024, there was one session that I wanted to write up in slightly more detail, as it is very relevant to those working with or supporting trans children and young people. (My original WPATH 2024 blog is available here). The session was titled “New long-term research on adolescent gender-affirming medical care”, with 5 presenters, three from the US, and two from the Netherlands.

I wanted to share my notes on these presentations here. First a big caveat – my notes and interpretation may not be 100% correct, I have not confirmed this post with the presenters of these studies, and these studies have not yet been finalised, peer reviewed or published. Therefore, the data in this study may change before acceptance into the formal literature. At WPATH, within the trans room, there was a discussion on the challenges of knowledge that is of vital importance to trans communities and families of trans kids being paywalled behind expensive and hard to attend conferences. Recognising the very slow timelines of academic publishing, there was a discussion on a duty to share early preliminary results not only with the clinicians and researchers who are able to attend WPATH, but also with the very interested and directly affected trans and family of trans kids communities, currently trying to defend our healthcare from attack, for whom new research is most important. In the trans room at WPATH we talked about our responsibility and duty of care as trans researchers with half a foot in clinical spaces to share information with those who cannot access. As part of this commitment I’m writing this blog.  

First Dr Diane Chen (she/her) presented on trajectories for mental health in the four years following gender affirming hormone initiation. She highlighted the six existing studies that examine psycho-social outcomes in US-based trans youth receiving oestrogen or testosterone (Allen; Achille; Kuper; Tordoff; Chelliah; Chen). These studies have generally found that aspects of mental health improve following initiation of gender affirming hormones. These studies have limitations including that they only follow youth for average of one year after treatment initiation, that they only focus on (internalising) areas like anxiety or depression, and the one article (by the presenter Chen et al) that looked at individual trajectories found significant individual variation around the average change in outcomes. For that study the presenter showed graphs showing, on average, a steep improvement in appearance congruence, a shallow reduction in depression and anxiety, and a shallow improvement in positive-affect and life satisfaction over 2 years. The individual dots show significant variability, suggesting a focus on the average experience may hide difference trajectories between sub-groups. The new study being presented here aims to look at potential distinct trajectories between sub-groups.

The new study (by Chen et al, not yet published), looked at data for 217 youth, average age 16 (range 11-20), 60% trans-masc, 34% trans-femme, 4% non-binary, 80% socially transitioned at baseline, 7.6% received gender affirming care in early puberty (defined as puberty blockers at tanner 2 or 3 or HRT at tanner 3). The study looked at internalising data on (anxiety/depression), at externalising (aggression, risk taking), experiences of gender minority stress, and parental acceptance. Data were collected at baseline, year 1, year 2, year 3 and year 4 [They applied latent growth curve modelling / growth mixture modelling for statistical analysis]. They presented graphs distinguishing three sub-groups that follow distinct pathways across the 4 years. 25% of trans youth in their study were identified as a ‘consistently low’ group who had low levels of anxiety/depression/risk-taking behaviours at baseline who continued to have low levels of anxiety/depression/risk-taking behaviours. 56% were classified as having ‘declining’ levels of anxiety/depression and consistently low levels of risk-taking behaviours, with levels of anxiety and depression slightly above a clinical diagnosis at baseline, later declining to slightly below clinical thresholds. 18% were categorised as elevated, having persistently high levels of anxiety/depression/risk-taking behaviours at baseline and later in study.

From further data analysis they discovered:

95% of youth who accessed early affirmative care were in the categories of consistently low (53%) and ‘declining’ levels of mental health problems, with only 5% of these youth in the category of having persistently high levels of anxiety/depression/risk-taking behaviours.

[Talking about ‘low’ and ‘declining’ as positive descriptors in a study on mental health at times feels a little counter intuitive, given we think of high mental health, or improving mental health as a good thing, whereas here we want to see low and declining mental health problems).

The youth who had consistently good mental health, or improving mental health had the following characteristics in common:

Less loneliness

Less gender minority stress

Higher parental acceptance

Higher emotional support

The study highlights that provision of HRT is not a magic cure to the mental health challenges of trans youth who are isolated, unsupported and facing anti-trans hostility and gender minority stress inside and outside of their homes.

Among youth with high levels of anxiety/depression/risk-taking behaviours at baseline, those with higher levels of baseline parental support were more likely to see improvements in their mental health.

Protection from gender minority stress, reduced isolation, emotional and social support, and parental support are all protective factors for trans youth mental health.

18% of the sample continued to have high levels of anxiety/depression/risk-taking behaviours throughout the study and this portion of trans youth would benefit from more targeted mental health support as well as support to reduce gender minority stress and isolation.

Next Dr Laura Kuper (they/them) presented preliminary findings of 5 – 8 year outcomes of the trans youth longitudinal survey. The study began in 2014 including annual youth and parent report surveys. It looked at quality of life, anxiety, depression, body dissatisfaction. Recently added new measures of gender dysphoria, socio-political stress and decision regret scale.

Wider study now includes 738 youth. At baseline ages 6-18 (mean 15), 64% assigned female at birth, 34% assigned male at birth. A few youth are now in year 9 of the study, most are currently in years 2-7 of the study (new enrolments to the study are being added each year).

Presented data on 267 youth and 317 parents who completed survey on access to treatment. The study looked at those who had started and at some point stopped treatment with oestrogen or testosterone. [For this presentation exact numbers were not provided and the graphs were hard to read precisely so there is a likely margin of error in the percentages I’ve given below – you’ll need to wait for publication of the proper research for the accurate numbers]

10% of those who had ever started oestrogen had at some point stopped oestrogen. The reasons for stopping oestrogen were examined. 1 was because was satisfied with the changes and didn’t need further oestrogen; 2 experienced unwanted changes; 2 had a change in their experience or understanding of gender; 2 stopped due to difficulties accessing oestrogen; 1 for other reasons. Just under half who ever stopped taking oestrogen ended up re-starting taking oestrogen. Youth and parents were asked the question re starting taking oestrogen “It was the right decision”. Around 70% of youth strongly agreed, 5% agreed, 2% neither agreed nor disagreed, 2% strongly disagreed. 60% of parents strongly agreed, 20% agreed, 2% neither agreed nor disagreed, 2% strongly disagreed. Youth and parents were asked the question re starting taking oestrogen “I regret the choice that was made”, and “the choice did me/my child a lot of harm” with the same findings (vast majority strongly disagreed, with only around 2% strongly agreeing).

32% of those who had ever started testosterone had at some point stopped testosterone, significantly higher than the portion who ever stopped oestrogen. The reasons for stopping testosterone were examined. 16 were because were satisfied with the changes and didn’t need further testosterone; 8 experienced unwanted changes; 8 had a change in their experience or understanding of gender; 2 had legal barriers to access; 23 (the largest portion) stopped due to difficulties accessing testosterone; 19 for other reasons. Just under half who ever stopped taking testosterone ended up re-starting taking testosterone, with several going through multiple points of stopping and re-starting. Youth and parents were asked the question re starting taking testosterone “It was the right decision”. Around 154 of youth strongly agreed, 8 agreed, 2 neither agreed nor disagreed, 1 (hard to read graph) disagreed, 1 (hard to read graph) strongly disagreed. 145 parents strongly agreed, 32 agreed, 7 neither agreed nor disagreed, 2 disagreed, 3 or 4 (hard to read graph) strongly disagreed. Youth and parents were asked the question re starting taking testosterone “I regret the choice that was made”, and “the choice did me/my child a lot of harm” with the same findings (vast majority strongly disagreed, with only around 1% strongly agreeing).

Dr Kuper then moved on to present findings on a 5 year longitudinal study of trans youth receiving oestrogen or testosterone. The study currently includes data for 558 youth at baseline, 431 at year one follow up, 275 at year two follow up, 163 at year three, 115 at year 4, 59 at year 5. The declining numbers at later years of follow up is because new youth keep being recruited into the study (not linked to drop out). [They applied linear mixed effect modelling to the dataset for statistical analysis].

Graphs were presented showing a significant and steady decrease in body dissatisfaction over 5 years time for both those on oestrogen and those on testosterone (with the same pattern for both). A graph of depressive symptoms showed a steady decrease in depression scores over the 5 years. The slope and change in depression was similar for both those on oestrogen and those on testosterone, but with those on testosterone having slightly higher depression at baseline and at current measure than those on oestrogen. Both groups were over the point for mild depression and near the level for moderate depression at baseline, and fell to at or just over the point for mild depression at current measure. Graphs showed some improvements in anxiety over time. Quality of life scores improved steadily over time for both groups.

Overall conclusions were:

Strong satisfaction with decision to receive treatment from youth and parents

Large improvements in body dissatisfaction, seen as the primary goal of treatment

Modest improvements in mental health and quality of life, which were also impacted by gender minority stress. They noted that this sample is in Texas where there are very significant socio-political stressors and state persecution, which is likely impacting on mental health measures.

This research also underscores the unsuitability of having mental health improvements as a key justifier for gender affirmative healthcare – especially for those youth who (through social support) have low levels of mental health at the start of puberty. Those youth do not see improvements in mental health, they see their good levels of mental health retained through medical transition. Reviews like the Cass review critiqued affirmative healthcare for not showing puberty blockers not having a significant enough boost to mental health – this is clearly the wrong variable to be tracking.   

Next Dr Kristina Olson presented on trans youth satisfaction with care. She presented existing knowledge on youth satisfaction with care, including the high levels of continuity of care, with the assumption that trans youth would not continue to take active efforts to continue healthcare that they did not want to continue. Also low rates of detransition to live as cis amongst trans youth who commence gender affirming healthcare. We also know there are cases of detransition / dissatisfaction, whilst noting that these two concepts are different and distinct.

This new study aimed to assess levels of satisfaction and regret following puberty blockers and HRT, and to assess continuity of care. Looked at trans youth project, more than 300 socially transitioned binary trans youth recruited between ages of 3 and 12 in years 2013-2017. Mostly US trans youth with some Canadians. Youth followed up every 1-2 years. Study has now been ongoing for 7 – 11 years. Youth have answered questions on average 3.8 times, and parents have answered questions on average 5.8 times. This study presents data from 2023 questionnaires, given to all youth who are currently 12+ and to one parent.

On average the cohort had socially transitioned at 6-7 years old. On average they had started blockers 5 years before the survey, at 11 years old. On average they had begun HRT 3.5 years before the survey, at 13 years old. This cohort, supported in childhood, has had good levels of mental health throughout childhood and into adolescence, with slightly elevated anxiety, matching well-being of cisgender peers.

269 were aged 12+ and had started gender affirming medical care and were eligible for this survey. 220 or 82% completed the survey. For the 18% who did not fill in this specific survey, the research team do have continuity of care medical records. Where data is provided by a youth and their parent, the data tables only show the youth report. Where youth data is not available, the parent reported data is provided.

215 reported on their experience with puberty blockers (160 direct from youth and 55 from parental report). Satisfaction was rated from 1 not at all happy to 7 extremely happy. Satisfaction was rated 6.4 average for youth and 6.7 average from parents. Regret was rated from 1 no regret to 7 strong regret. Regret was 1.5 for youth and 1.3 for parents.

170 reported on their experience with oestrogen or testosteone (119 direct from youth and 51 from parental report). Satisfaction was rated 6.5 average for youth and 6.9 average from parents. Regret was 1.4 for youth and 1.0 for parents.

Very high levels of satisfaction and very low levels of regret

Also asked participants if they would have preferred to receive healthcare treatment at a different time, with options: ‘wish earlier’, ‘correct age’, ‘wish later’, ‘wish never’. 2% of youth wished never to have received puberty blockers, 2% wished to have never received hormones, 1 parent in the sample wished never to have received puberty blockers. 18% of youth (4% parents) wished they had received puberty blockers earlier and 74% youth (86% parents) felt they had received them at the right time (in a sample receiving puberty blockers at average age 11). 34% of youth (19% parents) wished they had received oestrogen or testosterone earlier and 53% youth (75% parents) felt they had received them at the right time (in a sample starting oestrogen or testosterone at average age 13 years old.

From the overall sample, 97% have continued to access gender affirming medical care to this day. 2% have stopped accessing gender affirming medical care.

Overall – very high levels of satisfaction, very low rates of regret,

Only 9 individuals out of 220 sample (4%) experienced regret. 8 (3.6%) experienced regret for blockers, 3 (1%) experienced regret for hormones. From these 9 2 individuals (1%) expressed regret for both blockers and hormones. 4 of the nine stopped all treatment, 1 in the process of stopping treatment, 4 have continued to take blockers or hormones. From the nine expressing regret, about half regret ever starting treatment, about half regret a specific side effect or complication or regret not skipping straight to hormones without time on just blocker.

A majority of youth continue to express high satisfaction with care many years later. This cohort seems to align closely with their cisgender peers on mental health, well-being, and on rates of change of gender identity. Important to note that the access to gender affirming medical care that has accompanied this cohort, is harder to access today for their younger peers, with increasing barriers to trans healthcare across and beyond the USA.

Next Dr Marijn Arnoldussen from the Netherlands. The presentation was titled “gender related and psychological outcomes in adulthood after early gender related medical transition in adolescence”. Studies from the Netherlands tend be of interest, because they were an early supporter of a limited form of gender affirming care, with puberty blockers prescribed to a 13 year old trans boy starting in 1988, and with decades of follow up studies. Studies from the Netherlands also come with some significant baggage, in a highly controlled and potentially pathologizing and psychologically invasive model of care, where folks were expected to conform to a very defined stereotype of trans-ness to receive care. The narrowness of the model of expected transness has relevance to some of their outcomes. Knowing the UK children’s GIDS model sought to replicate the Dutch model, and knowing very closely just how abusive, invasive and harmful the UK approach to trans children has been, makes me approach data from the Dutch clinic with a significant degree of concern, especially where clinicians report data without asking centring the views of their patients, or where clinical control, coercion and pathologisation is apparent.

 The study aim was to describe long term gender outcomes, treatment regret, reflections on gender related medical care, and psychological outcomes for trans adults who received gender affirming medical care, including puberty blockers, during adolescence. The study focused on trans adults who took puberty blockers during adolescence and who started gender affirming hormones over 9 years ago. 145 service users were eligible, of whom 72 participated. This is clearly a pretty high drop out rate. In the UK service, high drop out rates are sometimes an indication of service users not having confidence in clinical research.

From the 72 participants, 51 (71%) were transgender men, 20 (28%) were transgender women. 1 (1%) non-binary. The binary focus of the cohort is perhaps unsurprising if, as was certainly the case in UK children’s clinics, non-binary transitions were not supported or permitted. Interesting that this  cohort who started medical transition in adolescence a decade ago, has significantly more trans men than trans women – when this phenomenon is noted in current youth it is blamed on tiktok which clearly did not exist a decade ago. This cohort started puberty blockers at an average age of 14.85 (range 11.47-17.97) and hormones at an average of 16.67 (range 13.93-18.46) and are followed up at average age 29.1 (range 25-36.29 year old). The oldest in this cohort are 36 years old. Hardly new treatment.  

94.4% had not experienced any change in their gender identity over time from starting blockers at  average age 14 to now being on average 29 years old.

83% (60 people) had not experienced any regret or doubt about their gender affirming medical.

17% (12 people) had experienced some form of doubt or regret – however:

For 2 people (3%) this was occasional thoughts what their life would be like if they hadn’t had medical transition, doubts rather than regrets.

3 people (4%) regretted the chosen surgical technique in genital surgery

4 people (5.6%) regretted either genital surgery or surgery to remove reproductive organs. This figure in particular need to be considered against two important realities – one, stating a desire for ‘full’ transition was in many places considered a key eligibility criteria for any form of medical transition, closing down possibilities for a less binary transition pathway, and two in the Netherlands until very recently surgical transition was deemed necessary for eligibility to change your legal gender and to access various state protections or rights as a trans person. I would assume that where there is pressure to engage in surgical transition, incidents of regret is arguably more likely.

2 people (2.8%) regretted becoming infertile and being unable to preserve sex cells

1 person regretted the hormones and surgery they received.

From the 72 patients followed into average age 29, only one stated a regret of hormones.

The cohort were asked about their ability to make decisions in adolescence. A significant majority, 50 people (69.4%) felt they were capable to make decisions at an even younger age then they were permitted to do under the Dutch model (where they received blockers at average age 14 and hormones at average age 16). 17 people (23.6%) felt they were at the right age for their decisions. 5 people (6.9%) felt they were too young, with these people particularly mentioning the impact on their fertility.

Overall, 98.6% of people were satisfied with their social and medical transition overall. 15% had some doubts or regrets, with this particularly related to aspects of surgical transition. 1 person regretted hormones and surgery. 93% felt, on reflection, they were capable to take decisions on medical transition during adolescence.

Finally in this session there was a presentation from Dr van der Meulen from the Netherlands entitled “sexual dysfunction after early endocrine treatment: long-term study in transgender adults”.

This session had elements of exoticisation and pathologisation of trans people that I found uncomfortable. I’ll share some of the results here. A study on 70 trans adults, comparing those who medically transitioned in early puberty (tanner 2 or 3) with those who medically transitioned in later puberty (tanner 4+). They were average age 29 during this research. For the 50 trans masculine participants, 18% medically transitioned in early puberty, for the 20 trans feminine participants 40% transitioned in early puberty.  

Amongst the groups of adult participants (average age 29), they were asked about experiences of sexual disfunction. For trans men 18% reported a problem with low sexual desire (80% reported no problem with sexual desire), and low sexual desire was reported for 22% of those who transitioned in early puberty compared to 17% for those who transitioned in late puberty. 16% of trans men reported too much sexual desire (64% reported no problem with too much sexual desire) and too much sexual desire was reported for 11% of those who transitioned in early puberty compared to 17% for those who transitioned in late puberty. 4% of trans men reported low sexual arousal (96% reported no problem with sexual arousal) and low sexual arousal was reported for 11% of those who transitioned in early puberty compared to 2% for those who transitioned in late puberty.; 24% reported difficulty orgasm (74% reported no problem orgasm) and difficulty to orgasm was reported for 33% of those who transitioned in early puberty compared to 22% for those who transitioned in late puberty.

For trans women 20% reported a problem with low sexual desire (60% reported no problem with sexual desire), and low sexual desire was reported for 38% of those who transitioned in early puberty compared to 33% for those who transitioned in late puberty. 0% of trans women reported too much sexual desire (100% reported no problem with too much sexual desire). 20% of trans women reported a problem with low sexual arousal (65% reported no problem with sexual arousal) and low sexual arousal was reported for 0% of those who transitioned in early puberty compared to 33% for those who transitioned in late puberty.; 35% reported difficulty orgasm (65% reported no problem orgasm) and difficulty to orgasm was reported for 0% of those who transitioned in early puberty compared to 58% for those who transitioned in late puberty.

Overall sexual disfunction was relatively low amongst these trans adults who medically transitioned in adolescence. There was no significant difference in sexual disfunction between those who medically transition in early puberty compared to those who sexually transition in late puberty. [Research on this topic surely, SURELY needs to better centre the voices and priorities of trans adults, and the multiple factors beyond early or late medical transition that likely impact on experiences – and surely some comparison to cis people’s experiences of sexual disfunction would make such research somewhat less exoticising and othering…]

A few follow up questions were held. One questioner stressed the importance of timeliness of publication of all the above new data – especially in contexts where healthcare is under attack. Another questioner asked about the mental health of neurodivergent populations, asking if datasets could be considered to see where autistic youth fitted on the mental health trajectories, noting the greater mental health challenges and [Is there a term like gender minority stress that applies to the stresses of navigating a neurotypical world?] that are carried by autistic youth that will not be ameliorated by gender affirmative care. There was also some discussion on what outcome indicators are best to track to monitor the impacts of gender affirmative healthcare, with panelists commenting that a narrow focus on mental health is probably not the right indicator.

I didn’t share any of my own research this time at WPATH, but given the WPATH content was very significantly dominated by US and Dutch research, I’ll end by sharing my contributions to the literature on puberty blockers here:

“I Didn’t Want Him to Disappear” Parental Decision-Making on Access to Puberty Blockers for Trans Early Adolescents – available here.

Experiences of puberty and puberty blockers: Insights from trans children, trans adolescents, and their parents – available here.