Puberty Blockers (GnRHa)

sherlock data

Safe and reversible

Puberty Blockers are recognised by credible experts around the world as a safe and reversible intervention that delays puberty for transgender or gender questioning adolescents.

According to the 2017 Endocrine Society Guidelines (Hebree et al, 2017):

“We suggest that adolescents who meet diagnostic criteria for GD/gender incongruence, fulfill criteria for treatment, and are requesting treatment should initially undergo treatment to suppress pubertal development

These recommendations place a high value on avoiding an unsatisfactory physical outcome when secondary sex characteristics have become manifest and irreversible, a higher value on psychological well-being, and a lower value on avoiding potential harm from early pubertal suppression.”

“We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists.”

Adolescents are eligible for GnRH agonist treatment if:

1. A qualified MHP has confirmed that:

  • the adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed),
  • gender dysphoria worsened with the onset of puberty,
  • any coexisting psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment,
  • the adolescent has sufficient mental capacity to give informed consent to this (reversible) treatment,

2. And the adolescent:

  • has been informed of the effects and side effects of treatment (including potential loss of fertility if the individual subsequently continues with sex hormone treatment) and options to preserve fertility,
  • has given informed consent and (particularly when the adolescent has not reached the age of legal medical consent, depending on applicable legislation) the parents or other caretakers or guardians have consented to the treatment and are involved in supporting the adolescent throughout the treatment process,

3. And a pediatric endocrinologist or other clinician experienced in pubertal assessment

  • agrees with the indication for GnRH agonist treatment,
  • has confirmed that puberty has started in the adolescent (Tanner stage $G2/B2),
  • has confirmed that there are no medical contraindications to GnRH agonist treatment.

The latest clinical guidelines for treating transgender children are the Australian Guidelines (Telfer et al, 2017). They say the following about puberty blockers:

“Referral of a Child with gender dysphoria to a paediatrician or paediatric endocrinologist experienced in the care of trans and gender diverse adolescents for medical treatment, ideally prior to the onset of puberty”

“puberty suppression typically relives distress for trans adolescents by halting progression of physical changes such as breast growth in trans males and voice deepening in trans females and is reversible in its effects”

“The adolescent is given time to develop emotionally and cognitively prior to making decisions on gender affirming hormone use which may have some irreversible effects”

“Puberty suppression is most effective in preventing the development of secondary sexual characteristics when commenced at Tanner stage 2”.

“puberty suppression medication is reversible”

“The main concern with use of puberty suppression from early puberty is the impact it has on bone mineral density”. Reduction in the duration of use of puberty suppression by earlier commencement of stage 2 treatment must be considered in adolescents with reduced bone density to minimise negative effects.”

 

Criteria for adolescents to commence puberty blockers

1. A diagnosis of gender dysphoria in adolescence

2. Medical assessment including fertility counselling

3. Tanner stage 2 pubertal status has been achieved. This can be confirmed via clinical examination with presence of breast buds or increased testicular volume and elevation of luteinising hormone

4. The treating team should agree that commencement of puberty suppression is in the best interest of the adolescent and assent from the adolescent and informed consent from their legal guardians has been obtained

Australian References:

The Australian evidence base regarding puberty blockers focuses on three main sources:

  1. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study, de Vries et al (2011)
AIM: To compare psychological functioning and gender dysphoria before and after puberty suppression in gender dysphoric adolescents.

METHOD: Of the first 70 eligible candidates who received puberty suppression between 2000 and 2008, psychological functioning and gender dysphoria were assessed twice: at T0, when attending the gender identity clinic, before the start of GnRHa; and at T1, shortly before the start of cross-sex hormone treatment.

MAIN OUTCOME MEASURES: Behavioral and emotional problems (Child Behavior Checklist and the Youth-Self Report), depressive symptoms (Beck Depression Inventory), anxiety and anger (the Spielberger Trait Anxiety and Anger Scales), general functioning (the clinician’s rated Children’s Global Assessment Scale), gender dysphoria (the Utrecht Gender Dysphoria Scale), and body satisfaction (the Body Image Scale) were assessed.

RESULTS: Behavioral and emotional problems and depressive symptoms decreased, while general functioning improved significantly during puberty suppression. Feelings of anxiety and anger did not change between T0 and T1. While changes over time were equal for both sexes, compared with natal males, natal females were older when they started puberty suppression and showed more problem behavior at both T0 and T1. Gender dysphoria and body satisfaction did not change between T0 and T1. No adolescent withdrew from puberty suppression, and all started cross-sex hormone treatment, the first step of actual gender reassignment.

CONCLUSION: Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents.

 

  1. Young Adult Psychological Outcome After Puberty Suppression and Gender Reassignment, de Vries et al, (2014)
BACKGROUND: In recent years, puberty suppression by means of gonadotropin-releasing hormone analogs has become accepted in clinical management of adolescents who have gender dysphoria (GD). The current study is the first longer-term longitudinal evaluation of the effectiveness of this approach.

METHOD: A total of 55 young transgender adults (22 transwomen and 33 transmen) who had received puberty suppression during adolescence were assessed 3 times: before the start of puberty suppression (mean age, 13.6 years), when cross-sex hormones were introduced (mean age, 16.7 years), and at least 1 year after gender reassignment surgery (mean age, 20.7 years). Psychological functioning (GD, body image, global functioning, depression, anxiety, emotional and behavioral problems) and objective (social and educational/professional functioning) and subjective (quality of life, satisfaction with life and happiness) well-being were investigated.

RESULTS: After gender reassignment, in young adulthood, the GD was alleviated and psychological functioning had steadily improved. Well-being was similar to or better than same-age young adults from the general population. Improvements in psychological functioning were positively correlated with postsurgical subjective well-being.

 

  1. Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria, Costa et al, 2015:

 

AIM: This study aimed to assess GD adolescents’ global functioning after psychological support and puberty suppression.

METHOD: Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents’ global functioning every 6 months from the first visit.

RESULTS: At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 ± 12.3. GD adolescents’ global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 ± 12.5; P < 0.001). Moreover, GD adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 ± 13.9) compared with when they had received only psychological support (60.9 ± 12.2, P = 0.001).

CONCLUSION: Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents.

101 adolescents were deemed ‘immediately available’ to receive blockers. This group was assessed at baseline, after 6 months of just therapy, after 12 months including 6 months blockers, and after 18 months including 12 months blockers. “The immediately eligible group, who at baseline had a higher, but not significantly different psychosocial functioning than the delayed eligible group, did not show any significant improvement after 6 months of psychological support. However, immediately eligible adolescents had a significantly higher psychosocial functioning after 12 months of puberty suppression compared with when they had received only psychological support. Also, their CGAS scores after 12 months of puberty suppression (Time 3) coincided almost perfectly with those found in a sample of children/adolescents without observed psychological/psychiatric symptoms.”

“In conclusion, this study confirms the effectiveness of puberty suppression for GD adolescents. Recently, a long-term follow-up evaluation of puberty suppression among GD adolescents after CSHT and GRS has demonstrated that GD adolescents
are able to maintain a good functioning into their adult years [De Vries 2014 see above]. The present study, together with this previous research [De Vries 2014], indicate
that both psychological support and puberty suppression enable young GD individuals to reach a psychosocial functioning comparable with peers.”

The American guidelines similarly describe blockers as “fully reversible” saying:

To prevent the consequences of going through a puberty that doesn’t match a transgender child’s identity, healthcare providers may use fully reversible medications that put puberty on hold. These medications, known medically as GnRH inhibitors but commonly called “puberty blockers” or simply “blockers,” are used when gender dysphoria increases with the onset of puberty, when a child is still questioning their gender, or when a child who has socially transitioned needs to avoid unwanted pubertal changes.

By delaying puberty, the child and family gain time — typically several years — to explore gender-related feelings and options. During this time, the child can choose to stop taking the puberty-suppressing medication. However, most children who experience significant gender dysphoria in early adolescence (or who have undergone an early social transition) will continue to have a transgender identity throughout life. Puberty-suppressing medication can drastically improve these children’s lives. They can continue with puberty suppression until they are old enough to decide on next steps, which may include hormone therapy to induce puberty consistent with their gender identity.

The UK service specification (citing Costa et al, 2015) agrees:

“In adolescents with GD, psychological support and puberty suppression have both been shown to be associated with an improved global psychosocial functioning. Both interventions may be considered effective in the clinical care of psychosocial functioning difficulties in adolescents with GD”.

As demonstrated by the above, there is a clear consensus amongst gender specialists worldwide that puberty blockers are fully reversible and this is supported by the peer reviewed academic literature.

Recent claims from the UK Gender Identity Service

In spite of the consensus and evidence in support of puberty blockers as safe and reversible, there have been recent reports from families with children in the UK Gender Identity Service that clinicians have advised against them. One clinician is reported as saying “puberty blockers may not be as reversible as we thought” and there have  been reported attempts  to dissuade dysphoric pubertal youth from puberty blockers. More worryingly there are also reports from parents that on occasion clinicians have stated that they will not permit referral to the Endocrinology service (for reversible puberty blockers) “until we are completely sure of things”.

If some clinicians are working in this way, this appears to be both outside of the UK Protocols and not in alignment to  the accepted international  good practice. While it is as yet unclear how widespread this reluctance to prescribe puberty blockers is, the crux seems to centre on a ‘feeling’ by some in the UK children’s gender service that puberty blockers ‘might change outcomes’, making children ‘continue as trans’ who may otherwise have ‘shifted to a cisgender identity’.

This unsubstantiated criticism of hormone blockers has recently started to filter into  mainstream media, for example, in this magazine article which raises concern about the reversibility of blockers:

“Blockers are often described as “fully reversible”, and it is true that if you stop taking them puberty will eventually resume. But it is not known whether they alter the course of adolescent brain development”

The above critique of blocker reversibility isn’t attributed in the article, but the main criticism of the gender affirmative approach in the article is Bernadette Wren, the Head of Psychology at the UK Children’s Gender Service who is described in the article as “nervous” of an approach where “children who begin taking blockers early on in puberty, followed immediately by cross-sex hormones, will never produce mature eggs or sperm of their own”. Wren continues,  “Can a 12-, 13-, 14-year-old imagine how they might feel as a 35-year-old adult, that they have agreed to a treatment that compromises their fertility or is likely to compromise their fertility?”.

It is puzzling that the UK service are dissuading use of blockers for dysphoric transgender adolescents, particularly given the clear consensus amongst respected centres of expertise globally. Perhaps there are further clues from a speech given at WPATH 2016 (the international forum for transgender health) by Polly  Carmichael, the Head of the UK children’s service:

Here’s is a lengthy extract from the last quarter of Polly Carmichael’s speech to WPATH in 2016 including the text from slides:

Slide text:

“Rationale for the blocker: Are all aspects reversible?

The blocker as a diagnostic aid

The blocker as time to explore, understand, consolidate

The blocker as reversible treatment

Experience some puberty? Tanner stage 2

Stage of puberty not age

Transcription of audio  for this slide:

“So to end  I want to raise some points for us to think about

Rationale of the blocker. Are all aspects of the blocker fully reversible? Is anything really fully reversible? If you don’t do something it has an effect. If you do something it has an effect

And also we are working within a developmental trajectory so things are changing all the time

However, I think we had the view of the blocker as a diagnostic aid. It was also a time to try and alleviate stress, unless I’ve got this completely wrong, to explore and understand more and consolidate, support young people to be thinking about their next step. It is a reversible step in terms of if you stop it then your pre-programmed milieu resumes, but I would question whether it is a completely reversible treatment, we also have the idea of young people should experience some puberty, to tanner stage 2. I think that was around the idea the majority of people presenting to services pre puberty not necessarily going forward post puberty and wanting physical interventions and so maybe within that there was some thought that puberty perhaps had a role to play in terms of young people’s development in terms of their sense of their gender identity”

Next slide text:

Balancing evidence and Practice

Behavioural and emotional problems, largely attributed secondary to gender dysphoria, are expected to be relieved by supressing puberty, whilst general functioning has shown to improve after a staged programme starting by blocking puberty  De Vries et al 2010, 2014

Dutch team have published longer term data – but little prospective data available – wide age range

No consensus yet between professionals in the field regarding the use of puberty suppression. Doubts related to lack of psychological and long term physical outcomes such as bone health and cardiovascular risks. Nevertheless, several teams are exploring the possibility of lowering the current age limits for early medical treatment although they acknowledge the lack of long term data Vrouenraets et al 2015 Cohen Kettenis and klinck 2015

Transcription of audio  for this slide:

“I think we all, you know, feel the blocker and physical treatments are crucial and vital and have been the biggest step forward for young people. And certainly their use that was pioneered in Holland has been incredibly successful, but actually the Dutch are the only team really who have published long term prospective studies about this, so there is very little data available and also the data we have is on very wide age ranges. And I guess I was surprised to see but it makes sense that very recently in 2015 an excellent paper giving young people a voice a qualitative study looking at the views of young people, 13 young people between the age of 13 and 18 and really was concluding that there is no consensus so I think around the world we are practicing very differently”

Next slide text:

Number Mean Age Age Range
Mean age young people at EI clinic 162 12.82 8.99-15.1
Natal Males 70 12.89
Natal Females 92 12.97
Mean age at started blockers 119 13.59 10.5-15.5
Natal Males 54 13.64
Natal Females 65 13.54
Mean age at start CSH 25 16.18 16-16.5
Natal Males 10 16.21
Natal Female 15 16.17

2 stopped treatment

Transcription of audio  for this slide:

“In terms of our service we have had 44 young people in our early intervention project, who were part of a research project but we have now had 162 young people go forward for early hypothermic blockers and the age range reflects the fact it is by stage not by their age, but 2, only 2 have stopped treatment. And in both of those cases they have stopped treatment because they are wanting to explore a different gender identity. One is in a very supportive environment and wishes to try living in a different role without treatment for a while.

So I guess there is a question about why, Why none, why none stop if they’ve started on the blocker more or less, so I guess that begs the question that either we are not putting forward enough, that there are some people who would benefit from this who are missing out on this treatment. Or that in some way this treatment in and of itself may have an impact and may put people on a path. I totally support this treatment but I think it is about how we conceptualise it, the framework within which it is offered”

Next slide text:

Summary

T1 Outcomes show

Overall no change in psychological functioning (YSR and CBL)

Natal girls showed an increase in internalising problems from To to T1 as reported by their parents

No change in self-harming thoughts or behaviours

No change in Gender Identity or Gender Dysphoric feelings

No change in perception on primary or secondary bodily characteristics

However a change over time in neutral sex characteristics (feet, face, nose, height, eyebrows, hands, chin, shoulders, calves, adam’s apple).

Transcription of audio  for this slide:

“So in terms of our early intervention I guess the other thing is that our results have been different to the Dutch we are about to publish these and we haven’t seen any change in terms of psychological wellbeing and so on. There was a change over time in neutral sex characteristics, but interestingly this was a change, there was a study done through our service looking at the general population in terms of this where also there was an increase in dissatisfaction and so it seems to reflect that rather than something specific to this group. I think this is to do with the timing at which we took our measures but what is more important in terms of the qualitative data all of the young people have been resoundingly thrilled to be on the blocker and not wanting to stop and found it to be an incredibly positive experience.”

This presentation was in March 2016 but the expected paper on the outcomes for the 162 adolescents on blockers has not (as far as we’re aware) yet come out. It does have some fascinating results mentioned – out of 162 people only 2 did not continue with treatment after blockers. Polly Carmichael considers this a troublingly high rate of continuation, and proposes two theories: either not enough people are getting an opportunity to use blockers, or blockers are changing the outcomes. The tone of the presentation and repeated use of the question ‘is anything reversible?’ gives a clear indication of which way she is inclined.

This is very much the territory of the ‘hunch’. A specialist seeing a certain trend and making a guess, or hypothesis, about causation. The step between hunch and proven theory is having some evidence and data to back this up.

There are several alternative explanations for the low drop out rate after using blockers:

One, Carmichael is mistaken in her starting assuming that a large number of adolescents normally desist from a transgender identity at puberty – after all, this assumption is based on desistance statistics that are very widely discredited. See here and here

Two, Carmichael is overlooking the extreme difficulties for a child to gain access to the service pre-puberty and the extreme delays and gate-keeping once in the service before any approval is given for blockers. These delays and barriers in the UK system mean that only the most clear, insistent and consistent children reach the point of early provision of blockers. Children who are in any way less certain (ironically, the youth who perhaps would most benefit from thinking time), are very much less likely to get listened to by their parents, referred by their GP, accepted by the service, and approved for blockers. If only the children who have a long track record of insistent and clear identities are prescribed blockers, then it is not at all surprising that those are the children who continue to be insistent and clear once ‘on’ blockers.

Importantly, despite having developed a ‘hunch’ about hormone blockers changing the outcomes (making children persist as trans who would otherwise be cis or making children who had expressed a desire for physical intervention continue to have this desire for physical intervention), the UK service is yet to provide any peer reviewed publication (nor any open access to service data), in support of this claim.

Anecdotes and hunches that seem to fit with a perceived data pattern are not evidence. Competent evidence based science needs to be based on data and research shared with the world in peer reviewed research journals. If the UK really has any evidence that blockers are not reversible (beyond the above speculation), they need to present it to the world through peer reviewed publication.

How are GIDS backing up their hunch?

UK families have asked UK GIDS for evidence of this ‘hunch’ of blockers not being reversible. In spite of having a dedicated research centre, the Tavistock GIDS rarely share research literature with families (and the research section of their website is woefully out of date). However  clinicians at Tavistock GIDS have recently been circulating a paper by a former member of staff called Giovanardi. This paper reportedly been distributed both following requests for information on blockers from parents, and also as part of their blocker information sessions:

“Buying time or arresting development? The dilemma of administering hormone blockers in trans children and adolescents – Guido Giovanardi – Porto Biomedical Journal Volume 2, Issue 5, September–October 2017, Pages 153-156

Now at first glance it might seem curious to choose a paper published in a new and not yet ranked journal – anyone with a knowledge of academic journals will be aware that quality and peer review standards vary widely between journals, which is why journal accreditation and ranking is so important, to separate the quality journals from those that will publish flawed or inaccurate material.

This paper provides very little in the way of positive evidence about the effectiveness of blockers. It states that “many professionals remain critical about the puberty-blocking treatment”, ignoring the substantial bodies from Endocrine Society, to American Academy of Pediatrics, the American College of Osteopathic Pediatricians and the Executive of the Australian and New Zealand Association of Transgender Health, not to forget the original pioneers from the Netherlands who endorse puberty blockers.

The three sources for the claim that many professionals are critical of blockers include:

i) Cohen‐Kettenis et al (2008) 

ii) A fringe view point (in a letter) from a group from Berlin who believe people can’t be considered trans until after “psychosexual development has been completed” and

iii) Stein (2012) which contrasts the expert opinion and clinical evidence in favour of puberty blockers of experts from US and Netherlands, against the author’s personal un-evidenced concerns.

These sources provide little by way of evidence that respected professionals in 2017 are critical of blockers as Giovanardi suggests.

Giovanardi focuses their paper heavily on potential negatives of blockers, listing nine reasons against blockers:

1. At Tanner stage 2 or 3, the individual is not sufficiently mature or authentically free to take such a decision.

2. It is not possible to make a certain diagnosis of GD in adolescence, because in this phase, gender identity is still fluctuating.

3. Moreover, puberty suppression may inhibit a ‘spontaneous formation of a consistent gender identity, which sometimes develops through the “crisis of gender”’.

4. Considering the high percentage of desisters, early somatic treatment may be premature and inappropriate.

5. Research about the effects of early interventions on the development of bone mass and growth – typical events of hormonal puberty – and on brain development is still limited, so we cannot know the long-term effects on a large number of cases.

6. Although current research suggests that there are no effects on social, emotional and school functioning, ‘potential effects may be too subtle to observe during the follow-up sessions by clinical assessment alone’ (p. 1895).

7. The impact on sexuality has not yet been studied, but the restriction of sexual appetite brought about by blockers may prevent the adolescent from having age-appropriate socio-sexual experiences.

8. In light of this fact, early interventions may interfere with the patient’s development of a free sexuality and may limit her or his exploration of sexual orientation.

9. Finally, for trans girls (natal boys with a female gender identification), the blockage of phallic growth may result in less genital tissue available for an optimal vaginoplasty.

Out of the 9 listed criticisms, 8 have no relevance to the reversibility of blockers.

Point one and two are saying adolescents are too young to decide about blockers or too young to be diagnosed as transgender. These are both disputed, neither point is a reason to go through the wrong puberty, especially assuming blockers are reversible (Giordano, 2008; 2010).

Point 4 and 6 refer to Steensma et al (2008) with point 4 discussing the problematic work on desistance. Point 6 is actually positive, in favour of hormone blocking treatment, albeit with some unsubstantiated ‘are there things we don’t know?’ tacked on, without clear rationale.

Point 5 merely mentions there is a lack of rigorous evidence. We know this. This is not however, a reason to do nothing as doing nothing is ‘not a neutral decision’ (Simona, 2008). It is not logical to say do nothing until we have excellent evidence, The Australian guidelines (Telfer et al, 2017) is neatly succinct:

“withholding of gender affirming treatment is not considered a neutral option, and may exacerbate distress in a number of ways including depression, anxiety and suicidality, social withdrawal, as well as possibly increasing chances of young people illegally accessing medications”

Giovanardi’s Point 7 and 8 suggest that blockers have some important impact on sexuality. The only reference for point 7 and one of two references for point 8 is an article by a fringe group from Berlin (Korte et al, 2008). They maintain that adolescents should complete all pyscho sexual development before any intervention at all, and wrote a letter arguing against the view of the Endocrine Society (2009 clinical practice guidance) on a variety of areas, including disagreement that there is any biological cause for gender identity. The global Endocrine Society (2017) has recently concluded there is significant and conclusive evidence for a biological underpinning.

Korte et al (2008),  crucially does not contain any new research or data, it instead reviews other people’s data meaning it is not a quality source for a new conclusion. This Berlin group are also firmly in the, now discredited, “blame the mother” camp, see for example, this delightful section in their paper:

“A profound disturbance of the mother-child relationship can often be empirically demonstrated and is postulated to be a causative factor”. ” The desire to belong to the opposite sex is held to be a compensatory pattern of response to trauma. In boys, it is said to represent an attempt to repair the defective relationship with the physically or emotionally absent primary attachment figure through fantasy; the boy tries to imitate his missing mother as the result of confusion between the two concepts of having a mother and being one (e15). In girls, the postulated motivation for gender (role) switching is the child’s need to protect herself and her mother and from violent father by acquiring masculine strength for herself”.

“This explanatory approach ascribes primary importance to a desire on the parent’s part for the child to be of the opposite sex. A high rate of psychological abnormalities in the parents of children with GID has been reported in more than one study. It is essential, therefore, to explore thoroughly the psychopathology of the child’s attachment figures and their “sexual world view,” including any sexually traumatizing experiences they may have undergone, in order to discover any potential “transsexualogenic influences”.

This old fashioned ‘blame the mother’ approach to transgender children has been discredited, see this from Winter et al (2016), in the Lancet:

“to date, research has established no clear correlations between parenting and gender incongruence”

The Berlin group go on to talk about autogynophelia and fetishistic transvestism. This is outdated, utterly discredited, and damaging nonsense. Are the Tavistock GIDS seriously endorsing and suggesting parents read such hurtful, uncredible, and transphobic material?

Point 9 mentions lack of penile tissue for later surgery. This has historically been a concern as a limiting factor on certain surgical techniques for trans women, however, surgeons have now developed, and are continuing to develop alternative techniques, noting that the desire for surgery is far from universal. Giovanardi’s argument here against puberty blockers for trans girls age 12 based on potential impact on surgery prospects as an adult, is deeply perplexing. It would perhaps be worth noting in a discussion of potential surgical interventions, but hardly a reason to not offer hormone blockers.

In summary, not one of the 8 reasons discussed above are related to the question of whether blockers are reversible.

Point 3 alone in Giovanardi’s paper is the critical one for this discussion. It is the only supposed ‘evidence’ presented for the irreversibility of blockers:

“3. Moreover, puberty suppression may inhibit a ‘spontaneous formation of a consistent gender identity, which sometimes develops through the “crisis of gender”’

Giovanardi’s paper provides one single reference for this claim; Simona Giordano (2007).

Giordano is a respected researcher in the field of medical ethics, who has written extensively on the importance of treatment of gender dysphoria. This reference, citing a proposal for new guidelines for treatment of gender dysphoric children and adolescents, seemed so unlikely I immediately re-read her paper to locate the section being referred to by Giovanardi. Here is a more lengthy quotation:

Clinical Benefits and Risks of treatments for AGIO

Puberty delaying hormones. These have the following benefits:

a. The main benefit of early physical treatment is arrest of pubertal development, and, consequently, arrest of the suffering of the patient (CohenKettenis et al., 2003, p. 171).
b. Arresting the progress of puberty gives adolescents more time in which to achieve greater certainty about their innate gender identity.
c. The administration of blockers will prevent the development of secondary sexual characteristics of the undesired sex. In turn, future treatment would be less invasive and painful (for example, breast removal in female-to-male patients and painful and expensive treatment for facial hair in male-to female patients will be prevented; the voice will not deepen, and nose jaw and crico-cartilage (Adam’s apple) will be less developed)) (Cohen-Kettenis et al., 2003, p. 171).
d. Successful adaptation is associated with early start of physical treatment (Cohen-Kettenis et al., 2003, p. 171).

The risks are currently under scrutiny. The British Society of Paediatric Endocrinology and Diabetes, composed by the UK team involved in the treatment of gender dysphoric young people, believes that interrupting the development of secondary sexual characteristics may disrupt the fluidity that characterises puberty, and arrest the natural changes that may occur in this period (BSPED). In other words, in theory, blockers may inhibit the spontaneous formation of a consistent gender identity, which sometimes develops through the ‘crisis of gender’.

Although the concern is serious and should always be taken into consideration when administering therapy in early puberty, it is also known, as stated above, that the vast majority of AGIO adolescents (unlike pre-pubertal children) almost invariably become AGIO adults (Cohen-Kettenis et al., 2003, p.172), even where hormone-blockers
have not been administered. This means that there is a clear expected benefit in the vast majority of cases of adolescents requiring treatment

Giordano’s paper outlines several evidence based reasons in favour of puberty blockers. She includes in one lone paragraph a note that some UK specialists involved in the treatment of children ‘believe’, (have a hunch), that puberty blockers could make people continue as trans who could otherwise be ‘saved’ and made ‘cisgender’ (I paraphrase…). This is presented as opinion with no evidence. Giordano clearly concludes the paper arguing in favour of hormone blockers “there is a clear expected benefit in the vast majority of cases of adolescents requiring treatment”.

The only ‘evidence’ of blockers not being reversible in Giordano’s paper is this description of UK specialists having a hunch about potential impact.

“My work has been misrepresented”

I wrote to Dr. Simona Giordano to ask if their work has been misrepresented. Here, with permission, is their reply in full:

“You are right. My work has been misrepresented, because I was only citing one possible concern, to say that this concern is misplaced. As many others.

Likewise other research is misrepresented. Sex typing, for example is usually completed at the age of 6 or 7 and it is not true that during adolescence gender identity fluctuates. It may and it may not.

The BSPED guidelines I referred to in my article at the time were withdrawn very soon after. My paper and all my work is very clear on my stance. Since my first 2007 article I have been consistently analysing the ethical and clinical arguments 1. Against provision of GnRHa to adolescents with GD and 2. For age-based provision, and I have been arguing for over 10 years now that I could not find one individual ethical or clinical argument that could justify a policy of non-intervention.

I have been arguing since then that “waiting” is not necessarily a “precautionary” approach; omission of treatment can have severe psychological, social and physical hideous consequences. Omissions in this area can be much more risky than action. Harm reduction is a legitimate goal of medical care. Moreover, importantly, blockers, in the very literature cited by Giovanardi, are regarded and presented as a diagnostic tool as well as a therapeutic tool. So it is incorrect, in my opinion, to talk about GnRHa just as a medical treatment; it is part of the diagnosis.

Of course, each individual adolescent deserves to receive a treatment plan adapted to his or her individual needs; professionals must retain discretion as to what they believe to be in the best interests of the child. A policy, or clinical guidance, that across the board sets an age, or suggests waiting till Tanner Stage 4 or until advanced phases of pubertal development is extremely risky, and may prevent professionals from making this type of judgement based on individual needs.

We shared our analysis with Dr Giordano and she was kind enough to read and make the following observations,

“There is a passage in your blog:

“Wren continues,  “Can a 12-, 13-, 14-year-old imagine how they might feel as a 35-year-old adult, that they have agreed to a treatment that compromises their fertility or is likely to compromise their fertility?”.”

From this point of view, an adolescent should be refused cancer treatment, because unable to imagine how she or he will feel at the age of 35 having agreed to a treatment that compromises fertility, and therefore be left to die with cancer. No valid response would be that ‘cancer is lethal and gender dysphoria isn’t’ because it is well known that gender dysphoria can be lethal and is often lethal if untreated. The oncologist would say: “She may lament being infertile when she’s 35 but at least she’ll be around to complain!”; the transgender adolescent may say the same: “Even if in the future I will suffer because of my infertility, at least I will be around to suffer!”.

Reversibility. The issue of ‘are blockers reversible?’ is misguided. It would be more precise to say that once the treatment is interrupted, spontaneous development re-occurs with no irreversible changes having taken effect, rather than ‘blockers are reversible’, or ‘treatment is reversible’.

The issue of bone mineral density is not an issue of ‘reversibiity’ but rather an issue of the side effects of the medications. These medications may have this side effect (potentially). There are no firm data as yet, but this has been a concern for a long time. It has not been possible to gather precise data, because peak bone mass is accrued around the age of 26-27, and the population of patients treated with GnRHa is still too young to have a solid evidence base. But even assuming that one day we have the data, and these data show that patients who have been treated with GnRHa are more likely to develop bone mineral density issues than untreated patients, this potential side effect is to be balanced with 1. The benefits and 2. The likelihood of harm and suffering associated with withholding treatment. There may be clinical arguments too to be evaluated (ie what can be done clinically to reduce the risks that may be associated with the medication).

I believe it is misguided to debate about reversibility, because of course nothing is ‘reversible’ in the sense that once we have done something, we can’t reverse (I wrote this in response to Russel Viner in 2008). Here what matters is the side effects, the benefits v harms. So when we discuss whether something is reversible or not we risk losing sight of the relevant issue, which, it seems to me, is rather whether the treatment is overall beneficial, considering the likely benefits and the potential risks.”

The UK service therefore distributed to parents a journal article as ‘evidence’ to back up their belief that blockers are not reversible. The sole evidence within this paper written by a former member of the UK GIDS staff (Giovanardi, 2017) is a reference to another paper (by Giordano, 2007), which was, in turn, quoting the UK service’s un-evidenced belief. An unpublished hunch evidenced by a paper that references another paper that refers to that same hunch. We have found ourselves lost in parody. Simply put, this is not good enough!

In summary

The journal article (Giovanardi, 2017) given out to parents of service users by the Tavistock GIDS misrepresents evidence on the question of reversibility of blockers. It quotes research that is far from mainstream (outdated, pathologising and transphobic).

In a paper that claims to be a summary of evidence, it omits major (positive) studies and, in the discussion on the risks of being on blockers for too long, omits entirely any discussion of the recommendations endorsed by gender affirmative specialists to proceed to cross sex hormones earlier in case impacts on bone mass (Hembree et al. 2017). A quote from Rosenthal, a leading US endocrinologists (and one of the authors of the global Endocrine Society Guidelines) is included in a recent magazine article:

“Rosenthal worries about the few British children who, having begun puberty at age nine, will have to take the blocker for seven years until they have reached the age of consent. “That can be very risky to their bone health and perhaps even for their emotional health, to be so far out of sync with their peers in terms of pubertal development,” he says. At his clinic, he has administered cross-sex hormones to patients aged 14, and sometimes younger.”

(Note, though we twice take expert quotes from a recent magazine article, this article is itself deeply flawed – see Marlo Mack’s compelling essay for further discussion).

It is extremely concerning that some clinicians in the Tavistock GIDS are handing out to parents such a poor article as this Giovanardi paper. We see three options. Either:

1 They believe in the type of positions outlined in the articles referenced in the Giovanardi paper (which means they are potentially deeply transphobic and hold discredited and out-dated views on transgender people). Or;
2 They don’t look at the quality of the research they are reading and take the conclusions as robust evidence without checking the actual evidence base (which would make them incompetent). Or;
3 They have a ‘hunch’ that blockers are bad and are actively looking for any research that confirms their feeling (from which we would assume they were unethical and biased).

There is significant evidence on the benefits of hormone blockers to trans youth. The UK withholding or delaying blockers is extremely damaging. The UK needs to put up peer reviewed data to substantiate any ‘hunch’ they may have, or desist from spreading unsubstantiated rumours. Advice to parents needs to accurately portray current evidence – to do otherwise is both unethical and risks harm.

So what have Tavistock GIDS published on puberty blockers?

It is equally curious that the Tavi are handing out the Giovanardi paper from a new journal, and not referring parents to their own paper on puberty blockers, from the respected Nature, (Costa et al, 2016).

Here are key quotes from this 2016 paper, written by two specialists at the Tavistock GIDS, indicating both the evidence for the timely use of hormone blockers and, in agreement with the wider research consensus, that they are clearly reversible:

“Puberty suppression using gonadotropin-releasing-hormone analogues (GnRHa) has become increasingly accepted as an intervention during the early stages of puberty (Tanner stage 2–3) in individuals with clear signs of childhood-onset gender dysphoria”

“The existing literature supports puberty suppression as an early, sufficiently safe, and preventive treatment for gender dysphoria in childhood and adolescence”

“To date, only one long-term follow-up study has indicated that a treatment protocol including puberty suppression leads to a psychosocial functioning in late adolescence that is comparable to non-gender-dysphoric peers”

“To date, only one study has assessed the effect of GnRHa on cognition in gender dysphoria, reporting no evidence for a deleterious effect of puberty suppression on brain activity and related executive functioning”

“Research has begun to focus on the effects of puberty suppression on quality of life in prepubertal and adolescent individuals with gender dysphoria, indicating that this early intervention could improve their psychosocial functioning and wellbeing”

“A team from the Netherlands has been an influential leader in promoting a protocol — the so-called Dutch protocol — which recommends treatment of minors with gender dysphoria after an extensive psychological and psychiatric evaluation, with puberty suppression at the age of 12 years and after the first stages of puberty (Tanner stage 2–3) have been reached. This team have also provided evidence that no young individual eligible for GnRHa has dropped out of treatment or shown regret during puberty suppression. The cornerstone of this approach is the evidence that, although puberty suppression seems to reduce the gender-dysphoria-related distress and seems to be a relatively safe and reversible procedure, not treating gender dysphoria in childhood cannot be considered a neutral option, as delaying treatment until late adolescence or adulthood might lead to the development of psychiatric concerns, social isolation, and impaired functioning.”

“Our opinion is that the enlightened decision would be to allow puberty suppression when the adverse outcomes of a lack of or delayed intervention outweigh the adverse outcomes of early intervention in terms of long-term risks for the child. In other words, if allowing puberty to progress seems likely to harm the child in terms of psychosocial and mental wellbeing, puberty should be suspended.”

“Since (the 1990s), puberty suppression has become increasingly accepted as an early intervention in young individuals with clear signs of gender dysphoria.”

“Puberty suppression is considered a fully reversible procedure and has been proven to be sufficiently safe. Suppression of puberty in children with gender dysphoria has the fundamental benefit for children of giving them time to reflect on their gender identity, obtain real-life experience living as the non-natal gender in dress and behaviour, and determine whether or not they desire the full transition. In our opinion, as the development of a body contrary to the experienced gender has been associated with several psychosocial distress parameters, puberty suppression can be considered a preventive treatment. The procedure has consistently been linked to an improved transition into the desired gender role, including in terms of physical appearance, and a more satisfactory outcome, even in the long term.”

“Despite a limited number of studies, the existing literature supports puberty suppression as an early, sufficiently safe, and preventive treatment for gender dysphoria in childhood and adolescence.”

This 2016 Tavistock GIDS paper merits further discussion and we will be looking in more detail in our next research evidence review.

 

 

References:

Carmichael, P., Presentation at WPATH 2016; February 2016

Cohen‐Kettenis, P. T., Delemarre‐van de Waal, H. A., & Gooren, L. J. (2008). The treatment of adolescent transsexuals: changing insights. The journal of sexual medicine5(8), 1892-1897.

Costa, R., Dunsford, M., Skagerberg, E., Holt, V., Carmichael, P., & Colizzi, M. (2015). Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. The journal of sexual medicine12(11), 2206-2214.

Costa, R., Carmichael, P., & Colizzi, M. (2016). To treat or not to treat: puberty suppression in childhood-onset gender dysphoria. Nature Reviews Urology13(8), 456-462.

De Vries, A. L., Steensma, T. D., Doreleijers, T. A., & Cohen‐Kettenis, P. T. (2011). Puberty suppression in adolescents with gender identity disorder: A prospective follow‐up study. The Journal of Sexual Medicine8(8), 2276-2283.

De Vries, A. L., McGuire, J. K., Steensma, T. D., Wagenaar, E. C., Doreleijers, T. A., & Cohen-Kettenis, P. T. (2014). Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics134(4), 696-704.

Giordano, Simona. “Gender Aytpical Organisation in Children and Adolescents: Ethico-Legal Issues and a Proposal for New Guidelines.” Int’l J. Child. Rts. 15 (2007): 365

Giovanardi, G. (2017). Buying time or arresting development? The dilemma of administering hormone blockers in trans children and adolescents. Porto Biomedical Journal2(5), 153-156.

Growing up Transgender, A plea for better transgender research on the perpetual myth of ‘desistance’ and the ‘harm’ of social transitioning; 2017. https://growinguptransgender.wordpress.com/2017/03/04/a-plea-for-better-transgender-research-on-the-perpetual-myth-of-desistance-and-the-harm-of-social-transitioning/

Growing up Transgender, Diagnostic importance of starting puberty; 2017. https://growinguptransgender.wordpress.com/2017/11/25/diagnostic-importance-of-starting-puberty/

Growing up Transgender, GIDS.NHS.UK All the support a parent needs….; 2016. https://growinguptransgender.wordpress.com/2016/11/11/gids-nhs-uk-all-the-support-a-parent-needs/

Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Murad, M. H., … & T’Sjoen, G. G. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism102(11), 3869-3903. https://doi.org/10.1210/jc.2017-01658

Korte, A., Goecker, D., Krude, H., Lehmkuhl, U., Grüters-Kieslich, A., & Beier, K. M. (2008). Gender identity disorders in childhood and adolescence: currently debated concepts and treatment strategies. Deutsches Ärzteblatt International105(48), 834.

Mac, Marlo, Hit by trans friendly fire, 2017. https://gendermom.wordpress.com/2017/11/21/hit-by-trans-friendly-fire/

McCann, C. (2017). When girls won’t be girls. 1843. [online] Available at: https://www.1843magazine.com/features/when-girls-wont-be-girls [Accessed 27 Nov. 2017].

Murchison, G. (2016). Supporting and Caring for Transgender Children. Human Rights Campaign11.

Stein, E. (2012). Commentary on the treatment of gender variant and gender dysphoric children and adolescents: Common themes and ethical reflections. Journal of Homosexuality59(3), 480-500.

Telfer, M.M., Tollit, M.A., Pace, C.C., & Pang, K.C. Australian Standards of Care and Treatment Guidelines for Trans and Gender Diverse Children and Adolescents. Melbourne: the Royal Children’s Hospital; 2017 https://www.rch.org.au/uploadedFiles/Main/Content/adolescent-medicine/Australian%20Standards%20of%20Care%20and%20Treatment%20Guidelines%20for%20Trans%20and%20Gender%20Diverse%20Children%20and%20Adolescents.pdf

Winter, S., Diamond, M., Green, J., Karasic, D., Reed, T., Whittle, S., & Wylie, K. (2016). Transgender people: health at the margins of society. The Lancet388(10042), 390-400.

 

2 thoughts on “Puberty Blockers (GnRHa)

  1. Pingback: Transmythbusting | In trouble again

  2. Pingback: UK GIDS Failing Publicly | Growing Up Transgender

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