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  • Writer's pictureNicole Athéa

HORMONE TREATMENTS USED FOR ADOLESCENTS IN TRANSITION

Dr Nicole Athéa

Gynecologist and endocrinologist

Former intern and head of clinic at Paris hospitals


Gender incongruence in minors, as defined by the DSM5 , a psychiatric textbook, corresponds to a strong and persistent feeling of gender identification that is the opposite of one's sexual identity and has lasted for at least 6 months, and which may be accompanied by "psychic suffering or alteration in the social field, or a risk of social and/or academic suffering, or even just a significant increase in the risk of suffering or impairment in these areas", and at least two other criteria, which are redundant and always expressed by young people who come for consultation for gender disorders (e.g. wishing to wear clothes of the other sex, or to be treated like a person of the other sex). This definition applies to adolescents.On the one hand, the 6-month duration of gender reversal, drastically shortened compared to previous definitions, and on the other, a risk of suffering, which is not proven suffering, now sufficient to support this diagnosis, have played an important role in the extension of medicalization. Although the definition is slightly different for children, with a greater number of gender-related behaviours associated with suffering, specialist teams such as K. Zucker's[1] show that, for the vast majority, the feeling of belonging to the other sex disappears in adolescence, particularly with the first signs of puberty, whereas the desire to be of the other sex is frequent in childhood. However, this data needs to be called into question, as the population of young people coming to transition consultations has recently been transformed: the exponential growth in this demand, which has exploded in all Western countries in recent years, is associated with an inversion of the sex ratio, and girls are at least two and a half times more likely to request transition than boys today[2]. But it's also often girls who, a few years after transitioning, detransition and revert to their native gender identity.


These changes in demand have taken hold in the wake of what many authors call a social epidemic[3] , referring to the importance of social networks, of which young people are major consumers. Indeed, in these neo-declarations of identity, identification with young Trans people who testify on social networks can be at the forefront, and the popularity acquired through transition plays an important role. While some activists and pro-Trans doctors dispute the role of social networks, even renowned pro-Trans doctors like Erika Anderson support the term contagion. There are many scientific arguments to support this, and many child psychiatrists around the world are working on the harmful effects of social networking. Increases in psychopathologies have been identified under conditions of net overuse: for example, a recent rise in eating disorders and Tourette's disease[4], which are usually very rare. All of these disorders have increased sharply in specific locations, following the prompting of testimonials. Similarly, with the spectacular rise in suicide attempts by teenage girls in 2021, an epidemic phenomenon linked to the overuse of social networks by young people is likely, as recent studies demonstrate the great vulnerability of very young teenage girls to the depressant action of social networks: yet it is in this population that suicide attempts or Trans identifications are most numerous. [5] What's more, many young people testify to the influence of social networks on their trans identification, to which more than 35% have been pressured[6] Finally, we shouldn't forget that the exponential growth in requests from young trans people corresponds to the explosion in internet use from 2006 onwards. All these arguments demonstrate the influence of social networks in the exponential growth in demand for gender reassignment today.


According to Prof. B. Golse, identity difficulties of the kind that have always existed in adolescence have found support, often transitory, in the form of hippie or punk identification, for example. Today, the identity difficulties of these young people are expressed in the form of transidentity, and risk being considered and medicalized as gender identity disorders. Clinically speaking, it's difficult to know which young people to treat: there's no clinical or biological evidence to suggest that gender dysphoria will persist. And the number of detransitioners who revert to their birth gender identity is increasing, demonstrating the fragility of the "diagnosis" of gender incongruence.

A study by the very serious British GIC, a world reference in terms of transidentity, found a rate that it considered underestimated at 6.7% of detransitioners and 3% of people very close to the definition of detransition, i.e. almost 10%[7] . Given the length of time needed to decide whether or not to detransition, estimated at at least 8 years, this rate should still be much higher than the initial assessment carried out 16 months after inclusion in the protocol. In some studies, these figures are even higher. [8] In the IAG publication, which included very young adults (their inclusions are from the age of 17 onwards, and very young girls are the most numerous), 90% of girls had undergone mastectomy, even though the duration of the transition had been very brief, and in studies of detransitions[9],[10], 33% (Littman) to 45% (Vandenbusche) of girls, who are the most numerous to testify to their detransition and probably the most numerous to detransition, underwent surgery.


The shortening of the DSM5 symptom duration is in line with the possibility of rapid initiation of puberty-blocking treatment at the very start of the pubertal process. In the past, a two-year delay was often required before medical treatment could be started, and Prof. Leibowitz, one of the authors of the latest Wpath guidelines[11], wanted to put this back on the agenda [12], taking into account the exponential growth in the number of young people who identify themselves as Trans, a number of whom do not present a demand that will last, as shown by the growth in detransitions. But he failed to impose this guideline: instead, Wpath indicates an unspecified duration which will allow many Trans-affirmative doctors to decide in a totally arbitrary and above all shortened way how long the reversed identity should persist before medicalization. Similarly, the Wpath has called for a careful psychological evaluation for the same reasons as above, but this has been widely contested by activists and many Trans doctors around the world, so that this directive too will be subject to arbitrary interpretation by Trans doctors according to their orientation. Here, more than ever, medicalization will be determined by ideology. What's more, the age for hormone surgery has been lowered in the new guidelines: to 8 for puberty blockers in young girls, to 14 for the use of sex hormones, to 15 for mastectomies known as "top surgery", and to 17 for sex surgeries known as "bottom surgery". All these changes are bound to lead to a major increase in gender incongruence diagnoses and their medicalization, at a time when the psycho-social factors behind an explosive rise in demand are very much in play. In this context, it is important to take stock of this medicalization of minors and evaluate it in the light of recent studies, which are methodologically much more reliable than those which seemed to show the benefits of such treatment, benefits which are now widely called into question.


I) Puberty blockers (LHRH agonists)

PAEDIATRIC INDICATIONS FOR TREATMENT

In pediatrics, this treatment was introduced to postpone puberty in children with very early onset of puberty. In the field of transition, it was the Dutch teams who set up a treatment protocol for very young Trans people some twenty years ago, using puberty blockers which are used in the treatment of early puberty, but which do not have marketing authorization. In this case, the aim is to treat Trans children at the very start of normal puberty (Tanner stage 1-2), which can begin at around 8-9 years for girls and 10-11 years for boys, to prevent the physiological puberty process from taking place. And yet, numerous studies show that puberty enables almost 75% of children to regain harmony with their gender. If they are treated well by their family during childhood, 88% of children are no longer in conflict with their gender identity[13].

Another indication for puberty blockers concerns young trans people whose puberty is in progress or completed: these treatments are administered while waiting for the prescription of reversed sex hormones, which will be started around age 14, 16 years earlier.

Dutch doctors developed this treatment by alleging a cerebral cause, a striated nucleus pathology, for transidentity. This etiology has never been confirmed, and the current increase in transidentity clearly argues for psycho-social causes. However, to use such a powerful treatment in such an anti-physiological way, a serious somatic legitimization had to be found. Even though it has never been confirmed, it continues to be alleged[14] and even today, some doctors, notably in the Netherlands, continue to assert this cause.

However, almost all clinical cases are related to life stories (cf. publications by K.Zucker, De Ceglio, F.Condat, S.Hefez and many others cited below), which shed light on these young people's identification difficulties. These difficulties can be diagnosed as a gender identity disorder of a quasi-structural nature[15], as the designation of sex assignment at birth in contradiction with a so-called authentic identity seems to support, which legitimizes medicalization, regardless of the many causal factors that account for the demand for a reversed identity. The adolescent period, the very frequent psychopathologies presented by these young people, the difficulties of pubertal metamorphosis, traumatic antecedents including sexual violence, dysfunctional families, the important role of social networks and the social devaluation of the feminine which we are witnessing today and which painfully affect girls, two and a half times or even more numerous than boys to request a transition[16], all these factors contribute to the identification of an inverted gender, and detransitioners bear witness to this[17]. The overriding issue at stake in this identification is not the desire to change gender, but the suffering induced by psychopathologies that 60 to 70% of detransitioners among them blame for their ailments, and they vigorously denounce the doctors who treated them for the gender of having neglected their psychic disorders, not having listened to their suffering and traumatic antecedents, having misled them with an erroneous diagnosis and having reinforced a problem that was not their own.

The denial of these problems is underpinned by an ideological factor that leads many "pro-affirmative" LGBT trans caregivers to deny the interactional etiologies we've just listed: the neo-identity they call "authentic" - an authenticity that would nevertheless be open to discussion - cannot, in their view, respond to psychological factors, in particular dysfunctional parental relationships or psychopathology. Trans-affirmative practitioners massively deny that psychological factors are involved, and the wrong body remains the main cause, despite the fact that no biological, hormonal or sexual developmental anomaly has ever been found in Trans people. The so-called authentic neo-identity is defined as a singular intimate feeling that would be exclusively self-referential...[18] This representation is radically opposed to that of many sociologists, such as A. Ehrenberg, philosophers like Foucault, or psychoanalysts like Pontalis, for whom subjectivity and gender identity are not given, but are a non-fixed construction that evolves with a person's history. But what's serious for young people in this representation is that, as it's an essence present from birth or even before, it defines a destiny from which no one can escape, when teenagers need to think of themselves as having an open future.

And yet, when the life stories of these children are told, family and psycho-social elements often shed light on their identity affirmation, in an expression of their psychological difficulties that can be described as psychosomatic, with somatization focusing on the rejection of the body, as it does for eating disorders, which are frequently associated with gender dysphoria. And it is to this somatization that today's puberty-blocking treatments respond, in short treating the effect for the cause, with the aim of improving or curing psychic disorders by modifying the body, as F. Condat shows in an article reporting on several clinical cases, including that of a 10-year-old girl who is going to be treated with puberty blockers[19].


These treatments were put in place to limit the often significant negative feelings and psychological difficulties associated with pubertal metamorphosis in dysphoric children, and to enable them "to explore feelings relating to gender identity...", it is said[20]. This being the case, pubertal metamorphosis is difficult for all young people; you only have to look at the statistics for depression, suicide attempts and self-mutilation at this age to realize this[21]. And the statistics for suicidality among Trans young people are not very different from the figures given here, the over-suicidality of adolescent girls being overwhelming in some studies. Trans suicidality, which is used as an argument for hormone treatments in some texts, and which some doctors assert to parents when the latter doubt the benefits of treatment, does not change either before or after treatment. [22], [23] It should also be put into perspective in relation to the massive psychopathology these young people carry: oversuicidality is well known in these situations, which also explains why it does not change after gender treatment, as the psychopathologies themselves remain intact, while the management of psychic disorders is the way to reduce adolescent suicidality.

The Dutch experience with these treatments has been published (DeVries et al [24]). Of 55 children treated, none changed their sex choice, and all underwent sex surgery shortly after the age of 18. These young people seem satisfied and, studied one year after surgery (i.e. around age 20), they are doing better psychologically than at age 13, before the start of puberty-blocking hormone treatment. But there was no control group, nor was there a group with social, family and psychological management of the gender disorder without medical-surgical treatment: it is indeed possible to live with the perceived gender without medicalization, and all the better for having good support, and some Trans people are living this today and campaigning for demedicalization. That said, if a majority of young people get better after adolescence, it's true for trans people as it is for other teenagers. Winnicott once said that "the treatment of adolescence is time."

We shall see that new studies do not support the optimism of De Vries' results. What this study does show, however, is that young people treated in this way almost never reconsider their inverted identity: not only is there no reflection or exploration of gender possibilities, but everything that is put in place - family, social, academic, medical, etc. - confirms the young person in an identity that can be said here to be assigned by all the protocols put in place, an assignment to an identity that is no more authentic than the previous one, since it was constructed like the previous one, but without having the full functionality of the anatomical sex of birth. The various medico-social supports claimed to be "gender-affirming", put in place as soon as a child or adolescent declares himself or herself trans, and widely advocated and organized by many of those working in this field, can only fix a young person in his or her inverted identity, and certainly don't allow him or her to reflect, and medicalization follows almost inevitably.

If the reason for using puberty blockers is to improve the psychological suffering of these young people, these results are not supported by numerous new studies. For example, the study published by the British GIDS, a world reference center for the care of Trans minors,[25] sought to reproduce the Dutch study. 44 adolescents, 25 boys and 19 girls, who had reached or had recently reached puberty, were diagnosed as having "gender dysphoria" after a 6-month assessment involving monthly consultations and psycho-social and somatic evaluations.The average age is 13.6 years. Treatment with puberty blockers was initiated, and regular somatic and psycho-social assessments were carried out, using comprehensive questionnaires validated in terms of the field to be analyzed. These assessments are carried out for the duration of the treatment (36 months), and the last one six months after cessation. At that point, 98% of them will begin treatment with reverse hormones. At 6-15 months, the mood was more positive, which meant that this was not the case for the remaining 51%, at a time of treatment initiation when the placebo effect was still greatest. Psychologically and socially, there was no change in quality of life, psychological functions, dysphoria or self-image. There is no change in self-harm behaviours, and self-aggressive ideations persist. 30% to 40% of young people report reduced vitality. Numerous side effects are reported, including frequent weight gain.


What these figures tend to demonstrate is that psychological suffering is not extinguished by medical care or by treatments aimed at bodily transformation. This study, initiated by P. Carmichael, a psychologist who massively supports medical treatment and denigrates psychological care, was very disappointed by these results, which do not prevent him from continuing to prescribe puberty blockers. This is one of the peculiarities of this field: no matter how much the studies show the opposite of what we want them to say, we continue with the treatments as if nothing had happened.

This suggests that the real reason for the indication of these treatments is something else: "it is important to consider anticipated future results and to increase the chances of achieving more desirable or comfortable aesthetic results for the individual"[26]. But then again, famous Trans surgeons such as E. Bowers[27] say that the underdeveloped sex organs caused by long-term use of puberty-inhibiting hormones, combined with the gonadal blockage engendered by reversed sex hormones, pose great operative difficulties in constructing a neo-sex, due to a lack of tissue necessary for reconstruction. The sexual difficulties secondary to these difficult surgeries are well described today: anorgasmia in particular. And fertility problems too. Once again, the expected results have belied expectations, but indications are continuing and W path has even lowered the starting age for puberty blockers. And activists are defending tooth and nail treatments that will have a major impact on young people who identify as Trans, since they will amputate the possibility of a fulfilled sexuality for Trans people: what should be designated as transphobic is supported by Trans people themselves...


- If teenagers arrive after puberty has started or finished, puberty blockers can still be used. However, this treatment does not prevent puberty that has already taken place; if the testicles or ovaries need to be put to rest, this could be done much more simply and with fewer side effects by progestins than by puberty blockers. Progestin treatments block both testicular and ovarian hormone production, with much better tolerability and lower cost. The enthusiasm of transition centers for puberty blockers in this second indication is hardly rational.

Do puberty blockers improve the lives of Trans women in the medium or long term? Turban is a famous Trans physician-epidemiologist, in the "affirmative" and pro-puberty-blocker vein. The conclusion of his latest study still wants us to believe in the anti-suicidal efficacy of these treatments, but it demonstrates the opposite in spite of himself. [28].

Turban rightly points out that the 2 published studies in which the positive effects of puberty-blocking treatment on the mental health of young transgender people have been examined have significant biases that make them implausible. In the first study (by De Vries), although the authors conclude that there is a positive effect, there is no control group. Numerous other criticisms of this study have since been made, seriously calling it into question, even though it is the conceptual linchpin of hormone treatment for young trans people. [29]In the second, researchers followed a group of 201 adolescents with gender dysphoria and found that those who received pubertal suppression in addition to psychological support had superior overall functioning, compared with those who received psychological support alone, but the families in which these children live are very different from those without treatment and are less supportive, which is a well-known major factor in children's well-being[30].


In Turban's publication, out of 20,619 trans respondents aged 17 to 36, two groups are selected: the group treated with puberty blockers represents 2.5% of trans people, i.e. 89; those who would have liked treatment, only 16%, i.e. 3,494. Thus, the desire for puberty-blocking treatment is very much in the minority among trans people. If only the last two groups are studied, the fact of wanting treatment and not having had it represents a bias in itself: those who want treatment are possibly worse off than the others, and may think that treatment would have changed their malaise.

The treated group is younger than the untreated group and includes more boys, whereas the untreated group has an over-representation of girls.


Suicidal ideation in the last year and throughout life, suicide attempts in the last year and attempts throughout life were studied. The treated group differed significantly from the untreated group, both in terms of socio-economic level and family support, all factors which were much poorer in the untreated group (23% of rejecting families and only 50% of supportive families in the untreated group, compared with over 80% of supportive families in the treated group). Once these differences have been statistically weighted, it is not possible to conclude that there is a benefit to hormone treatment. What this study clearly shows is that, in young people who were treated early and had all the treatments they seemed to want, reviewed later when they were adults, did not prevent psychological suffering and suicide attempts, contrary to what is usually claimed: 16 suicide attempts (18%) in the year preceding the study, 5 of which led to hospitalization, were made by trans people who had been medically cared for and treated since the start of puberty, and in the most supportive families. This over-suicidality is no higher in the group not treated early on, just as suicide attempts are equal in both groups throughout "all" life. Suicidal ideation in the treated group was also high: 45 (50%) had suicidal ideation in the last year; 32 (36%) had experienced psychological distress in the last month; 24 (27%) had used drugs in the last month. The only difference between the two groups is a slightly higher level of suicidal ideation during the lifetime of the untreated group, but this is not an easy question to answer when you're older, which is what the Trans people in the untreated group are, because more time has passed, so memories are less precise, whereas over the previous year the answers are equivalent; moreover, the over-representation of girls in the untreated group may help to explain the more frequent suicidal ideation: in the depression and TS statistics, girls are twice as well represented as boys.

This study, which focuses on the early use of puberty blockers, also shows that the reverse sex hormone treatments that immediately follow the blockers, given at 15 or 16 years of age, are equally ineffective in improving the psychological health and suicidality of these young people, whereas in the "untreated" group, reverse hormones are started after the age of majority, and these young Trans are neither worse nor better off than those in the early-treatment group. Turban's study therefore calls into question all early treatments. Other studies also show this[31].

This means that many of these young people, treated and transformed, are still not doing well. Given the social differences that play a very protective role for trans people in the treated group, we may even be surprised at the absence of any difference with the untreated group. What's more, these studies say nothing about those who may have died after HS or accidents, which often represent a masked HS.

The methodology of this study, by weighting factors that play a major role in the psychic health of Trans people, radically contradicts what we are told about adolescents who do so well when they have been treated.

If the use of puberty blockers in dysphoric young people was legitimized by the difficulty of experiencing pubertal transformations, in order to reduce the dysphoric experience, depressive symptoms and increased suicidal risk in these young people, these studies demonstrate the opposite: the persistence of these young people's difficulties, and their persistent oversuicidality is observed. There is therefore no longer any legitimacy for these treatments, and it is clear that they need to be offered other forms of care. One of the major hypotheses to emerge from these studies is that the associated psychopathologies, vulnerabilities and psychological suffering of adolescents, which concern more than half of all young people, have not been properly taken into account, as K. Zucker continues to emphasize, namely the overestimation of dysphoria, the underestimation, or even the failure to take psychopathology into account. And this is what these young people continue to suffer from.


PHARMACOLOGICAL ASPECTS OF PUBERTAL BLOCKERS[32].

The puberty blockers used are represented by

leuprorelin, marketed in France under the name Enanthone; it is available as an injection, with extended-release forms (11.25mg,). In English-speaking countries, this drug is marketed under the name LUPRON.

Triptorelin , marketed under the name Decapeptyl, in high-dose, extended-release injection form. (11.25mg).

In pediatrics, these are the forms used.

For early puberty indications, the only ones for which information is available in paediatrics, the 11.25mg dose is recommended and repeated every 3 months. For girls, treatment should be stopped before 12 years of bone age, and for boys before 13-14 years.

For young Trans children, treatment lasts longer, for around 5 years, until the age of 15. In the second mode of administration of puberty blockers, i.e. in young people who have partially or fully completed puberty, who are the most numerous, the duration of treatment is shorter, but for the former and the latter, the deleterious risks to bone capital and bone fragility caused by puberty blockers are significant risks about which we have little information. We'll come back to this point.


Side effects

Effects classified according to the Médra system, i.e.

Frequent is defined as occurring less than once in 100 (or equal to 1/100).

and infrequent an effect occurring from 1/100 to 1/1000.


Frequent or very frequent effects :

Decreased libido, Lower limb paresthesias, Back pain, Hyperhydrosis, Asthenia, Anemia, Allergic reactions, Headache, Dizziness, Hypertension, Dry mouth, Muscle pain, Pelvic pain, Injection site reactions

Increased weight

Loss of libido

Depression

Mood swings

These last effects are particularly noteworthy, as the risk of depression is already high in young Trans people. Suicidal ideals may be heightened by the treatments themselves.


Rare effects include

Confusional state Increased appetite, Insomnia, Irritability, Tinnitus, Dizziness, Testicular atrophy, Somnolence.

And this list is not exhaustive


As we can see, these drugs are not well tolerated, with numerous and frequent side effects.

While I have experience of this limited tolerance in gynecological indications, paradoxically, tolerance in pediatric publications seems to be quite good, whereas the side effects usually described in adults are numerous, some of them of proven seriousness, such as hypertension. Doctors who prescribe these treatments for children are involved in them, and are not inclined to express or listen to negative symptoms, whereas they tend to want to demonstrate their positive effects. The same is true of adolescents who, having vehemently demanded treatment, may tend to minimize its side effects, as Bourgeois et al[33] point out.However, in children, headaches occur in 1/3 of cases, which is significant and a disabling symptom. Hot flushes are not uncommon. A few digestive signs such as vomiting, nausea or diarrhea are observed in less than 5% of cases. Rare cases of local or general allergy have been reported. Pain at the injection site is constant, as marked with subcutaneous injections as with intramuscular ones. During the course of treatment, the body changes, with a marked reduction in lean body mass and an increase in fat mass; weight gain may be observed, which may be poorly tolerated by young people with body dysphoria...

Bone mineralization is affected by these treatments: puberty is the time of peak bone mass formation. This increase in bone capital is prevented by these treatments, as can be observed in young anorexics whose ovarian function is blocked. Bone mineralization seems to repair itself when treatment is stopped, but there is insufficient hindsight to provide reliable data. However, bone density remains lower than before treatment, even at the age of 22, after more than 5 years of treatment with sex hormones[34]. The risk of osteoporosis is also evident in post-pubertal indications, pending reverse hormone treatment.

The potential effects of sex hormones on the maturity of certain areas of the brain are suggested by studies demonstrating the importance of estrogen and testosterone during adolescence: testosterone is thought to promote spatial development, while estrogen promotes emotional maturation[35].

In fact, in the case of precocious puberty, treatment is stopped at the normal age of puberty, i.e. around 12.5 years, enabling these young people to enjoy a normal adolescence, something that endocrinologists and paediatricians have been concerned about until now. For young trans people, this medicalization, with its regular injections, biological and radiological monitoring, medical consultations... leads to a chronically ill status, with major and inescapable repercussions on the child and the family[36]. This treatment, more prolonged than that for early puberty, was stopped at 15 or 16 years of age, and is replaced by estrogens or androgens, used in reverse physiology. This change should be observed at the age of 14.However, young people treated with puberty blockers will have been prevented from experiencing a normal adolescence, both physiologically and psychologically, and the fact that the use of sex hormones has been brought forward to the age of 14 is not going to change the situation much, since the average age of first menstruation for girls is 12 and a half, and above all, the "chronically ill" status engendered by medicalization remains unchanged. These young trans people will experience a truncated adolescence, the consequences of which no one can foresee, except for one: the medicalization that has been put in place, understood in the broadest sense of the term - medical, social and family - will compromise the possibility of going back to the original sex if an adolescent realizes after adolescence that the problem was not gender, as reported by the growing number of young people who are detransitioning.


In a GIC (UK Transition Reference Centre) study of access to care and detransition for young adults[37] in a formal UK center, at least one previously diagnosed mental health problem was documented for 126/174 patients, or 72.4%, of whom 63.2% suffered from anxiety and/or depression, 7% with a personality disorder and 2.3% with a suspected personality disorder, and (4%) with an eating disorder. Neurodevelopmental" disorders (attention-deficit hyperactivity disorder, autism spectrum disorders, dyslexia or dyspraxia) were diagnosed in 13% of cases with adequate documentation; these diagnoses mainly concerned people under 25 (21% of cases); 22% had a regular use of alcohol or drugs. An overwhelming proportion of people (75%) had had negative or traumatic childhood experiences, including 22% who had experienced violence. 43% had documented concerns about their mental health during treatment, with just under half seeking help. There were three suicides among people accessing treatment. This is interpreted by the authors as "less than half of people with a mental health problem are taken into care," even though they are being monitored for their dysphoria . And the fact that people are not worried about their mental health is not a good criterion for assessing needs, given the frequency of denial in this area and the difficulty patients have in consulting a psychiatrist. As the authors conclude, the high incidence of these disorders in young Trans patients calls for greater caution in indications, and for follow-up that is not limited to endocrinology. One hypothesis is worth considering: given the importance of psychopathology, gender dysphoria could have become the socially-dictable mode of expression of psychic suffering, and we know that every period has had its own; this factor would also play a role in increasing its frequency. If this hypothesis proves to be true, the physical management of dysphoria would then see its credibility severely damaged. In this study, the young people were not doing well despite the treatments they had received, and the fact that their transition was no longer being monitored testifies to the inadequacy of care for their needs.


II Androgens (testosterone and dihydrotestosterone)

A) PHARMACOLOGY

This treatment is indicated for male hypogonadism; it is prescribed off-label for women.

"In children, in addition to virilization, testosterone may cause accelerated growth and bone maturation, as well as premature fusion of the conjugation cartilages, leading to a reduction in final height. Consequently, the use of this drug is not recommended in children and adolescents. There have been no clinical studies in children under 18 years of age.


1) Testosterone-containing drugs:


Androtardyl: injections every 15 days to 3 weeks

Nebido: injections every 10 to 14 weeks, less convenient and more expensive; not reimbursed.

Pantestone: per os gelules, less effective



The most widely used drug for trans-men is Androtardyl. Testosterone dosage

of testosterone can be used to adjust the spacing between injections.


-Effects of testosterone on girls: virilizing effects appear very rapidly and are irreversible.

-Voice changes

- Hair growth

-Hair loss: temporal gulfs

-Development of muscle mass

-Clitoromegaly

-Decrease in breast volume


2) Side effects

All have been reported regardless of the androgens used. The frequency of these effects has been studied with Nebido, and can be inferred from the other drugs since all are testosterone, with the possible exception of lesser metabolic and vascular effects of percutaneous treatments. Effects are classified according to the Médra system.

These effects were studied on an exclusive population of 422 men, and a causal link was demonstrated between side effects and testosterone administration.


-Common associated effects

-Irritability, weight gain, nervousness, altered libido with sexual hyperexcitation; hot flushes are frequent effects, as are hyperseborrhea and acne.

-The risk of polycythemia is also frequent, requiring regular monitoring of hemoglobin and hematocrit levels. With injectable products, reactions at the injection site are frequent. Vagal signs (malaise, dizziness) may also occur.


- in girls: gynaecological bleeding is not uncommon and requires the addition of progestins to stop it. Amenorrhea and dryness of the vulva are frequent.



-Side effects are infrequent but numerous

They include

-Psychiatric: mood disorders, nervousness, depression, aggressiveness: Trans girls often describe these disturbances.

-Cardiovascular effects: testosterone can increase blood pressure.

-Tumors:

"Liver cancers associated with high testosterone dosages are known, although rare".

Sex steroids are well known to promote the development and growth of certain tissues and hormone-dependent tumors.

- Fertility

"High doses of testosterone induce a reversible decrease in spermatogenesis and a reduction in testicular volume."


For young girls, when this effect of reducing ovarian volume occurs after that of puberty blockers, fertility may be affected.

"Androgens should not be used to increase muscle mass in healthy subjects, nor to increase physical capacity." This is not an uncommon use for trans-men, and may lead them to increase doses.

"Testosterone administration is contraindicated during pregnancy, with the risk of masculinization of a female foetus. This risk must be kept in view in Trans men who have sex with men, as gender dysphoria may prevent these boys with ovaries and uteruses from thinking they can be pregnant. "Research into embryotoxic or teratogenic effects has shown no evidence to suggest a subsequent embryo-toxic effect."

The side effects described are not exhaustive, others being very rare.


Overall: "The available results show no objection to the use of Androtardyl in men, in compliance with its indication and at the authorized dose", which is not the case for its administration to girls and women.

As far as androgens are concerned, no studies have been carried out to authorize their marketing authorization (MA) for women. This is a major limitation to the known effects of these treatments. [38]. The indications for marketing authorization, and the data on tolerance and side-effects of these treatments, are all derived from male-only studies. These data are insufficient to assess tolerance and adverse effects in women. As we know today, many pathologies do not express themselves in the same way in men and women, and drug tolerance can vary according to gender. We would need to conduct studies similar to those carried out for the marketing authorization with a female population in order to be able to market androgens under identical safety conditions.

Similarly, the administration of androgens to children and adolescents is sorely lacking in clinical studies to enable them to be prescribed.



3) Specific effects on women:

These are beginning to be demonstrated: recent publications report phlebitis and pulmonary embolism, which particularly affect women treated with androgens. The average risk of phlebitis is doubled and multiplied by 5 after two years of use, compared with men. The risk of stroke is multiplied by 10 compared with men and multiplied by 4 compared with the women's group after 6 years of use. [39]

A vascularly deleterious metabolic factor has also been demonstrated (increased LDL levels) [40].

Conclusion: Side effects are numerous. Young Trans people often complain that they have not been informed of the possible effects of treatment, some of which have an impact on their character, behavior or sexuality[41].

-The irreversibility of virilizing effects

The effects are rapid: a physical metamorphosis and voice change can be observed after three months of treatment.

More and more young girls are declaring themselves Trans. [42]For girls, pubertal metamorphosis is often unbearable. Depression, self-mutilation, suicide attempts, eating disorders, which affect at least 90% of girls, and today two-and-a-half times as many requests for transition demonstrate a major deterioration in young people's mental health. What specifically explains this suffering of the feminine and, in particular, this desire to destroy the feminine in oneself, as transidentity does? This is the crucial question facing our society. And the answer is not to erase the feminine by becoming trans. An in-depth study of this major social issue is absolutely essential.

What's more, many of these girls whose sexual orientation is lesbian find it difficult to affirm this orientation and declare themselves trans. Those who are detransitioning - and there are more and more of them - say so. We also need to take a fresh look at homophobia.

A period of 6 months (the time needed to "diagnose" gender incongruence) is a very short time in a young person's life to assert what can lead to the launch of a treatment whose effects are irreversible.

If the affirmation of an inverted gender identity is no longer a pathology, and if transidentity does not necessarily engender suffering [43], if any suffering is not resolved by hormonal treatments, as shown by Turban's study or those of GIDS and GIC, then paradoxically, it is medicalization that pathologizes this state and produces the risks. The use of treatments with significant side-effects, some of them serious, must be emphasized. The irreversibility of the virilizing effects can put a strain on the future of these girls, who are now the most numerous to detransition. In short, we can say that medical surgery in adolescence is one of the major risks to which these young people are exposed.

Never again should a young boy or girl be able to say like Keira Bell, a young Englishwoman who has lodged a complaint against the Tavistoc clinic in which she was treated: "I was an unhappy girl who needed help. Instead, I was treated like an experiment".


III Hormone treatments for Trans M-F

Boys, whether or not they have received puberty blockers, when they reach the age of 15-16 (now 14), will be treated with reverse sex hormones. Two types of medication may be combined:

The class of anti-androgens (which block the action of male hormones) includes several usable molecules.


In France, and more generally in Europe, cyproterone acetate (marketed under the name Androcure) was the most widely used, in doses of 50 to 100mg. This drug is the most powerful anti-androgen, because it blocks the secretion of male hormone (testosterone) produced in the testicles, and counteracts testosterone's action on hormone receptors present on target tissues, such as the hair follicle. It therefore has an essential hair-removal action, and for men with dense hair, it plays a very positive role in hair regression, particularly in conjunction with laser or electric hair removal. The drug, which has a very good tolerance and high efficacy, used to be widely used, but knowledge of a greatly increased risk of meningioma since 2018 has profoundly altered practices. Doctors and patients alike fear this effect, which occurs after a few years' use at doses of 50mg, the doses usually prescribed to Trans patients. Few patients are prepared for this risk, and cerebral monitoring, if the treatment is nevertheless used, is onerous: brain MRI before prescription and repeated every two years.


Spironolactone is a diuretic with low antiandrogenic activity which, despite its low efficacy, can be used in Trans women. This drug presents numerous contraindications when other treatments are prescribed, notably potassium-sparing treatments, or lithium, which can be used psychiatrically by young people with bipolar disorder. Anti-inflammatory drugs, often prescribed for pain, are also contraindicated. Numerous side effects have also been described. Given its very low anti-androgen efficacy, the benefit-risk balance of this drug in this indication is not positive.


B)-Estrogen treatments are used for their feminizing action.

In the past, these treatments were combined with Androcure, which had an important de-virilizing action, but now more and more Trans women are receiving estrogens alone, and are very attached to the feminizing action of these drugs. However, their action varies greatly from one subject to another, and takes time to become visible. The essential action of estrogens is mammary growth, which is slow; it begins after several months of treatment and can be estimated to remain unchanged after two years. There are extremely few other feminizing effects of estrogens. No obvious action on the skin (positive effects on the skin were often linked to cyproterone acetate), sometimes slight weight gain, very little change in fat distribution. In short, trans women are often disappointed, and some may exceed prescribed doses in the hope of achieving a greater effect, which is not the case. The effect on breast development, despite estrogen doses always higher than those given to women, is most often reduced and considered by many trans women to be insufficient. The result is a frequent demand for breast prostheses. When a supra-physiological dose of estrogen is given and the breasts don't grow, there's no point in increasing treatment doses: this simply means that these men's estrogen receptors are not very sensitive, particularly in their ability to multiply breast cells, just as in some genetic women who have little breast development. We must also bear in mind that the effect of estrogens given to women and men is not equivalent: it must be stressed once again that we are not dealing with a physiological action.


C) Several types of estrogen are prescribed:

-natural oral estrogens (estradiol 2 to 4mg) are to be preferred to ethynyl-estradiol estrogens, which have far more harmful metabolic and cardiovascular effects. They are generally well tolerated and easy to use. Provided the patient is young, has no personal or family history of thrombo-embolic disease, has no metabolic contraindications and is a non-smoker, this treatment can be used. There is no hepatic toxicity associated with these treatments, contrary to what is rumored on social networks. The impact on the liver concerns the slightly increased production of proteins that play a role in coagulation. As a result, vascular thrombosis may occur in certain at-risk subjects: the absence of any such history in them or in their family must be verified before any prescription.

-percutaneous estrogens (transdermal estradiol 100ùg): these are estrogens which, spread as a cream on the skin, can penetrate the body. They are much better tolerated metabolically and cardiovascularly, but more restrictive in application. However, they have the same contraindications as natural estrogens.

As in the case of androgens, all studies used to verify the safety of androgens for market authorization were carried out on women. Studies carried out on Trans are limited and do not ensure the validity of known pharmacovigilance data.

Recent studies show, by consensus, slightly increased metabolic and cardiovascular risks in M-F: triglyceride levels are significantly increased as early as 24 months of use; a small number of myocardial infarctions and vascular accidents, venous thrombosis and excess mortality have been described. Bourgeois et al[44] report frequent deliberate overdosing of prescribed estrogen doses, which I have also frequently observed. Disappointment at limited effects, belief in the greater efficacy of higher doses - which is not borne out - and use that can take on an addictive quality, are responsible. On the other hand, undesirable effects have often been caused by overdosing. It is extremely important to warn Trans women of the limited effects of estrogens, and of the risks associated with overdosing. Similarly, Bourgeois et al. point out "the potential for under-reporting and under-identification of hormone therapy-induced adverse events in trans people", which I have also noticed.

Concerning cancer: the cases of prostate cancer reported were possibly already present before these treatments, which reduce prostate volume. In the long term, cases of breast cancer are extremely rare. The only men at risk of breast cancer are those who carry a family genetic mutation that favours the onset of the disease, which can then appear in young men. That's why it's so important to be well-informed about your family history of breast cancer. At present, there is no significant association between hormone exposure and cancer or mortality in transsexuals[45].


D) Other estrogen side effects

According to Médra classification:

The following frequent effects are described: headache, weight change, plus or minus, breast tension or pain, pruritus or rash, nausea, abdominal pain.

Uncommon effects include dizziness, visual disturbances, palpitations, hives, anxiety, reduced libido and depressed mood. The latter must be taken into account in subjects who are often psychologically fragile and depressed.

Progesterone: This hormone has no direct feminizing action. There is no point in giving this hormone to a Trans M-F. Except sometimes, after sexual surgery, the hot flushes observed after castration are not always calmed by estrogens, so micronized natural progesterone (100 to 200 mg) may have a beneficial effect in helping sleep and limiting night-time awakenings caused by hot flushes. Some patients believe that this hormone promotes breast development, but no study has ever demonstrated this.


IV The endocrine-disrupting effect of sex hormones.

"An endocrine disruptor (ED) is a substance or mixture that alters the functions of the endocrine system and thereby induces adverse effects in an intact organism, in its offspring, or in (sub)populations". WHO 2002

Endocrine disruptors act through three main mechanisms. They can :

-inhibit the action of a hormone and provoke inappropriate reactions in the body,

-block the action of a hormone by preventing it from acting on its target cells,

-disrupt the production, transport, elimination or regulation of a hormone or its receptor.

Endocrine disruptors have other distinctive features. Unlike most "classic" chemical substances, the effects caused by endocrine disruptors do not necessarily seem to be linked to the dose received by an individual. Some effects may appear at low doses, diminish when doses are increased, and become more pronounced again at higher doses. This is known as a non-monotonic dose-response relationship.

Exposure to a mixture of several endocrine disruptors could have very different effects from exposure to the substances alone. These are known as "cocktail effects": their effects could add up, reinforce or, on the contrary, inhibit each other[46].

These effects are beginning to be well documented; the risks to the environment and the planet are not negligible: effects on the advancing age of puberty and the deterioration of male fertility have been shown to be linked to the action of sex hormones. Carcinogenic effects are also known. In his latest report, the president of the Réseau Environnement Santé of the INCA (French National Cancer Institute), calls for environmental factors to be taken into greater account by health authorities.

Adolescents, who are so rightly sensitive to environmental issues, need to be well informed of these actions and of the deleterious role of the use of sex hormones recommended to them.


Conclusion :

This report on the early treatment of Trans minors shows that :

The legitimacy of hormone treatments introduced at this age is radically called into question: the over-suicidality of Trans people treated young and those treated later is no different, and the psychological distress of young Trans people treated early remains very high both under medical treatment and after treatment, and no different from those treated late.

This proves that "PSYCHIC DISEASE IN ONE GENDER IS NOT SOLVED BY TRANSFER TO THE OTHER GENDER." (P-H.Castel)[47] Psychic suffering, very often engendered by psychopathology or a "neuro-developmental" disorder, remains intact after bodily care and unmodified by transition.

transition.

As the authors of an interesting piece of work on accompanying these young people through the arts put it, "Before subscribing to the label Trans, non-binary or questioning, young people are first and foremost teenagers. Adolescence, a major period of transition, is accompanied, among other things, by a need for self-expression, a search for identity, the development of autonomy and the challenging of societal rules."[48] This must be taken into account to avoid implementing treatments that are not only without legitimacy but dangerous. Respect for the adolescent period, its difficulties, but also its potential and creativity, must be preserved, allowing every adolescent the right to experience it.

[1] Singh D, Bradley SJ, Zucker KJ. A Follow-Up Study of Boys With Gender Identity Disorder. Front Psychiatry. 2021 Mar 29;12:632784. doi: 10.3389/fpsyt.2021.632784. PMID: 33854450; PMCID: PMC8039393. [2] Rapport du conseil national suédois de la santé fevr 2020 [3] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202330 [4] -Müller-Vahl K, Pisarenko A, i Jakubovski E, Fremer C, Stop that! It’s not Tourette’s but a new type of mass sociogenic illness Brain 23 August 20 [5] Orben, A., Przybylski, A.K., Blakemore, SJ. et al. Windows of developmental sensitivity to social media. Nat Commun 13, 1649 (2022. https://doi.org/10.1038/s41467-022-2929 [6] Littman L.,Individuals Treated for Gender Dysphoria with Medical and/or Surgical Transition Who Subsequently Detransitioned: A Survey of 100 Detransitioners 5 October 2020 Archives of Sexual Behavior https://doi.org/10.1007/s10508-021-02163-w [7] Hall J, Mitchell L., SachdevaJ, Accès aux soins et fréquence de détransition au sein d'une cohorte sortie d'une clinique nationale britannique d'identité de genre pour adultes : examen rétrospectif des notes de cas ;Publié en ligne par Cambridge University Press : 01 octobre 2021 [8] Boyd I, Hackett T, Bewley S. Care of Transgender Patients: A General Practice Quality Improvement Approach. Healthcare (Basel). 2022;10(1):121. Published 2022 Jan 7. doi:10.3390/healthcare10010121 [9] Vandenbusche E, Detransition-Related Needs and Support: A Cross-Sectional Online Survey J. of homosexuality2021, AHEAD-OF-PRINT, 1-19 https://doi.org/10.1080/00918369.2021.1919479 [10] Littman L. Ibid [11] W path : organisme rassemblant les experts pro-trans mondiaux de la médico-chirurgie des Trans, associés à des militants Trans et émettant régulièrement les directives de traitement [12] Certaines équipes adultes demandent encore deux ans entre évaluation, psychothérapie, et test « en real life », par exemple l’équipe marseillaise [13] Zucker K, Zucker, K. J. (2018). The myth of persistence: Response to “A critical commentary on follow-up studies and ‘desistance’ theories about transgender and gender non-conforming children” by Temple Newhook et al. (2018). International Journal of Transgender- ism, 19(2), 231–245. https://doi.org/10.1080/15532739.2018. [14] Le Pr d’endocrino-pédiatrie hollandais interrogé dans l’émission Documentaire « Devenir il ou elle » présenté par M.Carrère d’Encausse réalisé par l.Debaisieux et L Barneou diffusé Le 10/021/2017b sur Fr 5 [15] Chambry Jean, « Articulation chez l’enfant et l’adolescent des notions de genre et sexualité au regard de la notion de transidentité », Enfances & Psy, 2021/4 (N° 92), p. 41-50. DOI : 10.3917/ep.092.0041. URL : https://www.cairn.info/revue-enfances-et-psy-2021-4-page-41.htm [16] Athea N , Bonnet M-J, Quand les filles deviennet des garçons, une nouvelle forme de féminicide social ? A paraître a l’automne 2022 chez Odile Jacob [17] S.Hefez , Transitions, Réinventer le genre, Calmann-Levy, p 45 [18] A.Pullen Sans Façon D.Médico jeunes Trans et non binaires de l’accompagnement à l’affirmation , Les éditions du remue ménage , Ch 14, F.Susset et M. Rabiau « le soutien psychothérapeutique des enfants créatifs.v.es dans leur genre, Trans et non binaires. » [19] A.Condat, F.Bekhaled, N.Mendes, C.Lagrange, L.Mathivon, D.Cohen, « la dysphorie de genre chez l’enfant et l’adolescent : histoire française et vignettes cliniques, Neuropsychiatrie de l’enfance et de l’adolescence, 2016,64, 7-15 [20] S.Gosh, A.Gorogos, « l’accompagnement pédiatrique et les traitements hormonaux », Ch 17, in Jeunes Trans et non binaires Ibid [21] C.Chan et E. du Roscoet BEH n°3-4 « Parmi les personnes ayant fait une TS au cours de leur vie, plus d’un tiers (37,7%) ont déclaré en avoir fait au moins deux (39,9% des femmes vs 32,4% des hommes ; p<0,05). L’âge moyen de la dernière TS était de 29 ans pour les hommes et 27 ans pour les femmes (p<0,05) ; l’âge médian était de 25 ans (27 ans pour les hommes et 24 ans pour les femmes). La majorité des TS ont eu lieu avant l’âge de 25 ans, et c’est entre 15 et 19 ans que la proportion de suicidants était la plus importante, avec 30,1% de femmes concernées et 19,5% d’hommes (p<0,001) » [22] Turban JL, King D, Carswell JM, et al. Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation. Pediatrics. 2020;145(2):e20191725 [23] Dhejne, C., Lichtenstein, P., Boman, M., Johansson, A. L. V., Långström, N., & Landén, M. (2011). Long-term follow-up of transsexual persons undergoing sex reassignment surgery: Cohort study in Sweden. PLoS ONE, 6(2). [24] A.L.C.DeVries,J.K.Mac Guire, T.D.Steesma et al Young adult psychological outcome after puberty suppression and gender reassignment Pediatrics oct 2014 Vol 134 Issue 4 Page 225 [25] Carmichael P.,Butler G., et al short term of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK Plos one fevr 2021 [26] S. Gosh et A. Gorgos ibid [27] Weiss B. Entretien entre Abigail Schrier et M.Bowers 4 oct 2021 Commun senses [28]: Turban JL et al, Ibid [29] S. Levine, E. Abbruzzese & J. Reconsidering Informed Consent for Trans-Identified Children, Adolescents, and Young Adults Journal of Sex & Marital Therapy 17 Mars 2022 [30] Costa R, Dunsford M, Skagerberg E, Holt V, Carmichael P, Colizzi M. Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. J Sex Med. 2015; 12(11):2206–2214 [31] Bränström, R., & Pachankis, J. E. (2020). Reduction in Mental Health Treatment Utilization Among Transgender Individuals After Gender-Affirming Surgeries: A Total Population Study. American Journal of Psychiatry, 177(8), 727–734. https://doi.org/10.1176/appi.ajp.2019.19010080 Correction to Bränström and Pachankis. (2020). American Journal of Psychiatry, 177(8), 734–734. https://doi.org/10.1176/appi.ajp.2020.1778corrections [32] Pour tous les chapitres, toutes les données entre guillements non spécifiquement référées sont issues du dictionnaire VIDAL, bible de la pharmacologie française. [33] Bourgeois AL, Auriche P, Palmaro A, Montastruc JL, Bagheri H.et col Risk of hormonotherapy in transgender people: Literature review and data from the French Database of Pharmacovigilance.Ann Endocrinol (Paris). 2016 Feb;77(1):14-21. doi: 10.1016/j.ando.2015.12.001. Epub 2016 Jan 29.PMID: 26830952 Review. [34] Vlot MC, Klink DT, Heijer M den, Blankenstein MA, Rotteveel J, & Heijboer AC. Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents. Bone 2017 95 11–19. doi:10.1016/j.bone.2016.11.008. [35] S.Gosh et A.Gorgos, « l’accompagnement pédiatrique et et les traitements hormonaux », in Jeunes Trans et non binaires ibid [36] I.Adomnicai, Corps malade et adolescence, Adolescence et psychanalyse Ed In Press 2004 [37] Hall R, Mitchell L., Sachdeva J.Publié en ligne par Cambridge University Press :01/10/ 2021 [38] Getahun D, Nash R, Flanders WD, et al. Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med. 2018;169:205–213. doi:10.7326/M17-2785 [39] Ibid [40] Maraka S, Singh Ospina N, Rodriguez-Gutierrez R, Davidge-Pitts CJ, Nippoldt TB, Prokop LJ, Murad MH. Sex Steroids and Cardiovascular Outcomes in Transgender Individuals: A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3914-3923. doi: 10.1210/jc.2017-01643. PMID: 28945852 [41] Vandenbussche E (2021): Ibid [42] Pour les filles : entre 13 et 17 ans , 180/100 000 , entre 18 et 24 ans, 300/100 000 Pour les garçons entre 13 et 17 ans , 50/100 000, entre 18 et 24 ans, 150/100 000 [43] S.Hefez Chapitre I, Ibid [44] Bourgeois et col Ibid [45] Ibid [46] Document de L’anses disponible sur internet (Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail ) disponible sur internet [47] Castel P-H La métamorphose impensable Essai sur le transsexualisme et l'identité personnelle Gallimard 2003 [48] E. Abdellahi, C.A.Thibeault, « La thérapie par les arts : un outil pour accompagner les jeunes », in Jeunes Trans et non binaires, Ibid

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