Desired physical goals may range from changes that do not require any treatment to all the classic physical changes, hormone therapy and surgeries. Although it is rare,5 some individuals may choose to detransition back to the sex assigned at birth or end up identifying as non-binary, in most cases without regret for the initial transition, and there are also trans individuals that stop medication because they feel they no longer need it at a given point in their lifespan.14 For the purpose of treatment planning, the key is to focus on expressed needs after providing adequate information about the possible courses of action. In other cases, trans individuals detransition due to the loss of employment opportunities and lack of social support, choosing to revert to the sex assigned at birth due to psychosocial factors.

Table 1 presents the general recommendations for the care of trans minors.15 Other aspects to consider include:

• •

  Contemplate pubertal suppression with gonadotropin-releasing hormone (GnRH) analogues from Tanner stage 2 and subsequent gender-affirming therapy with testosterone or oestrogen. Health professionals should not assume that trans individuals feel aversion toward their genitalia, so it is recommended that information about potential future surgeries (Appendix A, Table S1) be given only if it is necessary. Before age 16 years, proxy informed consent should be signed by the legal guardians of the minor in adherence to the law.

• •

  Inform of the possibility, when feasible, of saving genetic material for fertility preservation (ovarian tissue, gametes), ideally before treatment initiation.

• •

  Take care of the general health of the minor, including healthy lifestyle habits, prevention of substance use, contraception and appropriate vaccination, especially administration of the vaccine against papillomavirus, which is recommended in every trans person under 26 years.

• •

  In the case of suspected abuse due to rejection of the gender identity and/or sexual orientation of the minor by one or both parents or any other social factors with an impact on health, the physician should consult make a social work consultation.16

An interview (Table 2)5–7,15,17,18 should be conducted to establish the needs of the minor and the family following the recommendations we have just presented.

Anthropometric measurements should be recorded (weight, height, growth velocity, body mass index and waist circumference if applicable), in addition to blood pressure and the Tanner pubertal stage. The physical examination should explore possible signs suggestive of disorders of sexual development (DSDs).

The physical examination of the trans individual can be a delicate juncture, as some may feel that they need to have a physical appearance fitting a binary model category to be affirmed in their perceived identity, so it is important to develop trust and never force this examination on the patient. In some cases, the examination reveals lesions in the chest and genital areas due to the use of bandages and/or tape to conceal certain primary and/or secondary sex characteristics.19

Table 34,15,20 lists the tests that should be ordered.

If at onset of puberty or during puberty the child develops or experiences exacerbation of dysphoria due to the development of secondary sex characteristics, pubertal suppression therapy may be indicated, and it is always important to consider that it should not be delayed so avoid irreversible changes that the child does not want. Thus, puberty blocking is not always indicated, but the individual and their family must be adequately informed of its potential benefits and risks so that they can ask for it if needed.

At present, the eligibility criteria for pubertal suppression established by the World Professional Association for Transgender Health (WPATH)17 are not being applied, and puberty blocking is performed in individuals under the age threshold used to define a mature minor, typically set at 12 years. Table 4 presents the drugs used for puberty blocking.4,15,20–23 The standard of care is administration of gonadotropin-releasing hormone (GnRH) analogues monthly or every 3 months. In the initial months, puberal suppression is better guaranteed with monthly administration of GnRH analogues, although there have been no differences in effectiveness in studies that compared administration of monthly doses versus 2 trimestral doses.24

The effects of pubertal suppression therapy and its ongoing management after initiation of treatment are presented in Appendix A of the online supplemental material.4–6,15,20,24–28

The factors to consider for initiation of hormone therapy are the wishes, physical and emotional wellbeing, height, bone age and sex assigned at birth of the minor, and the age at initiation of puberty blocking. Gender-affirming hormone therapy is partially irreversible, a fact that must be stated in the specific informed consent that has to be signed before its initiation.

As regards the age at initiation of gender-affirming hormone therapy, initiation before 16 years is becoming increasingly frequent in current clinical practice to help physical development to correspond to that of peers of the same age and promote the development of desired secondary sex characteristics. At present, an individualised approach is recommended, as there is no empirical evidence to support recommendations regarding the optimal age for initiation of oestrogen or testosterone therapy.

Pubertal suppression therapy poses risks to bone health if it lasts for many years without initiation of gender-affirming hormone therapy. Furthermore, mental health may deteriorate if the emergence of the secondary sex characteristics of the self-identified gender is delayed in adolescents who are inherently vulnerable due to their sex status, as they may be subject to abuse and stigmatization because of their physical appearance. The unavailability of hormone therapy for those who wish a physical change is a powerful predictor of mental health disorders.5

Use of oral estradiol valerate or oral or transdermal 17ß-estradiol is recommended in the doses presented in Table 5.4,20,21 The following are aspects to consider:

There is broad variability in the feminising effects of oestrogen therapy. A higher dose of oestrogen does not necessarily translate to an increase in breast size.

The transdermal route is associated with a lesser hepatotoxicity and a lower risk of thrombosis compared to the oral route, and it achieves concentrations closer to physiological levels. It is the recommended route in patients with liver disease and/or risk factors for cardiovascular disease, such as diabetes mellitus or smoking, or in patients that prefer this route.4,15 In patients with known thrombophilia, a history of thrombosis or a family history of thromboembolism, use of transdermal oestrogen and/or concomitant anticoagulant therapy may need to be considered, although the available data are insufficient to recommend a specific therapeutic approach.5

If bone mineral density deteriorates, bone mineralization is not progressing or the goal is to reduce the final height, the oestrogen dose can be escalated faster, higher doses used, or oestrogen therapy initiated before the planned age.20

The dose should be adjusted over time based on the clinical response and plasma levels of oestradiol, although usually, at the beginning of treatment, the dose of oestrogen can only be adjusted based on the clinical response since most hospitals are not equipped with ultrasensitive systems capable of detecting plasma concentrations of less than 5pg/mL.

Table 6 presents alternative drugs that can be used in the maintenance phase of treatment.4,15,17,20

In transgender girls, the doses of oestrogen need to be at least doubled, with the risks that this entails, to ensure the development of desired secondary sex characteristics and the suppression of endogenous testosterone, unless GnRH analogues, cyproterone acetate or spironolactone are administered concomitantly.4 For this reason, these drugs must be maintained until performance of gonadectomy, if the patient desires it, once the age of majority is reached.

Some clinicians29 advocate for administration of oral micronized progesterone based on its beneficial effects in cisgender women (optimal breast maturation in Tanner stages 4-5, among others), but there is a lack of rigorous evidence supporting that these effects extend to trans women.

Recommendations for management and diagnostic testing in the follow-up of trans female adolescents after initiation of hormone therapy are presented in Table S2 in Appendix B of the supplemental material online.4,15,17,19–21,30–32

Table 74,5 shows the time that can be expected to elapse before the physical changes achieved with gender-affirming hormone therapy start to become apparent in trans female adolescents, and the time that can be expected to elapse before treatment achieves the maximum effect.

Clinicians are encouraged to help trans female adolescents to have realistic expectations about the physical changes that will take place with hormone therapy, especially if it is initiated at an advanced Tanner stage. When it comes to breast development, there is a lack of studies in minors that received pubertal suppression therapy in the early stages, but studies in adult trans women have shown a modest increase in breast volume in most women.33,34

Adverse effects had seldom been described during adolescence, and the most frequent are headaches or exacerbation of existing migraines, mood swings and fatigue, the latter in association with cyproterone acetate. There are cases of hyperprolactinaemia, liver dysfunction or thromboembolism, adverse events associated with higher doses and reported in adults.5,6,20

The goal is to maintain oestrogen and testosterone levels within the physiological range of cisgender women to avoid adverse effects like thromboembolism and liver dysfunction.4 The risks associated with hormone therapy are presented in Table 8.4,15,17,31,32,35,36