1. Home
  2. Knowledge Base
  3. Medical
  4. Puberty
  5. Pubertal Induction in Transgender Youth

Pubertal Induction in Transgender Youth

Overview

Gender-affirming hormone treatment helps transgender and gender-diverse adolescents experience puberty that aligns with their gender identity, mirroring their peers’ developmental timeline. Transgender girls and transfeminine adolescents receive estrogen to feminize their bodies, while transgender boys and transmasculine adolescents are prescribed testosterone for masculinisation. Additionally, medications like GnRH agonists are used to suppress the body’s natural production of hormones (testosterone in transgender girls and estrogen in transgender boys) that don’t align with their gender identity.

The goal of this treatment is to allow these adolescents to undergo puberty that feels right for them and matches the development of others their age. For a young person to start gender-affirming hormone treatment, they need to understand the treatment’s long-term effects and demonstrate the ability to make an informed decision. This understanding includes knowing the benefits and risks of the treatment and other available options.

If a young person has started early puberty (Tanner stage 2 and above), there’s no minimum age for starting gender-affirming hormone treatment. However, their emotional and cognitive maturity is crucial. Even if parental support isn’t present, as long as the young person can give informed consent, treatment can proceed.

Treatment should not begin if the young person doesn’t fully understand or agree to the treatment. For those who start treatment, hormone doses are initially low and gradually increased to match the stages of puberty, ensuring a natural and healthy development process.

Monitoring hormone levels every six months and having yearly health checks are part of the treatment to ensure everything is progressing well. This approach to pubertal induction in transgender youth is supported by guidelines from renowned health organisations like the Endocrine Society and the World Professional Association for Transgender Health.

Progress

Although current recommendations typically suggest increasing doses of gender-affirming hormones every six months, this timeframe can sometimes be too long, potentially delaying essential pubertal progress in transgender youth. It’s crucial to not just rely on fixed schedules but also to closely monitor for age-appropriate physical developments, mimicking natural puberty as much as possible.

People’s response to hormone therapy can vary, and adjustments may be necessary to align with their progress and needs. Regular assessment of physical changes, along with hormone level monitoring, allows for a more tailored approach. This ensures that the hormonal treatment not only follows best practice guidelines but also adapts to the specific growth and developmental milestones of the individual, leading to a more effective and responsive pubertal transition.

Tanner Stages by Age

The aim for transgender youth is to closely mimic the natural pubertal development process.

Tanner stages in feminisation Age at the start Noticeable changes
Stage 1 After the 8th birthday None
Stage 2 From age 9–11 Breast “buds” start to form; pubic hair starts to form
Stage 3 After age 12 Acne first appears; armpit hair forms; height increases at its fastest rate
Stage 4 Around age 13 Further developments§
Stage 5 Around age 15 Reproductive organs and genitals are fully developed
Tanner stages in males Age at the start Noticeable changes
Stage 1 After the 9th or 10th birthday None
Stage 2 Around age 11 Pubic hair starts to form
Stage 3 Around age 13 Voice begins to change or “crack”; muscles get larger
Stage 4 Around age 14 Acne may appear; armpit hair forms
Stage 5 Around age 15 Facial hair comes in

Adapted from https://www.healthline.com/health/parenting/stages-of-puberty#summary

An Evidence-Based Protocol

Aim

The aim of puberty initiation is to allow transgender and gender diverse adolescents to go through puberty that is congruent with their gender identities and that matches the pubertal development of their peers of similar ages. The rationale behind the treatment regimen is to produce the hormonal and developmental changes usually seen in endogenous puberty.

Criteria

Given that young people who are seeking gender-affirming care will already have commenced early puberty (Tanner stage 2 and above), there is no minimum age criterion for the prescription of gender affirming hormone treatment for puberty initiation in people taking puberty suppressing medication.

However, there is a criterion based on the level of emotional and cognitive maturity. In order for a young person to receive gender affirming hormone treatment, it must be established that they have the capacity to provide informed consent. It must be demonstrated that:

  • The young person understands the implications of gender affirming hormone treatment, including its long-term impact;
  • The young person understands the intended benefits and potential risks of gender affirming healthcare treatment;
  • The young person has knowledge of the alternative options available and their likely outcomes;
  • The young person is able to explain their reasoning involved in their decision making;
  • The young person’s decision is not coerced or pressured by someone else.

It also helpful to seek information from the parents to corroborate the above assessment of mental capacity and to confirm whether the young person has parental support regarding the treatment decision. However, the lack of parental support does not necessarily preclude treatment, as the establishment of capacity allows treatment to proceed even if the parents do not agree with the young person’s decision.

Contraindication

Do not proceed with gender affirming hormone treatment if the young person is deemed not to have the capacity to provide informed consent. In this case, further counselling may be offered to the young person and their family to assess what is in the best interests of the young person and to facilitate future decision making.

Dosage

In order to accord with the hormone profiles associated with different stages of puberty, oestrogen and testosterone commence at low doses. These are gradually increased at intervals of 3-6 months until adult doses are reached.

The initial doses and the increments of change also depend on the stage of puberty at which puberty initiation is commenced.

The following tables are the recommended regimens for feminising hormone treatment and masculinising hormone treatment for puberty initiation in young people at different pubertal stages.

Feminising hormone treatment

Step Transdermal gel (Oestrogel® 0.06%) Transdermal patches (Evorel® or Estradot®) Oral tablets (Progynova®)
1 0.75mg (1 pump) every 2 days 12.5mcg/24hr twice weekly 0.5mg every 2 days
2 0.75mg (1 pump) daily 25mcg/24hr twice weekly 0.5mg daily
3 0.75mg and 1.5mg on alternate days 37.5mcg/24hr twice weekly 0.5mg and 1mg on alternate days
4 1.5mg (2 pumps) daily 50mcg/24hr twice weekly 1mg daily
5 2.25mg (3 pumps) daily 100mcg/24hr twice weekly 2mg daily

Early puberty

  • In transgender girls commencing oestrogen in early puberty (Tanner stage 2), begin treatment at step 1.
  • Proceed to the next step every 6 months.
  • When step 5 has been reached, proceed as per the protocol for feminising hormone treatment in adults.

Middle to late puberty

  • In transgender girls commencing oestrogen in middle to late puberty (Tanner stages 3 and 4), begin treatment at step 4.
  • Proceed to the next step after 6 months.
  • When step 5 has been reached, proceed as per the protocol for feminising hormone treatment in adults.

Postpubertal

  • In transgender girls who are postpubescent (Tanner stage 5), use the protocol for feminising hormone treatment in adults.

Other medications

  • A GnRH analogue (e.g., nafarelin, triptorelin, leuprorelin) or another puberty suppressing medicine (e.g., spironolactone) should be prescribed throughout treatment in order to suppress the endogenous production of testosterone.
  • The optional addition of progesterone (e.g., Utrogestan® 100mg daily) can be added if wanted.

Masculinising hormone treatment

Step Transdermal gel (Testogel® 16.2g/g) Intramuscular injection
(Sustanon® 250mg/ml)
Testosterone enanthate (250mg/ml injection)
1 20.25mg (1 pump) every 2 days 50mg (0.2ml) every 3 weeks 25mg (0.1ml) every 2 weeks
2 20.25mg (1 pump) every 2 days 60.25mg (0.25ml) every 3 weeks 25mg and 50mg on alternating 2 weeks
3 20.25mg (1 pump) daily 100mg (0.4ml) every 3 weeks 50mg (0.2ml) every 2 weeks
4 20.25mg (1 pump) daily 125mg (0.5ml) every 3 weeks 60.25mg (0.25ml) every 2 weeks
5 40.5mg (2 pumps) daily 250mg (1ml) every 3 weeks 100mg (0.4ml) every 2 weeks

A note on testosterone gel

  • If Testogel® 16.2g/g is unavailable, then Testogel® 50g/5g sachets can be used.
  • The equivalent dose for 40.5mg (2 pumps) of Testogel® 16.2g/g is 50mg (1 sachet) of Testogel® 50g/5g.
  • The equivalent dose for 20.25mg (1 pump) of Testogel® 16.2g/g is 25mg (half a sachet) of Testogel® 50g/5g.

Alternate dose frequencies for Sustanon® 250mg/ml intramuscular injections

  • Dose frequencies may be adjusted to every 4 weeks if there are clinical indications.
  • For step 1, the roughly equivalent dose is 60.25mg (0.25ml) every 4 weeks.
  • For step 2, the roughly equivalent dose is 75mg (0.3ml) every 4 weeks.
  • For step 3, the roughly equivalent dose is 125mg (0.5ml) every 4 weeks.

Early puberty

  • In transgender boys commencing testosterone in early puberty (Tanner stage 2), begin treatment at step 1.
  • Proceed to the next step every 6 months.
  • When step 5 has been reached, proceed as per the protocol for masculinising hormone treatment in adults.

Middle to late puberty

  • In transgender boys commencing testosterone in middle to late puberty (Tanner stages 3 and 4), begin treatment at step 4.
  • Proceed to the next step after 6 months.
  • When step 5 has been reached, proceed as per the protocol for masculinising hormone treatment in adults.

Postpubertal

  • In transgender boys who are postpubescent (Tanner stage 5), use the protocol for masculinising hormone treatment in adults.

Other medications

  • A GnRH analogue (e.g., nafarelin, triptorelin, leuprorelin) or another puberty suppressing medicine (e.g., spironolactone) should be prescribed throughout treatment in order to suppress the endogenous production of oestrogen.

Tanner staging

Tanner stage Pubic hair People with testes People with ovaries
1 – None – Prepubertal – Prepubertal
2 – Sparse hair – Change in texture of scrotum
– Increase in testicular volume
– Breast buds form
– Labia become pigmented
– Clitoris enlarges
3 – Thicker curly hair
– Spreads to the pubis
– Increase in penis length
– Further increase in testicular volume
– Voice begins to deepen
– Increased muscle mass
– Breast tissue grows but no contour
– Underarm hair growth
– Acne
4 – Thicker curly hair
– Covers pubic area
– Further growth of penis and testes
– Further voice deepening
– Underarm hair growth
– Acne
– Further breast growth with projection of the areolae and nipples
– Menstruation commences
5 – Adult hair
– Spreads to inner thighs
– Facial and bodily hair growth – Breasts reach an adult size and contour

Monitoring

After commencing puberty initiation with testosterone or oestrogen, the serum oestrogen and serum testosterone must be checked every 6 months to monitor the effectiveness of treatment.

For transgender boys taking testosterone, a full blood count must be checked every 6 months to monitor for polycythaemia.

A full health check should be performed yearly, which includes a full blood count, urea and electrolytes, liver function tests, lipid profile, bone profile, HbA1C, and blood pressure check.

Evidence

Sources

This protocol integrates information from different clinical recommendations that have been published to date. An important resource is the guideline for puberty initiation in transgender youth by the Endocrine Society (Hembree et al., 2017). In addition, the protocol draws on the guidelines for puberty initiation in cisgender youth with delayed puberty by the Endo-European Reference Network (Nordenström et al., 2022) and the British Society for Paediatric Endocrinology and Diabetes (El-Khairi et al., 2016; Matthews et al., 2016). Studies on hormonal changes during puberty were also consulted (Balzer et al., 2019; Frederiksen et al., 2020).

The World Professional Association for Transgender Health (2022) and the Endocrine Society (Hembree et al., 2017) recommend that the decision of when to commence puberty initiation should not be based on chronological age, but should be informed by whether the young person has attained the level of cognitive development and maturity to be able to give informed consent. The legal framework for informed consent in young people under 16 in England and Wales is Gillick competence (Gillick v West Norfolk and Wisbech Area Health Authority [1985] AC112).

Dosage

The recommended dosing regimen is adapted from the regimens for puberty initiation proposed by the Endocrine Society (Hembree et al., 2017), the Endo-European Reference Network (Nordenström et al., 2022), and the British Society for Paediatric Endocrinology and Diabetes (El-Khairi et al., 2016; Matthews et al., 2016). There are some variations between the different regimens regarding the recommended preparations and specific doses. For example, the Endocrine Society guideline recommends calculating doses according to weight and height, while the other guidelines recommend standardised doses. Nonetheless, all of the guidelines recommend commencing on a low dose and increasing the dose every 6 months over a period of 24–30 months until an adult dose is reached. The dosing regimen for Sustanon® 250mg/ml intramuscular injection is partly informed by the Nottinghamshire Area Prescribing Committee guideline for the treatment of hypogonadism in male adolescents, although the dose frequencies have been adapted.

Monitoring

The value of monitoring hormone levels during puberty induction is unclear. Research on the hormonal changes during puberty in cisgender youth suggests that adult levels of sex hormones tend to be reached by Tanner stages 3 to 4, which is approximately two to three years after the commencement of puberty. However, before that point, hormone levels may vary considerably between individuals (Balzer et al., 2019; Frederiksen et al., 2020). Hence, while adult ranges may be used to guide treatment in late puberty, it may not be feasible to construct hormone reference ranges to guide treatment in early puberty. At most, monitoring of hormone levels could tell us whether there has been a relative increase in the oestrogen or testosterone during treatment.

Accordingly, the Endo-European Reference Network guideline suggests that “serum testosterone concentrations cannot be used to monitor efficacy, which relies exclusively on clinical improvement and general wellbeing” (Nordenström et al., 2022, p. G38). The British Society for Paediatric Endocrinology and Diabetes guideline for puberty initiation with oestrogen suggests aiming for a low serum oestrogen level <50pmol/l early in treatment in order to accelerate linear bone growth, but also concede that such low levels are not measured by most clinical laboratory methods (Matthews et al., 2016). The Endocrine Society guideline recommends monitoring hormone levels every 6 months, but does not give any indication of how such monitoring can be used to inform changes in treatment (Hembree et al., 2017).

In view of the above, the effectiveness of treatment in puberty initiation may be better guided by clinical response and patient report than by hormone levels, at least in the early stages of treatment. However, testosterone and oestrogen levels may be checked every 6 months for reassurance that the hormone levels are increasing appropriately as the doses are increased towards adult levels.

References

  • Balzer, B. W. R., Garden, F. L., Amatoury, M., Luscombe, G. M., Paxton, K., Hawke, C. I., Handelsman, D. J., and Steinbeck, K. S. (2019). “Self-rated Tanner Stage and Subjective Measures of Puberty are Associated with Longitudinal Gonadal Hormone Changes”. Journal of Pediatric Endocrinology and Metabolism, 32 (6): 569–576.
  • Breehl, L. and Caban, O. (2022). “Physiology, Puberty”. StatPearls, https://www.ncbi.nlm.nih.gov/books/NBK534827/
  • El-Khairi, R., Shaw, N., and Crowne, E. C. (2016). “Testosterone Replacement Therapy”. British Society for Paediatric Endocrinology and Diabetes Clinical Committee Clinical Guideline, revised November 2016.
  • Frederiksen, H., Johannsen, T. H., Andersen, S. E., Albrethsen, J., Landersoe, S. K., Petersen, J. H., Andersen, A. N., Vestergaard, E. T., Schorring, M. E., Linneberg, A., Main, K. M., Andersson, A. M., and Juul, A. (2020). “Sex-Specific Estrogen Levels and Reference Intervals From Infancy to Late Adulthood Determined by LC-MS/MS”. Journal of Clinical Endocrinology and Metabolism, 105 (3): 754–768.
  • Gillick v West Norfolk and Wisbech Area Health Authority [1985] AC112.
  • Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Hassan Murad, M., Rosenthal, S. M., Safer, J. D., Tangpricha, V., and T’Sjoen, G. G. (2017). “Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline”. Journal of Clinical Endocrinology and Metabolism, 102 (11): 3869–3903.
  • Matthews, D., Bath, L., Hӧgler, W., Mason, A., Smyth, A., and Skae, M. (2016). “Guidance Statement: Hormone Supplementation for Pubertal Induction in Girls”. British Society for Paediatric Endocrinology and Diabetes Working Group, 30th September 2016.
  • Nordenström, A., Ahmed, S. F., van den Akker, E., Blair, J., Bonomi, M., Brachet, C., Broersen, L. H. A., Claahsen-van der Grinten, H. L., Dessens, A. B., Gawlik, A., Gravholt, C. H., Juul, A., Krausz, C., Raivio, T., Smyth, A., Touraine, P., Vitali, D., and Dekkers, O. M. (2022). “Pubertal Induction and Transition to Adult Sex Hormone Replacement in Patients With Congenital Pituitary or Gonadal Reproductive Hormone Deficiency: An Endo-ERN Clinical Practice Guideline”. European Journal of Endocrinology, 186 (6): G9–G49.
  • Nottinghamshire Area Prescribing Committee (2023). “Testosterone (Sustanon® injection and Tostran® gel) for Hypogonadism and Constitutional Delay in Growth and Puberty in Male Children and Adolescents”. https://www.nottsapc.nhs.uk/media/1511/testosterone-information-sheet.pdf
  • World Professional Association for Transgender Health (2022). “Standards of Care for the Health of Transgender and Gender Diverse People, Version 8”. International Journal of Transgender Health, 23(S1): S1–S259.
Updated on January 12, 2024

Was this article helpful?

Related Articles

Request an article
If you would like some knowledge added to our knowledge base, send your suggestions here.
Request Knowledge