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GAHT in Female-to-male Transgender Adolescents

Induction of secondary sex characteristics with injectable testosterone in female-to-male transgender adolescents

GAHT in female-to-male transgender individuals may differ from male-to-female transgender individuals with regards to drug administration. Oral testosterone is not well absorbed via the gastrointestinal tract, while transdermal testosterone is costly and requires daily application. Therefore, the popular testosterone formulation for female- to-male transgender individuals is intramuscular injections. An example of injectable testosterone is testosterone enanthate. Gradually increase the dosage every six months to mimic the effects of natural puberty as closely as possible.

Examples of injectable testosterone therapy in female-to-male transgender adolescents in the prepubertal or pubertal period.

Start with injections of testosterone enanthate at a dose of 25 mg per unit body surface area (m2) every two weeks for six months. Alternatively, inject half of the dose weekly or double the dose every four weeks. Then, adjust the dosage using the following guidelines:

50 mg/body surface area (m2) every two weeks for six months.
followed by 75 mg/body surface area (m2) every two weeks for six months.
followed by 100 mg/body surface area (m2) every two weeks for six months.

The final dose adjustment would be to inject 100-200 mg/body surface area (m2) every two weeks with the goal of reaching total testosterone levels similar to normal levels for biologic males (400-700 ng/dl).

Induction of secondary sex characteristics with testosterone therapy in female-to-male transgender in the postpubertal period

Because most transgender people seek consultation for GAHT quite late, healthcare providers must start with a higher dose as seen in table. Examples of injectable testosterone therapy in female-to-male transgender adolescents in the postpubertal period.

Start with injections of testosterone enanthate at a dose of 75 mg per unit body surface area (m2) every two weeks for six months. Then increase dosage to 125 mg/body surface area (m2) injections once every two weeks. This dose is equivalent to the final dose used in female-to-male GAHT for adults. Adjust dosage requirements based on total testosterone levels. The goal is to have total testosterone levels in the 400-700 ng/dl range.

Post-GAHT monitoring in transgender adolescents

Assessment conducted every three to six months: Assess weight, height, blood pressure, and sexual development by Tanner staging.
Assessment conducted every six to twelve months:
- Female-to-male transgender individuals: Monitor blood levels of testosterone and vitamin D, lipid profile.
- Male-to-female transgender individuals: Monitor blood estradiol and vitamin D levels.
Assessment conducted every one to two years: Test bone mineral density (BMD) until the age of 25-30 or the period of peak bone mass. • Bone age study (as indicated)

GAHT in Female-to-male Transgender Adults

The key principles of GAHT in female-to-male transgender adults are to aim for testosterone levels close to the normal range in biologic males while avoiding potential side effects of therapy. These latter include erythrocytosis, high blood pressure, salt and water retention, changes in lipid profile, severe acne, and obstructive sleep apnea. As mentioned earlier, female-to-male transgender adults can take testosterone only without the need for ovarian suppression drugs. Testosterone is currently available in Thailand for hormone-deficient biologic male individuals but has been used off-label for female-to-male transgender GAHT. Below are the different formulations used in current clinical practice:

Testosterone Enanthate or Cypionate

These are the most commonly used forms because of their low price. However, it should be used with caution because of increased risk of erythrocytosis. More frequent injections than testosterone undecanoate are required. The recommended dose of testosterone enanthate is 100-200 mg injected either subcutaneously or intramuscularly every two weeks. Alternatively, the dose can be reduced by half but with weekly injections. Testosterone cypionate is currently not available in Thailand.

Testosterone Undecanoate

This oil-based hormone is slowly absorbed and can be injected every 12 weeks, which is an advantage. However, it is costly and requires a greater volume for each injection. The recommended dose is 1000 mg per injection every 12 weeks. Pulmonary oil microembolism has been reported but is rare.

Testosterone Gel 1%

Transdermal gels can be applied once a day. The recommended dose is 50-100 mg/day. However, it is expensive and may be transferred to other people via physical contact with skin areas with applied gel.

Testosterone Transdermal Patch

The recommended dosage of a testosterone patch is 2.5-7.5 mg/day (currently not available in Thailand).

Regardless of the testosterone formulation, dosage must be adjusted based on total testosterone levels, targeted at approximately 400 -700 ng/dl. Oral testosterone with alkylation of the 17th carbon atom is not recommended because it may cause hepatotoxicity. Furthermore, it requires absorption via the lymphatic system, which may be inconsistent.5 On the other hand, injectable and transdermal testosterone formulations rarely cause hepatotoxicity.

Cessation of menses in female-to-male transgender individuals will result after a few months of testosterone treatment, however, some individuals may require a higher dose. If bleeding continues, a short course of progestogen can be prescribed. Physicians may also consider injecting depot medroxyprogesterone or GnRH agonists as another option for menstrual cessation before initiating testosterone treatment.

Monitoring female-to-male transgender adults on testosterone hormonal therapy

Perform quarterly assessments in the first year and monitor patients every six to twelve months to track the virilization progress and potential side effects.
Measure total testosterone blood levels quarterly until it reaches a level normal for biologic males (400-700 ng/dl).
For testosterone enanthate or cypionate injections, draw blood levels midway between injections. For example, if the drug is injected every four weeks, draw blood levels in the 2nd week after injection. If this is inconvenient and the blood testosterone level is 400-700 ng/dl, collect blood at any time.
For testosterone undecanoate injections, draw a blood level on the day prior to the next injection to measure testosterone levels. If the blood testosterone level is lower than 400 ng/dl, increase the frequency of testosterone undecanoate injections.
For transdermal testosterone, measure testosterone levels at least a week after treatment. Blood should be drawn at least two hours after application.
Baseline hematocrit or hemoglobin levels are recommended. This should then be repeated quarterly in the first year, followed by every six to twelve months. Moreover, blood pressure, weight, and blood lipid levels should be monitored periodically, depending on each patient.
Conduct osteoporosis screening tests in those who stop taking testosterone, use it irregularly, or in those with other risks of osteoporosis.
Individuals who have not undergone a hysterectomy (with the natal cervix still in place), cervical cancer screening is recommended, just like in biologic females.
Consider hysterectomy and oophorectomy if patients so desire, and have been treated with gender-affirming hormones for at least a year.
Individuals who have undergone mastectomies should have a clinical breast examination once a year, which special emphasis on areas under and around the nipples because some residual breast tissue may be left in these areas. Those who have not undergone a mastectomy should have breast cancer screening mammograms following the same guidelines as biologic females.

Refer: Gender-Affirming Hormone Treatment in Transgender People - The Thai Handbook of Transgender Healthcare Services, Center of Excellence in Transgender Health, Chulalongkorn University

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