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    Management of adolescents with gender dysphoria

     

    Children and adolescents with GD are at risk of bullying and social rejection and are at high risk of adverse mental health outcomes including anxiety, depression, self-harm and suicide, poor school performance, and drug and alcohol abuse.3 Thus, the mental health provider should continue to evaluate and support the child during social and biological transition.

    Puberty suppression

    Some children with GD experience increasing distress during puberty as their body begins to change. The Endocrine Society guidelines support the use of puberty blockers starting when a child reaches Tanner 2 stage of puberty (breast budding in girls and testicular volume of 4 cc in boys).

    The mental health provider should assess whether the patient meets DSM-5 criteria for GD and provide a letter of support for the pediatric endocrinologist or gynecologist to begin puberty blockers.2 Such treatment not only addresses the child’s mental distress but also prevents development of secondary sexual characteristics that may later be difficult to alter, such as the Adam’s apple or large breasts.

    In general, puberty suppression is achieved with gonadotropin-releasing hormone agonists (GnRH) such as a Histrelin rod or Depo-Lupron. If insurance does not cover the costs of these medications, Depo-Provera (depo medroxyprogesterone acetate) can be utilized after appealing to the insurance provider for reimbursement.

    Given their experience with administration of injectable contraceptives and hormonal implants, gynecologists are in a unique position to initiate puberty suppression, as placement of the histrelin rod is similar to placement of the etonorgestrel contraceptive implant.

    Puberty suppression is considered completely reversible but may have adverse effects (AEs) on final bone mineral density (BMD), an outcome that has not been well studied.3 The Endocrine Society guidelines recommend annual testing for BMD and bone age. Evaluation of gonadotropin (LH/FSH) and testosterone/estradiol levels, height and weight measurements, and Tanner staging should be performed every 3 months.2

    Cross-sex hormones

    Regardless of whether puberty is suppressed, the Endocrine Society guidelines support initiation of cross-sex hormones around age 16. Physicians should extensively counsel adolescents who are considering cross-sex hormones and their families regarding the expected results of feminizing/masculinizing medications and their possible AEs. Discussions should include the effects on fertility and options for fertility preservation.

    Prior to initiation of cross-sex hormone therapy, the WPATH recommends that a mental health professional provide documentation (such as a referral letter) about the patient’s personal and treatment history, DSM-5 eligibility, and need for cross-sex hormone therapy. Health professionals who recommend hormone therapy share the ethical and legal responsibility for that decision with the gynecologist who provides the service.3

    In some cases, parental consent may not be required; however obtaining it is preferable because parental support improves clinical outcomes during hormone therapy.4 Of note, a patient’s goals need to be discussed often as he or she matures, as puberty suppression does not inevitably lead use of cross-sex hormone therapy or surgery.5 While surgical transition is an important (and expensive) component of gender affirmation, puberty suppressing and cross-sex hormone therapy serves as the endpoint to transition for many people.

    Testosterone treatment for female-to-male (FtM) adolescents

    Hormone therapy for adolescents with GD who have received puberty suppression differs considerably from therapy for adults, largely because it involves induction of puberty.

    Testosterone is generally administered intramuscularly or subcutaneously. Other methods (creams and patches) are not as widely prescribed because data are limited regarding their use for puberty induction. Testosterone esters are often administered every 2 to 4 weeks at the onset of induction, with a dosage goal set as the lowest dose needed to maintain the desired clinical result.3 This requires discussion not only of the risks of masculinizing hormone therapy but also of the timing of the desired effects so the adolescent has reasonable expectations (Table 2).

    Following completion of puberty induction, the Endocrine Society recommends maintaining testosterone levels within normal male physiologic levels (320–1000 ng/dL). Monitoring for AEs includes both clinical and laboratory evaluation specific to the risks of hormone therapy and the patient’s individual risks/comorbidities (Table 2).6 Unintended pregnancies have occurred in transgender men receiving testosterone, so contraceptive needs should be addressed, especially with older adolescents.7

     

    Estrogen treatment for male-to-female (MtF) adolescents

    Hormone therapy for adolescents who desire feminizing therapy is more complex. Most clinical studies report concurrent use of antiandrogens with estrogen therapy if the patient has not undergone puberty suppression.8 Puberty induction, in suppressed patients, may be undertaken with oral estrogen as well as transdermal (patch) and parenteral formulations. The risk of venous thromboembolism (VTE) is lower in adolescents than in adults and transdermal preparations may lower the risks further.3

    Following puberty induction, serum estradiol should be maintained at premenopausal levels (<200 pg/mL) and testosterone should be in the physiologic female range (<55 ng/dL). In individuals who have experienced native testosterone-induced puberty, this treatment may require high doses of estradiol (2–6 mg) as well as androgen blockers such as spironolactone. As with testosterone therapy, regular clinical and laboratory assessment should be performed to monitor for AEs. Suggested protocols for monitoring can be found in Table 2.

     

    Jason Jarin, MD
    Dr Jarin is Fellow, Pediatric and Adolescent Gynecology, Washington Hospital Center, Washington, DC

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