The Clinician's Guide to Transgender Care
Key strategies necessary to provide comprehensive, sensitively delivered care

Transgender Hormone Therapy to Match Gender Identity

Chapter 3: Providing transgender hormone treatment follows conventional paradigms, but with a more judicious approach when patients are adolescents.

Let's begin with the understanding that gender identity has a durable biological basis, the Endocrine Society Position Statement on Transgender Health,1 states that “medical intervention for transgender individuals, including both hormone therapy and medically-indicated surgery, is effective and relatively safe when appropriately monitored and has been the established standard of care.”

Nearly every trans* person will articulate their gender identity without hesitation, yet the desire to transition is a very personal consideration. The pace and level of physical change that is desired will vary from person to person. Once the clinical team and the patient have come to an understanding of the patient's desire to transition, transgender-specific hormone treatment is introduced with the same anticipated concerns and effects as may arise when hormones are prescribed for any other purposes.2

Prior to initiating hormone therapy, however, determination of transgender identity must be assessed, paying close attention to concerns that arise and will vary based on the age of the trans* patient—with children and adolescents requiring a more circumspect approach than necessary with adults.

Determination of Transgender Identity

Gender identity is organic, biological in nature, and hard-wired from birth.1 Most transgender individuals, when asked, will trace their gender identity as far back as they can remember, and typically well before puberty.

While hormones, chromosomes, and anatomy are associated with gender identity for most individuals, these physiological factors do not confer gender identity, which is for most individuals, not changeable. Environment plays no physiological role.

Presentation as transgender in late adolescence and during adulthood has been more the norm than the exception. Still, gender identity presentation is occurring and will likely become more common at younger ages as familiarity with and public acceptance of transgender identity increases.

Consider this: Transgender adults were once transgender children and had their identity been addressed prior to puberty, they may have benefitted from hormone blockers and/or gender-affirming hormones for a higher quality of life much sooner.3

Therapy Considerations for Adolescents

For adolescents and children who present for the first time as nonbinary or transgender, an accurate assessment is necessary. The best practice for managing trans youth is very individual. The age at which adolescents begin to question their gender identity or articulate experiencing gender dysphoria varies for each person.

Given the heightened challenges regarding the provision of hormone blockers, it is highly recommended that youth should be evaluated and treated by a multidisciplinary team with expertise in trans relevant mental health, primary care, and endocrinology. Often, the team will need to provide support to both the trans” youth and their families.

An advance of great benefit to the care of transgender adolescents and their families is the use of a gonadotropin-releasing hormone (GnRH) agonist initiated at the onset of puberty or as early as is feasible to arrest physical changes. The hormone-blocking treatment puts a ''pause'' on pubertal development, allowing the individual and the clinical team to take more time, and be more deliberative, in determining appropriate next steps based on individual needs. However, the usual course of GnRH is no more than three years.

The role of specially trained therapists is critical to both the short and long-term care of trans youth. As much to provide support as the youth tackles the social adjustments of family and friends, when gender identity shifts from the assigned sex at birth, it is not unusual for adolescents to experience depression and anxiety, and other emotional challenges.4

After the ''pause,'' transgender hormone therapy can be initiated for physical sexual adjustment when both the individual and healthcare team (with family support) deem the timing to be appropriate.1

Assessing Timing for Medical Intervention

The consistency of personal gender identify occurs for most children as young as 4 to 7 years old. For children who experience gender nonconformity, if their identity as other than the sex identified at birth, arose at a very early age, it is highly likely that their experience will only intensify.5 When adolescents present as gender questioning, they may later identify as gay or lesbian.

While there is a published clinical tool to aid in assessing adults for their readiness for medical treatment, Deborah Coolhart and colleagues have recently published a comparable tool for trans* youth.Since most gender non-conforming adolescents will want hormone treatment, their desire should be supported sooner, rather than delaying the shift into adulthood, to minimize struggles with gender dysphoria.

As there is no “appropriate” timeline or timing, the best approach is one of taking the youth’s lead by respecting the pace and timing of medical treatment should be in accordance with the patient's wishes, and with appropriate involvement of parent(s).

For an in-depth exploration of the mental health needs of trans* individuals, one good source is the Guidelines for Psychological Practice with transgender and gender nonconforming people.5

Adolescents who have medical hormone therapy with solid social support are assured of better outcomes and higher quality of life. Therefore, it is equally important for therapists to attend to the parents, and siblings, of the trans* adolescent, in addition to addressing the mental health needs of the gender-nonconforming adolescent.

Transgender Hormone Therapy in Adulthood

For the vast majority of adults, the determination of their gender identity is clearly articulated. However, whether and the degree to which a person may choose to act to trans is a personal, very singular decision.

Input from a mental health provider may help individuals to prepare for the challenges that will inevitably arise when medical hormone therapy is initiated, so that possible reactions from family and friends, and from their community may be anticipated. Mental health providers can also uncover rare psychiatric conditions that may confound transgender diagnoses.

While it should be obvious, it still bears stating that when transgender individuals seek medical intervention, they should have full access to providers who are knowledgeable in trans-specific primary care, trans-specific mental health, and transgender hormone therapy.

Transgender Therapy Regimens

For trans men (Female-to-Male, FtM)—hormone therapy will consist of prescribing testosterone sufficient to adjust the serum testosterone from typical female levels to a normal male range.

Doses are similar to what would be used, in general, for the treatment of male hypogonadism. Subcutaneous and intramuscular injections at doses of 50 to 100 milligrams, every 1 to 3 weeks, has resulted in stable testosterone levels in small case series.3 Other administration options exist including transdermal hormone delivery, either in gel form and patch.

For transgender women (Male-to-Female, MtF)—when testes are present, hormone treatments will consist of an antiandrogen, or a testosterone-lowering agent, to reduce testosterone levels and inhibit androgen action. Estrogen supplementation may also act to suppress the endogenous axis to further lower testosterone levels

For a quick primer on the current approach to therapy, see Table 1.1

Spironolactone is the leading antiandrogen of choice in the US. This preference is driven by its low cost and long-term safety profile given a half-century of use as a potassium-sparing diuretic for treatment of hypertension.4 Higher doses of spironolactone are used to manage hormone levels in transgender individuals that are needed for blood pressure control. The doses can be divided, as needed, to improve tolerance.

For estrogen replacement, multiple options are available, including 17B-estradiol (pure laboratory produced estradiol) and Premarin (mixed estrogens derived from horse urine) with pure estradiol easier to monitor given standard assays. A sensitivity to patients having special reasons for choosing a specific estrogen (eg, those who may be vegetarian or Vega) is warranted in the selection of which preparation to recommend.

Doses are generally double to quadruple the level used for hormone replacement therapy in postmenopausal women, or at least 1 to 2 milligrams. For trans women with intact testes, the dose may need to be as high as 4 to 8 mg a day. Lower estrogen doses along with parenteral or topical products are thought, by some, to mitigate the risk of thrombosis.1

Some Clinical Caveats and Concerns
Hormone Therapy Side Effects

For trans men

Concerns—When trans masculine patients undergo testosterone therapy, they should be monitored for testosterone-stimulated erythropoiesis, evident as an increase in hematocrit with a goal to keep hematocrit levels less than 50%. As well, monitoring should include lipid profile where shifts toward lower levels of protective HDL might be seen. However, long-term data are lacking about whether there is an increased risk of coronary disease in trans men.  There is frequently a link between androgen therapy and an increased risk of sleep apnea.5

Thus, regular and ongoing serum monitoring should include testosterone, hematocrit, and lipids to assure appropriate levels are achieved and maintained.

Trans men with a cervix or residual breast tissue should be advised to continue with routine preventive Pap testing and mammography (or chest self-exam for trans men who have undergone chest reconstruction surgery with removal of breast tissue).

For trans women

When trans feminine individuals are given antiandrogen therapy of any type, clinicians should communicate that decreased libido may occur. Dose adjustments are possible depending on the patient preference.

Monitoring of trans women who are taking hormone therapy should include serum testosterone to evaluate therapy success, as well as appropriate surveillance of estrogen level, prolactin level, potassium level (if using spironolactone), and lipid profile.

Routine screening for malignancy should include any existing tissue, independent of its association with a specific sex (eg, prostate tissue for transgender women even if they’ve had genital reconstruction surgery because the surgery leaves the prostate intact).

Long-Term Health Concerns

The only known pitfalls are: hypogonadism with increased risk for osteoporosis and perhaps metabolic concerns and supra-physiologic levels, which may expose individuals to harm without any known benefit (eg, erythrocytosis with testosterone, and thrombosis risk with estrogen.1

Gender-Affirming Surgery
Only some transgender individuals elect to have gender-affirming surgeries. (Kailas). While the opportunities available for surgery have increased, given greater supply of specialists, and greater access to insurance coverage, the interest in surgery by some transgender patients may actually decline if increased societal acceptance lessens external pressure.1

Issues of Fertility

When evaluating and treating transgender individuals, it is crucial to remember that many transgender medical and surgical interventions can interfere with fertility.  Health care providers can offer reassurance to their patients that planning may facilitate protecting some reproductive function.2

Transgender patients will benefit from counseling regarding the effects that certain treatments can have on fertility, as well as options for fertility preservation and reproduction in the future.2

Chapter 4 will offer insights to common questions and concerns that arise in the onging care of transgender patients.


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Common Clinical Concerns in Ongoing Transgender Care
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