Gender Affirming Care

Plan to spend at least 60 minutes preparing for this talk by using the Interactive board for Learning/Preparing, clicking through the graphics, and becoming familiar with the order the content appears on the graphic. The teaching script below details how to walk through the talk. Every interactive or “clickable” element is denoted with a mouse icon that should serve as a prompt to ask the audience a question before clicking it.

Anticipated time to deliver the talk without cases: 30 minutes.

Anticipated time to do cases: 15 minutes.

The talk is meant to be presented with the interactive board and audience participation throughout.

Overview

This guide is meant to serve as an introduction to gender affirming care concepts and medical management for adult patients, with the intention to provide a base level of understanding of concepts critical to inpatient and outpatient management. More specific information, including precise formulations and dosing of gender affirming hormone therapy (GAHT) as well as perioperative, surgical, and mental health management may be found in the resources at the end of this guide.

Children and adolescents represent a population with specific medical and ethical considerations which are beyond the scope of this guide; this module also assumes care based on medications approved within the USA. Gender affirming care is a rapidly evolving field, and staying up to date with the most recent state, national, and international guidelines as appropriate is strongly recommended: these guidelines may be found at the bottom of this workshop. Also note that these guidelines are meant to form a general scaffolding, and each decision should be made in a context and patient-centered context.

Although provider comfort with Gender Diverse Care topics is increasing, the vast majority of physicians have never received formal training in working with gender diverse individuals or unique considerations in their medical management[1]. Surveys of gender diverse individuals have demonstrated appropriate language is key to a trusting therapeutic relationship.[2] Thus, the first of goal of this workshop is to create a shared framework for language and concepts.

Terminology 

For each of the below terms, prompt the audience to offer up the definition, then click term to reveal examples. 

• • Gender identity – a personal sense of one’s own gender, which may include female, male, or other identities. Note that many gender identities exist throughout the world that do not correspond to traditional binary “male” or “female” gender stereotypes.
    • Gender diverse – individuals whose gender identity and/or expression is not congruent with traditional societal roles associated with maleness or femaleness, or different than their assigned sex at birth.
    • Cisgender – having a gender identity that traditionally aligns with sex assigned at birth.
    • Transgender – traditionally, used as an umbrella term for individuals whose gender identity does not align with their sex assigned at birth. Note that terms used may vary and terminology should follow patient preference. Common terms include “trans male” (tM) or “trans female” (tF), or simply “male” or “female” as congruent with gender identity. For clarity in medical record-keeping, many will use the terminology “assigned female, identifying male,” or “assigned male, identifying female,” etc.
    • Nonbinary –generally, individuals who identify with both, some qualities, or no qualities associated with either gender.
    • Genderfluid – generally, individuals whose gender identity and/or expression may change depending on context or time.
  • Gender expression – how gender identity may be translated into behavior or appearance (for example: dress, vocal patterns, body posturing and language).
  • Sex assigned at birth – typically refers to anatomy at birth. Individuals are typically assigned a sex at birth that is primarily based on external genitalia.
    • Assigned female at birth (AFAB) – patients born with biologically female organs (ovaries, uterus, cervix, vagina).
    • Assigned male at birth (AMAB) – patients born with biologically male organs (testes, penis, scrotum).
    • Difference of Sexual Development “DSD” (formerly Intersex) – patients who are born with a phenotype between male and female (often due to sex hormonal pathway differences), or are biologically discordant to genetic sex
  • Sexual orientation – relates to sexual attraction to a particular gender. Note that sexual orientation/behaviors should not be assumed based on sex or gender. Also note that romantic attraction may be different than emotional attraction.
  • Epidemiology – Estimating prevalence of transgender individuals is difficult due to stigma, difficulty capturing the entire spectrum of gender diversity, and because most population based surveys do not ask about gender identity. Within the millennial generation a Gallup poll estimates gender diverse individuals represents 1.0% of all millennials and 2% of generation Z[3]; The US Census Bureau estimates that 2.6 million Americans identify as transgender[4].

How to ask

Ask the audience how they would ask a patient their preference for each of the following term.  Click on the term to reveal an example phrase. 

• • Name: What name do you go by (it is important to recognize that many patients do not use their legal name. Referring to a patient by the legal name they do not use is called “deadnaming,” and this can trigger significant dysphoria)
  • Pronouns: What are your pronouns?
    • He/him/his
    • She/her/hers
    • They, them, theirs
    • Alternate pronouns may also be used (Ze, Zim, Zirs, etc.)
    • Note that patients may prefer more than one or a mixture of pronouns and some patients do not use pronouns and prefer their name to be used instead.
  • Gender identity: How would you describe your current gender identity?
  • Sex: What sex was assigned to you at birth? (What was marked on your birth certificate when you were born?)

**Mis-gendering or incorrectly ascribing identity, “Deadnaming”**

It is important to destigmatize the experience of incorrectly ascribing identity. Several studies have shown it is not the incorrect identification of a patient that is perceived as most harmful, but rather lack of recognition and willingness to change[5]. A model which is suggested is a three-part model in which a provider: 1. Articulates recognition of the incorrect assumption or language; 2. Apologizes for incorrect use; and 3. Uses correct terminology and expresses how they will respect that identity in the future.

Organ inventory

• • Organ inventory – a survey of present or absent anatomical structures in a mindful way to guide medical care
  • When should an organ inventory be performed?
    • When medically necessary; i.e. when necessary for gender affirming care, treatment of relevant organ systems, age-appropriate screening, or establishing primary care.
  • Patient centered language –gender diverse individuals may or may not identify with their anatomical sexual organs, which may be associated with various degrees of dysphoria. It is thus crucial to ask how a gender diverse patient refers to their own sexual organs. The following neutral terms are suggestions for use. As always, use the terminology the patient states they would like you to use. Some suggested terms include:
    • Options for sexual organs: gonads, pelvic organs, genitals
    • “Chest” instead of breasts
    • “Bleeding” instead of menses
  • Elements of an organ inventory – An organ inventory is guided by a patient’s sex assigned at birth. (Click on the relevant category to reveal the anatomical items below, which will also present on the mannequin)
    • Organs that may be present at birth or surgically constructed:
      • Breasts (reduction, implant, etc.)
      • Vagina
      • Penis (including native, constructed)
      • Urethra (history urethral surgery?)
    • Organs specific to assigned female at birth (AFAB) patients:
      • Uterus
      • Cervix
      • Ovaries
    • Organs specific to assigned male at birth (AMAB) patients:
      • Testes
      • Prostate

The formal evaluation of a patient for gender affirming therapy will likely take place in the primary care setting, sometimes with the assistance of specialists given provider confidence and unique patient needs (endocrinology, mental health, surgery, fertility specialists, etc.). However, it is crucial that all providers know general principles of evaluation so that patients with gender affirming care needs receive relevant treatment and receive referral to appropriate specialists.

• Step 1: Diagnosis gender dysphoria. (click “Diagnosis gender dysphoria” for relevant subheadings below).
  • Definition – Gender dysphoria as defined by both the World Professional Association for Transgender Health[1] and the DSM-5[2][3] consists of “A marked incongruence between one’s experienced/expressed gender and assigned gender, of at least six months’ duration, leading to clinically significant distress or impairment.” Both guidelines explicitly state that diversity of gender identity or gender incongruence are not pathological, however psychological and social conflict secondary to incongruence leads to distress seen in gender dysphoria. Both organizations agree that treatment of gender dysphoria is medically necessary (class A recommendation).[4]
  • Who can diagnose – Multiple bodies agree that a mental health professional does not need to be the provider to diagnose gender dysphoria. However, it may be helpful in cases of mental health complexity (below). Primary care providers are able to make the diagnosis of gender dysphoria.
  • Mental health considerations – As above, gender incongruence is not pathological. However, as transgender individuals often experience marked stigma, many individuals may have coexisting mental health disorders including mood disorders and trauma spectrum disorders such as PTSD. Note that the presence of a primary mental health condition is not a contraindication to gender affirming care, and treatment of gender dysphoria is associated with significant reduction in mood symptoms amongst gender dysphoric populations[5]. Other diagnoses that may present with patients seeking gender affirming care may include secondary gain, fetishism, etc. Should there be doubt, we recommend a referral to a mental health professional with experience in gender affirming care.

• Step 2: informed consent
  • Capacity—The patient should have full capacity as measured by standard capacity tools[6]; unique considerations for adolescents/minors may be found within transgender care guidelines[7].
  • Assessment for contraindications – The patient should be assessed for medical contraindications (see learning objective three).
  • Expectations, anticipated changes, and side effects – Expectations, changes, and side effects/risks should be discussed with the patient (see third learning objectives), including reversible and irreversible changes of GAHT and surgical management. Several resources exist to help guide this discussion[8].
  • Fertility preservation including gametocyte/embryo freezing and referral to relevant fertility specialists should be discussed with the patient prior to initiation, as GAHT has variable effects on gametogenesis and future fertility.

• Step 3: options for gender affirming treatment
  • Note that patients may wish to participate in all, some, or no gender affirming interventions, and that gender affirming care should be provided based on the order and context most appropriate for the patient. All of the following should be offered to/provided to the patient with gender incongruence if available:
    • Gender affirming hormone therapy – gender affirming hormones, which may be titrated to the patients’ desired effects (see learning objective three)
    • Gender affirming procedures/surgery – a number of surgical interventions which may address physical features of gender dysphoria, a list of which can be found in multiple resources[9]
    • Voice therapy – voice training (typically from SLP trained therapists), which consists of training in methods of speech most consistent with the patients’ gender identity
    • Mental health—patients will often benefit from mental health support which can assist with support in navigating societal stigma and discrimination, and treat any primary mental health diagnoses

• Step 4: Monitoring
  • • Role of medical home – as in primary care generally, continuity with the same provider is suggested
    • Medical monitoring – with visits at appropriately timed intervals, as outlined in objective three

Overview

Introduce the concept that these hormones should be titrated to achieve their desired effects balanced against their side effects.

 Ask learners the elements of masculinizing and feminizing therapies to reveal the below.  

• Feminizing therapies: Feminizing GAHT consists of an estrogen plus an anti-androgen. Note that anti-androgens vary in their use internationally; this talk will focus on the medical therapies available in the United States.
• Masculinizing therapies: bioidentical testosterone (this is the only necessary medication!)

Feminizing hormones

For each medication ask learners about the available formulations, principal effects, contraindications/side effects, and lab monitoring, then click on the medication icon to reveal the answers.

• •  Estradiol
    • Overview: It is a grade A recommendation to use bioidentical estrogen (17-estradiol, referred to here and in most contexts as “estradiol”)[1]; other hormones, for example equine estradiol have a greater risk of side effects and complicate laboratory interpretation.
      • Although there is minimal evidence to suggest that progesterone has efficacy in breast development, there is little evidence to suggest harm[2].

• • • Formulations: Oral, transdermal patch, IM/SQ injection. Transdermal patch and IM/SQ injection are currently preferred due to more stable concentrations within the serum. Note that the transdermal patch is preferred in patients with a history of DVT/PE because of lower association with DVT/PE[3]. Oral is usually least expensive in the USA.

• • • Principal effects: Breast development (typically to tanner stage 2-3), fat redistribution, reduction in body hair, arrests scalp hair loss, erectile dysfunction may occur

• • • Contraindications/side effects:
      • Contraindications: Hemodynamically significant DVT/PE is an absolute contraindication. Increased risk of VTE and migraine with aura are relative contraindications.  These risks should be discussed with the patient and weighed against the benefits of the therapy while addressing modifiable risks (e.g., smoking) whenever possible.
      • Side effects: Erectile dysfunction, libido suppression, weight gain, hyperprolactinemia (small risk, a few case reports)[4]

• • • Lab monitoring:
      • Total estradiol should be measured at three and six months, then yearly or whenever a dosage change occurs. According to Endocrine Society guidelines, the target range is 100-200 pg/mL.   It is reasonable to titrate estradiol levels up to patients’ desired secondary sex effects, while counseling on/monitoring for side effects, although titration beyond physiologic levels is not recommended.
      • Total testosterone should be measured at three months, six months, and then yearly/whenever dose change is maintained. Likewise, total testosterone levels are debated however the goal is for suppression into the female range for patient age.

• • Spironolactone
    • Overview: potassium sparing diuretic with anti-androgen effects.

• • • Formulations: Daily oral pill. This is often transitioned to twice daily once above 100 mg to decrease orthostasis.

• • • Principal effects: Reduction body hair, reduction secondary male sex characteristics, also some evidence for greater breast bud development, erectile dysfunction may occur

• • • Contraindications/side effects:
      • Contraindication: severe, sustained hyperkalemia
      • Side effects: orthostasis, polyuria, AKI

• • • Lab monitoring:
      • Lab monitoring (BMP) every 3 months, 6 months, and then yearly especially within patients with any conditions which may result in hyperkalemia

• • Five alpha-reductase inhibitors
    • Overview: including finasteride, dutasteride, etc.; blocks the peripheral conversion of testosterone to metabolites, reducing expression of secondary sex characteristics. Note that testosterone levels may be elevated in patients under treatment with five alpha reductase inhibitors because of mechanism of action.

• • • Principal effects: reduction male pattern baldness, peripheral secondary sex male hair

• • • Formulations: oral daily pill

• • • Side effects/contraindications:
      • Contraindication: none
      • Side effects: Orthostasis, low libido

• • • Lab monitoring:
      • No monitoring needed

• • GnRH agonists
    • Overview: including leuprolide, etc. Suppresses FSH/LH production within the pituitary, resulting in block of testosterone production in testes. In the USA, GnRH agonists are typically used to delay puberty in children and adolescents before decision is made to pursue GAHT. However, they are sometimes used within the context of gender affirming hormone care, usually with the assistance of an endocrinologist.

• • • Formulations: usually intramuscular injection, although surgical implementation of pellet is sometimes used.

• • • Principal effects: Repress secondary sex characteristics/puberty delay.

• • • Contraindications/side effects:
      • Contraindication: pituitary tumor, severe osteoporosis
      • Side effects: osteoporosis (causes severe osteoporosis if the patient is not supplemented with physiological levels of hormone), increased cardiovascular/CVA events. 

• • • Lab monitoring:
      • When used for gonadal suppression, testosterone/estrogen levels (testosterone should be near zero). FSH/LH may be used if investigating efficacy of GnRH agonist. 

Ask what timeline learners anticipate for the principal changes with feminizing GAHT and click the timeline button at the bottom.

Ask which changes are reversible and which are irreversible

• • • Reversible (generally): strength, body fat distribution, reduction facial hair growth
    • Irreversible (generally): breast development (usually max Tanner stage 2-3)

Masculinizing hormones (testosterone)

• •  Overview: Grade A recommendation to use bioidentical testosterone, instead of anabolic equivalents or metabolites[5], here “testosterone”.

• • Formulations:
    • Gel –may be transdermal patch, gel applied (usually on top of arm or in axial area)
    • SubQ/IM – Usually injected weekly or every other week. IM recommended against in individuals with likely long term (5+ years) use because of long term fibrosis/scarring

• • Principal effects:
    • Facial hair, virilizing vocal changes, increased muscle mass, increased body hair, clitoral growth, cessation menses

• • Contraindications, side effects:
    • Contraindications: sex hormone receptive cancer, pregnancy (due to teratogenic effects). Recommend beta HCG before starting therapy if possibility patient may be pregnant
    • Side effects: Erythrocytosis (with sequelae of severe erythrocytosis: end organ infarct, MI, CVA), polycythemia, acne, frontal/temporal hairline recession, +/- hyperlipidemia, +/-CV risk[6]
    • Note that culturally, testosterone/anabolic steroid use is associated with worsening of mood symptoms. However, there is significant evidence that testosterone supplementation does not worsen mood disorders when supplemented within physiological ranges, and instead lessens mood symptoms when gender dysphoria is present[7].

• • Lab monitoring:
    • Total testosterone, CBC at 3 months, 6 months, and then yearly, or when testosterone dose/formulations are changed.
    • There is currently no role for estradiol measurement, as estradiol levels vary widely in individuals assigned females at birth and have not been associated with testosterone efficacy[8]. Testosterone is usuallyenough to suppress estrogen levels.
    • Lipids, A1C should be performed in accordance with USPSTF guidelines for individuals assigned male at birth
    • Goal total testosterone level depends on local lab. Goal trough level between 400-700 ng/dL. It is reasonable to titrate hormone therapy upwards to a patients’ desired secondary sex effects with close monitoring of CBC and counseling on risks. There is currently no consensus on timeline/appropriate levels for free testosterone levels.

Ask what timeline learners anticipate for the principal changes with feminizing GAHT and click the timeline button at the bottom.

Ask which changes are reversible and which are irreversible.

• • • Reversible (generally): acne/skin oil production, strength/body fat distribution, facial hair growth, cessation of menses
    • Irreversible (generally): vocal tone deepening, clitoromegaly

Each of the below describe clinically important or common situations/considerations in gender affirming medical care for the adult practitioner regardless of specialty. Click each picture to reveal considerations below. Note that the below information includes general recommendations and each situation should be addressed in its unique medical and social context.

• DVT/PE in a patient on estradiol GAHT – GAHT has been shown to significantly reduce mood symptoms, gender dysphoria, and risk of death through suicide, and every effort should be made to maintain feminizing therapies[1]. However, risk of clot progression/medical consequences must be weighed in a risk-benefit discussion with the patient. In general, guidelines suggest continuation of estradiol therapy in a patient with a non-hemodynamically significant DVT/PE[2]. Anticoagulation may be considered in this case; there is currently no evidence for antiplatelet therapy. Professional associations also recommend a transition to transdermal estrogen patch as this formulation is associated with fewer DVT/PE events, likely due to less pharmacokinetic variability[3].
• Cardiovascular disease risk – Discussion about cardiovascular disease risk in those receiving gender affirming hormones is still largely unclear because of a paucity of data within the gender affirming care context specifically. However, the largest study of American patients (STRONG study, retrospective cohort study performed through the Kaiser Permanente database and published in 2017) demonstrated very minimal absolute risk increase in, MI, PAD, or unstable angina amongst populations that received either feminizing or masculinizing GAHT[4]. There was also minimal elevation of DVT/PE incidence amongst both groups, although large cohort studies of estrogen therapy (in postmenopausal women) have demonstrated both increased DVT and cardiovascular event risk. Current consensus is this that there is perhaps a mildly elevated cardiovascular risk profile of GAHT with respect to peers who have not undergone GAHT, however at this time this elevated cardiovascular risk profile is not enough to change USPTF screening guidelines or discourage GAHT within those with diagnosed gender dysphoria[5].
• Management of testosterone therapy in a patient with polycythemia – similar to the above, risks should be weighed given the patient’s individual context and values. Hct >50 is associated with significant risk including end organ infarct; in this setting, smoking cessation, weight loss, treatment of underlying respiratory disease, and therapeutic phlebotomy may be entertained. It is important to also look for secondary causes of polycythemia.
• Periprocedural hormone use – although there is not yet expert consensus, studies suggest it is safe to continue hormones in the peri-operative period. There is no evidence to hold testosterone therapies, and the general recommendation is to continue estrogen therapies in the absence of specific risk factors (smoking, malignancy, personal/family history of DVT)[6].
• Cancer screening – Perform cancer screening on any organs present as normally would be performed on patients of that sex.
• Cost of GAHT/access – access to gender affirming care is a major health equity issue, especially as individuals who identify as gender diverse are often disadvantaged socioeconomically. State Medicaid coverage of GAHT varies quite widely, although surgical procedures are typically self-pay. Medicare officially covers gender affirming care if offered to cisgender patients. Check local support resources, as financial or social support groups often exist for patient receiving gender affirming care.

Case one

A 24-year-old assigned female at birth (AFAB) who has been on masculinizing therapy for 6 months presents to the hospital for 2 months of generalized fatigue as well as two weeks of fevers, chills, and dysuria.

• Role play an initial interaction with this patient using appropriate terminology.

An appropriate role play will contain: 1. asking name, pronouns 2. asking about gender, gender identity, and sex in a patient-centered way; see objective 1.

• Evaluate whether an organ inventory is appropriate in this case, and if so how to perform one.

Yes, a focused organ inventory is appropriate. Correct organ inventory should include: 1. Asking about patient preference in referring to organs; 2.  Using neutral language when appropriate; 3. Assessing for the presence of relevant organs, which in this case is suggested to include vagina, uterus, penis (constructed), urethra (history of surgery).

• Create a list of expected anatomic and physiological changes at six months.

Changes at six months of masculinizing therapy likely include: increased production of skin oil/acne; vocal deepening; menstrual interruption; possible increase in strength and male secondary sex body hair. We also suggest a discussion about fertility (I.e. the patient could still become pregnant) and sexual history (recent male/female partners, protection).

• Demonstrate which medications may be used to provide gender affirming hormone therapy to this patient, and what laboratory levels may be appropriate at this time.

Testosterone (bioidentical). We suggest a CBC to check for polycythemia (no clear role for testosterone level based on presenting symptoms).

• Discuss whether gender affirming medication should be held during this hospitalization.

There is no evidence to stop testosterone while this patient is hospitalized unless clear signs/symptoms of polycythemia.

• The patient has a question about whether they still need cancer screening. Explain to the patient how hormone therapy effects age-appropriate cancer screening guidelines.

The patient should receive cancer screening based on USPTF guidelines for any relevant organs (in this patient, PAP smear every three years age 21-65 or screening with cytology/HPV every 5 years if negative). Note that patients trans male patients often experience dysphoria surrounding cervical cancer screening.

Case two

A 38-year-old individual presents to outpatient clinic to discuss initiation of feminizing hormones. Their sex assigned at birth is male.

• Role-play an initial interaction with this patient using appropriate terminology.

An appropriate role play will contain: 1. asking name, pronouns 2. asking about gender, gender identity, and sex in a patient-centered way.

• Discuss considerations when evaluating a patient for start on gender affirming hormone therapy or gender affirming surgery.

Considerations include: 1. Diagnosis gender dysphoria (see objective two) 2. Capacity, evaluating for contraindications, expectations/goals/side effects, and fertility counseling.

• Explain to the patient which medications are available for feminizing hormone therapy and the timeline of anticipated changes.

Feminizing hormone therapy consists of a bioidentical estrogen plus one or more anti-androgens (spironolactone, alpha-reductase inhibitors, and rarely in adults GnRH agonists). Although changes are variable, a patient can expect to see decrease in strength, body fat redistribution, breast bud development, and often erectile dysfunction at three months; male secondary sex hair often decreases at about six months.

• Create a list of possible side effects for the patient and how these side effects may present clinically.

For patients on estrogen, DVT/PE may present as typically unilateral swelling/cord or as sudden shortness of breath/elevated heart rate/chest pain. The principal side effects of spironolactone are increased potassium (typically asymptomatic unless extreme), increased urination, and sometimes orthostasis. Alpha reductase inhibitors rarely cause orthostasis and sometimes cause decrease in libido. All medications can cause erectile dysfunction.

• Counsel the patient on whether feminizing hormones have long term impacts on cardiovascular or bone health.

See the STRONG study above. In general, we do not have good data on long term impact of feminizing hormones on cardiovascular or bone health, although current studies do not demonstrate a significant impact when either feminizing or masculinizing hormones are used in physiologic ranges. They do, however, in large studies that are not focused on the transgender population specifically demonstrate slightly increased risk of DVT/PE.

Case three

Rain is a 35 yo trans female (tF) non-binary person (they/them) on estrogen therapy presents with leg pain and swelling. On ultrasound they are found to have a deep vein thrombosis (DVT) DVT extending through the right popliteal and femoral veins.

• Discuss the benefits and risks of stopping hormone therapy to this patient.

Benefits and risks should be discussed in a patient-centered way. Note that the principal risk of continuing estrogen in this patient is extension of the DVT or conversion into a PE, which may be life threatening. However, psychological and medical risks of stopping gender affirming hormone therapy may also be profound, see objective four.

• Create a plan for moving forward if the patient chooses to continue gender affirming hormone therapy (GAHT).

The backbone of therapy for a patient with DVT on estrogen is treatment-dose anticoagulation. It is suggested to begin treatment anticoagulation with strict return precautions.