Gender-diverse individuals may identify in different ways, such as transgender, nonbinary, genderqueer, gender fluid, gender creative, gender independent, or noncisgender. See Terms Related to Gender-Affirming Care below for more terms and brief definitions.

A thoughtful history and examination during the initial patient encounter help the clinician understand their patient’s gender journey. This includes:

• Social transition: Where is the patient with regard to social transition? Are they using gender-affirming pronouns? Are they using their desired name? Is physical presentation congruent with desired expression? Do their family and friends also use their desired names and pronouns?
• Psychosocial support: Do they feel supported by their loved ones? Who are their sources of support? Are they involved with community support groups? Do they have family/friends who can provide support through a social/medical transition?
• Mental health therapy: Is the patient seeing anyone for gender-focused therapy? Would this therapist provide a letter of support to help facilitate a medical transition?

In addition, it is important to ask questions about the patient’s desire to transition in order to document gender dysphoria and ascertain their goals:

• How many years has gender dysphoria been present?
• Can the patient describe their attitudes about pubertal changes?
• What are the patient’s feelings about their birth-assigned sex?
• Does the patient desire hormones, surgery, both, neither?

A physical exam does not have to be performed at the initial encounter but should be performed before initiating puberty blockers or gender-affirming hormones. The physical exam may be especially distressing; providers should use a gender-affirming approach. It is often useful to introduce the need for a physical examination during the initial encounter to help the patient prepare. It can also help to ask the patient when they prefer to do the exam (e.g., beginning or end of the appointment). The physical examination should be relevant to the anatomy that is present, regardless of gender presentation and without assumptions as to anatomy or identity. Specifically for the genitalia examination, discuss the examination beforehand. Avoid using medical terms for body parts unless discussed beforehand. Make sure the patient has support in the room if they would like, as well as a medical chaperone for the physician or medical provider completing the exam to help protect and enhance the patient’s comfort, safety, privacy, security, and/or dignity during sensitive examinations or procedures.

Transgender and gender-diverse are personal identities, not a diagnosis. In contrast, gender dysphoria is diagnosed. Gender dysphoria had been defined as a mental health disorder in DSM-5; however, global medicine no longer identifies gender dysphoria as a mental health disorder. [Coleman: 2022] [American: 2013]
In children, a gender dysphoria diagnosis involves at least 6 of the following and an associated significant distress or impairment in function, lasting at least 6 months.

1. A strong desire to be of the other gender or an insistence that one is the other gender
2. A strong preference for wearing clothes typical of the opposite gender
3. A strong preference for gender-affirming roles in make-believe play or fantasy play
4. A strong preference for the toys, games, or activities stereotypically engaged in by the other gender
5. A strong preference for playmates of the other gender
6. A strong rejection of toys, games, and activities typical of one's assigned gender
7. A strong dislike of one's sexual anatomy
8. A strong desire for the physical sex characteristics that match one's experienced gender

For adolescents and adults, a gender dysphoria diagnosis involves a difference between one's experienced/expressed gender and assigned gender, significant distress or problems with daily functioning such as occupational or social functioning, and gender dysphoria lasting at least 6 months and shown by at least 2 of the following:

1. A marked incongruence between one's experienced/expressed gender and primary and/or secondary sex characteristics
2. A strong desire to be rid of one's primary and/or secondary sex characteristics because of a marked incongruence with one’s personal or expressed gender (or in young adolescents, a desire to prevent the development of the anticipated secondary sex characteristics)
3. A strong desire for the primary and/or secondary sex characteristics of the other gender
4. A strong desire to be of the other gender (or some alternative gender different from one’s designated gender)
5. A strong desire to be treated as the other gender
6. A strong conviction that one has the typical feelings and reactions of the other gender

Children who meet criteria for gender dysphoria may or may not continue to experience it into adolescence and adulthood. Some research shows that children who had more intense symptoms and distress, who were more persistent, insistent, and consistent in their gender-affirming statements and behaviors, and who used more declarative statements, such as "I am a boy (or girl)" rather than "I want to be a boy (or girl)," were more likely to become transgender adults. [Steensma: 2013] Many individuals who express gender incongruence during childhood may eventually identify as having a diverse sexual identity (gay, lesbian, bisexual) rather than a diverse gender identity. Families should be encouraged to allow their children to explore these components of their identity.

Surveillance for a gender nonconforming identity, gender dysphoria, and related issues can be accomplished with a detailed social history, including a thorough HEEADSSS assessment.

• HEEADSSS Assessment Guide (USU) ( 1017 KB) provides examples of open-ended questions about home, environment, education, and employment; eating; peer-related activities; drugs; sexuality; suicide/depression; and safety from injury and violence.

Use open-ended questions:

• "Hi, my name is Dr. Smith, and I prefer she/her/hers pronouns. What name would you prefer to be called?”
• “What are your pronouns?”

Screening questions for gender dysphoria:

• "Do you feel you are a different gender from how others have thought of you since you were born?”
• “If you were to use a bathroom at school or in public, would you use the women’s, men’s, or gender-neutral bathroom?”
• “Do you feel this is in line with your gender identity?”
• “Are there any parts of your body that make you unhappy or that you wish you did not have?”
• “Have you thought about your body having certain characteristics or traits of another gender?”
• “Have you ever tried on clothes from the opposite gender and felt less discomfort with your body?”

Questions to help understand existing gender dysphoria:

• “What about your body bothers you the most? The least?”
• “How do you feel when others do not perceive you as the gender you identify with the most?”

While not necessary for identifying gender-diverse behavior or gender dysphoria, screening and obtaining a social history of the family can provide clues to the family dynamic and information related to mental health disorders.

The development of gender identity is poorly understood and can be influenced by the central nervous system, genes, hormones and hormone receptors, and environmental factors. Ongoing research and studies have revealed that some genes are more prevalent in individuals experiencing gender dysphoria; however, no direct correlation has been proven yet.

Although data on the prevalence of transgender and gender-diverse people are limited, current data suggests about 1.2 - 2.7 % of young adults are transgender, and about 2.5 - 8.4 % are gender-diverse. [Coleman: 2022] [Eisenberg: 2017] [Kidd: 2021] More and more children and adolescents are presenting to gender clinics each year, whether that be due to more societal acceptance or more access. The etiology behind this new phenomenon is unclear. [Coleman: 2022]

There are several associated conditions and other adversities that clinicians should be aware of while caring for individuals who are transgender and gender-diverse.

Autism
There has been a described co-occurrence of gender identity disorder in patients with autism spectrum disorder. Clinicians should be aware of this potential co-occurrence and the challenges it creates for clinical management. [de: 2010] For screening and management information, see Autism Screening and Autism Spectrum Disorder.

Child abuse and toxic stress in the family
If family dynamics are not supportive of a child who is gender diverse, that child is at increased risk for child abuse and exposure to trauma or increased stress at home. SEEK Parent Screening Questionnaire (PSQ-R) is a free parent questionnaire with scoring instructions that screens for child maltreatment and toxic stress using 15 yes/no questions. Toxic Stress Screening may also be helpful.
Disordered weight management
Transgender youth report more unsafe weight management behaviors than cisgender youth. These behaviors include fasting for more than 24 hours, diet pill use, and laxative abuse. [Guss: 2017] Additionally, transgender men have an increased risk of developing midline fat distribution after starting androgen therapy. See Screening for Eating Disorders and refer to Dieticians and Nutritionists (see NW providers [1]) if there are concerns.
Human immunodeficiency virus (HIV)/sexually transmitted infection (STI)
Transgender youth are at increased risk of acquiring HIV and other sexually transmitted infections. HIV and STIs disproportionately affect transgender women when compared to transgender men. [Rosenthal: 2014]
Homelessness/unemployment/education
In 2015, the U.S. Transgender Survey examined the experiences of 27,715 transgender persons; 30% of the respondents reported experiencing homelessness during their lifetime, and 12% reported homelessness in the year before completing the survey. Additionally, up to 32% of youth identified leaving school due to mistreatment. Unemployment rates were double the weighted national average. [James: 2016]
Homicide and violence
In 2011, youth who identified as transgender or gender diverse reported rates of harassment (78%), physical assault (35%), and sexual violence (12%) while attending K-12 education. [James: 2016] In the United States, homicide rates of transfeminine black and Latina individuals were higher than that of cisgender counterparts. [James: 2016]
Substance abuse/tobacco use
Transgender youth are 3 times more likely to use substances than their non-transgender peers. [Day: 2017] For screening and management information, see Substance Use Disorders.
Suicide
Rates of suicide, suicide attempts, and suicidal thoughts are elevated compared to the general population. Among adolescents (11-19 years), 51% of transmales, 30% of transfemales, 42% of non-binary, and 28% of those questioning their gender identity attempted suicide in the past year before completing the Profiles of Student Life, Attitudes and Behaviors Survey. Among non-transgender adolescents who completed the survey, 18% of females and 10% of males had attempted suicide in the past year. [Toomey: 2018] Family support and school safety are major protective factors. [Adelson: 2012] Suicide-Screening Questions (ASQ) is a free, 5-question screening tool with scoring instructions. When the ASQ is positive, a follow-up assessment is necessary, and then decide if inpatient care or an outpatient safety plan will be adequate. See Suicidality & Self-Harm.
Major depression
Individuals who identify as transgender have an increased risk of having major depression requiring medical intervention. [Wylie: 2016] For screening and management information, see Depression.

The following definitions are from the WPATH Standards of Care [Coleman: 2022] and American Academy of Pediatrics [Rafferty: 2018]. Evolving vocabularies individuals use to describe themselves can be found at List of LGBTQ+ Definitions (itspronouncedmetrosexual.com) and Glossary of Terms – Transgender (GLADD). These brief definitions may help but do not truly capture the nuances of this evolving field. New guidelines from the World Professional Association for Transgender Health 8th version shy away from specific terminology and highlight the importance of using culturally appropriate and inclusive language with our transgender and gender-diverse population.

Affirmed gender: When a person’s true gender identity, or concern about their gender identity, is communicated and validated by others as authentic

Agender: Does not identify as having a particular gender

Cisgender: Identifies and expresses a gender within the culturally defined norms of the sex they were assigned at birth
Gender: A psychological status that denotes attitudes, feelings, and behaviors within a given culture that are associated with being male or female
Gender binary: A cultural construct that ascribes to the belief that there are only 2 genders, and these match the sexes male and female

Gender-diverse: Gender behaviors, appearances, or identities incongruent with those culturally assigned to their birth sex; gender-diverse individuals may refer to themselves with many different terms, such as transgender, nonbinary, genderqueer,7 gender fluid, gender creative, gender independent, or non-cisgender. “Gender diverse” acknowledges and includes the vast diversity of gender identities. It replaces the former term, “gender nonconforming,” which has a negative and exclusionary connotation.
Gender dysphoria: Distress that is caused by a discrepancy between a person’s gender identity and the sex assigned at birth or a clinical symptom that is characterized by a sense of alienation to some or all of the physical characteristics or social roles of one’s assigned gender

Gender identity: A person’s deep internal sense of being female, male, a combination of both, somewhere in between, or neither, resulting from a multifaceted interaction of biological traits, environmental factors, self-understanding, and cultural expectations
Genderqueer: An identity used by individuals whose gender identity does not conform to a binary understanding of gender
Gender non-binary: A gender that is neither solely male nor female - gender in varying degrees, fluid, or a gender unattached to the poles of male and female

Gender perception: The way others interpret a person’s gender expression
Intersex: Atypical, congenital variations in the reproductive tract, “genital ambiguity”
Sex: A biological status categorized as male, female, or intersex, as indicated by factors that include chromosomes, gonads, internal reproductive organs, and external genitalia

Sexual orientation: A person’s sexual identity in relation to the gender(s) to which they are attracted; sexual orientation and gender identity develop separately.

Transgender: A diverse group of individuals who cross or transcend culturally defined categories of gender - their gender identity differs to varying degrees from the sex they were assigned at birth
Transition: The period when individuals change from the gender role associated with their sex assigned at birth to a different gender role. For many people, this involves learning how to live socially in “the other” gender role; for others, this means finding a gender role and expression most comfortable for them. Transition may or may not include feminization or masculinization of the body through hormones.

Patients and families often have concerns about the use of gender-affirming hormones, steps for transitioning, gender-affirming surgery, and restroom use. Parents may have additional concerns about identifying resources, child safety at school, and mental health. [Lawlis: 2017] The medical home should help with these questions and/or direct the patient and family to appropriate resources. See Transgender and Gender-Diverse Youth (FAQ), Services & Other Resources (below), and Sample Letter for Transgender Student Bathroom Access (Medical Home Portal) ( 138 KB). Primary care clinicians may need to provide documentation to promote a gender change on government-issued documentation (driver's license, passport, etc.). [Schuster: 2016]

Feminizing/masculinizing hormone therapy—the administration of exogenous endocrine agents to induce feminizing or masculinizing changes—is a medically necessary intervention for many transgender and gender-nonconforming individuals with gender dysphoria. [Coleman: 2022] In some cases, the primary care clinician may be the same person who prescribes gender-affirming hormones, monitors labs and the response to treatment. However, this role is generally performed by specialists in adolescent medicine, transgender care, or an endocrinologist. The primary care clinician provides ongoing support and helps monitor the individual and their family from a holistic perspective.

Ongoing assessment should include:

• Record height and weight, BMI, and BMI percentile for desired gender and age. Monitor these parameters regularly in patients undergoing pubertal suppression and hormone therapy. Switching to a gender-appropriate growth chart can be helpful once the initiation of gender-affirming hormones begins. While there is no consensus on when switching growth charts is appropriate, many providers will compare affirmed growth charts to natal growth charts after a year of gender-affirming hormones.

• Note changes in affect, weight, fitness, changes in muscle mass, fat distribution, grooming, skincare, and body habitus, which may each reflect the healthiness of habits and adaptation. Be aware that those undergoing androgen therapy as testosterone can experience weight gain and increased visceral fat.
• Examine skin for body hair distribution, acne, androgenic alopecia, acanthosis nigricans, facial hair, and hair loss. Examine breast for pubertal staging in assigned females and evidence of gynecomastia in transgender women taking estrogen. Transgender men may often use a chest binding device under their clothes to conceal breast tissue. You may need to ask the patient to remove their chest binding since binding can lead to skin breakdown and infection. Additionally, breast cancer screening guidelines should be followed for those receiving estrogen.

Primary care clinicians may need to provide letters of medical necessity to insurance companies for appropriate interventions. [Schuster: 2016]

The following information is intended for prescribers of gender-affirming hormones, as some primary care clinicians will be in this role. During the first year of starting an individual on gender-affirming hormones, clinical assessments should be performed at least every three months [Coleman: 2022]. All primary care providers should be familiar with medications, side effects, and suggested monitoring with gender-affirming hormonal treatment. [Coleman: 2022]

Before prescribing hormones, be sure to perform an evaluation that includes a discussion of a patient's physical transition goals, health history, risk assessment, and relevant laboratory tests.

• History of a blood clot or venous thromboembolism
• Hypertension
• Diabetes (type 2)
• Obesity and weight trends
• History of smoking and other substance use
• History of breast, cervical, or prostate cancer

Family conditions that may confer increased risk for the adolescent or young adult taking hormone therapy include obesity, heart disease, and osteoporosis.

Be aware of the existing criteria specifically for children or adolescents who are wanting initiation for hormonal therapy:

1. The adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed).
2. Gender dysphoria emerged or worsened with the onset of puberty.
3. Any coexisting psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment.
4. The adolescent has given informed consent, and, particularly when the adolescent has not reached the age of medical consent, the parents or other caretakers or guardians have consented to the treatment and are involved in supporting the adolescent throughout the treatment process. [Coleman: 2022]

Treatment goals, possible outcomes, and realistic expectations should be discussed with each patient, and hormone therapy must be individualized based on each patient’s goals. Most physical changes, whether feminizing or masculinizing, occur over 2 years. The amount of physical change and the exact timeline of effects can be highly variable. The following table may be helpful:

• Expected time course of physical changes in response to gender-affirming hormone therapy WPATH Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 Appendix C

Laboratory testing is usually performed every 6 months while initiating hormone therapy; then annually once secondary sex characteristics are achieved: [Hembree: 2017]

• Total testosterone, free testosterone, estradiol for patients undergoing gender-affirming hormone therapy
• Comprehensive metabolic panel (CMP) to evaluate liver enzymes while on hormone therapy and potassium if being treated with spironolactone
• Complete blood count (CBC) to evaluate for polycythemia while on testosterone therapy
• Lipid panel to evaluate for hyperlipidemia while on hormone therapy
• Vitamin D to evaluate need for supplementation to reduce potential risk of developing osteoporosis while taking puberty blockers
• Follicle-stimulating hormone/luteinizing hormone (FSH/LH) in prepubertal and early patients being treated with sex hormone suppression therapy, such as gonadotropin-releasing hormone (GnRH) agonists (leuprolide acetate, histrelin, etc.). Monitoring estrone to estradiol ratio is not supported by current published evidence.

A bone age may be useful in determining pubertal development prior to initiating sex hormone suppression. A bone densitometry (DEXA) scan may help determine bone mineral density in individuals who have been receiving puberty blockers for more than 1 year. In adolescents who have completed puberty, starting gender-affirming hormonal treatment will not affect height since epiphyseal plates have fused and bone maturation has completed. Discontinuing hormonal therapy may result in bone loss in transgender and gender-diverse patients and will definitely result in loss if gonads have been removed. [Wiepjes: 2020]

The following provides guidance for prescribers of feminizing/masculinizing medications:

• WPATH Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 Appendix C

Suppressing Puberty

Gonadotropin-releasing hormone (GnRH) agonist delay the development of secondary sexual characteristics. Puberty blockers can be started in patients at sexual maturity rating 2 to 3. This includes agents like leuprolide acetate (Lupron Depot intramuscular injection every 3 months, Eligard subcutaneous injection every 4 months) and Vantas (a subcutaneous implantable rod effective for 12 months). Puberty blockers are 100% reversible. Adolescent physicians often prescribe these medications as they can suppress menstruation, hair, muscular definition, voice changes, etc., which can be very distressing for those who already feel uncomfortable in their physical appearance and body. Consider referral to an endocrinologist or specialized adolescent medicine provider for assistance in treatment and monitoring.

Suppressing puberty will prevent any permanent unwanted changes from occurring. For example, a transgender boy who begins puberty blockers at tanner stage 2 will likely never need chest masculinizing surgery later on in his life. Blocking puberty at tanner stage 2 in a transgender girl will prevent her voice from virilizing/becoming deeper. Suppressing puberty for children and adolescents with gender dysphoria has been shown to have positive outcomes for their lives. Transgender youth demonstrate lower psychological functioning compared to their cisgender peers given the distress and euphoria they experience. However, when they undergo puberty suppression, they demonstrate better functioning than their peers. [Grannis: 2021] [van: 2020]

Puberty blockers are 100% reversible.

Therapy for Transgender Females

Gender-affirming hormone therapy is appropriate for patients who have progressed through puberty (or who have been on puberty blockers for at least 1 year), demonstrated gender dysphoria, and wish to express physical attributes congruent with their identified gender. Starting hormone therapy requires a letter of support from a mental health provider who has identified that the patient's gender dysphoria is causing extreme distress and that the hormone therapy may help lessen this distress.

Hormone regimens for transgender MtF include various derivatives and vehicles of estrogen. The goal of estrogen therapy is to achieve estradiol levels within the physiologic range for an assigned female. Estrogen can be delivered as daily oral estradiol or through an estradiol patch (transdermal delivery) that is replaced every 3-5 days. Parenteral preparations of estrogen are available as estradiol valerate or cypionate. Doses for these preparations vary based on weekly or bi-monthly dosing. Estrogen therapy is often insufficient to suppress testosterone levels, and anti-androgens, GnRH agonists, and spironolactone (100-400mg/day) are often used. [Coleman: 2022] More information about side effects will be found in the relevant systems below.

Therapy for Transgender Males

Hormone regimens for transgender FtM include various derivatives and vehicles of testosterone. Traditionally, parenteral testosterone enanthate or cypionate is used. Dosing varies based on the use of intramuscular or subcutaneous injections. Transdermal preparations of testosterone include testosterone gel or transdermal patch. The goal of testosterone therapy is to achieve physiologic testosterone levels for an assigned male. [Coleman: 2022] More information about side effects will be found in the relevant systems below.

Testosterone is not an adequate form of birth control. For transgender men, counseling regarding effective forms of contraception is important, especially since testosterone can have teratogenic effects on a developing fetus. For many, using a long-acting reversible contraception (LARC) device, such as Nexplanon or other progesterone forms of birth control, is appropriate.

Therapy Costs

Puberty blockers are costly, and many insurance programs do not cover these medications. Injectable GnRH analogs can be administered every 3-6 months and their cost can range from $2,000 to 8,000. The implantable rod, Supprelin, can cost around $54,000.

Intramuscular testosterone generally costs about $40 for a 90-day supply. Estrogen is available in different modalities (oral, injectable, patch), but a 3-month supply can cost anywhere from $10 to $30. While many insurance companies are starting to cover medications for transgender and gender-diverse individuals, supporting documents from a physician may be necessary.

The primary care clinician should collaborate with specialists as needed to address the patient’s concerns and desired outcomes. Some suggested topics include:

• Discuss unwanted/wanted effects of puberty (e.g., menses, spotting, erections)
• Discuss sexual orientation, history of sexual encounters, and use of contraception. It is important to stress the need for use of contraception in adolescents who are thinking of potentially becoming sexually active. Understanding the patient's sexual history can help guide the need to screen for sexually transmitted infections and high-risk sexual behavior.
• Discuss future childbearing/rearing (fertility). Patients undergoing hormone therapy should be counseled about reproductive options prior to the initiation of gender-affirming therapy. This includes harvesting and freezing of eggs and sperm. Patients should be referred to a reproductive endocrinology clinic to discuss the options, processes, and costs if future fertility is desired.

Examination tips:

• An understanding of the patient's sexual maturity can help guide the use of puberty-blocking agents and the use of gender-affirming pharmacologic therapy.
• Examine for any evidence of genital lesions or vaginal discharge, which may be associated with a sexually transmitted infection.
• Transgender and gender-diverse youth often disguise their anatomy to promote a more affirming self-image. A transgender boy may use a binder to make breast tissue less obvious, which can lead to rashes, discomfort, or tissue damage. Prosthetic devices known as "packers" are often used to resemble male genitalia. These devices may also allow a transgender boy to urinate while standing. Transgender girls may go to extremes to hide male genitalia, including "tucking" the penis between one's thighs as well as displacing the testicles into the inguinal canal. Evaluating for hernia or areas of skin breakdown around the testicles is also important if the patient has tried to tuck their testicles.

Primary care clinicians should be aware of the following cardiovascular risks of gender-affirming hormone therapies:

For patients undergoing feminizing hormone therapy:

• Estrogen use has been shown to increase the risk of venous thromboembolic events. This risk may be amplified in smokers, obese individuals, and those with known thrombophilia disorders.
• Estrogen use increases the risk of cardiovascular events in patients older than 50 with known cardiovascular risk factors. Oral estrogen has been shown to increase triglycerides and increase LDL cholesterol.
  • The risk for venous thromboembolic events and cardiovascular events is increased with the additional use of third-generation progestins.
  • The use of transdermal estrogen does not have as much impact on lipid profiles as oral estrogen.
• Estrogen use can increase blood pressure; however, the long-term clinical significance of this is unknown.
• Spironolactone is used as an androgen-blocking agent and may be useful for patients who are hypertensive. It can increase thirst in patients.

For patients undergoing masculinizing hormone therapy:

• Testosterone decreases HDL cholesterol and has varying effects on LDL and triglycerides. High levels of testosterone outside the normal male range have been associated with poor lipid profiles.
• Testosterone may increase the risk of cardiovascular disease in patients with underlying risk factors.
• Individuals with risk factors such as a family history of hypertension or who have polycystic ovarian syndrome may be at increased risk of hypertension.

Primary care management tips:

• Check blood pressure and heart rate. Monitor for hypertension in patients taking gender-affirming hormone therapy.
• It may be beneficial to get a baseline electrocardiogram and electrolytes in patients taking QT/QTc prolonging medications. The use of GnRH agonists in adult men with prostate cancer has been associated with prolonged QT/QTc interval. There is no existing data for adolescents and young adults. Take special care in patients taking QT/QTc prolonging medications such as antidepressants, antiepileptics, opioids, and anticholinergic medications.
• Ensure routine labs are followed with the specialist or in the medical home.

For patients undergoing masculinizing hormone therapy (FtM), therapy involving testosterone or other androgenic steroids increases the risk of polycythemia. Very little is known about cancer risks and protective factors.

For patients undergoing feminizing hormone therapy:

• Estrogen therapy may increase the risk of developing type 2 diabetes, especially among patients with a known family history of type 2 diabetes or metabolic syndrome.
• Estrogen use increases risk of developing hyperprolactinemia during the first year of treatment.
• High-dose estrogen therapy can enhance clinical features of a preexisting prolactinoma that were previously not clinically evident.

For patients undergoing masculinizing hormone therapy:

• Individuals with risk factors such as obesity, family history, or polycystic ovarian syndrome may be at increased risk of type 2 diabetes.
• Individuals can still ovulate for 1 to 5 cycles after initiating testosterone therapy. [Taub: 2020]

Surgery is a broad topic that is evolving rapidly and exceeds the scope of this module. Of note, many transgender individuals will express different surgical needs, and many institutions require the patient to be at least 18 years of age prior to undergoing any surgical intervention. It is recommended that patients give gender-affirming hormonal therapy at least six months to achieve the desired surgical result unless hormone therapy is not desired or medically contraindicated. [Coleman: 2011]

A current literature review when considering referring or advising patients related to gender-affirming surgery is encouraged.

• PubMed search for articles about male-to-female gender affirming surgery published within the last year
• PubMed search for articles about female-to-male gender affirming surgery published within the last year

For transgender women, surgical procedures may include:

• Breast/chest surgery: augmentation mammoplasty (implants/lipofilling)
• Genital surgery: penectomy, orchiectomy, vaginoplasty, clitoroplasty, vulvoplasty
• Non-genital, non-breast surgical interventions: facial feminization surgery, liposuction, lipofilling, voice surgery, thyroid cartilage reduction, gluteal augmentation, hair removal

For transgender men, surgical procedures may include:

• Breast/chest surgery: subcutaneous mastectomy, creation of a male chest (wider areolae/nipple position). Many centers will consider chest masculinization surgery prior to age 18 years.
• Genital surgery: hysterectomy/oophorectomy, reconstruction of the fixed part of the urethra to extend urethra, which can be combined with a metoidioplasty or with a phalloplasty (employing a pedicled or free vascularized flap), vaginectomy, scrotoplasty, and implantation of erection and/or testicular prostheses
• Non-genital, non-breast surgical interventions: voice surgery (rare), liposuction, lipofilling, pectoral implants, and various aesthetic procedures

Not all transgender individuals will express the same surgical needs. Hormonal therapy is not needed or required for an individual to undergo any of these procedures. Depending on the surgery, it is recommended to be on hormonal replacement therapy to prevent adverse effects on the cardiovascular and musculoskeletal systems. [Hembree: 2017] [Richards: 2016] For additional information, the WPATH Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 summarized surgical interventions on pages S128 - S136 as well as in their Appendix (Appendix D, Appendix E).

The primary care clinician may be the first medical provider to identify a mood disorder, suicidal ideation, findings of self-harm, substance abuse, and post-traumatic stress. Look for signs of cutting on arms and thighs. Monitor for school bullying, child abuse, school failure, eating disorders, and mood or anxiety disorders that can occur in youth with gender dysphoria or during and after the transition process. Assess for enamel erosion or parotid hypertrophy, which may be evidence of purging behavior. Masculinizing hormone therapy may increase risk of hypomanic, manic, or psychotic symptoms in patients with related psychiatric disorders. There appears to be a direct association with supraphysiologic blood levels of testosterone. Hormones also can exacerbate mood swings and irritability.

If a comorbid mental health disorder is present, consider treatment with anti-depressants or other psychotropic medications and provide prompt referral to a mental health provider. General counseling services provide gender-focused psychotherapy and other therapy as needed. Refer to mental health providers known to be gender-affirming; avoid mental health providers who purport to "fix" gender identity*. For individuals with more complicated evaluation and treatment needs, refer to psychiatry. See  Depression and Anxiety Disorders for more specific treatment information.

Conversion or reparative therapy is harmful. This is primarily a religious-based concept that pathologizes non-cis-gender identities and insists that the transgender/gender-diverse identity can be "cured." Both are ineffective and increase mental health illness and poorer psychological functioning. [Green: 2020] [Turban: 2017] This notion is contrary to official positions of medical and mental health organizations, including the American Psychological Association, American Medical Association, American Academy of Family Physicians, American Academy of Pediatricians, Society for Adolescent Health and Medicine, and others.

Many institutions may require a letter of support from a mental health provider prior to the initiation of gender-affirming hormones or surgical procedures. A mental health evaluation is important for any mental health disorders, as these may hinder a patient’s ability to provide informed consent for medical treatment. Early involvement with a provider who is skilled with gender-focused therapy is encouraged during the initiation of a social transition.

Appropriate developmental screens should be performed if there is concern of autism spectrum disorder or other mental health conditions.

• Autism Screening
• Mental Health Screening for Children & Teens

Asking about academic performance could help identify barriers and difficulties at school, such as bullying. Primary care clinicians may need to provide letters of support to use gender-affirming restrooms at school. [Schuster: 2016]

Assessing extended-family dynamics and psychosocial support is useful to identify needs or barriers to receiving care and transitioning successfully to adulthood. Ask about bullying, abuse, school-related issues, disordered eating, and mood/anxiety disorder.

At each encounter, consider asking parents about how the family is functioning and coping with their gender-diverse child. The primary care clinician can advocate and intervene on the youth's behalf when indicated or refer to mental health specialists for more support. Make recommendations for family or couples therapy as appropriate. Helpful educational books could include:

• The Gender Creative Child: A 304-page book that explains the rapidly changing cultural, medical, and legal landscape of gender and identity - by Diane Ehrensaft, PhD (2016)
• Where's My Book?: A Guide for Transgender and Gender Non-Conforming Youth, Their Parents, & Everyone Else: A 390-page book to help transgender youth through puberty. Explains the basics of gender identity, sexual orientation, puberty, puberty blockers, hormone treatments, and gender-affirming surgeries - by Dr. Linda Gromko

When it is time for an adolescent to transition to an adult health care provider, the most important information to summarize for the new clinician, along with any chronic health conditions/events, is the list of current medications with doses, contact information for the therapist (if there is one) and other providers involved in the patient’s care, an organ inventory if surgery has been performed, and a brief discussion of the patient’s desired gender journey. See Transition to Adult Healthcare.