Medical Management of Transgender Individuals
Core Treatment Framework
Transgender and gender-diverse (TGD) individuals should receive multidisciplinary care that includes mental health support, gender-affirming hormone therapy (GAHT) when desired, and surgical interventions when appropriate, with all treatment decisions guided by the patient's affirmed gender identity rather than sex assigned at birth. 1
Essential Team Components
The multidisciplinary team must include:
- Endocrinologist for hormone management and monitoring 1
- Mental health professional (psychologist/psychiatrist) for assessment and ongoing support—though gender identity itself is not a mental health condition 2, 1
- Primary care physician knowledgeable in transgender health 2
- Surgeon experienced in gender-affirming procedures when surgical intervention is considered 1
- Social work and nursing support when available 1
Gender-Affirming Hormone Therapy for Transfeminine Individuals
Feminizing Hormone Regimen
Estradiol is the cornerstone of feminizing therapy, combined with anti-androgen medication to suppress testosterone to female range (<50 ng/dL). 2, 1
Estradiol Administration Options:
- Oral estradiol: 1-2 mg daily initially, adjusted to control symptoms 3
- Transdermal patches or gel 2
- Parenteral (injectable) formulations 2
Target estradiol levels should be maintained in the cisgender female reference range 1
Anti-Androgen Options:
Expected Physical Changes
Physical feminization includes 2, 1:
- Breast development (9% achieve A-cup, 16% B-cup, sustained over first 3 years) 2
- Decreased lean body mass (3-5% reduction) 2, 1
- Decreased muscle volume (5% thigh muscle volume, 4% quadriceps cross-sectional area) 2, 1
- Skin softening and decreased body/facial hair 1
- Feminized body fat distribution 2
- Significant hemoglobin decrease to female reference range 2, 1
Critical Monitoring for Transfeminine Patients
Monitor hemoglobin levels as they will decrease significantly to female reference range within months of starting therapy. 2, 1
Additional monitoring parameters 2:
- Testosterone levels (target <50 ng/dL)
- Estradiol levels (target cisgender female range)
- Liver function tests at baseline and periodically
- Lipid profiles regularly
- Thrombotic risk assessment (estrogen increases VTE risk) 4
Gender-Affirming Hormone Therapy for Transmasculine Individuals
Masculinizing Hormone Regimen
The standard regimen consists of testosterone cypionate or enanthate administered via intramuscular or subcutaneous injection, targeting serum testosterone levels of 300-1,000 ng/dL (mid-normal male range). 5, 1
Testosterone Dosing:
- Target trough levels: 300-1,000 ng/dL 5, 1
- Aim for mid-normal range to optimize safety and efficacy 5
- Injectable formulations preferred (testosterone cypionate or enanthate) 5, 1
- Transdermal options available but less commonly used 5
Critical warning: Testosterone cypionate should not be used interchangeably with testosterone propionate due to differences in duration of action, and is not for intravenous use. 6
Expected Physical Changes
Masculinization effects include 5, 1:
- Voice deepening due to thickened vocal cords 5
- Facial and body hair growth 5
- Menstrual suppression (achieved in most patients) 5
- Clitoral growth 5
- Increased muscle mass (15% thigh muscle volume increase, 6% quadriceps cross-sectional area increase) 2
- Decreased fat mass 5
- Increased libido 5
- Hemoglobin increase to male reference range within 3 months 5, 1
Critical Monitoring for Transmasculine Patients
Monitor for erythrocytosis/polycythemia, which is particularly common with injectable testosterone formulations—if hematocrit rises above normal male reference range, consider temporarily withholding therapy, reducing dose, performing phlebotomy, or switching to transdermal route. 5
Additional monitoring parameters 5, 6:
- Hemoglobin and hematocrit levels (to detect polycythemia) 6
- Blood pressure (testosterone may increase BP) 5
- Lipid profiles (testosterone may increase triglycerides and LDL, decrease HDL) 5
- Liver function tests at baseline (screen for liver abnormalities before initiating) 5
- Testosterone trough levels (300-1,000 ng/dL target) 5
Common Adverse Effects to Anticipate
Avoid supraphysiologic testosterone dosing, which increases risk of adverse effects without additional benefit. 5
Expected side effects include 5, 6:
- Androgenic alopecia and acne (common) 5
- Gynecological effects including pelvic pain and genital dryness 5
- Reduced HDL cholesterol 5
- Potential increased myocardial infarction risk 5
- Priapism or excessive sexual stimulation (if occurs, stop androgen and restart at lower dose) 6
Surgical Considerations
Gender-affirming surgery should only be performed after confirmation of persistent gender dysphoria by the multidisciplinary team and demonstration of informed consent capacity. 1
Surgical options vary by patient goals and may include 2, 1:
- Chest masculinization (for transmasculine individuals)
- Breast augmentation (for transfeminine individuals)
- Gonadectomy (orchiectomy or oophorectomy)
- Genital reconstruction procedures
- Vocal pitch-altering procedures (require special perioperative considerations) 2
Important: Decisions regarding surgical intervention should consider diagnosis, genital appearance, potential fertility preservation, therapeutic requirements, and familial/cultural factors. 1
Essential Clinical Practice Considerations
Documentation and Communication
The correct documentation of gender markers, affirmed names, and pronouns in the electronic health record is an essential first step in reducing transgender-related discrimination in healthcare settings. 2
Best practices for clinical encounters 2:
- Ask and use correct pronouns (she/her for trans women, he/him for trans men, they/them for non-binary individuals) 2, 1
- Use patient's affirmed name throughout the visit 2
- Ask about sex assigned at birth (not "biological sex" or "natal sex") 2
- Obtain organ inventory to guide appropriate screening 2
- Avoid stigmatizing language (never use "transgenders," "transvestite," "transgenderism," or outdated term "transsexual") 2
- Use "assigned female/male at birth" rather than "biologically female/male" 2
Addressing Healthcare Trauma
Use a trauma-informed approach recognizing that 33% of TGD individuals report at least one negative healthcare experience in the past year, and 23% avoid seeking care due to fear of mistreatment. 2
If you inadvertently cause offense 2:
- Acknowledge: "It seems I may have said something that hurt you"
- Allow patient to respond
- Apologize appropriately
- Commit to discontinuing harmful language
Perioperative Management Considerations
Pain Management
Postoperative pain management should follow the same recommendations for TGD persons as for cisgender persons, with special considerations for socioeconomic or other comorbidities that may impact the postoperative course. 2
Intraoperative considerations include 2:
- Avoid benzodiazepines
- Use clonidine, dexmedetomidine, droperidol, or promethazine as appropriate
- Provide minimally stimulating environment
Airway Management After Vocal Surgery
For patients who have undergone vocal pitch-altering procedures, avoid elective surgery for 8-12 weeks postoperatively where possible. 2
If surgery is unavoidable during this period, attempt in order of preference 2:
- Local anesthetic or spinal anesthesia with sedation (avoid general anesthesia)
- Supraglottic airway device (if general anesthesia necessary)
- Smaller tracheal tube if intubation necessary (glottic aperture may be decreased by up to 33% after anterior web formation procedures) 2
Cancer Screening and Oncologic Care
Screening Based on Organ Inventory
TGD individuals appear to be under-screened for cancer and often present with late-stage diagnoses and early mortality—screening must be based on organs present, not gender identity. 2
Key principles 2:
- Screen based on anatomy present, regardless of gender identity
- Consider impact of GAHT on cancer risk (data still emerging)
- Address barriers to screening (many TGD patients delay or avoid care)
- Collect gender identity data in cancer registries to improve research 2
Concurrent Cancer Treatment and GAHT
The efficacy and safety of continuing GAHT during cancer treatment is an area requiring more research, but gender-affirming care may offer quality-of-life benefits that outweigh modest concerns. 2
Reproductive Health and Contraception
Fertility Preservation Counseling
All patients seeking gender-affirming medical treatment should receive information and counseling for fertility preservation before initiating GAHT or surgery. 2, 7
Contraception Needs
Gender-affirming hormone therapy is NOT effective contraception—sexually active individuals with retained gonads who do not wish to become pregnant or cause pregnancy must be counseled about contraception if engaging in sexual activity involving sperm and oocytes. 8
Mental Health Considerations
Depression and Anxiety Management
TGD individuals experience higher rates of depression, anxiety, and suicide risk due to stigma, discrimination, and minority stress—mental health support is essential but gender identity itself is not a mental health condition. 2
Antidepressant Selection in Transfeminine Patients
All SSRIs including citalopram, escitalopram, sertraline, paroxetine, fluoxetine, and venlafaxine are acceptable options for patients on feminizing estradiol therapy—there is no need to avoid specific SSRIs due to CYP2D6 inhibition concerns (this concern is specific to tamoxifen metabolism, not estradiol). 4
Monitoring considerations 4:
- Screen for other serotonergic medications to avoid serotonin syndrome
- Assess bleeding risk factors, particularly if patient is on anticoagulation for VTE prevention given elevated thrombotic risk with estradiol
- Consider venlafaxine for patients experiencing both depression and vasomotor symptoms on estradiol
Gender Dysphoria vs. Gender Identity
Gender dysphoria describes psychological distress from gender incongruence—not all transgender individuals experience dysphoria, and not everyone desires hormone treatment or surgery. 2, 1
The ICD-11 has replaced "gender dysphoria" with "gender incongruence" in a new chapter on sexual health, moving away from pathologizing gender identity 2
Common Pitfalls to Avoid
Clinical Pitfalls
- Never assume all TGD patients want medical intervention—some seek only social transition 8
- Do not use supraphysiologic testosterone dosing—increases adverse effects without benefit 5
- Do not conflate gender and sex—they are not interchangeable 2
- Never force patients to educate you—50% of TGD patients report having to teach their providers about transgender care 2
- Do not delay care due to lack of "certification"—specific certification for prescribing GAHT is not required and should not limit access to care 8
Documentation Pitfalls
- Avoid misgendering in medical records—use affirmed name and pronouns consistently 2
- Do not use outdated or offensive terminology 2
- Ensure EHR systems can capture gender identity, sex assigned at birth, and pronouns separately 2
Screening Pitfalls
- Do not skip cancer screening based on gender identity—screen based on organs present 2
- Do not assume contraception is unnecessary—GAHT is not contraception 8
- Do not overlook cardiovascular and metabolic monitoring on hormone therapy 5
Special Populations
Adolescents
Approximately 300,000 youth aged 13-17 in the United States identify as transgender—adolescent care requires additional considerations including parental involvement, pubertal suppression options, and careful assessment of decision-making capacity. 2, 7
Nonbinary Individuals
40% of TGD individuals identify as nonbinary and 22% as gender-nonconforming—treatment goals may differ from binary transgender individuals and may include lower-dose or intermittent hormone therapy to achieve desired effects without full masculinization or feminization. 2, 1
Institutionalized Individuals
TGD people in institutional environments (prisons, long-term care facilities) face unique barriers to accessing gender-affirming care and require special advocacy. 7
Key Takeaway for Providers
The combination of lower socioeconomic status and lack of trust in the medical community due to decades of discrimination are two primary reasons why TGD persons suffer from poorer long-term health outcomes—all physicians must become knowledgeable on best practices for culturally agile and sensitive care to reduce these health inequities. 2