II. Definitions

  1. Assigned Gender at Birth
    1. Assumed gender at birth based on physical characteristics
    2. Assigned Female at Birth (AFAB)
    3. Assigne Male at Birth (AMAB)
  2. Transgender
    1. Person's expressed gender differs from their gender assigned at birth
    2. Distinct and separate from sexual orientation, Sexual Development, external gender expression
    3. Female to Male (FTM, Transgender man, transman)
      1. Refers to assigned female at birth (AFAB) who identifies as a man
    4. Male to Female (MTF, Transgender woman, transwoman)
      1. Refers to assigned male at birth (AMAB) who identifies as a woman
  3. Gender Identity
    1. Person's sense of being a man, woman, both or neither
  4. Gender Dysphoria
    1. Distress or functional problems in Transgender or gender diverse persons
  5. Gender Incongruence
    1. Discrepancy between experienced gender and assigned sex without mention of dysphoria or treatment
  6. Transsexualism
    1. Severe Gender Dysphoria, and persistent wish for physical characteristics and social roles of opposite sex
  7. Cisgender (cis men, cis women)
    1. Non-Transgender, in which patient's expressed gender aligns with their gender assigned at birth
  8. Cross Dresser
    1. Previously referred to as transvestite (now considered derogatory term)
    2. Clothing, jewelry or makeup not typically associated with a person's anatomic gender
    3. Not synonymous with Transgender
  9. Sexual Orientation
    1. Includes heterosexual, homosexual, bisexual, pansexual or asexual
    2. Sexual orientation is independent of Gender Identity

III. Epidemiology

  1. Prevalence: 140,000 teens, 1.4 Million overall or 0.6% (U.S., 2017)
  2. Unequal treatment in healthcare reported by 24% of patients, and refusal of care in 19% of patients
  3. Race and ethnicity
    1. Non-Hispanic white: 35%
    2. Latino or Hispanic: 21%
    3. Black: 16%
  4. Gender
    1. Male to Female (MTF): 1 in 20,000
    2. Female to Male (FTM): 1 in 50,000

IV. Pathophysiology

  1. Stria Terminalis changes have been associated with Transgender
    1. Stria terminalis, a part of the Limbic System, is found on the ventricular surface of the Thalamus
      1. Increased in cis men, and decreased in cis-women
    2. SomatostatinNeurons within the stria terminalis are also associated with Transgender identity
      1. Increased in cis men, and decreased in cis-women
    3. Androgen exposure in early brain development impacts stria terminalis
      1. Stria Terminalis is sensitive to andriogens
      2. Lack of androgens in early development may predispose to transfemale
      3. Excess androhens in late development may presdispose to transmale
  2. Male to Female (MTF) Transgender associated changes are similar to cis-women (non-Transgender women)
    1. Stria terminalis is smaller in transwomen (similar to cis women) than cis men
    2. SomatostatinNeurons are reduced in transwomen (similar to cis women) than cis men
  3. Female to Male (FTM) Transgender associated changes are similar to cis-men (non-Transgender men)
    1. Stria terminalis is larger in transmen (similar to cis men) than cis women
    2. SomatostatinNeurons are increased in transmen (similar to cis men) than cis wo,men

V. Approach

  1. Ask patients their preferred name, gender and pronoun (may differ from medical record)
    1. Intake forms and medical record should reflect both chosen Gender Identity and assigned sex at birth
    2. Consider re-writing patient intake forms to be gender neutral
  2. Establish rapport and offer a welcoming and safe environment for Transgender patients
    1. Clinicians and staff may benefit from additional training on culturally sensitive terminology and topics
    2. Refer to body parts in gender neutral terms (e.g. chest, genitalia) when possible
  3. Preventive health screening should be directed towards their birth gender
    1. Billing for preventive services should be based on birth gender
    2. Transgender men who have intact Breast tissue should have Breast Cancer Screening
    3. Transgender men who have intact Uterus and Cervix should have Cervical Cancer Screening
    4. Base medical calculations (e.g. GFR, Cardiac Risk) on birth gender

VI. History

  1. Gender Dysphoria and Gender Incongruence history
    1. Assess duration, severity and stability
    2. Management to date (e.g. hormonal therapy, multispecialty care, surgical procedures)
  2. Mental health
    1. Anxiety Disorder
    2. Uncontrolled Major Depression (esp. Suicidality)
    3. Posttraumatic Stress Disorder
    4. Intimate Partner Violence
    5. Eating Disorder
    6. Victim of Bullying
    7. Substance Abuse
  3. Social Situation
    1. Homelessness
    2. School Truancy
  4. Sexual History
    1. Are you sexually active?
    2. What gender are your partners?
    3. What type of sex do you have (e.g. oral sex, vaginal sex, anal sex, shared sex toys?)
    4. What do you do to protect against Sexually Transmitted Infection (STI)?
    5. Do you use Contraception?

VII. Exam

  1. Chaperoned exam specific to patient's current anatomy
  2. Patient may limit the exam based on their level of comfort
  3. Identify Sexual Development incongruent with assigned sex at birth that precedes hormonal or surgical treatment
    1. Endocrinology and other specialty Consultation may be warranted

VIII. Associated Conditions

  1. Overall mortality is 50% higher for MTF Transgender patients than the general population
  2. Lower socioeconomic conditions
    1. Poverty
      1. Four fold higher risk of household income <$10,000/year
    2. Homelessness and evictions
    3. Discrimination in hiring, firing and job promotions
  3. Abuse
    1. Sexual Assault
    2. Physical Abuse
  4. Mental Health
    1. Suicidality (82%)
      1. Attempted Suicide (41%, esp. ages 18 to 44 years, and two thirds tried more than once)
    2. Drug Abuse (29%)
    3. Tobacco Abuse (30%)
  5. HIV Infection
    1. Prevalence - Male to Female (MTF): 28%
    2. AIDS related mortality is 30 fold higher for Transgender than Cisgender HIV patients
    3. Mechanisms
      1. Unprotected receptive anal intercourse (MTF)
      2. Needle sharing for Hormone injections
      3. Sex Work
  6. Other Sexually Transmitted Infections are also very high risk in Transgender patients
    1. Syphilis
    2. Gonorrhea
    3. Chlamydia
    4. Genital Herpes
    5. Human Papillomavirus
  7. Other Conditions
    1. Cardiovascular Disease

IX. Management: General

  1. Consultation with Transgender specialists including mental health
    1. Help guide patient in gender exploration (teen), as well as Gender Dysphoria and Gender Incongruence
    2. Ensure safe environment and timing for patient's social affirmation
  2. Do NOT recommend Gender conversion therapy
    1. Gender conversion therapy is an effort to convert a person's Gender Identity to align with birth assigned sex
    2. Gender conversion therapy is considered unethical and not consistent with guidelines including from AAFP
  3. Health Maintenance
    1. Follow general Health Maintenance guidelines
    2. Standard screening and management for Hypertension, Hyperlipidemia, Diabetes Mellitus, Obesity
    3. Tobacco Cessation and Substance Abuse management
    4. Contraception (based on anatomical gender)
      1. Ensure reliable Contraception
      2. Testosterone is not a contraceptive Hormone
    5. Pregnancy
      1. Pregnancy screening in Amenorrhea, Abnormal Uterine Bleeding or Pelvic Pain in transmasculine patients
      2. Observe for dysphoria related to body changes in pregnancy and postpartum
      3. Stop Testosterone if trying to conceive or if pregnancy is diagnosed
      4. Review patient's support system and multidisciplinary team (e.g. mental health, social work) as needed
      5. Dakkak (2022) Am Fam Physician 106(6): 608-11 [PubMed]
    6. Sexually Transmitted Infection screening and management
      1. HPV Vaccine
      2. STD Screening including HIV Screening
      3. See HIV Preexposure Prophylaxis
      4. See HIV Post Exposure Prophylaxis
    7. Cancer screening is based on patient's current anatomy
      1. Screening Mammography if Breast tissue present as per standard guidelines
      2. Cervical Cancer Screening
      3. Prostate Cancer Screening

X. Management: Hormonal Therapy

  1. Precautions
    1. Hormonal therapy (esp. synthetic Estrogen) increases Venous Thromboembolism Risk
      1. Avoid high Estrogen doses and Ethinyl Estradiol
      2. Tobacco Cessation
    2. Hormonal therapy (feminizing or masculinizing) are partially irreversible
    3. Monitor Bone Mineral Density (esp. in teens on GnRH agonists, until age 25-30 years old)
    4. Relative contraindications to hormonal therapy
      1. Hormone-sensitive active cancer (absolute contraindication)
      2. Older age
      3. Tobacco Abuse
      4. Severe comorbidity
      5. VTE history or current
    5. Indications (all must be met)
      1. Well documented Gender Dysphoria
      2. Medical decision making capacity to consent
      3. Age of Majority (State or region defined age at which a person considered an adult)
      4. Stable comorbid medical and psychiatric conditions
  2. Adolescents (Puberty to 16 years old)
    1. Consultation with Transgender specialists and mental health specialists
      1. Delayed treatment with "wait and see" may cause harm with psychosocial stress, Gender Dysphoria
    2. GnRH agonists (e.g. Leuprorelin or Lupron; Goserelin, Triptorelin)
      1. Used to suppress Sexual Development of their birth gender (peds endo)
      2. Puberty suppression started once child reaches stage 2-3 of sexual maturity
      3. GnRH agonists have reversible effects and allow for stable Gender Identity
      4. Expensive medications that require Subcutaneous Injection every 4 to 12 weeks
      5. Hormonal suppression often achieved within first week of therapy
      6. Repeat labs at 6-12 months
        1. Serum LH and Serum FSH
        2. Vitamin D
        3. Serum Estradiol (if ovaries)
        4. Serum Testosterone (if Testes)
    3. Other measures to be considered in FTM Transition
      1. Menstrual suppression with Oral Contraceptives
      2. Breast binding
  3. Adults (and adolescents over age 16 years old)
    1. Transgender women (transfeminine, male to female transition)
      1. Estrogens
        1. Dose: Estradiol 50 mcg/day
        2. Goal Serum Estradiol >200 pg/ml
        3. Effects may be present at 3-12 months, but full effect may take 2-3 years
        4. Increases Breast development, redistributes fat, softens skin
        5. Lowers Serum Testosterone, decreases Erections, atrophies Prostate and Testes
        6. Increases risk Venous Thromboembolism, Breast Cancer, Prolactinoma, Cholelithiasis, Hypertriglyceridemia
      2. Antiandrogens (Spironolactone, Finasteride)
        1. Goal Serum Testosterone < 50 ng/dl
        2. Decreases Muscle mass, libido and Terminal Hair growth
        3. Voice does not typically change
        4. Spironolactone
          1. Inhibits Testosterone secretion and androgen receptor binding
          2. Dose: 50 mg orally twice daily
          3. Monitor for Hyperkalemia, Kidney injury, Hypotension on Spironolactone
        5. Finasteride (off-label, second-line to Spironolactone)
          1. 5a-Reductase Inhibitor blocks Testosterone to dihydrotestosterone conversion
          2. Dose: 5 to10 mg orally daily
    2. Transgender men (transmasculine, female to male transition)
      1. Non-estrogen Contraception (e.g. IUD, Implanon, depo-Provera)
      2. Testosterone
        1. See Testosterone Replacement
        2. Dose: 5 to 10 g gel topically (or 200 to 250 mg every 2 weeks IM)
        3. Goal Serum Testosterone 320 to 1000 ng/dl
        4. Effects may be present at 1-6 months, but full effect may take 4-5 years
        5. Amenorrhea by 3 to 5 months (but Ovulation may continue, use Contraception!)
        6. Clitoromegaly (enlarges to 3-5 cm) and may serve as microphallus
        7. Increases acne, scalp Hair Loss, body hair, deeper voice, weight gain, Muscle mass
        8. Increased risk of erythrocytosis
        9. Risk of Endometrial Cancer (Unopposed Estrogen from Testosterone conversion)
          1. Pelvic Ultrasound surveillance after 3 years of Testosterone and intact Uterus
        10. Testosterone is Teratogenic should Unintended Pregnancy occur
          1. Results in fetal abnormal genitalia
          2. Reliable Contraception is critical in those with intact Uterus and ovaries

XI. Management: Gender-Confirmation Surgery

  1. Background
    1. Prevalence: 11,000 gender confirmation surgeries per year (U.S., 2019)
    2. Male to Female (MTF) gender confirmation surgery outnumber FTM by 3:1 ratio
  2. Precautions
    1. Many Transgender patients will not require surgery
    2. Surgery is pursued when significant Gender Dysphoria persists despite hormonal management
  3. Indications (all must be met)
    1. Persistent, well-documented Gender Dysphoria
    2. Referral from mental health provider
      1. Two mental health providers if genital surgery
    3. Medical decision making capacity to consent
    4. Age of Majority (State or region defined age at which a person considered an adult)
    5. Stable comorbid medical and psychiatric conditions
    6. Twelve months of continuous Hormone therapy (if not contraindicated)
    7. Twelve months of continuous living in Gender Identity role
  4. Contraindications of fertility limiting surgery (gonadectomy)
    1. Under legal age
    2. Coexisting conditions are not controlled
    3. Social affirmation and hormonal treatment <12 months
    4. Noncompliance or unwillingness to follow guidelines
      1. Continued hormonal therapy to prevent BMD loss
  5. Perioperative recommendations
    1. Avoid Tobacco for 1 month before and 6 months after surgery
    2. Avoid Estrogen for 2-4 weeks before surgery to reduce Venous Thromboembolism Risk
  6. Transgender women (transfeminine, male to female transition)
    1. Breast Augmentation or augmentation mammoplasty (performed in 60-70% of MTF)
    2. Facial feminization surgery
    3. Voice therapy
    4. Hair removal
    5. Tracheal shave (Laryngeal or Adam's Apple Reduction)
    6. Orchiectomy
      1. Well tolerated, with few surgical complications
      2. Scrotal Hematoma may require drainage
    7. External genitalia construction
      1. Labia Minora is constructed from penile skin
      2. Labia Majora are constructed from scrotal skin
      3. Neoclitoris constructed from glans penis (with intact dorsal nerve and vessels)
    8. Vaginoplasty
      1. Constructed from rectosigmoid colon segments
      2. Prosthesis is initially placed inside the neovagina for first 5 days (and regular lifelong dilation required)
      3. Functional, self lubricating, deep vagina-like structure
      4. Avoid sexual intercourse for 8-12 weeks after surgery
      5. Complications
        1. Intravaginal scarring
        2. Persistent pain
        3. Urethral Stricture or stenosis
        4. Hypergranulation (may present with bleeding or discharge)
          1. May respond to Silver Nitrate, topical intravaginal Estrogen
        5. Rectovaginal fistula (1 in 400 surgeries)
          1. Vaginal tampon will discolor from food coloring dyed rectal water enema
          2. Small fistulas may heal on liquid or low residue diet
          3. Larger or refractory fistulas may require skin grafts
        6. Vaginal Stenosis
          1. Often results from non-compliance with regular vaginal dilation regimen
          2. Gradual dilation with topical lubricant (Lidocaine 2% jelly or Lidocaine/Prilocaine cream)
          3. Consider Estradiol Vaginal Tablets
  7. Transgender men (transmasculine, female to male transition)
    1. Mastectomy and chest reconstruction (performed in 93% of FTM)
    2. Gonadectomy (often performed in FTM)
      1. Hysterectomy
        1. Vaginal Hysterectomy is difficult procedure if Testosterone Replacement (Vaginal Atrophy)
      2. Bilateral salpingo-oopherectomy
      3. Vaginectomy
    3. Reconstructive Surgery (less commonly performed)
      1. Phalloplasty
        1. Seven inch penis construction
        2. Functional for Erection and penetration (with Penile Prosthesis implant)
        3. Constructed from non-dominant radial Forearm free flap transplant (skin, fat, nerves, vessels)
        4. Risk of Urethral fistula and Urethral Stricture
        5. Risk of flap necrosis
          1. Postoperative hourly monitoring of color, Temperature, color, pulse, Capillary Refill for 2 days
      2. Metoidioplasty
        1. One to 6 inch penis construction from enlarged clitoris
        2. Does not allow for penetration
        3. Urethral lengthening may be performed (requiring Suprapubic Catheter for 2-4 weeks)
        4. Risk of Hematoma, Urethral Stricture, Urinary Incontinence, flap necrosis
      3. Scrotoplasty (Scrotum construction)
        1. Constructed from hollowed-out labia majora and testicular implants
        2. Risk of implant rejection, implant migration, neoscrotum rupture

XII. Resources

  1. UCSF Transgender
    1. http://transhealth.ucsf.edu/
  2. UCSF Primary Care Guidelines
    1. http://transhealth.ucsf.edu/trans?page=guidelines-home
  3. World Professional Association for Transgender Health (WPATH)
    1. https://www.wpath.org/
    2. Standard of Care guidelines including hormonal therapy, surgery and postoperative care

XIII. References

  1. (2016) Presc Lett 23(11)
  2. Allen (2021) Crit Dec Emerg Med 35(10): 17-28
  3. Klein (2018) Am Fam Physician 98(11): 645-53 [PubMed]

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