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Lecture 3 Gender Affirming Medical Therapy Townsend
HISTORICAL CONTEXT OF TRANSGENDER HEALTHCARE:
• Care limited to specialized gender clinics (psychiatry,
psychology, sexual medicine, endocrinology)
• Pathologization of trans identities
• Reparative therapy
• Excessive gate-keeping
• Lengthy assessments prior to treatment
• Expectation of binary transition
BARRIERS TO CARE AND CONSEQUENCES:
BARRIERS • Prior negative experiences in healthcare settings
• Fears or expectations of negative experiences
• Body dysphoria (and clinician discomfort with trans bodies)
• Lack of provider comfort, knowledge/trans competence
CONSEQUENCES • Postponing care until problems are more serious
• Avoidance of care leads to missed screening, untreated health conditions
• Self-medicating (hormone therapy)
• False narratives, omission of important information
SHIFTS IN APPROACH:
• Shift away from pathologization
o From disease-based to identity-based model
• Explicit endorsement of the provision of gender
affirming care to those with non-binary identities
• Shift towards a range of care providers (including
GPs, NPs and nurses) doing assessments and
delivering gender affirming care
WORLD PROFESSIONAL ASSOCIATION FOR TRANSGENDER HEALTH (WPATH):
• Mission: to promote evidence-based care, education, research, advocacy, public policy, and
respect in transsexual and transgender health
• “Standards of Care”: guidelines for working with children, adolescents and adults, to provide
appropriate mental health, endocrine, surgical, reproductive, voice/communication,
preventative and primary care
o Evidence-based; represent consensus among leading international experts in trans care
GENDER DYSPHORIA:
• Discomfort or distress that is caused by a
discrepancy between a person’s gender identity and
that person’s sex assigned at birth (and the
associated gender role and/or primary and
secondary sex characteristics)
GENDER AFFIRMATION:
Social Steps • Name and pronoun change
• Clothing, makeup, hairstyle
Medical Intervention
• Puberty blockade
• Hormone therapy
• Other individualized intervention
Surgical Intervention
• Upper body surgeries o Male chest contouring o Breast augmentation
• Gonadectomy o Hysterectomy o Orchiectomy
• Genital Reconstruction o Vaginoplasty o Metoidioplasty o Phalloplasty
• Other procedures: o Electrolysis o Tracheal shave o Facial feminization
MEDICATIONS FOR GENDER AFFIRMATION:
• Off-label use
• Contraindications are often relative
o Carefully weigh risks and benefits of
treatment vs. no treatment
o Actively mitigate risks
• Research is limited
• Thorough informed consent process (i.e. forms)
PATHWAY TO MEDICAL TREATMENT:
Step 1 Pre-treatment readiness assessment:
• A range of care providers with training and experience (GP, NP, pediatrician, social workers, nurses, psychiatrists and psychologists) will complete the assessment and either write a letter of recommendation for hormone therapy or initiate treatment
Step 2 Initiation of hormone therapy:
• Medical doctor or nurse practitioner with training & experience
• + physical assessment (if not already done)
Step 3 Maintenance of treatment:
• Any medical doctor or NP (with specialist support as needed)
READINESS ASSESSMENT:
• Does this person meet the WPATH criteria for treatment?
• Are they ready from a psychosocial point of view?
• Do they have a plan for ongoing care and support?
o If not, how can we support them to ensure they get the medically necessary txt?
• Is further evaluation required?
WPATH CRITERIA:
1. Persistent well-documented gender dysphoria
2. Capacity to make a fully informed decision and to consent for treatment
3. If significant medical/mental concerns are present, they must be reasonably well-controlled
4. Age of majority in a given country
GENERAL TIPS TO KEEP IN MIND:
• Focus on presenting concern
• Do not overly focus on gender
• Ask relevant health questions and be prepared to
justify your questions
• Recognize that the need to affirm gender may be
prioritized over other health issues
• Be prepared that due to stigma & past negative
experiences some patients may seem defensive
REVERSIBLE MEDICAL INTERVENTION:
PUBERTY BLOCKERS: LEUPROLIDE (a GnRH analogue)
• For younger youth, started at Tanner 2 development or later
• Blocks natural puberty
o Gives time to mature and consider decision
o Eases distress associated with pubertal changes
• IM injection q4-12 weeks
• Dosing is weight-based (typically 7.5 – 15 mg monthly)
• 5% risk of sterile abscess
OPTIONS FOR SUPPRESSION OF MONTHLY BLEEDING:
• Medroxyprogesterone 150 mg IM q12 weeks
• Continuous OCP
• Progesterone-releasing IUD
o Higher progesterone dose = more effective
Lecture 3 Gender Affirming Medical Therapy Townsend
FEMINIZING THERAPY: ESTROGEN + T BLOCKERS
• GOAL: to reduce testosterone-related secondary sex characteristics, induce estrogen-related secondary sex characteristics and reduce gender dysphoria
• Start low and titrate q4-6 weeks (or more slowly if clinically indicated or desired by patient)
• Dose changes based on lab values, patient goals, response, side effects
SYSTEMIC TESTOSTERONE BLOCKERS:
• GOAL: suppress testosterone to female range (or higher if desired by pt)
• Allows us to use lower doses of estrogen than otherwise needed
• Typically discontinued post-gonadectomy
SPIRONOLACTONE:
MECHANISM K+ sparing diuretic with anti-androgen effect
CONTRAINDICATIONS Renal failure, hyperkalemia
DOSE Starting dose = 50 mg daily, and titrate to typical range of 200-300 mg daily
SIDE EFFECTS Frequent urination, dizziness, fatigue
INTERACTIONS Medications that lower BP or increase risk of hyperkalemia (ex// ACEIs, ARBs)
MONITOR Blood pressure, electrolytes, Cr
CYPROTERONE:
MECHANISM Acts via blockade of the androgen receptor, inhibition of LH
CONTRAINDICATIONS Liver disease
DOSE Starting dose = 25 mg daily, and titrate to typical range of 25-100 mg daily
SIDE EFFECTS Depression
INTERACTIONS Cyproterone is a major CYP3A4 substrate = possible interactions with statins, anti-coagulants, anti-diabetic agents
MONITOR Mood, ALT
COVERAGE Requires special authority application
ESTROGEN THERAPY:
• GOAL: to maintain testosterone levels in the female range, estrogen
levels in the 300-800 pmol/L range, minimize side effects and maintain
expected rates of physical changes (based on patient preference)
• Typically used lifelong, lower dosing maybe possible post-gonadectomy
ESTROGEN:
MECHANISM Direct action on estrogen receptors
CONTRAINDICATIONS Unstable ischemic cardiac disease, estrogen-dependent cancer, end-stage liver disease
DOSE Depending on dosage form
SIDE EFFECTS Nausea, headaches, decreased libido
INTERACTIONS Estrogen is a major substrate of CYP3A4 = possible interactions with anti-epileptics, HIV medications, St. John’s Wort
RISKS VTE, increased triglycerides, gall stones, liver inflammation
MONITOR E level, ALT, metabolic parameters
ESTROGEN DOSING:
ORAL (17B ESTRADIOL)
Starting dose = 1-2 mg and titrate to typical range of 4-8 mg daily
ESTRADIOL PATCH
Starting dose = 50 mcg and titrate to typical range of 200-300 mcg twice weekly
• Indicated if > 40 yrs + risk factors (ex// smoking)
• Requires special authority
ESTRADIOL VALERATE INJECTION
Starting dose = 5 mg IM q2 weeks and titrate to usual dose of 10-20 mg q2wks
• Only available compounded
EFFECTS & EXPECTED TIME COURSE (estrogen + blocker):
Effect Expected Onset
Expected Max Effect
Body fat re-distribution 3-6 months 2-5 years
↓ muscle mass/strength 3-6 months 1-2 years
Softening of skin / decreased oiliness
3-6 months Unknown
↓ libido 1-3 months 1-2 years
↓ spontaneous arousal (erections)
1-3 months 3-6 months
Breast growth 3-6 months 2-3 years
↓ testicular volume 3-6 months 2-3 years
Changes to body & facial hair 6-12 months > 3 years
Fertility * variable effects
RISKS (estrogen + T-blocker):
Risk level Estrogen Likely increase risk VTE, ↑ TGs, gallstones, ↑ LEs, ↑ wt
Likely increase risk with additional risk factors
Cardiovascular disease
Possible increase risk ↑ BP, ↑ prolactin, prolactinoma
Possible increase risk with additional risk factors
Type 2 diabetes
No increase risk or inconclusive Breast cancer
LAB MONITORING (estrogen + T-blocker):
• GOAL: typically to maintain hormone levels in the female range, induce
physical changes at expected rate, and minimize adverse effects
Baseline (and q6-12m thereafter):
• Testosterone
• CBC, GFR, TSH, ALT
• Electrolytes, fasting glucose, lipids
Following dose changes: • Testosterone, estrogen levels
• ALT, electrolytes
FINASTERIDE:
• May augment use of spironolactone or cyproterone
• Not typically used as main anti-androgen
MECHANISM Peripheral action only – inhibits conversion of testosterone to dihydrotestosterone
DOSE Finasteride 5 mg – ¼ tab daily or ½ tab q2 days
SIDE EFFECTS Typically none, hypotension, reduced libido uncommon
PROGESTERONE:
• GOAL: use is controversial (benefits unproven, risks may be increased);
typically for breast growth, other reasons include libido, sleep
• 3-6 month trial is reasonable for a fully informed patient
DOSE Micronized progesterone: starting dose 100 mg daily, can titrate up to 400 mg daily Medroxyprogesterone: starting dose 10 mg daily, can titrate up to 15 mg daily
SIDE EFFECTS Weight gain, mood changes, edema
INTERACTIONS Progesterone is a major substrate of CYP3A4 and CYP2C19; decreased effect of anti-coagulants, anti-diabetics
RISKS Combo of estrogen and progesterone increased risk of blood clots, heart disease, breast cancer
MONITOR E level, ALT, metabolic parameters
Lecture 3 Gender Affirming Medical Therapy Townsend
FEMINIZING THERAPY:
COMMON SIDE EFFECTS AND OTHER CONCERNS:
Persistent dizziness/postural hypotension
• Caused by spironolactone, usually temporary and mild
• If severe or persistent switch to cyproterone (eligible for special authority)
Low libido • Consider maintaining testosterone at higher level
• Trial of progesterone
Difficulty having/maintaining arousal (erections)
• Consider maintaining testosterone at a higher level
• Trials of phosphodiesterase-5 inhibitor (Sildenafil, Tadalafil)
Elevated prolactin • Common and typically benign with estrogen therapy
• If > 80 mcg/L or if symptomatic (headaches, visual changes, excessive galactorrhea), consider pituitary imaging
Elevated transaminases • Usually transient unless another cause of hepatic dysfunction identified
Scalp hair loss • Minoxidil 5% and/or finasteride 2.5 mg q2days
Post-vaginoplasty vaginal discharge • The lining of the vagina is inverted penile/scrotal skin (squamous epithelium)
• Oral antibiotics usually ineffective
• Intravaginal metronidazole gel bid + plain water douching recommended
MASCULINIZING THERAPY: TESTOSTERONE
• GOALS: to reduce estrogen-related secondary sex characteristics, induce testosterone-related secondary sex characteristics & reduce gender dysphoria
• Start low and titrate q4-6 weeks
• Base dose changes on lab values, patient goals, response, side effects
TESTOSTERONE:
• GOAL: to maintain mid-injection cycle levels in the middle-high end of
male range, minimize side effects and maintain expected rates of
physical change (based on patient preferences)
• Typically used lifelong, lower dosing may be possible post-gonadectomy
• Available in several forms; special authority application required
TESTOSTERONE THERAPY:
MECHANISM Direct action on androgen receptors
CONTRAINDICATIONS Pregnancy, active androgen-sensitive cancer, unstable ischemic cardiac disease, uncontrolled psychosis or mania
DOSE Depending on dosage form
SIDE EFFECTS Acne, insomnia, libido changes
INTERACTIONS Vit K antagonists, anti-diabetics, cyclosporine
RISKS Polycythemia, dyslipidemia, sleep apnea
TESTOSTERONE DOSING:
INJECTABLE Starting dose = 25 mg IM/SC weekly and titrate to maintenance dose of 50-100 mg weekly
PATCH Starting dose = 2.5 mg daily and titrate to typical dose of 5-10 mg daily
GEL/CREAM Starting dose = 2.5 g daily and titrate to a typical dose of 5-7.5 g daily
EFFECTS AND EXPECTED TIME COURSE (testosterone):
Effect Expected Onset Expected Max Effect
Skin oiliness/acne 1-6 months 1-2 years
Facial/body hair growth 3-6 months 3-5 years
Scalp hair loss > 12 months Variable
↑ muscle mass/strength 6-12 months 2-5 years
Body fat redistribution 3-6 months 2-5 years
Cessation of menses 2-6 months N/A
Enlargement of external genitals (clitoris)
3-6 months 1-2 years
Internal genital (vagina) atrophy
3-6 months 1-2 years
Deepened voice 3-12 months 1-2 years
Fertility * variable effects
RISKS (testosterone):
Risk level Testosterone Likely increase risk Polycythemia, ↑ weight, acne,
balding, sleep apnea
Possible increase risk Hyperlipidemia, ↑ LEs
Possible increase risk with additional risk factors
CVD, ↑ BP, increased mania or psychosis, T2DM
No increase risk or inconclusive Breast, cervical, ovarian or uterine cancer, loss of bone density
LAB MONITORING (testosterone):
• GOAL: typically to maintain hormone levels in the male range, induce physical changes at expected rate, and minimize adverse effects
Baseline (and q6-12m thereafter): • Testosterone, CBC, ALT, fasting glucose & lipids, TSH
Following dose changes: • Testosterone, CBC, ALT
COMMON SIDE EFFECTS AND OTHER CONCERNS:
Acne • Typically most problematic in the first year of hormone therapy
• Treat as per usual, consider lower doses or switching to testosterone type if persistent
Scalp hair loss • Minoxidil – will not impact facial hair growth; finasteride – will inhibit facial hair growth
Polycythemia • Usually a misinterpretation – ensure the HB/HCT are being interpreted based on male laboratory ranges
• If HB > 175 g/L or HCT > 0.52, or if symptomatic (headaches, facial flushing), increase frequency of dosing to weekly, reduce dose, or switch to a patch/gel to minimize peak/trough variation
Elevated transaminases • Usually transient unless another cause of hepatic dysfunction identified
Unexpected bleeding • Bleeding typically supressed in 6m of starting testosterone; unexplained persistent abnormal bleeding should be evaluated
• Evaluate for missed/inconsistent/excessive testosterone dosing; check trough testosterone levels, estradiol, LH, FSH o Testosterone can convert to estrogen with theoretical risk of endometrial proliferation
• Consider more frequent dosing (weekly), or dose adjustment
Internal genital (vaginal) dryness
• Topical estrogen inside the genital opening (vagina)
• Estradiol cream 0.5 – 1 g twice weekly or estradiol tablet 10 mcg twice weekly
Lecture 3 Gender Affirming Medical Therapy Townsend
HORMONE THERAPY FOLLOW-UP:
• Follow-up q4-6 weeks while titrating, and then q6-12 months
• Review effects of hormones, dose, side effects, mood, supports, social challenges
• Check BP, other physical exam as indicated
• Review labs
• Adjust dose if indicated
HORMONE THERAPY VARIATIONS:
• As always, care should be individualized
• Some possible variations:
o Lower dose of hormones
o More gradual titration
o Temporary use of hormones
o Using T-blocker w/o estrogen (not recommended long-term)