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)