Exam 1 - 508: Transgender Pharmacotherapy in Adults

Learning Objectives

• Identify appropriate terminology used when providing care for transgender individuals

• Recommend specific therapies used to help MTF and FTM transition

• Recognize the expected and desired effects of hormonal therapy

• Identify and manage adverse events of hormonal therapy

Differentiate sex assigned at birth, gender identity, and gender expression:

• Sex Assigned at Birth → Based on assessment of external genitalia, as well as chromosomes and gonads

• Gender Identity → A person’s internal sense of self and how they fit in the world, from the perspective of gender

• Gender Expression → The outward manner in which an individual expresses or displays their gender. May include choices in clothing, hairstyle, speech and mannerisms

Define cisgender and nonbinary

• Cisgender = individuals who identify with their sex assigned at birth

• Nonbinary = Gender identity or expression not exclusively male or female

Define transfeminine and transmasculine

• Transgender = gender identity and/or expression differs from cultural expectations based on the sex that was assigned at birth

• Transfeminine (Transgender female/AMAB) = a person with female gender identity who was assigned male sex at birth

• Transmasculine (Transgender male/AFAB) = a person with male gender identity who was assigned female sex at birth

AMAB = assigned male at birth; AFAB = assigned female at birth

What gender affirming hormone therapy (GAHT)?

• Medications used to assist with the transition; Includes sex hormones and hormone blockers used to align physical characteristics with gender identity

• Must be individualized

  • Patient’s goals

  • Presence of other medical conditions

  • Consideration of economic issues – insurance cost vs. cash cost

What are goals of transfeminine therapies? What agents are used?

• GOALS

  • Promote the development of female secondary sex characteristics

  • Reduce endogenous effects of testosterone

• Approaches to therapy

  • 17 β-estradiol

  • Anti-androgens (spironolactone, finasteride, dutasteride)

  • GnRH agonists (leuprolide)

  • Progesterone

What labs do you have to monitor for feminizing hormone therapy?

• Renal function & Potassium

  • At baseline and Q3 months until 1 year, then yearly afterwards + PRN

• Estradiol

  • Every 3 months up until 1 year + PRN

• Total testosterone

  • Every 3 months up until 1 year + PRN

• CBC

  • As needed

What are the different types of estrogen given for transfeminine therapy?

• 17-beta-estradiol valerate (oral estradiol)

• Estradiol cypionate (IM)

• Estradiol valerate (IM)

• Vivelle-dot (Transdermal estradiol patch)

Which estrogen is used in gender affirming hormone therapy?

17-beta estradiol valerate (oral)

>2 mg recommended BID dosing due to adverse effects

Can measure estrogen levels at any time

What are side effects seen with 17-beta estradiol valerate?

Mood changes (both good and bad), migraines, hot flashes, weight gain, nausea, thromboembolic events (low risk)

What are AEs and clinical pearls of estradiol cypionate (IM)?

• Fluctuations in AEs

• Less thromboembolic risk than oral

• Measure levels at midpoint of treatment (IM injections given weekly)

• Full effects last 11 days

• Brand only

What are AEs and clinical pearls of estradiol valerate (IM)?

• Fluctuations in AEs

• Less thromboembolic risk than oral

• Measure level at midpoint (IM injection given weekly)

• Full effects last 11 days

• Generic only

What are AEs and clinical pearls of transdermal estradiol (Vivelle-dot)?

• Skin reactions observed

• Least likely risk of thromboembolic events compared to IM and PO therapies

• Slower onset

• Can measure estrogen levels at anytime

What are counseling points of the transdermal estradiol patch?

• Do not cut the patch

• Adhesive does not work well sweaty, prolonged time in water

• Change patch 2x/week

What other AEs are observed with estrogen therapy?

• Decreased insulin sensitivity/DM

• Increased risk of DVT/PE

• Breast cancer risk is same as for cisgender women

• Bone mineral density preserved while on estrogen and antiandrogens

• Prostate cancer - not enough data

What are equivalencies of estrogen formulations?

What are our androgen lowering agents?

• Spironolactone - most common

• Finasteride/Dutasteride

• Leuprolide

What is the MOA of Spironolactone?

Binds to androgen receptor and directly inhibits testosterone production (antiandrogen)

What AEs are seen with Spironolactone? Which is one desired in GAHT?

• Hyperkalemia

• Gynecomastia → Desired effect in GAHT

• Hypotension

What is the MOA of Finasteride/Dutasteride?

5-alpha reductase inhibitors: Block conversion of testosterone to dihydrotestosterone (DHT)

It is an antiandrogen

What effects are seen with Finasteride/Dutasteride?

Decrease male pattern baldness

Used for benign prostatic hyperplasia

What is the MOA of leuprolide?

• It is a GnRH agonist, binds to GnRH receptors in the anterior pituitary → Allows for sustained receptor stimulation, leading to paradoxical down regulation and desensitization of pituitary GnRH receptors

What AEs are seen with leuprolide?

• Injection site pain

• Headaches

• Hot flashes

• Increased prolactin

Why are androgen lowering therapies and estrogen therapies sometimes used together?

Blocking testosterone allows the use of a lower estradiol dose

What forms of progesterone are used?

• Medroxyprogesterone (Provera)

• Micronized progesterone (Prometrium & Endometrin)

• Depo-Provera

How long is progesterone therapy used for? Why?

Only used for 3-6 months due to increased risk of CV events

Which progesterone agent is contraindicated in patients with peanut allergy?

Micronized progesterone (Prometrium & Endometrin) → It is dissolved in peanut oil

What AEs are seen with progesterone products?

• Possible increased risk of VTE

• Dizziness/somnolence

• Weight gain

What permanent effect does estrogen and anti-androgen therapies have?

Increase in breast tissue/size, seen anywhere between 3-6 months and 2-5 years

List of Estrogen and Anti-androgen effects

What are treatment recommendations for transwomen >40 years old?

• Consider adding aspirin

• Transdermal estradiol patch is preferred due to less VTE

• Smoking cessations interventions

• Adding statins

Can you use GAHT with antiretroviral therapy?

Yes, potential interactions should not prohibit use of ART

• INSTIs

  • Least potential to affect GAHT

  • No adjustments necessary

• Protease Inhibitors (PIs)

  • Limited data, impact unclear (may increase or decrease GAHT concentrations)

  • Monitor for AEs; titrate GAHT dose based on desired clinical effects and hormone concentration

What drug interactions does Estrogen have?

• Partially metabolized through CYP3A4

  • Watch out for inducers and inhibitors

• Truvada (TDF/FTC) used for HIV PrEP

  • TDF decreased slightly (12-27%) but still provided protection

  • No change in estrogen tho

What are the goals of transmasculine therapies? Which agents do we use?

• Goals

  • Promote the development of male secondary sex characteristics

  • Decrease secondary female sex characteristics

• Approaches to therapy

  • Testosterone

  • Vaginal Estrogen cream

  • Progesterone → to help stop menses

  • Hair loss prevention

  • Birth control

Which labs we do monitor in transmasculine therapy?

• Total testosterone

  • q3 months, up until 1 year + PRN

• Complete metabolic panel (LFTs/Glu/Alb)

  • q3 months, up until 1 year + PRN

• CBC (Hb/Hct)

  • q3 months up until 1 year, then yearly afterwards

What agents do we use for masculinization?

• Testosterone enanthate (sesame oil)

• Testosterone cypionate (cottonseed, olive, or grapeseed oil)

• Testosterone undecanoate (castor oil)

• Topical gel (Androgel)

Which testosterone formulations are injectable?

• Testosterone enanthate (sesame oil)

• Testosterone cypionate (cottonseed, olive, or grapeseed oil)

What AEs do testosterone enanthate/cypionate have?

Acne

Polycythemia

Sleep apnea

Dyslipidemia

Injection site reactions

Pelvic pain

Genital atrophy

Hot flashes

Emotional changes

For which testosterone formulation do we have to monitor 30 mins after for?

• Testosterone undecanoate (castor oil)

  • Rare cases of pulmonary oil micro embolism (POME) and anaphylaxis

  • Observe for 30 min after injection

What AE is seen with androgel?

Potential for secondary exposure

Hypersensitivity

Musky odor

How should androgel be applied?

• Apply to upper arms, shoulders

• Keep area dry for ≥2 hours after (no swimming, showering, sweating)

• Can check T levels at anytime

  • Less variation in levels than IM/SQ

Testosterone Formulation Equivalency

What are ways we can supplement transmasculine therapy?

• Estrogen cream to decrease vaginal atrophy - if desired

  • Start applying ~ 2 weeks prior to cervical cancer screening to ↓ pain

• Topical Minoxidil or oral Finasteride for androgenic alopecia

• Use of Progesterone

  • May help in the cessation of menses

  • Depo medroxyprogesterone 150 mg every 3 months or 5-10 mg PO HS

  • Discontinue after 3-6 months on testosterone if menses stop

• Birth control interventions

• Testosterone does not always eliminate ovulation

• Also, Testosterone will be converted into estrogen

Which effects/consequences of testosterone are permanent?

• Decreased fertility

• Increased clitoral size

• Increased facial and body hair

• Increased androgenic alopecia

• Voice deepening

What drug interactions does testosterone have?

• It is a CYP3A4 substrate

  • CYP3A4 inducers and inhibitors will affect testosterone levels

• P-gp substrate and inhibitor

• Increases the anticoagulant effects of Warfarin → Monitor INR

• Decreases blood glucose → May need to decrease the dose of diabetes medications

What is the goal testosterone level in transmasculine therapy?

300-1000 ng/dL

How often can we check testosterone levels during treatment?

• Check hormone levels at any time when using topical testosterone

• Check levels at the midpoint of the dosing interval when using injectable testosterone

What is the goal testosterone level in transfeminine therapy?

< 50ng/dL

What is the goal estradiol level in transfeminine therapy?

100-200 pg/mL