9/29/2020
Pharmacology of HRT
~Victoria LB Grieve, PharmD
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Introduction • Victoria Grieve, PharmD • Asst. Prof./Instructional Designer • Coordinate LGBTQIA+ Elective • PRIDE list member • GSWS Affiliated faculty
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Disclosures
I have no financial disclosures
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Objectives
● Describe the role of hormone therapy in transition care. ● Discuss nuances of different hormone transition regimens. ● Evaluate common misconceptions around HRT
● Understand HRT recommendations from guidelines ● Discuss the reasoning behind those guidelines
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My Assumptions
● All familiar with nuances of gender/sex/expression ● Agree that HRT isn’t for everyone but is extremely necessary for those who need it ● Being trans is a normal aspect of humanity ● We are all here with the patient’s best interests in mind
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Why Hormone Therapy
● Physical: ○ Help with bodily autonomy ○ Re-align physical with mental image of self ● Psychological: ○ Connect with expected emotions ○ Brain receptor theory
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Common Guidelines - Baseline for HRT
● WPATH (last updated 2011) ● UCSF (last updated 2016)
● Standard vs Informed Consent ● “Trans enough” vs “Informed enough”
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Criteria for Care - Both
● Persistent, well-documented gender dysphoria* ● Capacity to make a fully informed decision and to consent for treatment* ● Age of majority* ● If significant medical or mental health concerns are present, they must be reasonably well controlled*
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Limits to Therapy
● Genetics ● Age ○ Human Growth Hormone ● Wildcard
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Feminizing Therapy
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Feminizing Therapy Effect Expected Onset Expected Max Effect Decreased Libido* 1 – 3 Months 1 – 2 Years Male Sexual Dysfunction* Highly Variable Highly Variable Body Fat Redistribution 3 – 6 Months 2 – 5 Years Decreased Muscle Mass 3 – 6 Months 1 – 2 Years Skin Changes 3 – 6 Months Highly Variable Breast Growth 3 – 6 Months 2 – 3 Years* Decreased Testicular Vol. 3 – 6 Months 2 – 3 Years Decreased Sperm Prod. Highly Variable Highly Variable Reduced Body/Facial Hair 6 – 12 Months > 3 Years Male Pattern Baldness* Loss stops 1 – 3 Months 1 – 2 Years
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Feminizing Therapy - Risks
● Autoimmune disorders* ● Migraines* ● Gallstones* ● Many “non-clinically significant”* ● Venous Thromboembolism
● **Can always start with lower dose if concerned
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Feminizing Therapy - Risks
● Venous Thromboembolism ○ Increased effect of other risk factors ○ VTE Triad: ■ Exogenous estrogen (oral) ■ Smoking tobacco ■ Age > 35
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Feminizing Therapy - Options
● Standard regimen: ○ Estradiol + Antiandrogen ● Options: ○ Type of Estradiol (PO, SL, TD, IM, SubQ?) ○ Type of AA (Spiro, Finasteride, Bicalutamide?) ○ Progestin (Micronized Progesterone)
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Feminizing Therapy - Monitoring
● Guidelines suggest: ○ BUN/Cr/K+ ○ Lipids ○ A1C ○ Prolactin(?) ○ Estradiol (E2)/Total Estrogen (E1,E2,E3) ○ Testosterone
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Feminizing Therapy - Monitoring
● Guidelines suggest: ○ Estrogen level = “endogenous female range, luteal phase” ○ 100 - 200 pg/mL* ○ Estrogen cycle*
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Feminizing Therapy - Tablets
● Estradiol Tablets ○ Start 2 - 4mg, Split dose if possible ○ Max recommended = 8mg/day ● PO vs SL ● Escalation dose?
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Feminizing Therapy - Patches
● Estradiol Transdermal Patch ○ Start 0.1mg, switch twice a week (brand dependant) ○ Max recommended = 0.4mg ● Steady release, avoids first-pass ● Can be a burden with multiple patches ● Thought to be safest option, but rarely used
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Feminizing Therapy - Injection
● Estradiol Intramuscular Injection - 2 types ○ Valerate: Start 20mg, q2wk, Max = 40mg q2wk ○ Cypionate: Start 2mg, q2wk, Max = 5mg q2wk ● Can split into weekly doses* ● Faster breast growth? ● SubQ?
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Feminizing Therapy - Antiandrogens
● Spironolactone - aldosterone antagonist ○ Start 50mg BID or 100mg QD ○ Max Recommended = 200mg BID or 400mg QD ● Potassium concern? ● Breast growth concern? ● Urination!
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Feminizing Therapy - Antiandrogens
● Finasteride - 5-alpha-reductase inhibitor (DHT) ○ Start 1mg QD PO ○ Max Recommended = 5mg QD PO ● Possibly better for hair growth ● Dutasteride also possible to use
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Feminizing Therapy - Antiandrogens
● Bicalutamide? ○ Possible, expensive, rare ● Cyproterone acetate? ○ Not legal in US, used in other countries as first line ● Needed at all? ○ Depends on person, possibly only at beginning
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Feminizing Therapy - Progestins
● Micronized Progesterone ○ Start 100mg PO QHS ○ Max Recommended = 200mg PO QHS* ● Controversial use (breast, hips, skin, hair, mood) ● Will make drowsy, help sleep ● Medroxyprogesterone? ● Don’t stick it in your butt!
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Masculinizing Therapy
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Masculinizing Therapy Effect Expected Onset Expected Max Effect Skin Changes 1 – 6 Months 1 – 2 Years Cessation of Menses 2 – 6 Months n/a Body/Facial Hair Growth 3 – 6 Months 3 – 5 Years Body Fat Redistribution 3 – 6 Months 2 – 5 Years Clitoral Enlargement 3 – 6 Months 1 – 2 Years Vaginal Atrophy 3 – 6 Months 1 – 2 Years Deepened Voice 3 – 12 Months 1 – 2 Years Increased Muscle Mass 6 – 12 Months 2 – 5 Years Scalp Hair Loss >12 Months Highly Variable
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Masculinizing Therapy - Risks
● Acne/Balding* ● Hyperlipidemia* ● Destabilization of psychiatric disorders** ● Polycythemia
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Masculinizing Therapy - Risks
● Polycythemia ○ Thrombogenic erythrocytosis ○ Reason T is a controlled substance ○ Unlikely to be clinically significant
● Pregnancy is absolute contraindication
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Masculinizing Therapy - Options
● Standard Therapy: ○ Testosterone ● Options: ○ Type of Testosterone (IM, TD, Implant, PO?) ○ Other supportive medications (E mods, finasteride, depo- provera)
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Masculinizing Therapy - Monitoring
● Guidelines suggest: ○ Lipids ○ A1C ○ Estradiol (E2) ○ Testosterone ○ SHBG/Albumin (complex cases only)
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Masculinizing Therapy - Monitoring
● Guidelines suggest: ○ Testosterone level = “endogenous male range, average” ○ 350 - 700 ng/dL*
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Masculinizing Therapy - Injection
● Testosterone Intramuscular Injection -2 types ○ Enanthate: Start 50mg, Qwk, Max = 100mg Qwk ○ Cypionate: Start 50mg, Qwk, Max = 100mg Qwk ● Sesame vs Cottonseed oil ● IM or SubQ
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Masculinizing Therapy - Transdermal
● Testosterone Transdermal Patches ○ Start 4mg QPM, Max = 8mg QPM ● Testosterone Transdermal Cream/Gel ○ Start 50mg QAM, Max = 100mg QAM ● Risk of accidental exposure
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Masculinizing Therapy - Other T-options
● Testosterone Pellets ○ 75mg pellets, implanted subQ every 3-6 months ● Testosterone Undecanoate Injection ○ 750mg Q4wks, eventually Q10wks ● Testosterone Undecanoate Capsule? ○ Recent release, could be used in future
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Masculinizing Therapy - Other Medications
● Depo-Provera, 150mg Q3months ○ Can be used to halt stubborn menses ● Finasteride, 1mg QD ○ Can be used to halt balding, but will conflict with T=>DHT ● Aromatase Inhibitors ○ Prevents estrogen production from androgens
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HRT Summary
● Guidelines are fine, with some blind spots ○ Not recently updated ○ Dubious evidence to be built from ○ Uphold transmedicalist attitude ● Lack of strong evidence allows for misinformation ● Trans men are men (in all ways) ● Trans women are women (in all ways)
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Questions?
Email: [email protected] [email protected]
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References
1. Deutsch, M. B. (Ed.). (2016). Guidelines for the primary and gender-affirming care of transgender and gender nonbinary people. University of California, San Francisco. 2. World Professional Association for Transgender Health. (2011). Standards of care for the health of transsexual, transgender, and gender nonconforming people. World Professional Association for Transgender Health. 3. Grant, J. M., Mottet, L. A., Tanis, J., Herman, J. L., Harrison, J., & Keisling, M. (2010). National transgender discrimination survey report on health and health care. Washington, DC: National Center for Transgender Equality and the National Gay and Lesbian Task Force. 4. Haas, A. P., Rodgers, P. L., & Herman, J. L. (2014). Suicide attempts among transgender and gender non- conforming adults. work, 50, 59. 5. Meerwijk, E. L., & Sevelius, J. M. (2017). Transgender population size in the United States: a meta- regression of population-based probability samples. American journal of public health, 107(2), e1-e8.
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References
6. National Center for Transgender Equality. 2015 U.S. Transgender Survey. http://www.ustranssurvey.org. Published December 2016. Accessed September 4, 2018. 7. Legal, L., & New York City Bar Association. (rev 2016). Creating equal access to quality health care for transgender patients: Transgender-affirming hospital policies. 8. Rosendale, N., Goldman, S., Ortiz, G. M., & Haber, L. A. (2018). Acute Clinical Care for Transgender Patients: A Review. JAMA Internal Medicine. 9. Coleman, E., Bockting, W., Botzer, M., Cohen-Kettenis, P., DeCuypere, G., Feldman, J., ... & Monstrey, S. (2012). Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. International journal of transgenderism, 13(4), 165-232.
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