Gender-Affirming Primary Care

Educational Objectives

The goal of this program is to improve management of patients seeking gender-affirming care. After hearing and assimilating this program, the clinician will be better able to:

1. Advise patients on the course and outcome of hormone therapy.
2. Choose the appropriate drug, route of administration, and dosage to minimize adverse effects of hormone therapy.

Summary

Gender vs sex: sex is based on biological characteristics evident at birth, ie, chromosomes, sex organs; gender is an internal sense of being male, female, neither, or both; the gender identity of cisgender persons aligns with the sex recorded at birth; the gender identity of transgender persons aligns with the inverse of the sex recorded at birth; the gender identity of nonbinary/gender-nonconforming persons is not aligned with either male or female sex; may have features of both or neither

Gender dysphoria: a diagnosis from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition of discomfort or distress stemming from a misalignment of the sex recorded at birth and gender identity; gender incongruence is a proposed term for persons whose gender identity does not align with the sex recorded at birth

Patient care: an affirming environment should be provided; clinicians should use the patient’s chosen pronouns and names verbally and in the electronic medical record (EMR); a gender inclusive environment is recommended (with, eg, signage, gender neutral bathrooms, representative literature); staff members may require training; a diverse workforce and use of gender neutral language is recommended

Gender affirming treatment: medical or surgical interventions for gender nonconforming individuals; patients with untreated gender dysphoria are at high-risk for morbidity and mortality

Types of gender affirmation: social transition refers to self-presentation, eg, naming, clothing, hairstyle, pronouns; medical transition aims to achieve desired gender-related features through, eg, hormone therapy, hair removal, speech therapy; surgical transition may include chest, facial, or genital surgeries; legal transition involves changing names and gender markers on legal documentation

Criteria for hormone therapy: patients must have persistent and well-documented gender dysphoria, the capacity to make a fully informed decision, and be of age; medical or psychosocial comorbidities must be well controlled before starting therapy

Gender-affirming providers: primary care providers may diagnose gender dysphoria and prescribe treatments; initial visit — the patient’s gender dysphoria should be identified, described, and documented; the patient should be asked to specify what is dysphoric in their experience of gender; the goals of the gender affirmation plan should be recorded; all prior treatments, complications, or previous providers should be documented; providers should elicit a patient’s family history and potential risk factors (eg, diabetes, obesity, blood clots, mental illness); patients should be informed of the 3 A's of hormone therapy, ie, affirming, annoying, and adverse effects; highlighting the limits of hormones in effecting change is recommended; a patient’s reproductive plans should be discussed; baseline laboratory reports should be obtained; provision of educational resources and the timeline for hormone therapy is beneficial; second visit — providers may repeat discussions of, eg, reproductive plans, abnormal laboratory results, understanding of educational materials, the 3 A's of hormone therapy, benefits of treatment, consent; written consent is not required for hormone therapy

Feminizing hormone therapy: 17-beta estradiol is exclusively used for treatment; ethinyl estradiol should not be used; may be administered orally, sublingually, or with an injection or patch; the primary anti-androgen is spironolactone; 5-α reductase inhibitors or progesterone also may be used; effective for the suppression of male-pattern baldness; timeline — libido and spontaneous erections decrease during transition; body fat is redistributed; muscle mass decreases; skin softens and breast growth begins; testicular volume can be expected to decrease; terminal hair growth decreases and male pattern baldness may occur at a later stage; adverse effects — increased risk for venous thromboembolic disease, hypertriglyceridemia, gallstones, weight gain, and transaminitis; patients also are at risk for, eg, cardiovascular disease, hypertension, diabetes, hyperprolactinemia, acute kidney injury, hyperkalemia, orthostatic hypotension, emotional instability

Contraindications: patients with active blood clots may still be treated; administering transdermal formulations with concomitant anticoagulation is required; patients with end-stage liver disease, active and unstable cardiac disease, and active hormone-sensitive cancers are not eligible

Practical considerations: the transdermal patch is associated with a lower risk for blood clots; multiple patches often are required for adequate dosing; patients ≥40 yr of age should receive transdermal formulations or be given aspirin; estrogen may affect the metabolism of other drugs (eg, pre-exposure prophylaxis drugs, anti-epileptic drugs); patients who are not good candidates for hormone therapy may benefit from early orchiectomy; breast development may be facilitated by starting with low doses of estradiol, without spironolactone

Masculinizing hormones: testosterone is given intramuscularly (IM), transdermally, or as a gel (eg, Androgel, Axiron, Fortesta); progestins may be used for menstrual suppression; patients may develop severe and cystic acne; cessation of menses and increased sex drive are expected; clitoral enlargement, vaginal atrophy and fat redistribution occurs at 3 to 6 mo; facial and body hair growth, scalp hair loss (which may be treated with finasteride), increased muscle mass, and change in vocal tones occur at 6 mo; clitoral enlargement, terminal thickness and coarseness of body hair and facial hair, and deepening of voice are irreversible

Adverse effects of testosterone: patients may experience, eg, polycythemia, weight gain, obstructive sleep apnea (OSA); additional risks include hyperlipidemia, hypertension, transaminitis, destabilization of mood disorders, and diabetes; an increased risk for breast cancer, ovarian cancer, cervical cancer, uterine cancer, or bone loss has not been observed; contraindications — unstable psychiatric illness, polycythemia with hematocrit >55%, unstable coronary disease, pregnancy, hormone sensitive cancers, and undiagnosed vaginal bleeding; the goal level for testosterone is ≤1100 ng/dl; testosterone is limited by polycythemia; the clinical target is cessation of menses at 6 mo; estradiol may be suppressed to a level of 15 to 30 pg/ml; alpha blockade may treat male pattern baldness

Hormone treatment considerations: patient goals, potential adverse effects, and response to treatment determines increases in dosage; a low dose may titrated upwards every 2 to 3 mo; patients should be assessed for, eg, side effects, affirming characteristics, weight change, blood pressure (BP) changes, mental health status, laboratory reports; the final dose is commonly ≈100 mg testosterone IM weekly or 4 to 6 mg estradiol daily; estradiol levels of patients on estrogen should be monitored; a basic metabolic panel can give spironolactone levels; total testosterone levels and hematocrit should be monitored in patients receiving testosterone therapy; changes in BP, weight, and mood should be recorded

Primary care: patients are at high-risk for sexually transmitted diseases and HIV; patients ≥65 yr of age should be screened for osteoporosis; also screen patients 50 to 64 yr of age with risk factors or patients who recently underwent gonadectomy without hormone therapy >5 yr; screening for cancer is based on anatomy

Readings

Cahill S, Singal R, Grasso C, et al. Do ask, do tell: high levels of acceptability by patients of routine collection of sexual orientation and gender identity data in four diverse American community health centers. PLOS ONE. 2014; 9(9): e107104; Goldstein Z, Khan M, Reisman T, Safer JD. Managing the risk of venous thromboembolism in transgender adults undergoing hormone therapy. J Blood Med. 2019;10:209-216. Published 2019 Jul 10. doi:10.2147/JBM.S166780; Harris MS, Goodrum BA, Krempasky CN. An introduction to gender-affirming hormone therapy for transgender and gender-nonbinary patients. Nurse Pract. 2022;47(3):18-28. doi:10.1097/01.NPR.0000819612.24729.c7; Korpaisarn S, Chiewchalermsri D, Arunakul J, Chinthakanan O, Poomthavorn P, Sriphrapradang C. Effects of testosterone treatment on transgender males: a single-institution study. SAGE Open Med. 2021;9:20503121211051546. Published 2021 Oct 10. doi:10.1177/20503121211051546; Safer JD, Tangpricha V. Care of the transgender patient. Ann Intern Med. 2019; 171:ITC1-ITC16; Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877-884. doi:10.21037/tau.2016.09.04; Wierckx K, Elaut E, Van Hoorde B, et al. Sexual desire in trans persons. J Sex Med. 2014; 11: 107-118.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Tilstra was recorded at 2021 Update in Internal Medicine (UIM): Advances Changing Practice, held October 21-22, 2021, and presented by University of Pittsburgh School of Medicine. For information on future CME activities from this presenter, please visit https://meded.dom.pitt.edu/. Audio Digest thanks the speakers and the University of Pittsburgh School of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

Lecture ID:

IM693501

Qualifies for:

ABIM MOC

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.