Endocrine Testing in Transgender Adults

Treatment Monitoring

Youth and Adolescents

For recommendations for adolescents, refer to the Endocrine Society Clinical Practice Guideline.  The UCSF Transgender Care and Treatment Guidelines  and WPATH Standards of Care  also offer guidance for children and adolescents.

Adult Transgender Males on Testosterone Hormone Therapy

Monitoring of Hormone Therapy

The Endocrine Society Clinical Practice Guideline  and WPATH Standards of Care  recommend that serum testosterone concentrations be measured every 3 months until serum testosterone is within the reference interval for an adult cisgender male. The UCSF Transgender Care and Treatment Guidelines  suggest that annual monitoring is reasonable after reaching the desired range. The WPATH Standards of Care  suggest monitoring once or twice a year after the first year of hormone therapy. The timing of measurements depends on the type of therapy used.

• For testosterone enanthate/cypionate injections, the suggested serum testosterone concentration is 400-700 ng/dL; measurements can be taken either midway between injections or at peak and trough concentrations.  
• For parenteral testosterone undecanoate, the dose interval should be increased if testosterone concentrations are <400 ng/dL. Measurements should be taken right before the next injection (ie, at trough concentrations).  
• For transdermal testosterone, measurements should be taken no sooner than after 1 week of daily application and at least 2 hours after application.  

Testing can be performed using either tandem mass spectrometry or immunoassay. Tandem mass spectrometry is more specific and accurate across a wider range of concentrations and is preferable if low testosterone concentrations are expected (eg, at baseline or at initiation of some gender-affirming hormone therapies). Testing by immunoassay is accurate at higher hormone concentrations and may be more cost-effective when clinically appropriate (eg, for monitoring long-term gender-affirming hormone therapy use).

Free or bioavailable testosterone tests may provide supportive information for patients with unexpected responses to hormone therapy.  Free and bioavailable testosterone concentrations are typically estimated using calculations that include testosterone, albumin, and/or sex hormone-binding globulin (SHBG) measurements.  Tests that measure SHBG may be useful in individuals with protein-binding abnormalities. Equilibrium dialysis may be used for the direct measurement of free testosterone, but it is not frequently used as a first-line test for monitoring of hormone therapy. Calculated methods of determining free testosterone concentrations are sufficient in most clinical circumstances.

For a visual overview of testing associated with this topic, please refer to the Monitoring of Gender-Affirming Hormone Therapy testing algorithm.

For a comparison of ARUP testosterone tests, refer to the Testosterone Tests Comparison table.

Other Testing

In addition to serum testosterone measurements, the Endocrine Society Clinical Practice Guideline  recommends the following tests or assessments. Additional tests may also be recommended by other organizations.

• Clinical assessment of masculinization and monitoring for adverse reactions should be performed every 3 months in the first year, then once or twice annually. 
• Hematocrit or hemoglobin should be tested before beginning gender-affirming hormone therapy, then every 3 months during the first year of therapy, and then once or twice annually.  

Adult Transgender Females on Estrogen Hormone Therapy and/or Testosterone-Suppressing Hormone Therapy

Monitoring of Hormone Therapy

The Endocrine Society Clinical Practice Guideline  recommends that serum testosterone and serum estradiol concentrations be measured every 3 months. These and other guidelines suggest a goal of testosterone concentrations <50 ng/dL and serum estradiol concentrations within the peak physiologic range of 100-200 pg/mL.   The UCSF Transgender Care and Treatment Guidelines  recommend measurement of estradiol at 3 months, 6 months, and then as needed, and recommend total testosterone and SHBG/albumin (to calculate bioavailable testosterone) at 3 months, 6 months, and 1 year.

Testing can be performed using either tandem mass spectrometry or immunoassay. Tandem mass spectrometry is more specific and accurate across a wider range of concentrations and is preferable if low hormone concentrations are expected (eg, at baseline or at initiation of some gender-affirming hormone therapies). Testing by immunoassay is accurate at higher hormone concentrations and may be more cost-effective when clinically appropriate (eg, for monitoring long-term gender-affirming hormone therapy use). Equilibrium dialysis may be used to directly measure free estradiol in individuals on hormonal contraception and/or with protein-binding abnormalities.

Free or bioavailable testosterone tests may provide supportive information for patients with unexpected responses to hormone therapy.  Free and bioavailable testosterone concentrations are typically estimated using calculations that include testosterone, albumin, and/or SHBG measurements.  Tests that measure SHBG may be useful in individuals who have protein-binding abnormalities or are taking estrogen supplementation.

For a visual overview of testing associated with this topic, please refer to the Monitoring of Gender-Affirming Hormone Therapy testing algorithm.

For comparisons of ARUP estrogen and testosterone tests, refer to the Estrogen Tests Comparison and Testosterone Tests Comparison tables.

Other Testing

In addition to serum hormone measurements, the Endocrine Society Clinical Practice Guideline  recommends the following tests or assessments. Additional tests may also be recommended by other organizations.

• Clinical assessment of feminization and monitoring for adverse reactions should be performed every 3 months in the first year, then once or twice annually. 
• Serum electrolyte concentrations (particularly potassium concentrations) should be measured every 3 months in the first year, then annually in individuals on spironolactone.   An assessment of renal function (particularly creatinine) is also recommended.  
• The Endocrine Society Clinical Practice Guideline  recommends the periodic monitoring of prolactin concentrations in transgender individuals treated with estrogens.  The WPATH Standards of Care  suggest that, in consideration of accessibility and costs, prolactin monitoring should be based on clinical judgment informed by an individual’s specific treatment regimen and symptoms.

Preventive Care Screening

The following preventive screenings for applicable health risks are recommended as part of treatment monitoring. Other screenings may also be recommended.

• Osteoporosis screening should be performed in individuals who stop testosterone treatment or otherwise develop risk for bone loss. 
• Routine cancer screening should be performed for all tissues present.  For example, cervical cancer screening, if cervical tissue is present, should be performed according to the recommendations from the American College of Obstetricians and Gynecologists.   Breast cancer screenings for individuals who retain breast tissue should follow recommendations for cisgender women.  Alternative breast cancer screening strategies may be needed for individuals who have had a mastectomy.  Screening should be performed according to individual risk for prostatic disease and prostate cancer. 
• Cardiovascular disease risk should be assessed in transgender individuals treated with hormones.  This risk assessment should take into consideration an individual’s hormone regimen, duration of hormone use, age at which therapy was started, and serum hormone concentrations. 

Glossary

This glossary is presented solely to define terms as they are used in this ARUP Consult topic and the following resources:

• Monitoring of Gender-Affirming Hormone Therapy testing algorithm
• Testosterone Tests Comparison table
• Estrogen Tests Comparison table

This glossary is intended to facilitate appropriate laboratory test selection for individuals who are on gender-affirming hormone therapy. The terminology in this field changes rapidly, and these terms may be used differently by others and in different contexts.

Sex and Gender Terms

Cisgender female: An individual with a female gender identity who was assigned a female sex at birth.

Cisgender male: An individual with a male gender identity who was assigned a male sex at birth.

Gender: Nonbiologic characteristics (eg, behaviors, roles, social attributes) that a culture associates with an individual’s sex.  Gender identity is defined as an individual’s internal sense of their gender.   

Gender dysphoria: Distress associated with discordance between an individual’s gender identity and their sex assigned at birth.    

Sex: A combination of biologic characteristics (eg, chromosomes, genes, genitalia, gonads, hormones, secondary sex characteristics). Sex is often assigned at birth based on external genital anatomy.    

Transgender female: An individual with a female gender identity who was assigned a male sex at birth.   

Transgender male: An individual with a male gender identity who was assigned a female sex at birth.   

Hormone Therapy Terms

Estrogen hormone therapy: Hormone treatment intended to maintain exogenous estrogen within a desired range.

Estrogen-suppressing hormone therapy: Hormone treatment intended to suppress an individual’s endogenous estrogen to within a desired range. This may include aromatase inhibitor therapies.

Gender-affirming hormone therapy: Hormone treatment that is intended to help change an individual’s physical characteristics to best align with their gender identity. This may include therapies to suppress endogenous sex steroids and/or maintain exogenous sex steroids within a desired physiologic range.

Testosterone hormone therapy: Hormone treatment intended to maintain exogenous testosterone within a desired range.

Testosterone-suppressing hormone therapy: Hormone treatment intended to suppress an individual’s endogenous testosterone (or testosterone activity) to within a desired range. This may include antiandrogen therapies such as spironolactone and cyproterone.