madman
Super Moderator
Reproductive Endocrinology Reference Intervals for Transgender Men on Stable Hormone Therapy
Dina N. Greene, Robert L. Schmidt, Gabrielle Winston-McPherson, Jessica Rongitsch, Katherine L. Imborek, Jane A. Dickerson, Julia C. Drees, Robert M. Humble, Nicole Nisly, Nancy J. Dole, Susan K. Dane, Janice Frerichs, and Matthew D. Krasowskig
Background: Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but the interpretation of results can be difficult due to the lack of published reference intervals.
Methods: Healthy transgender individuals who had been prescribed testosterone (n=82) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, SHBG, prolactin, progesterone, anti-Mu¨llerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines.
Results: When evaluating general endocrine laboratory tests in people using masculinizing hormones, reference intervals for cisgender men can be applied for total and free testosterone and SHBG and reference intervals for cisgender women can be applied for prolactin. Reference intervals for estradiol, LH, FSH, AMH, and DHEAS differ from those used for cisgender men and cisgender women, and therefore should be interpreted using intervals specific to the transmasculine population. For testosterone and estradiol, results from immunoassays were clinically equivalent to mass spectrometry.
Conclusion: Masculinizing hormones will alter the concentrations of commonly evaluated endocrine hormones. Providers and laboratories should use appropriate reference intervals to interpret the results of these tests.
INTRODUCTION
Gender-affirming hormone therapy is the standard of care for transgender people who seek to medically transition (1). Testosterone is prescribed to people assigned female at birth that identifies as male (transgender male) or identify as being masculine of center (nonbinary; transmasculine). Testosterone administration promotes masculinizing secondary sex characteristics such as increased muscle mass, increase in facial and body terminal hair development, decreased vocal pitch, and cessation of menses (2). Additionally, testosterone administration will alter the concentrations of routinely monitored laboratory values, such as hemoglobin and hematocrit (3). Recent studies have shown that people administering gender-affirming testosterone for at least a year will have hematological parameters that parallel those of cisgender men (3).
Serum testosterone concentrations are commonly monitored in people who are prescribed gender-affirming hormone therapy (1). The Endocrine Society Guidelines state that testosterone should be measured every 3 months for the first year and at least annually thereafter. Suggested treatment goals are concentrations of 400–700 ng/mL, or to fall within the age-matched cisgender male reference interval (1). This recommendation is not graded within the guideline, indicating there is limited evidence in the medical literature to support the interval and that the range is empirically derived through clinical judgment. The guidelines have no mention of the expected or appropriate concentration interval for other endocrine markers specific to people on masculinizing hormones, although estradiol will commonly be measured, and in some cases, particularly if fertility is a goal, progesterone, LH, and/or FSH concentrations may also be evaluated (4, 5).
Interpretation of endocrine laboratory values in people on masculinizing therapy is limited by the lack of published literature establishing reference intervals specific to this population (6). The objective of this study was to establish reference intervals for common endocrine laboratory measurements in transgender people receiving masculinizing hormone therapy, specifically testosterone, estradiol, SHBG, FSH, LH, progesterone, prolactin, AMH, and DHEA-S. We selected these analytes because they are the most commonly measured endocrine-related analytes in the clinical laboratory and they have sex-specific reference intervals. Further, testosterone and estradiol are almost always evaluated before and after the initiation of gender-affirming therapy, even if threshold concentrations are empirically derived. An additional objective was to evaluate the adequacy of immunoassay measurements relative to mass spectrometry for testosterone and estradiol monitoring in this population.
In conclusion, we have derived reference intervals for common endocrine hormones in transgender people using testosterone therapy. These reference intervals can aid laboratories and providers in interpreting hormone concentrations in this population.
Dina N. Greene, Robert L. Schmidt, Gabrielle Winston-McPherson, Jessica Rongitsch, Katherine L. Imborek, Jane A. Dickerson, Julia C. Drees, Robert M. Humble, Nicole Nisly, Nancy J. Dole, Susan K. Dane, Janice Frerichs, and Matthew D. Krasowskig
Background: Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but the interpretation of results can be difficult due to the lack of published reference intervals.
Methods: Healthy transgender individuals who had been prescribed testosterone (n=82) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, SHBG, prolactin, progesterone, anti-Mu¨llerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines.
Results: When evaluating general endocrine laboratory tests in people using masculinizing hormones, reference intervals for cisgender men can be applied for total and free testosterone and SHBG and reference intervals for cisgender women can be applied for prolactin. Reference intervals for estradiol, LH, FSH, AMH, and DHEAS differ from those used for cisgender men and cisgender women, and therefore should be interpreted using intervals specific to the transmasculine population. For testosterone and estradiol, results from immunoassays were clinically equivalent to mass spectrometry.
Conclusion: Masculinizing hormones will alter the concentrations of commonly evaluated endocrine hormones. Providers and laboratories should use appropriate reference intervals to interpret the results of these tests.
INTRODUCTION
Gender-affirming hormone therapy is the standard of care for transgender people who seek to medically transition (1). Testosterone is prescribed to people assigned female at birth that identifies as male (transgender male) or identify as being masculine of center (nonbinary; transmasculine). Testosterone administration promotes masculinizing secondary sex characteristics such as increased muscle mass, increase in facial and body terminal hair development, decreased vocal pitch, and cessation of menses (2). Additionally, testosterone administration will alter the concentrations of routinely monitored laboratory values, such as hemoglobin and hematocrit (3). Recent studies have shown that people administering gender-affirming testosterone for at least a year will have hematological parameters that parallel those of cisgender men (3).
Serum testosterone concentrations are commonly monitored in people who are prescribed gender-affirming hormone therapy (1). The Endocrine Society Guidelines state that testosterone should be measured every 3 months for the first year and at least annually thereafter. Suggested treatment goals are concentrations of 400–700 ng/mL, or to fall within the age-matched cisgender male reference interval (1). This recommendation is not graded within the guideline, indicating there is limited evidence in the medical literature to support the interval and that the range is empirically derived through clinical judgment. The guidelines have no mention of the expected or appropriate concentration interval for other endocrine markers specific to people on masculinizing hormones, although estradiol will commonly be measured, and in some cases, particularly if fertility is a goal, progesterone, LH, and/or FSH concentrations may also be evaluated (4, 5).
Interpretation of endocrine laboratory values in people on masculinizing therapy is limited by the lack of published literature establishing reference intervals specific to this population (6). The objective of this study was to establish reference intervals for common endocrine laboratory measurements in transgender people receiving masculinizing hormone therapy, specifically testosterone, estradiol, SHBG, FSH, LH, progesterone, prolactin, AMH, and DHEA-S. We selected these analytes because they are the most commonly measured endocrine-related analytes in the clinical laboratory and they have sex-specific reference intervals. Further, testosterone and estradiol are almost always evaluated before and after the initiation of gender-affirming therapy, even if threshold concentrations are empirically derived. An additional objective was to evaluate the adequacy of immunoassay measurements relative to mass spectrometry for testosterone and estradiol monitoring in this population.
In conclusion, we have derived reference intervals for common endocrine hormones in transgender people using testosterone therapy. These reference intervals can aid laboratories and providers in interpreting hormone concentrations in this population.
