Reproductive Endocrinology Reference Intervals for Transgender Men on Stable Hormone Therapy

Abstract

Background Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but 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-Müllerian 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.

Sex and Gender Differences in Clinical Pharmacology: Implications for Transgender Medicine

“…The World Professional Association for Transgender Health and other professional organizations endorse individualized hormone regimens, 7 and several sex hormone preparations, administration routes, and doses are available based on patient preference, affordability, and individual drug safety profiles 32,33 . Changes in laboratory parameters during hormone therapy are listed in Table 3 10,34–39 …”

“…Sex hormone preparations, doses, and adjunctive agents varied across cohorts. Cisgender reference intervals were unavailable for all studies; we included reference intervals from Greene et al 35 . for reader interest, although interlaboratory variability may influence comparisons among referenced studies.…”

“…Clinicians may adjust testosterone doses to achieve desired therapeutic effects during the first year of treatment 33 . Before initiating testosterone treatment, sex hormone concentrations are generally within reference ranges for premenopausal cisgender females (total testosterone, 0–75 ng/dL; estradiol (follicular phase), 12–233 pg/mL) 35 ( Table 3 ). In a prospective clinical cohort of transgender men taking at least 12 months of testosterone treatment in the United States ( n = 82), the upper limit of the total testosterone reference range was numerically higher than the cisgender male reference interval (e.g., total testosterone: 199–1149 vs. 249–836 ng/dL, respectively) 35 .…”

“…Before initiating testosterone treatment, sex hormone concentrations are generally within reference ranges for premenopausal cisgender females (total testosterone, 0–75 ng/dL; estradiol (follicular phase), 12–233 pg/mL) 35 ( Table 3 ). In a prospective clinical cohort of transgender men taking at least 12 months of testosterone treatment in the United States ( n = 82), the upper limit of the total testosterone reference range was numerically higher than the cisgender male reference interval (e.g., total testosterone: 199–1149 vs. 249–836 ng/dL, respectively) 35 . Individual testosterone concentrations may vary based on the route of hormone administration, hormone dose, and timing of blood sample relative to the last administered hormone dose.…”

Research gaps in medical treatment of transgender/nonbinary people

“…Many transgender women seek hormone treatment to better align their bodies with their gender identities (1,2). The current approach relies on reference ranges for testosterone levels as the main treatment target to decrease testosterone levels from the male range (300-1000 ng/dL) to the female range (<50 ng/ dL), although such levels are not always achieved (50,51). While orchiectomy is the most effective means to decrease testosterone levels, many transgender women opt only for medical treatment, Work from the Veterans Health Administration has identified health disparities among transgender veterans (16,(22)(23)(24)(25).…”