The following article is part of our coverage of the Endocrine Society’s annual meeting (ENDO 2021) that is being held virtually from March 20-23, 2021. Endocrinology Advisor‘s staff will report on the top research in hormone science and clinical care. Check back for the latest news from ENDO 2021.
In late 2020, the Endocrine Society and the Pediatric Endocrine Society released their latest position statement on transgender health.1 According to the statement authors, there has been a “rapid expansion” in the understanding of both gender identity and the implications of providing gender-affirming care to transgender and gender diverse individuals.
This year’s annual meeting of the Endocrine Society — ENDO 2021, held virtually from March 20 to March 23 — included a robust session on transgender care. Twenty-one presentations covered topics from optimal hormone therapy dosing to mental health to clinical practice guidelines. Of particular interest, though, was the role of gender-affirming hormone therapy.
A team of Brazilian researchers, led by Leonardo A.M. Alvares, MD, from the Endocrinology Department at the University of Sao Paolo in Sao Paolo, Brazil, presented 4 of these crucial studies. Specifically, Dr Alvares and colleagues examined how gender-affirming hormone therapy impacts patients’ body composition,2 muscle strength,3 and cardiovascular (CV) systems.4,5
Methodology of the Study
Each study utilized the same cohort of patients: 8 transgender women, 8 cisgender men, and 8 cisgender women, matched by age and body mass index. Transgender women (mean age, 34.0±4.8 years) had not undergone a gonadectomy and were undergoing estrogen plus cyproterone acetate therapy (transdermal estradiol n=2, oral estradiol n=3, conjugated estrogen n=3) over an average of 15.6 (±8.7) years of treatment.2-5
At the time of studies, mean total testosterone levels were 83.5 ng/dL (range, 12.0-637.0 ng/dL) in transgender women, 20.5 ng/dL (range, 12.0-41.0 ng/dL) in cisgender women, and 480.5 ng/dL (range, 264.0-843.0 ng/dL) in cisgender men.
According to Dr Alvares and colleagues, there are few studies evaluating body composition in transgender women on long-term, gender-affirming hormone therapy.2 Results of a cross-sectional study showed that overall, the percentage of fat mass was lower in transgender women compared with cisgender women (29.59±7.56 vs 32.9±3.99; P =.5394) and higher compared with cisgender men (23.58±6.44; P =.1512).
Skeletal muscle mass, though, was higher (33.6%) compared with cisgender women and lower (14.7%) compared with transgender men.2 Among cisgender men, the Baumgartner Index measure was 17.7% higher than the transgender women group, which was in turn 20.3% higher than cisgender women (P =.001 and .002, respectively).2
“[Body composition] changes in the first two years of [gender-affirming hormone therapy] in [transgender women] were consistent with loss of lean mass and gained fat mass associated with an increase in body weight,” Dr Alvares and colleagues wrote, adding that — unlike young transgender women who undergo short-term gender-affirming hormone therapy — body composition parameters among transgender women using estrogen plus cyproterone acetate (study n=8) “did not present [a percentage of fat mass] statistically different from [cisgender women] and [cisgender men].” 2
Long-Terms Results of Treatment
In a second study, researchers sought to evaluate the muscular strength of transgender women undergoing long-term gender-affirming hormone therapy. 3 While cisgender women may typically be weaker than cisgender men, these differences in strength disappear when strength is expressed relative to body weight or fat free mass, suggesting that both innate muscle qualities and motor control mechanisms are similar regardless of sex. The effects of previous pubertal testosterone exposure, though, are still relatively unknown.3
Participant strength was measured via handgrip strength tests using the Stoelting handheld hydraulic dynamometer. Mean maximum strength was 31.9 (±2.4) kg, 29.2 (±4.4) kg, and 47.5 (±8.6) kg in transgender women, cisgender women, and cisgender men, respectively. In each group, free fat mass was measured as 55.56 (±6.88) kg, 38.98 (±4.09) kg, and 64.98 (±6.29) kg, respectively. When evaluated as median strength by free fat mass, means of 0.54 in transgender women and 0.76 in cisgender men and cisgender women were observed.3
Results of this study, the researchers noted, indicate that there are “important functional changes” in the intracellular oxidation mechanism, elucidated by a decrease in muscle unit functionality in transgender women after beginning gender-affirming hormone therapy.
Impacts on the Cardiovascular System
In their final studies, Dr Alvares and colleagues focused on the implications of gender-affirming hormone therapy on the cardiovascular system. The first of these studies sought to evaluate the cardiovascular (CV) risk factors associated with long-term gender-affirming hormone therapy use in transgender women — as few data regarding long-term CV risks currently exist. 4
Laboratory values for total mean testosterone (reported above), median blood glucose; HbA1c; total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; and triglycerides were collected for all groups. Compared with cisgender men and cisgender women, the researchers found no statistically significant differences. In particular, they emphasized that HDL cholesterol in transgender women was “exactly the same” as that of cisgender men (P >.999) and lower than that of cisgender women (43 mg/dL vs 60 mg/dL; P =.0720).4
Systolic blood pressure was higher in transgender women compared with cisgender women (126±13 mmHg vs 95±11 mmHg) but equal to cisgender men (115±9 mmHg). Median diastolic blood pressure was 80 mmHg, 60 mmHg, and 80 mmHg, respectively.4
In an evaluation of cardiopulmonary capacity of transgender women, mean maximum VO2 (VO2max) in transgender women was 2648 (±575.5) L/min, compared with a mean VO2max of 2128 (±394.0) L/min and 3235 (±554.0) L/min in cisgender women and cisgender men, respectively). 5 Analyses of VO2max/free fat mass found rates of 46.6 (±6.2) L/min/kg in transgender women, 54.6 (±8.4) L/min/kg in cisgender women, and 49.4 (±6.1) L/min/kg in transgender men.
While O2 pulse, ventilatory equivalents (VE)/VO2, and VE/VCO2 were similar across groups, a high correlation of O2 pulse and free fat mass/height2 was observed in transgender women but not cisgender men or women. Percentage of predicted heart rate at effort was also higher in transgender women compared with cisgender women and cisgender men.
Results of these final 2 studies indicate that metabolic findings in transgender women appear to be consistent over the long-term, with increases in both systolic and diastolic blood pressure over time.4 Cardiopulmonary measures like VO2max are similar between transgender and cisgender women, despite previous exposure to testosterone in transgender women.5
“These preliminary results should be confirmed,” the researchers concluded, “by increasing the number of individuals studied.”5
Across all 4 studies, one key commonality stands out: Regardless of the specific topic, data has either been not reported or has been reported scarcely. This dearth of data in the current literature underscores just how much work remains to be done in the field of transgender care.
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1. Transgender health position statement. The Endocrine Society and the Pediatric Endocrine Society. https://www.endocrine.org/advocacy/priorities-and-positions/transgender-issues. Published December 2020. Accessed March 18, 2021.
2. Alvares LAM, Santos LM, Santos MR, et al. Body composition of transgender women after long-term hormone therapy — a cross-sectional study. Presented at: ENDO 2021; March 20-23, 2021; Presentation P43-3
3. Alvares LAM, Santos MR, Souza FR, et al. Muscle strength in transgender women after long-term hormone therapy: a cross sectional study. Presented at: ENDO 2021; March 20-23, 2021; Presentation P43-4
4. Alvares LAM, Santos LM, Ramos HA, et al. Cardiovascular risk factors in transgender women undergoing long-term gender-affirming hormone therapy: a cross sectional study. Presented at: ENDO 2021; March 20-23, 2021; Presentation P43-5
5. Alvares LAM, Santos MR, Souza FR, et al. First evidence of cardiopulmonary adaptation to physical effort in transgender women after long-term hormone therapy: a cross-sectional study. Presented at: ENDO 2021; March 20-23, 2021; Presentation P43-6