Abstract and Introduction
Abstract
Context: The effects of androgen therapy on arterial function in transgender men (TM) are not fully understood, particularly concerning long-term androgen treatment.
Objective: To evaluate arterial stiffness in TM receiving long-term gender-affirming hormone therapy by carotid–femoral pulse wave velocity (cf-PWV).
Methods: A cross-sectional case–control study at the Gender Dysphoria Unit of the Division of Endocrinology, HC-FMUSP, Sao Paulo, Brazil. Thirty-three TM receiving intramuscular testosterone esters as regular treatment for an average time of 14 ± 8 years were compared with 111 healthy cisgender men and women controls matched for age and body mass index. Aortic stiffness was evaluated by cf-PWV measurements using Complior device post-testosterone therapy. The main outcome measure was aortic stiffness by cf-PWV as a cardiovascular risk marker in TM and control group.
Results: The cf-PWV after long-term testosterone therapy was significantly higher in TM (7.4 ± 0.9 m/s; range 5.8–8.9 m/s) than in cisgender men (6.6 ± 1.0 m/s; range 3.8–9.0 m/s, P < .01) and cisgender women controls (6.9 ± .9 m/s; range 4.8–9.1 m/s, P = .02). The cf-PWV was significantly and positively correlated with age. Analysis using blood pressure as a covariate showed a significant relationship between TM systolic blood pressure (SBP) and cf-PWV in relation to cisgender women but not to cisgender men. Age, SBP, and diagnosis of hypertension were independently associated with cf-PWV in the TM group.
Conclusion: The TM group on long-term treatment with testosterone had higher aging-related aortic stiffening than the control groups. These findings indicate that aortic stiffness might be accelerated in the TM group receiving gender-affirming hormone treatment, and suggest a potential deleterious effect of testosterone on arterial function. Preventive measures in TM individuals receiving testosterone treatment, who are at higher risk for cardiovascular events, are highly recommended.
Introduction
The goals of gender-affirming hormone therapy using testosterone in transgender men (TM) are to promote the interruption of menstrual cycles and to induce virilization by producing a male pattern of facial and body hair growth, clitoral enlargement, and increased muscle mass.[1] These effects promote the phenotypic gender transition.
Long-term androgen treatment effects on the cardiovascular systems of TM are not yet well established, because most of the literature data are based on small cohorts of younger TM, who have received gender-affirming hormone therapy for a short period of time.[2–4]
Some of the potential side effects of androgen treatment for TM, such as erythrocytosis, weight gain, hypertension, and lipid abnormalities, are known to be risk factors for cardiovascular diseases (CVDs).[5]
The exact role of male sex hormones in arterial vessels is not well recognized, but sex steroids seem to be able to modulate arterial properties. An indirect effect of testosterone, through estrogen originating from the peripheral aromatization of testosterone, has been demonstrated in the vasculature.[6] Additionally, direct testosterone action on arterial vessels has been suggested by evidence of androgen receptor expression in both the endothelial and smooth muscle cells of multiple vessels.[7]
Increased cardiovascular risk and progression of subclinical arterial disease has been established in cisgender women with endogenous hyperandrogenism.[8] Furthermore, cardiovascular comorbidities, including systemic arterial hypertension and endothelial dysfunction, have been observed in young women with polycystic ovary syndrome who are chronically exposed to androgen excess.[9,10] The current evidence for the role of testosterone therapy in the atherogenic profile and cardiovascular risk in cisgender women is controversial. Some studies that evaluated the chronic use of testosterone in climacteric patients demonstrated an increase in arterial vasodilation,[11–13] while others showed an increase in ischemic arterial disease and coronary disease.[14]
Changes in the structural and functional properties of the large arteries are correlated with increased cardiovascular risk in different populations.[15,16] Nonclassical cardiovascular risk markers, such as arterial stiffness estimated by carotid–femoral pulse wave velocity (cf-PWV) measurements and carotid structure evaluated by carotid intima–media thickness measurements, are recommended by different guidelines for the complementary assessment of subclinical atherosclerosis and as predictors of additional cardiovascular risk.[17,18]
Some studies have demonstrated the effects of testosterone on these markers in different conditions. A more androgenic profile of endogenous sex hormones was associated with worse endothelial function in a large cohort of postmenopausal women analyzed in the Multi-Ethnic Study of Atherosclerosis (MESA).[19] Moreover, patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, a disease of adrenal origin that is manifested by adrenal failure and hyperandrogenism, presented higher values of carotid intima–media thickness than control subjects.[20]
Central arterial stiffness, aortic stiffness, has emerged as a strong cardiovascular risk factor.[21] The cf-PWV, a methodology to measure aortic stiffness, has been shown to have good accuracy in estimating cardiovascular and all-cause mortality risk, and an excellent accuracy to estimate cardiovascular mortality.[22] The cf-PWV is the recommended arterial stiffness measurement method according to the American Heart Association scientific statement,[23] the European expert consensus document,[24] and European Society of Cardiology and the European Society of Hypertension guidelines for the management of arterial hypertension[25] due to the large preponderance of longitudinal data from cohort studies. The cf-PWV, a parameter with simple reproducibility and high reliability, has been considered the gold standard method for assessing aortic stiffness.[24,26]
Although not all studies are in concordance, transgender literature has suggested that TM receiving testosterone therapy may be at higher risk for myocardial infarction and that the vascular changes might be an underlying mechanisms.[27,28] Testosterone therapeutic use in the TM represents a particular model for evaluating this relationship between an exogenous source of testosterone and vascular modifications in 46,XX subjects.
In this study, we evaluated arterial stiffness by cf-PWV measurements of TM after long-term testosterone therapy to investigate the presence of subclinical atherosclerosis and to establish a predictor of cardiovascular risk.
J Endo Soc. 2023;7(5) © 2023 Endocrine Society
