The effects of testosterone on transgender males on carotid intima-media thickness and serum inflammatory markers compared within patients with polycystic ovary syndrome

Balık, Ayşe Özlem; Vural, Fisun; Alpogan, Okşan; Özoğul, Murat; Dönmez, Emin Erhan

doi:10.1080/09513590.2022.2112942

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…A review of clinical data on the effects of testosterone administration in female-to-male transgender patients does not show a significant increase in overall cardiovascular events [ 7 ]. While a recent systematic review highlights mixed results, some individual studies find that androgen therapy in transitioning patients significantly increases arterial stiffness as well as carotid intima-media thickness [ 10 – 12 ]. Similarly, hormone therapy in the female-to-male transgender population increases the incidence of PCOS, resulting in a higher risk for obesity and associated cardiometabolic disturbances [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Dihydrotestosterone induces arterial stiffening in female mice

Horton,

Wilkinson,

Kilanowski-Doroh

et al. 2024

Biol Sex Differ

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Background Androgens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido. Androgens also circulate at higher levels in women with polycystic ovarian syndrome, a condition that increases the risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via downregulation of GPER. Methods The impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice at 15–16 weeks of age were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n = 8–9/group). Results In cultured vascular smooth muscle cells, GPER mRNA was decreased by DHT (P = 0.001) but was not impacted by dexamethasone or medroxyprogesterone. In contrast, ERα expression in cultured cells was significantly suppressed by all three hormones (P < 0.0001). In control mice or mice treated with a single or double dose of DHT, a dose-dependent increase in body weight was observed (control 22 ± 2 g, single dose 24 ± 2 g, double dose 26 ± 2 g; P = 0.0002). Intracarotid stiffness measured via pulse wave velocity showed a more than two-fold increase in both DHT-treated groups (control 1.9 ± 0.3 m/s, single dose 4.3 ± 0.8 m/s, double dose 4.8 ± 1.0 m/s). This increase in arterial stiffness occurred independent of changes in blood pressure (P = 0.59). Histological analysis of aortic sections using Masson’s trichrome showed a significant decrease in collagen between the control group (24 ± 5%) and the double dose group (17 ± 3%, P = 0.007), despite no changes in aortic wall thickness or smooth muscle content. Lastly, ddPCR showed that in vivo DHT treatment decreased aortic expression of both GPER (control 20 ± 5, single dose 10.5 ± 5.6, double dose 10 ± 4 copies/ng; P = 0.001) and ERα (control 54 ± 2, single dose 24 ± 13, and double dose 23 ± 12 copies/ng; P = 0.003). Conclusions These findings indicate that androgen promotes arterial stiffening and cardiovascular damage in female mice and is associated with decreased estrogen receptor expression. These data are important for transgender men, women using testosterone for fitness or reduced libido, as well as patients with polycystic ovarian syndrome.

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Section: Discussionmentioning

confidence: 99%

Dihydrotestosterone induces arterial stiffening in female mice

Horton,

Wilkinson,

Kilanowski-Doroh

et al. 2024

Biol Sex Differ

View full text Add to dashboard Cite

show abstract

“…While a recent systematic review highlights mixed results, some individual studies find that androgen therapy in transitioning patients significantly increases arterial stiffness as well as carotid intima-media thickness [36][37][38]. Similarly, hormone therapy in the female-to-male transgender population increases the incidence of PCOS, resulting in a higher risk for obesity and associated cardiometabolic disturbances [39].…”

Section: Discussionmentioning

confidence: 99%

Dihydrotestosterone Induces Arterial Stiffening in Female Mice

Horton

Wilkinson

Kilanowski‐Doroh

et al. 2023

Preprint

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Background: Testosterone is the predominant sex hormone in men and is increased in women with polycystic ovarian syndrome. These patients also experience an increased risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via regulation of GPER. Methods: The impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n=8-9/group). Results: GPER mRNA was only decreased by DHT (P=0.001), while ERα expression was significantly suppressed by all hormones (P<0.0001). While blood pressure was not different between groups (P= 0.59), there was a dose-dependent increase in body weight (control 22±2 g, single dose 24±2 g, double dose 26±2 g; P=0.0002). Intracarotid stiffness measured via pulse wave velocity showed a more than two-fold increase in both DHT-treated groups (control 1.9±0.3 m/s, single dose 4.3±0.8 m/s, double dose 4.8±1.0 m/s). Histological analysis of aortic sections using Masson’s trichrome showed a significant decrease in collagen between the control group (24 ± 5%) and the double dose group (17 ± 3%, P=0.007), despite no changes in aortic wall thickness or smooth muscle content. Lastly, ddPCR showed that in vivo DHT treatment decreased aortic expression of both GPER (control 20±5, single dose 10.5 ± 5.6, double dose 10±4 copies/ng; P=0.001) and ERα (control 54±2, single dose 24±13, and double dose 23 ± 12 copies/ng; P=0.003). Conclusions: These findings indicate that testosterone promotes arterial stiffening and cardiovascular damage in female mice and is associated with decreased estrogen receptor expression. These data are important not only for polycystic ovarian syndrome patients but also women using testosterone for fitness, gender transitioning, or reduced libido.

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The cardiovascular subtleties of testosterone on gender-affirming hormone therapy

Santos

Neto

Tostes

2023

American Journal of Physiology-Heart and Circulatory Physiology

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The growing number of people who identify themselves as transgender has gained increased attention in recent years and will certainly impact personalized clinical practices and healthcare worldwide. Transgender and gender non-conforming individuals frequently undergo gender-affirming hormone therapy (GAHT), i.e. they use sex hormones to align their gender identity with their biological characteristics. Testosterone is the main compound used in GAHT by transmasculine people, leading to the development of male secondary sexual characteristics in these individuals. However, sex hormones, testosterone included, also influence hemodynamic homeostasis, blood pressure, and cardiovascular performance by direct effects in the heart and blood vessels, and by modulating several mechanisms that control cardiovascular function. In pathological conditions and when used in supraphysiological concentrations, testosterone is associated with harmful cardiovascular effects, requiring close attention in its clinical use. The present review summarizes current knowledge on the cardiovascular impact of testosterone in biological females, focusing on aspects of testosterone use by transmasculine people (clinical goals, pharmaceutical formulations, and impact on the cardiovascular system). Potential mechanisms whereby testosterone may increase cardiovascular risk in these individuals are discussed, and the influence of testosterone on the main mechanisms that control blood pressure and that potentially lead to hypertension development and target-organ damage are also reviewed. Additionally, current experimental models, which are key to reveal testosterone mechanistic aspects and potential markers of cardiovascular injury, are reviewed. Finally, research limitations and the lack of data on cardiovascular health of transmasculine individuals are considered, and future directions for more appropriate clinical practices are highlighted.

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The effects of testosterone on transgender males on carotid intima-media thickness and serum inflammatory markers compared within patients with polycystic ovary syndrome

Cited by 5 publications

References 28 publications

Dihydrotestosterone induces arterial stiffening in female mice

Dihydrotestosterone induces arterial stiffening in female mice

Dihydrotestosterone Induces Arterial Stiffening in Female Mice

The cardiovascular subtleties of testosterone on gender-affirming hormone therapy

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