Background
Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear.
Aims
We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias.
Methods
Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age (range) 1.5 (1.2, 2.7) yrs) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17β-estradiol, dihydrotestosterone (DHT) and testosterone.
Results
In controls, testosterone and 17β-estradiol increased contraction (Emax: 83.74 basal vs 125.4 after testosterone, p < 0.0002 and 83.74 vs 110.2 after estradiol, p = 0.02). 17β-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine (ACh), p < 0.0001 and Emax: 14.6 vs 20.5 to sodium nitroprusside (SNP), p < 0.0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, p = 0.01) and 17β-estradiol (Emax: 156.9 vs 23.6, p < 0.0001) reduced contraction. Androgens, but not 17β-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, p = 0.02 and vs 48.2 with DHT to ACh, p = 0.0001; Emax: 43.0 vs 39.5 with testosterone, p = 0.02 and vs 39.6 vs 37.5 with DHT to SNP, p = 0.04).
Conclusion
In healthy boys, testosterone and 17β-estradiol promote a vasoconstrictor phenotype whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone independent and the impact of early-life variations in androgen exposure on vascular function needs further study.