Testicular Microvascular Flow Is Altered in Klinefelter Syndrome and Predicts Circulating Testosterone

Abstract

Context Experimental studies on Klinefelter syndrome (KS) reported increased intratesticular testosterone (T) levels coexisting with reduced circulating levels. Abnormalities in testicular microcirculation have been claimed; however, no studies investigated in vivo testicular blood flow dynamics in humans with KS. Objective To analyze the testicular microcirculation in KS by contrast-enhanced ultrasonography (CEUS) and correlate vascular parameters with endocrine function. Design and Setting Prospective study. University Setting. Patients 68 testicular scans, 34 testes from 19 T-naïve subjects with KS and 34 testes from age-matched eugonadal men (CNT) who underwent CEUS for incidental nonpalpable testicular lesions. Main Outcomes. CEUS kinetic parameters. Results CEUS revealed slower testicular perfusion kinetics in subjects with KS than in age-matched CNT. Specifically, the wash-in time (Tin, p = 0.018), mean transit time (MTT, p = 0.035), time to peak (TTP, p < 0.001), and washout time (Tout 50%, p = 0.004) were all prolonged. Faster testicular blood flow was associated with higher total T levels. Principal component analysis and multiple linear regression analyses confirmed the findings, and supported a role for reduced venous blood flow as independent predictor of total T levels. Conclusions Testicular venous blood flow is altered in KS and independently predicts T peripheral release.

Repeat Microdissection Testicular Sperm Extraction in Azoospermic Men with Nonmosaic Klinefelter Syndrome

“…Significant enrichment in Leydig cell within a testicular biopsy sample can 4 Andrologia likely explain the excessive production of testosterone, whereas the markedly increased intratesticular/serum testosterone ratio was believed to result from altered testicular vascularization and dynamic perfusion. These all indicated that impairment of testosterone released into the systemic circulation rather than inhibited testicular steroidogenesis was the cause of hypogonadism in men with KS [21].…”

“…Our result demonstrated that patients with successful sperm recovery at their 2nd mTESE attempt appeared to have relatively high baseline testosterone and an adequate response to medical treatment. Since better testicular perfusion kinetic, particularly venous blood flow, was associated with relatively higher serum testosterone level [21], we postulated that patients with successful sperm recovery at their 2nd mTESE attempt presented with less disturbed testicular circulation, thus better overall testosterone releasing capability. Additionally, it is plausible that these patients with successful 2nd attempt may have a higher sperm reserve that is sufficient for repeated recovery, which is supported by the fact that improved testicular vascularization correlates with a higher serum testosterone level.…”

Testicular microlithiasis in paediatric patients with Klinefelter syndrome from infancy till adolescence: early start of degenerative process in the testes—preliminary results

“…This contradiction has been explained by a disturbed vascularity around the Leydig cells in KS testes since reduced artery diameters were previously found in KS men as well as an increased vessel density of the smallest blood vessels (0–100 µm 2 ) in prepubertal KS tissue [ 33 , 35 , 36 ]. In a recent in vivo study by Carlomagno et al [ 37 ], contrast-enhanced ultrasonography (CEUS) revealed slower testicular perfusion kinetics that was associated with lower total testosterone levels in subjects with KS [ 37 ].…”

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

“…Uterine and placental MD predispose to the onset of preeclampsia [46,47] and to early postnatal microvascular rarefaction and development of MD in offspring [48,49]. Finally, testicular MD and penile skin MD are linked to endocrine disturbances and the future development of hypertension and CV diseases [50,51]. Collectively, an integrative approach to understanding MD is needed to implement effective early diagnosis and treatment strategies.…”