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Abstract Hypoxia is a potent stimulator for angiogenesis and glycolysis. It is generally detrimental to tissue function. Irrespective of the dynamics of blood flow, recent studies have demonstrated tissue hypoxia in experimental models of varicocele (90). Lee et al(91)studied the expression of hypoxia inducible factor (HIF-1) in the internal spermatic vein samples of 8 patients with grade 3 varicoceles. HIF-1 is one of the principal regulators of response to hypoxia. They noted significantly higher levels of HIF-1 in the patients with varicoceles, when compared with a group of 6 men who did not have varicocele. Tissue hypoxia has also been seen in a rat model of varicoceles, and was associated with increased angiogenesis (92). 4-Reflux of renal and adrenal metabolites: The role of refluxing adrenal steroids as a cause of impaired spermatogenesis in men with varicoceles has been first suggested in 1965 by Macloed (83). This theory of adrenal and renal metabolite reflux stems from early anatomical radiographic studies documenting the reflux of blood from the renal vein into the internal spermatic vein (93). Reflux of blood down the testicular vein has been demonstrated in patients with varicocele(94). In humans, the mean concentration of catecholamines in refluxing testicular venous blood obtained during surgery compared to the peripheral blood was 3-folds |