madman
Super Moderator
ABSTRACT
Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.
1. Introduction
Infertility is a global issue that affects approximately 15% of couples, with male factor infertility contributing to up to 50% of the cases [1,2]. Various etiologies for male infertility have been described, including congenital or acquired disorders of spermatogenesis, hormone abnormalities, and reproductive tract structural anomalies. Varicoceles, or abnormally dilated veins within the spermatic cord, including internal spermatic and pampiniform plexus veins, are a common cause of male factor infertility (Fig. 1). Varicoceles were first discovered in the 1st century A.D. by a Greek physician, Celsus, who noted that testis size was smaller due to "swollen and twisted" veins overlying the testicle [3,4]. The term varicocele, however, was not coined until 1843 by T.B. Curling, a British surgeon [4,5]. More recently, varicoceles have been shown to play a role in decreased testicular function, leading to altered spermatogenesis and diminished testosterone levels. This review discusses normal testicular function, varicocele pathophysiology, and effects on testicular function (specifically spermatogenesis and testosterone production), indications for varicocele repair, and options for varicocele management.
2. Epidemiology
3. Varicocele etiologies
4. Normal testicular function and physiology
4.1. Testicular structure
4.2. Testicular function
4.2.1. Testosterone production and hormonal regulation
4.2.2. Spermatogenesis and spermiogenesis
5. Varicocele and spermatogenesis
5.1. Oxidative stress and apoptosis
5.2. Altered expression of heat shock proteins and factors
5.3. Decreased expression of cold-inducible RNA-binding protein
5.4. Increased expression of hypoxic factors
5.5. Leukocytospermia
5.6. Toxin accumulation
5.7. Blood-testis barrier disruption
5.8. Oxidative stress and sperm DNA damage
6. Varicocele and testosterone production
7. Varicocele pathology
8. Clinical evaluation and management of varicoceles
8.1. Presentation
8.2. Evaluation
8.3. Varicocele examination
8.4. Indications for treatment
8.5. Varicocele management
9. Conclusions
Varicoceles are a common finding in men. The majority of men with varicoceles are asymptomatic. However, 3% of men with grade 3 varicoceles are at greatest risk for impaired testicular dysfunction and, in those men, conservative management should be microsurgical repair in order to preserve testicular function. Men with varicoceles should have a complete evaluation, and following review of treatment indications offered observation or varicocele repair. While precise mechanisms of effects on testicular function remain inconclusive, varicoceles appear to have negative impacts on spermatogenesis and testosterone production, which clinically manifest as male infertility and testosterone deficiency. More research is needed to shed light on mechanisms of varicocele-induced testicular dysfunction, so that new targeted therapies and treatments may be developed for men with varicoceles.
Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.
1. Introduction
Infertility is a global issue that affects approximately 15% of couples, with male factor infertility contributing to up to 50% of the cases [1,2]. Various etiologies for male infertility have been described, including congenital or acquired disorders of spermatogenesis, hormone abnormalities, and reproductive tract structural anomalies. Varicoceles, or abnormally dilated veins within the spermatic cord, including internal spermatic and pampiniform plexus veins, are a common cause of male factor infertility (Fig. 1). Varicoceles were first discovered in the 1st century A.D. by a Greek physician, Celsus, who noted that testis size was smaller due to "swollen and twisted" veins overlying the testicle [3,4]. The term varicocele, however, was not coined until 1843 by T.B. Curling, a British surgeon [4,5]. More recently, varicoceles have been shown to play a role in decreased testicular function, leading to altered spermatogenesis and diminished testosterone levels. This review discusses normal testicular function, varicocele pathophysiology, and effects on testicular function (specifically spermatogenesis and testosterone production), indications for varicocele repair, and options for varicocele management.
2. Epidemiology
3. Varicocele etiologies
4. Normal testicular function and physiology
4.1. Testicular structure
4.2. Testicular function
4.2.1. Testosterone production and hormonal regulation
4.2.2. Spermatogenesis and spermiogenesis
5. Varicocele and spermatogenesis
5.1. Oxidative stress and apoptosis
5.2. Altered expression of heat shock proteins and factors
5.3. Decreased expression of cold-inducible RNA-binding protein
5.4. Increased expression of hypoxic factors
5.5. Leukocytospermia
5.6. Toxin accumulation
5.7. Blood-testis barrier disruption
5.8. Oxidative stress and sperm DNA damage
6. Varicocele and testosterone production
7. Varicocele pathology
8. Clinical evaluation and management of varicoceles
8.1. Presentation
8.2. Evaluation
8.3. Varicocele examination
8.4. Indications for treatment
8.5. Varicocele management
9. Conclusions
Varicoceles are a common finding in men. The majority of men with varicoceles are asymptomatic. However, 3% of men with grade 3 varicoceles are at greatest risk for impaired testicular dysfunction and, in those men, conservative management should be microsurgical repair in order to preserve testicular function. Men with varicoceles should have a complete evaluation, and following review of treatment indications offered observation or varicocele repair. While precise mechanisms of effects on testicular function remain inconclusive, varicoceles appear to have negative impacts on spermatogenesis and testosterone production, which clinically manifest as male infertility and testosterone deficiency. More research is needed to shed light on mechanisms of varicocele-induced testicular dysfunction, so that new targeted therapies and treatments may be developed for men with varicoceles.
