Platinum Priority – AndrologyEditorial by Raul I. Clavijo and Ranjith Ramasamy on pp. 1030–1031 of this issueVaricocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries☆
Introduction
Varicocele is the medical term for dilated, tortuous spermatic veins in the pampiniform plexus. In the adult general population, the prevalence is approximately 15% [1], [2], [3]. It is 35–44% in men with primary infertility and 45–81% in men with secondary infertility [4], [5]. The association between the presence of a varicocele and poorer semen quality is well documented in men presenting to fertility clinics [6] and in small-scale studies of patients not selected on fertility criteria [7], [8]. Several meta-analyses report improvements in semen quality following varicocelectomy in infertile men [9], [10]. However, far from all men with a varicocele are infertile [11].
Varicocele is most commonly observed on the left side, although some men are affected bilaterally. The isolated right-sided varicocele is rare [12]. The right testicular vein drains obliquely into the vena cava, whereas the left drains perpendicularly into the left renal vein, resulting in higher hydrostatic pressure on the left compared with the right side. Also believed to increase left-sided hydrostatic pressure is the so-called nutcracker effect with compression of the left renal vein between the aorta and the superior mesenteric artery [13], [14]. The exact pathophysiology behind the adverse effect of varicocele on semen quality remains uncertain. A number of proposed mechanisms have been examined including scrotal hyperthermia, altered testicular blood flow, increased venous pressure, hypoxia, testicular hormonal dysfunction, accumulation of toxic substances, and catecholamine reflux [13], [14].
Studies comparing reproductive hormones in infertile men with varicoceles with unaffected infertile men have reported conflicting results. Some reported higher follicle-stimulating hormone (FSH) among infertile men with varicoceles compared with controls but no difference in fertile men [15], whereas others detected no difference among infertile men with varicocele compared with controls [16]. Serum inhibin B was lower in men with varicocele compared with controls in some studies [16], [17] but not all [18]. Serum testosterone has been reported lower [16], unchanged [15], or higher in grade 3 varicocele patients compared with grade 1 [19].
Our present knowledge on the potential impact of varicoceles on semen quality and reproductive hormones is largely based on studies of subfertile and infertile men, as well as observations of increased prevalence in groups of men referred to fertility and urology clinics where the cause of infertility might not be limited to the varicocele. Even in cases where varicocele is the only discernible cause of infertility, preselection of infertile patients will include only the severely affected cases. The lack of large-scale population-based studies makes it difficult to extrapolate the impact of the varicocele on reproductive health to the general population. We therefore describe associations between varicocele and hormonal and semen variables in a large number of young men from general populations in Europe who were not selected due to fertility status, semen quality, or presence of varicocele to evaluate the potential impact of the varicocele on testicular function.
Section snippets
Materials and methods
The current study is based on a large cross-sectional investigation of semen quality in unselected young men from the general population, standardised and coordinated between six European countries. The local Science Ethics Committees approved the studies, and participants gave written informed consent before participation. Information about inclusion and assessment procedures were previously described in detail [20], [21]. We offer a very brief overview, with expanded details in Supplement 1.
Descriptions
Table 1 summarises the results from the physical examination and questionnaire. Most of the men were Danish. Age differed very slightly between the four varicocele subgroups, and BMI seemed lower with increasing grade of varicocele, most likely due to a slightly higher height across the varicocele groups. Median ejaculation abstinence was above the requested minimum of 48 h, but in all subgroups of men, some had shorter abstinence time (<11% in all groups; differences between groups were
Discussion
In this large-scale study of 7035 healthy young men from general European populations, the presence of varicocele was associated with poorer semen quality, even in men with the mildest form of varicocele (grade 1). In accordance, the concentrations of the spermatogenesis-related reproductive hormones FSH and inhibin B were associated with the presence of a varicocele. Men with varicocele also had a higher LH concentration, although testosterone and free testosterone levels did not significantly
Conclusions
Our large cross-sectional clinical study of men from the general population showed that semen quality was significantly impaired in men presenting with all grades of varicocele, even at the mildest stage, with the most severe impairment at higher grades.
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