The present meta-analysis is the largest to date to assess the impact of VR on Leydig cell and Sertoli cell function using a before-after analysis for uncontrolled studies, and using data from patients with unrepaired varicoceles or healthy patients without varicocele as controls. VR was found to increase and restore to normality serum levels of total testosterone and LH. This evidence could be of value in considering the treatment of varicocele in patients with low testosterone or those who show a progressive decline in testosterone levels.
Male hypogonadism is defined by a reduced production of testosterone by the testis, ascribed to a primary dysfunction of the gonad or to a lack of stimulation of the testes by the hypothalamic-pituitary axis. The latest guidelines of the Endocrine Society consider the value of 264 ng/dL (9.2 nmol/L) as the cut-off for the diagnosis of hypogonadism, in the presence of symptoms suggestive of the disease . The 2022 position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS), however, set the cut-off at 346 ng/dL, highlighting the lack of consensus on the serum testosterone value below which diagnosis of hypogonadism can be made.
Hypogonadism may be observed in patients with male infertility. This includes those with varicocele, which may impair Leydig cell function. It is commonly reported in men with variable prevalence, depending on their age, fertility status, and the method to diagnose varicocele. In a large study of 7,035 young healthy men, median age 19 years, from the general population of six European countries and do not selected for infertility, 15.7% had clinical varicoceles. In this study, the presence of varicocele was associated with poorer semen quality, higher serum levels of follicle-stimulating hormone (FSH), lower inhibin B, and higher levels of luteinizing hormone (LH). However, in this study, testosterone and free testosterone were not significantly different between patients with and without varicocele and healthy men.
The link between varicocele and deterioration of spermatogenesis is well established. Nevertheless, varicocele could also impair Leydig cell function leading to reduced testosterone synthesis which is a significant risk factor for hypogonadism and spermatogenesis failure. Although still controversial, evidence supporting positive effect of varicocele repair (VR) on serum testosterone levels has been demonstrated in experimental and clinical studies. The proposed detrimental effects of varicocele are suggested to be related to oxidative stress, heat stress, local hormonal imbalances, testicular hypoperfusion, and stasis of blood with accumulation of toxins. The evidence that varicocele decreases Leydig cell production of testosterone is increased. Some studies indicate the presence of low testosterone levels in patients with varicocele and their improvement after VR. However, no definitive conclusion has been reached due to opposite results from other studies.
Given the controversial effects of VR on testicular steroidogenesis, the aim of this systematic review and meta-analysis was to investigate the impact of VR on serum total testosterone (TT), LH, FSH, and inhibin B levels in patients with clinical varicocele, whose varicocele was treated due to testicular pain or as part of infertility management. The results of the current review may allow the development of clear guidelines on the management of these varicocele-associated endocrine abnormalities.
https://link.springer.com/content/pdf/10.1007/s10815-024-03030-y.pdf
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