Testosterone Serum Levels Are Related to Sperm DNA Fragmentation Index Reduction after FSH Administration in Males with Idiopathic Infertility

Abstract

Purpose: Although a robust physiological rationale supports follicle stimulating hormone (FSH) use in male idiopathic infertility, useful biomarkers to evaluate its efficacy are not available. Thus, the primary aim of the study was to evaluate if testosterone serum levels are related to sperm DNA fragmentation (sDF) index change after FSH administration. The secondary aim was to confirm sDF index validity as a biomarker of FSH administration effectiveness in male idiopathic infertility. Methods: A retrospective, post-hoc re-analysis was performed on prospectively collected raw data of clinical trials in which idiopathic infertile men were treated with FSH and both testosterone serum levels and sDF were reported. Results: Three trials were included, accounting for 251 patients. The comprehensive analysis confirmed FSH’s beneficial effect on spermatogenesis detected in each trial. Indeed, an overall significant sDF decrease (p < 0.001) of 20.2% of baseline value was detected. Although sDF resulted to be unrelated to testosterone serum levels at baseline, a significant correlation was highlighted after three months of FSH treatment (p = 0.002). Moreover, testosterone serum levels and patients’ age significantly correlated with sDF (p = 0.006). Dividing the cohort into responders/not responders to FSH treatment according to sDF change, the FSH effectiveness in terms of sDF improvement was related to testosterone and male age (p = 0.003). Conclusion: Exogenous FSH administration in male idiopathic infertility is efficient in reducing sDF basal levels by about 20%. In terms of sDF reduction, 59.2% of the patients treated were FSH-responders. After three months of FSH administration, a significant inverse correlation between sDF and testosterone was detected, suggesting an association between the FSH-administration-related sDF improvement and testosterone serum levels increase. These observations lead to the hypothesis that FSH may promote communications or interactions between Sertoli cells and Leydig cells.

Are they functional hypogonadal men? Testosterone serum levels unravel male idiopathic infertility subgroups

“…This implies that a subset of subjects, albeit limited, may exhibit conditions such as cryptorchidism, varicocele, and other factors potentially associated with infertility, even if not clinically demonstrated. In addition, testosterone serum levels measurements were performed using immunometric assays, that could be less accurate - especially for low values—if compared to the gold standard method, i.e., liquid chromatography-mass spectrometry [ 65 ]. Moreover, the testosterone serum level threshold selected to classify patients is not demonstrated to be the most accurate to discriminate eugonadal/hypogonadal patients, although supported by available literature.…”

Circle(s) of Life: The Circadian Clock from Birth to Death

“…As a result, the ability of females in terms of reproduction rapidly drops to zero, whereas andropause in men is characterized by a rather gradual reduction in testosterone levels over decades [ 152 ]. This testosterone level reduction, however, has only little effect on the viability of sperm cells and, thus, the principal ability to reproduce [ 153 , 154 , 155 ].…”

Sperm DNA fragmentation testing in clinical management of reproductive medicine

“…As a result, several studies have focused on therapies that can modulate the hypothalamic–pituitary‐gonadal axis and/or the peripheral conversion of hormones to explore their impact on SDF. Some evidence suggests that letrozole (a peripheral aromatase inhibitor) or direct administration of follicle‐stimulating hormone (FSH) can significantly reduce SDF and contribute to successful intrauterine pregnancy 117,118 . Age, baseline testosterone levels, and testicular volume may be predictors of response to FSH administration 117,118 .…”

“…Some evidence suggests that letrozole (a peripheral aromatase inhibitor) or direct administration of follicle‐stimulating hormone (FSH) can significantly reduce SDF and contribute to successful intrauterine pregnancy. 117 , 118 Age, baseline testosterone levels, and testicular volume may be predictors of response to FSH administration. 117 , 118 Regarding treatment regimens, there is currently no definitive evidence to guide specific paradigms.…”