An update on male infertility and intratesticular testosterone—insight into novel serum biomarkers

Sidhom, Karim; Panchendrabose, Kapilan; Mann, Uday; Patel, Premal

doi:10.1038/s41443-021-00507-7

Cited by 9 publications

(7 citation statements)

References 64 publications

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“…From a physiological point of view, the strict connection between seminiferous and interstitial testicular compounds is expected, since effective spermatogenesis requires both FSH action and adequate intratesticular testosterone levels [ 28 ]. However, this link has been generally underestimated in clinical practice, since intratesticular testosterone assessment is very complex, requiring testicular biopsy or sampling [ 29 ]. In addition, testosterone measured in the peripheral blood correlates poorly to its intratesticular levels, which are estimated to be at least 100 times higher [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, testosterone measured in the peripheral blood correlates poorly to its intratesticular levels, which are estimated to be at least 100 times higher [ 30 ]. For these reasons, several attempts have been made to identify surrogate markers of intratesticular testosterone levels [ 29 ]. Among these, serum 17-hydroxyprogesterone (17-OHP) and Insulin-like factor 3 (INSL3) have been proposed [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

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

Lispi

Drakopoulos²,

Spaggiari

et al. 2022

Biomedicines

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Lispi

Drakopoulos²,

Spaggiari

et al. 2022

Biomedicines

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“…To date, the decrease in male fertility is thought to be due to the negative feedback of androgens on the HPG axis, thus diminishing spermatogenesis and, in the long run, decreasing testicular volume. Of note, even though the circulating testosterone levels are at supraphysiological concentrations during the AAS cycle, the intratesticular testosterone concentration lowers due to the hypogonadotropic state induced by AAS usage ( Sidhom et al, 2022 ), which diminishes the testosterone production via the Leydig cells ( Sidhom et al, 2022 ). Specifically, the Leydig cells under the AAS abuse effect might decrease their population because of the AAS-induced hypogonadotropic state ( Feinberg et al, 1997 ).…”

Section: Anabolic Androgenic Steroids and Male Infertilitymentioning

confidence: 99%

Abusive use of anabolic androgenic steroids, male sexual dysfunction and infertility: an updated review

Azevedo,

Gualano,

Teixeira

et al. 2024

Front. Toxicol.

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The evolving prevalence of anabolic androgenic steroids (AAS) abuse among nonathletes is alarming because of the known harm to an individual’s health. Among the adverse effects of AAS abuse, male infertility and sexual dysfunction have been often reported in the literature, but little is known regarding its actual prevalence, possible underpinning mechanisms, and potential treatments either during or post-AAS usage. Thus, the current narrative review summarizes the state-of-art regarding the effects of AAS on male fertility and sexual function. Evidence was gathered from the latest reviews and recent original studies, specifically from prospective cohorts and clinical trials, ultimately resulting in five main topics of discussion. First, AAS usage is briefly characterized by its historical background, main physiological mechanisms, and the most frequently used AAS substances. Second, data on the prevalence of AAS-induced male infertility and sexual dysfunction are described. Third, some new insights on possible underpinning mechanisms of AAS-induced male infertility and sexual dysfunction are thoroughly discussed, with particular attention to histological data derived from animal models and the latest insights from prospective cohorts in humans. Fourth, the potential treatments during and after the AAS usage are presented, highlighting the odds of resolving male infertility and sexual dysfunction. Fifth, future directions on this topic are discussed, focusing on the methodological robustness of scientific studies.

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“…The clinical findings of this are oligospermia, decreased morphology, and motility [16]. Within the testicle, testosterone is produced by Leydig Cells with a minimum intratesticular testosterone being vital for intact spermatogenesis [17]. Growing evidence suggests that varicoceles also appear to be implicated as a possible risk factor for low testosterone, with recent studies demonstrating that previously hypogonadal men will become eugonadal at a rate of 60–80% following varicocele repair [18].…”

Section: Anatomic Risk Factorsmentioning

confidence: 99%

Counseling for the man with severe male infertility

Belladelli

Muncey

Seranio

2022

Current Opinion in Urology

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Purpose of reviewThis review summarize the proper counseling for men with severe male factor infertility.Recent findingsMen who are experiencing infertility should have a semen analysis, the results of which may imply additional investigations, including genetic and hormonal. Moreover, possible modifiable factors that may harm men's reproductive health should be carefully evaluated. Finally, different treatment options are available.SummaryApproximately 15% of couples struggle with infertility. Complete evaluations of both men and women are required to determine the etiology of infertility and determine appropriate treatment.

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An update on male infertility and intratesticular testosterone—insight into novel serum biomarkers

Cited by 9 publications

References 64 publications

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

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

Abusive use of anabolic androgenic steroids, male sexual dysfunction and infertility: an updated review

Counseling for the man with severe male infertility

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