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. 2024 May;84(2):757-767.
doi: 10.1007/s12020-024-03717-3. Epub 2024 Feb 19.

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

Giorgia Spaggiari  1   2 , Francesco Costantino  1   3 , Leonardo Dalla Valentina  1   3 , Marilina Romeo  1   3 , Chiara Furini  1   3 , Laura Roli  4 , Maria Cristina De Santis  4 , Giulia Canu  4 , Tommaso Trenti  4 , Antonio R M Granata  1   2 , Manuela Simoni  1   3 , Daniele Santi  5   6   7
Affiliations

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

Giorgia Spaggiari et al. Endocrine. 2024 May.

Abstract

Purpose: To evaluate total testosterone distribution in male idiopathic infertility.

Methods: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL).

Results: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020).

Conclusion: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile.

Keywords: FSH; Hypogonadism; Idiopathic; Male infertility; Testosterone.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Total testosterone serum levels distribution in the cohort of idiopathic infertile men (A), and controls (B). C shows together cases and controls
See this image and copyright information in PMC

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