Acquired Male Hypogonadism in the Post-Genomic Era-A Narrative Review

Giuseppe Grande; Andrea Graziani; Luca De Toni; Andrea Garolla; Domenico Milardi; Alberto Ferlin

doi:10.3390/life13091854

Therapeutics · Hormonal Agents

Acquired Male Hypogonadism in the Post-Genomic Era-A Narrative Review

Grande G, Graziani A, De Toni L, Garolla A, Milardi D, Ferlin A

Published September 2023 Life (Basel, Switzerland)

DOI 10.3390/life13091854 PMID 37763258 PMC PMC10532903

RRM Academy Synopsis

Semen from 20 men with secondary hypogonadism lacked 33 of 61 proteins

A narrative review of hypogonadism studies reports that in 20 men with secondary hypogonadism, 33 of 61 semen proteins found in controls were missing in all of them. Fourteen of the 33 reappeared after 6 months of testosterone replacement.

Key Findings

Semen proteomics compared 20 men with hypogonadotropic hypogonadism (low testosterone from a pituitary cause) with 10 normogonadic controls. Of 61 proteins found in controls, 33 were missing in all patient samples.
After 6 months of testosterone replacement therapy, 14 of the 33 missing proteins were found in patients' semen. Seven of those 14 fell in a protein-protein network centered on the androgen receptor.
Sperm proteomics compared 5 men with isolated LH deficiency and oligozoospermia with 5 fertile control men. Of 986 proteins found, 43 were differentially expressed: 32 reduced and 11 increased in the patients.
Serum metabolomics compared 15 men with hypogonadism and normal insulin sensitivity with 15 controls. Men with functional hypogonadism (obesity and insulin resistance) were studied before and after 60 days of testosterone replacement.
Testosterone replacement was associated with decreased free carnitine in patients with primary hypogonadism and with the development of ketone bodies in patients with functional hypogonadism.

Interpretation

The paper is a narrative review, an expert summary of the literature. The authors include their own studies of semen proteins, sperm proteins and blood metabolites. The protein studies enrolled 5 to 20 patients each. The authors write that further studies are needed to learn whether the semen protein panel can be used in clinical practice. They describe the metabolic changes after testosterone replacement as associations.

RRM Context

Restorative reproductive medicine evaluates both partners. The male partner's hormones belong in that workup. The review calls functional hypogonadism potentially treatable and names obesity and type 2 diabetes among its suspected causes. Men who lost weight often saw testosterone rise in the population studies cited. The review lists desire of fatherhood as a reason to avoid testosterone replacement.

Our editorial summary of this paper, not the article's abstract.

Abstract

Although precision medicine took its first steps from genomic medicine, it has gone far beyond genomics, considering the full complexity of cellular physiology. Therefore, the present time can be considered as the "post-genomic era". In detail, proteomics captures the overall protein profile of an analyzed sample, whilst metabolomics has the purpose of studying the molecular aspects of a known medical condition through the measurement of metabolites with low molecular weight in biological specimens. In this review, the role of post-genomic platforms, namely proteomics and metabolomics, is evaluated with a specific interest in their application for the identification of novel biomarkers in male hypogonadism and in the identification of new perspectives of knowledge on the pathophysiological function of testosterone. Post-genomic platforms, including MS-based proteomics and metabolomics based on ultra-high-performance liquid chromatography-HRMS, have been applied to find solutions to clinical questions related to the diagnosis and treatment of male hypogonadism. In detail, seminal proteomics helped us in identifying novel non-invasive markers of androgen activity to be translated into clinical practice, sperm proteomics revealed the role of testosterone in spermatogenesis, while serum metabolomics helped identify the different metabolic pathways associated with testosterone deficiency and replacement treatment, both in patients with insulin sensitivity and patients with insulin resistance.

Topics

Therapeutics › Hormonal Agents › Androgens and DHEA · Diagnostics › Hormone Testing › Serum Panels · Male Fertility › Male Endocrine and Genetic Factors › Male Hormonal Axis

Giuseppe Grande, Andrea Graziani, Luca De Toni, Andrea Garolla, Domenico Milardi, Alberto Ferlin

G Grande, A Graziani, L Toni, A Garolla, D Milardi, A Ferlin

PMID 37763258 37763258 DOI 10.3390/life13091854 10.3390/life13091854 Grande et al. 2023, Grande 2023

Acquired Male Hypogonadism in the Post-Genomic Era-A Narrative Review

Semen from 20 men with secondary hypogonadism lacked 33 of 61 proteins

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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