A Cross-Sectional Study Reveals Hormonal Signatures of Smoking-Related Infertility

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F25%3A43927761" target="_blank" >RIV/62156489:43210/25:43927761 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/tre.70015" target="_blank" >https://doi.org/10.1002/tre.70015</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/tre.70015" target="_blank" >10.1002/tre.70015</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A Cross-Sectional Study Reveals Hormonal Signatures of Smoking-Related Infertility

Popis výsledku v původním jazyce

Cigarette smoking remains a common modifiable lifestyle risk factor for male infertility, yet the exact mechanisms linking smoking to overall fertility decline are not fully understood. This study investigates how smoking affects sperm quality deterioration and examines the potential role of hormonal pathways in mediating these effects. Robust causal approaches have been utilized to measure both the overall impact of smoking and its hormonal mediation on semen parameters. Additionally, a unidimensional Sperm Quality Index (SQI) has been developed and validated internally, while latent reproductive phenotypes have been analyzed through unsupervised clustering techniques. This observational study involved 104 infertile men, with 52 smokers and 52 nonsmokers. Inverse-probability-of-treatment weighting (IPTW) and augmented IPTW (AIPW) were used to balance 21 baseline covariates. Parallel mediation analysis evaluated four pituitary-gonadal hormones-follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone-as mediators of smoking&apos;s impact on five key semen parameters: concentration, total count, progressive motility, morphology, and live sperm percentage. Principal component analysis (PCA) was used to create a PCA-based SQI by combining nine logarithmically transformed, z-standardized variables. The mediation analysis was also repeated using the SQI. K-means clustering, using the gap statistic, identified four latent semen-hormone phenotypes. After IPTW, smoking was associated with standardized AIPW average treatment effects (ATEs) of -0.29 to -0.66 standard deviation (SD) across semen parameters (e.g., live sperm % ATE = -0.67, 95% confidence interval (CI) -1.01 to -0.33; morphology ATE = -0.40, 95% CI -0.75 to -0.05). Parallel mediation indicated LH as the principal mediator, explaining 40%-63% of smoking&apos;s total effect on individual outcomes. The PCA-derived SQI explained 65% of semen variance, and smoking&apos;s ATE on SQI was -0.44 SD (95% CI -0.80 to -0.07), with 66% mediated via hormones (suppression effect). Clustering revealed four phenotypes: (1) normozoospermic, (2) subclinical endocrinal disruption, (3) intermediate, and (4) severely impaired (high LH, low SQI), with smokers predominating cluster 4 (85% smokers vs. 15% nonsmokers). Cigarette smoking primarily impacts semen quality by disrupting endocrine hormones. The PCA-based SQI offers a more sensitive overall measure of impairment compared to individual parameters and can serve as a straightforward biomarker for evaluating sperm quality, aiding clinicians in diagnosing male infertility. The characterized phenotypes suggest potential for personalized treatment strategies. These findings emphasize the importance of quitting smoking for fertility treatment and indicate that pituitary-gonadal hormones could be promising targets for therapy.

Název v anglickém jazyce

A Cross-Sectional Study Reveals Hormonal Signatures of Smoking-Related Infertility

Popis výsledku anglicky

Cigarette smoking remains a common modifiable lifestyle risk factor for male infertility, yet the exact mechanisms linking smoking to overall fertility decline are not fully understood. This study investigates how smoking affects sperm quality deterioration and examines the potential role of hormonal pathways in mediating these effects. Robust causal approaches have been utilized to measure both the overall impact of smoking and its hormonal mediation on semen parameters. Additionally, a unidimensional Sperm Quality Index (SQI) has been developed and validated internally, while latent reproductive phenotypes have been analyzed through unsupervised clustering techniques. This observational study involved 104 infertile men, with 52 smokers and 52 nonsmokers. Inverse-probability-of-treatment weighting (IPTW) and augmented IPTW (AIPW) were used to balance 21 baseline covariates. Parallel mediation analysis evaluated four pituitary-gonadal hormones-follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone-as mediators of smoking&apos;s impact on five key semen parameters: concentration, total count, progressive motility, morphology, and live sperm percentage. Principal component analysis (PCA) was used to create a PCA-based SQI by combining nine logarithmically transformed, z-standardized variables. The mediation analysis was also repeated using the SQI. K-means clustering, using the gap statistic, identified four latent semen-hormone phenotypes. After IPTW, smoking was associated with standardized AIPW average treatment effects (ATEs) of -0.29 to -0.66 standard deviation (SD) across semen parameters (e.g., live sperm % ATE = -0.67, 95% confidence interval (CI) -1.01 to -0.33; morphology ATE = -0.40, 95% CI -0.75 to -0.05). Parallel mediation indicated LH as the principal mediator, explaining 40%-63% of smoking&apos;s total effect on individual outcomes. The PCA-derived SQI explained 65% of semen variance, and smoking&apos;s ATE on SQI was -0.44 SD (95% CI -0.80 to -0.07), with 66% mediated via hormones (suppression effect). Clustering revealed four phenotypes: (1) normozoospermic, (2) subclinical endocrinal disruption, (3) intermediate, and (4) severely impaired (high LH, low SQI), with smokers predominating cluster 4 (85% smokers vs. 15% nonsmokers). Cigarette smoking primarily impacts semen quality by disrupting endocrine hormones. The PCA-based SQI offers a more sensitive overall measure of impairment compared to individual parameters and can serve as a straightforward biomarker for evaluating sperm quality, aiding clinicians in diagnosing male infertility. The characterized phenotypes suggest potential for personalized treatment strategies. These findings emphasize the importance of quitting smoking for fertility treatment and indicate that pituitary-gonadal hormones could be promising targets for therapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

40201 - Animal and dairy science; (Animal biotechnology to be 4.4)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Trends in Urology &amp; Men&apos;s Health

ISSN

2044-3730

e-ISSN

2044-3749

Svazek periodika

16

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

"e70015"

Kód UT WoS článku

001651955000004

EID výsledku v databázi Scopus

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