Clinical, endocrine, and testicular factors associated with sperm concentration: insights from a real-world cohort of 521 infertile men

Factores clínicos, endocrinos y testiculares asociados con la concentración espermática: perspectivas de una cohorte del mundo real de 521 varones infértiles

Background: Male infertility results from a complex interplay of hormonal, testicular, and clinical factors. Identifying reliable non-invasive markers of spermatogenic function remains clinically relevant. This study evaluated the independent associations of follicle-stimulating hormone (FSH), testicular volume, and luteinizing hormone (LH) with sperm concentration and developed a parsimonious predictive model for predicting oligozoospermia. Methods: We retrospectively analyzed 521 men with infertility between 2020 and 2024. Clinical variables, testicular volume, and reproductive hormones were assessed, including FSH, LH, and total testosterone (TT). Multivariable linear regression estimated predictors of log-transformed sperm concentration. For oligozoospermia (<15 × 106/mL), a baseline clinical model (with age, body mass index (BMI), smoking, and varicocele) was compared with a parsimonious enhanced model (baseline model + FSH + testicular volume + LH). Model performance was evaluated using the area under the curve (AUC), ∆AUC, calibration, and bootstrap internal validation. Results: FSH (β = −0.0265; p < 0.001) and testicular volume (β = 0.0474; p = 0.0006) were independent predictors of sperm concentration, while LH showed a weaker effect (β = −0.012; p = 0.04). The baseline clinical model showed limited discrimination (AUC = 0.65), whereas the enhanced model achieved superior performance (AUC = 0.75; ∆AUC = +0.10) with good calibration (slope ≈ 1.02) and an optimism-corrected AUC of 0.73. Sensitivity analysis in men with normal sperm counts (≥20 × 106/mL; n = 92) showed results consistent with the main findings. Conclusions: A simple combination of FSH, testicular volume, and LH provides internally validated, moderately discriminative prediction of oligozoospermia beyond standard clinical parameters. These non-invasive biomarkers may help early risk stratification in male infertility, although external validation remains warranted.

Resumen

Antecedentes: La infertilidad masculina resulta de una compleja interacción entre factores hormonales, testiculares y clínicos. Identificar marcadores no invasivos y fiables de la función espermatogénica sigue siendo clínicamente relevante. Este estudio evaluó las asociaciones independientes de la hormona foliculoestimulante (FSH), el volumen testicular y la hormona luteinizante (LH) con la concentración espermática, y desarrolló un modelo predictivo parsimonioso para predecir oligozoospermia. Métodos: Se analizaron retrospectivamente 521 hombres con infertilidad entre 2020 y 2024. Se evaluaron variables clínicas, volumen testicular y hormonas reproductivas, incluyendo FSH, LH y testosterona total (TT). Se utilizó regresión lineal multivariable para identificar predictores de la concentración espermática transformada logarítmicamente. Para la oligozoospermia (<15 × 106/mL), se comparó un modelo clínico basal (edad, índice de masa corporal (IMC), tabaquismo, varicocele) con un modelo mejorado parsimonioso (basal + FSH + volumen testicular + LH). El rendimiento del modelo se evaluó mediante el área bajo la curva (AUC), ∆AUC, calibración y validación interna mediante bootstrap. Resultados: La FSH (β = −0.0265; p < 0.001) y el volumen testicular (β = 0.0474; p = 0.0006) fueron predictores independientes de la concentración espermática, mientras que la LH mostró un efecto más débil (β = −0.012; p = 0.04). El modelo clínico basal mostró una discriminación limitada (AUC = 0.65), mientras que el modelo mejorado alcanzó un rendimiento superior (AUC = 0.75; ∆AUC = +0.10), con buena calibración (pendiente ≈ 1.02) y un AUC corregido por optimismo de 0.73. El análisis de sensibilidad en hombres con recuentos espermáticos normales (≥20 × 106/mL; n = 92) mostró resultados coherentes con los hallazgos principales. Conclusiones: Una combinación simple de FSH, volumen testicular y LH ofrece una predicción validada internamente, de discriminación moderada, de la oligozoospermia más allá de los parámetros clínicos estándar. Estos biomarcadores no invasivos pueden facilitar la estratificación temprana del riesgo, si bien se requiere validación externa.

Follicle stimulating hormone; Infertility; Luteinizing hormone; Semen analysis; Smoking; Testicular volume; Testosterone; Varicocele

Palabras Clave

Análisis de semen; Hormona foliculoestimulante; Hormona luteinizante; Infertilidad; Tabaquismo; Testosterona; Varicocele; Volumen testicular

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