Compensated reduction in Leydig cell function is associated with lower semen quality variables: a study of 8182 European young men

• Published in: Human reproduction (Oxford) 2016-05, Vol.31 (5), p.947-957
• Main Authors: Jørgensen, N., Joensen, U.N., Toppari, J., Punab, M., Erenpreiss, J., Zilaitiene, B., Paasch, U., Salzbrunn, A., Fernandez, M. F., Virtanen, H.E., Matulevicius, V., Olea, N., Jensen, T.K., Petersen, J.H., Skakkebæk, N.E., Andersson, A-M.
• Format: Article
• Language: English
• Subjects: Adult; Cross-Sectional Studies; Europe; Fertility; Humans; Leydig Cells - physiology; Luteinizing Hormone - blood; Male; Prospective Studies; Reference Values; Semen Analysis; Testosterone - blood
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dew021

Abstract STUDY QUESTION Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996–2010. PARTICIPANTS, SETTING AND METHOD Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease the likelihood of detecting associations between reproductive hormone levels and semen variables, suggesting that the presented associations might in reality be even stronger than shown. Although we adjusted for confounders, we cannot of course exclude that our results can be skewed by selection bias or residual confounding. WIDER IMPLICATIONS OF THE FINDINGS Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower sem