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Impaired Leydig Cell Function in Infertile Men: A Study of 357 Idiopathic Infertile Men and 318 Proven Fertile Controls

Department of Growth and Reproduction, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Anna-Maria Andersson, M.Sci., Ph.D., Department of Growth and Reproduction, Copenhagen University Hospital, Section GR 5064, Blegdamsvej 9, DK-2100 Copenhagen OE, Denmark. E-mail: anna{at}rh.dk.

To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E₂), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E₂/T ratio, and calculated free T index (cFT) were compared between the two groups.

A shift toward lower serum T levels, cFT, and T/LH ratio and higher serum LH, E₂, and E₂/T levels was observed in the group of infertile men. On average, the infertile men had 18, 26, and 34% lower serum T, cFT, and T/LH levels, respectively, and 19, 18, and 33% higher serum LH, E₂, and E₂/T levels, respectively, than the fertile men. Twelve percent of the infertile men had a serum T level that fell below the 2.5 percentile of the fertile levels, and 15% of the infertile men had a LH level that was above the 97.5 percentile of the fertile levels.

Thus, the group of infertile men showed significant signs of impaired Leydig cell function in parallel to their impaired spermatogenesis. The association of decreased spermatogenesis and impaired Leydig cell function might reflect a disturbed paracrine communication between the seminiferous epithelium and the Leydig cells, triggered by distorted function of the seminiferous epithelium. On the other hand, the parallel impairment of spermatogenesis and Leydig cells may reflect a congenital dysfunction of both compartments caused by a testicular dysgenesis during fetal/infant development.

This work was supported by the European Commission under the 5th framework program (Environmental Reproductive Health, Contract QLK4-1999-01422).

Abbreviations: BMI, Body mass index; cFT, calculated free T index; CV, coefficient of variation; E₂, estradiol; IFMA, immunofluorometric assays; TDS, testicular dysgenesis syndrome; T, testosterone.

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