Attrition of the human Leydig cell population with advancing age

Existing evidence suggests that the aging human male experiences a gradual decline in testosterone production, a phenomenon that should be reflected in the Leydig cell population of the testis. It has been proposed that Leydig cells diminish in number with increasing age, but conflicting claims characterize reports of this topic. We have reinvestigated this possibility by histometric analysis of perfused testes from 25 men ranging from 18 to 87 years of age. Average single Leydig cell volume (2,943 +/- 623 micrometer 3, X +/- S.D.) did not change significantly with increasing age (r = 0.24, P greater than 0.2), suggesting that surviving cells remain active. Total testis weight (43.5 +/- 13.9 g) also did not change with age (r = 0.04, P greater than 0.5). However, both total Leydig cell volume and the absolute number of Leydig cells per individual decreased significantly as functions of age (r = -0.71, P less than 0.002, and r = -0.61, P less than 0.005, respectively). Analysis of relationship between these two parameters indicates that the total volume of Leydig cell cytoplasm contained within the human testis is determined by the number of cells present. Our results show that a pair of young adult testes endowed with more than 700 million Leydig cells at 20 years of age may be expected to undergo an attrition rate of approximately 80 million cells per subsequent decade of life. Thus, Leydig cell attrition is an important correlate of declining androgen status in aging men.