Leydig Cell Numbers, Daily Sperm Production, and Serum Gonadotropin Levels in Aging Men*

Abstract

Age-related changes in Leydig cell number, daily sperm production, and circulating hormone levels were studied in 15 men between 20 and 48 yr of age and 15 men between 50 and 76 yr of age. Testes and blood samples were obtained at autopsy less than 15 h after death due to trauma or heart attack. Leydig cell number was determined by quantitative histometric estimation of the proportion of glutaraldehyde-perfused, decapsulated testicular parenchyma occupied by Leydig cell nuclei of measured average volume in both testes of each subject. Daily sperm production was determined by phase contrast cytometry of round spermatid nuclei in homogenates of both fixed testes from each individual. LH, FSH, PRL, and testosterone in serum from the heart or large veins were quantified by RIA. No relationship was detected between any of the testicular or hormonal values and postmortem time. The average total number of Leydig cells was reduced by 44% in the older men and was negatively correlated with age (p = -0.62) in all men. Mean serum LH was elevated more than 2-fold in the older men and was positively correlated with age (p = +0.53) in all men. Neither serum testosterone nor serum PRL changed significantly with age. Daily sperm production was more than 50% lower in older men and was negatively correlated with age (p = -0.76) in all men. Serum FSH was more than 3-fold higher in the older men and was positively correlated with age (p = +0.72) in all men. The highest FSH levels were found in men with the lowest rates of sperm production, and FSH and daily sperm production were inversely correlated even after the effects of age were removed. These findings show that the response of the human testis to aging is variable and that the predictive value of age for most testicular characteristics is weak at the level of individual men. Nevertheless, age accounts for more than a third of the variation in Leydig cell number, and it explains more than half the variation in daily sperm production. Hence, age is the largest single contributing factor yet identified in the search for explanations underlying the variation in testicular structure and function found in groups of normal men.

Effects of aging on the male reproductive system

“…Daily sperm production, total sperm count, and sperm viability are negatively correlated with age. Daily sperm production decreases more than 30 % in men over the age of 50 and is negatively correlated with age in men in general [13,20,21]. In a study where semen values of men above 45 years of age were analyzed, four measured parameters (semen volume, sperm concentration, sperm motility, and sperm morphology) and one derived parameter (total sperm count) were calculated according to the age range, and these values were compared to the reference values of the World Health Organization.…”

“…Despite personal differences, the number of Leydig cells also decreases with age [13]. Leydig cells in aging men have many cytoplasmic or intranuclear Reinke crystals and paracrystalline inclusions, and contain a large number of vacuoles and lipid droplets.…”

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…The work of Sasano and Sadatoshi [149] and Takizawa and Hatakeyama [150] has demonstrated that changes in the microvasculature of the testis may be indirectly responsible for degenerative changes seen in the Leydig cells of older individuals. Several studies have provided evidence that loss of Leydig cell population in the adult human testis as a function of increasing age is caused by Leydig cell hyperplasia, dedifferentiation, degeneration and dissolution [151][152][153]. In addition, there is evidence for an impaired hypothalamic GnRH outflow and decreased pulse generation of GnRH, with pulses being generated more irregularly, normal or enhanced LH secretion when stimulated by exogenous GnRH pulses, reduced pulsatile LH-stimulated testosterone synthesis, and decreased negative feedback in older men [131,132,[154][155][156].…”

Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study

“…Actually, testosterone deficiency has been implicated with decline of the quality of the erections, loss of libido, osteoporosis, weight gain, muscle weakness, decreased lean body mass, diabetes mellitus and cognitive changes (2). The decrease in serum testosterone (T) may be due to primary testicular failure (3) and/or dysfunction of the hypothalamic-pituitary axis (4). This deficiency in aging males is associated with increased Vol.…”