REPRODUCTIVE FUNCTIONS OF THE AGEING MALE

1. REPRODUCTIVE FUNCTIONS OF THE AGEING MALE Moshe Shalev MD Department of Urology Meir Medical Center Kfar-Saba, Israel

2. REPRODUCTIVE FUNCTIONS OF THE AGEING MALE • Do semen parameters show age-dependent alterations? • Is there a male contribution to reduced fertility and fecundity of older couples? • Is there a genetic risk for offspring attributable to increased paternal age?

3. REPRODUCTIVE FUNCTIONS OF THE AGEING MALE • Do semen parameters show age-dependent alterations? • Is there a male contribution to reduced fertility and fecundity of older couples? • Is there a genetic risk for offspring attributable to increased paternal age?

4. Age dependent alterations in testes • Testis volume remains constant over a long period of life • Specific effects of age demonstrated a reduction of testicular volume only in the 8th decade of life • Testes volume in this age group is 31% lower than in 18-40 year old men. (Handelsman 1985, Mahmoud 2003)

5. Morphological characteristics of aging testes • Reduced number of sperm arising from one cell division of a spermatogonium. • Reduced number of type-A dark spermatogonia • Increased occurrence of multinucleated spermatogonia. • Megalospermatocytes, giant spermatids • Multilayered spermatogonia and diverticula of the seminiferous tubules. (Holstein 1988, 1989; Johnson 1990)

6. Morphological characteristics of aging testes • Reduced number of sertoli cells and accumulation of lipid droplets in their cytoplasma. • Reduced number of leydig cells which may be multinucleated. • Tubule involution leading to progressive sclerosis • Testicular sclerosis is associated with defective vascularization of the testicular parenchyma and with systemic arteriosclerosis of affected men. (Harbitz 1973, Johnson 1986, Paniagua 1986, 1987; Regadera 1985)

7. Causes for alteration of semen parameters • Urogenital infections : a retrospective cross-sectional study in 3698 infertile men showed infection rate of the accessory glands in 6.1% in pts aged <25y but in 13.6% of pts >40 with sig. lower total sperm count. • Accumulation of toxic substances: polychlorinated biphenyls (PBC) and cadmium.

8. Variations in semen volume over time • Decrease of semen volume(5 controlled studies) in ranges between 0.5% per year. • Decrease of semen volume of 20% when comparing 50 year old with 30 year old men. • One controlled study failed to detect a significant change of semen volume with age when including men up to an age of 50. • Fructose decreases with age but zinc and -glucosidase remain constant over the age range. • (Rolf 1996, 2002; Andolz 1999, Fisch 1996, Eskenazi 2003)

9. Variations in sperm motility and concentration over time • Six controlled studies found a significant decrease of sperm motility over time in a range of 0.17% and 0.7% per year. • Focusing on sperm concentration studies could not provide a uniform picture. ( Fisch 1996, Eskenazi 2003, Schwartz 1983, Auger 1995, Rolf 1996,2002; Andolz 1999,)

10. Variations in sperm morphology over time • Four well controlled studies found a significant deterioration with age in both fertile and non fertile men. • The decrease per annum of normal sperm ranges between 0.2% and 0.9%. (Kidd 2001, Andolz 1999, Auger 1985)

11. Age dependent changes in testes and semen • Develop gradually without a sudden age threshold • Alterations in semen parameters fall within normal ranges. • Age-dependent alterations of testicular histology and semen parameters are accompanied by a significant increase in FSH and a slight but significant decrease in Inhibin B, which are also found in men with apparently normal semen parameters.