The ageing male reproductive tract

Abstract

Ageing of the male reproductive system is characterized by changes in the endocrine system, hypogonadism, erectile dysfunction and proliferative disorders of the prostate gland. Stochastic damage accumulating within ageing leads to progressive dysregulation at each level of the hypothalamic-pituitary-gonadal (HPG) axis and in local auto/paracrine interactions, thereby inducing morphological changes in reproductive target organs, such as the prostate, testis and penis. Despite age-related changes in the HPG axis, endocrine functions are generally sufficient to maintain fertility in elderly men. Ageing of the male reproductive system can give rise to clinically relevant manifestations, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and erectile dysfunction (ED). In this review, we discuss morphological/histological changes occurring in these organs and current views and concepts of the underlying pathology. Moreover, we emphasize the molecular/cellular pathways leading to reduced testicular/penile function and proliferative disorders of the prostate gland.

Effects of aging on the male reproductive system

“…Prostate enlargement in older men is one of the most common age-related diseases and is defined as benign prostatic hyperplasia (BPH). Although any DNA mutation associated with BPH has not been reported to date, in general DNA methylation has been shown to decrease in BPH [15,16]. Prakash et al have identified 511 differentially expressed genes that can distinguish symptomatic BPH from asymptomatic BPH and most of these genes encode epithelium/stroma-derived growth factors [17].…”

“…Premalignant dysplastic lesions (prostatic intraepithelial neoplasia, PIN) are characterized by enlarged nuclei, decline in basal epithelial layer, and proliferation and abnormal differentiation of secretory cells. PIN is regarded as pre-invasive stage of prostatic adenocarcinoma [16,19].…”

Advanced paternal age and reproductive outcome

“…12 The manifestations include decreased bone and muscle mass, sexual body hair and beard growth, and increased abdominal obesity, as well as higher incidence of erectile dysfunction, which increases to .30%-40% in the eighth decade. 7,12,13 Age-related erectile dysfunction has also been associated with endothelial dysfunction due to atherosclerosis of the penile arteries and a reduction in the production of nitric oxide. 7 In a retrospective study of 3698 infertile patients, the incidence of infection in the accessory glands increased from 6.1% among males aged ,25 years to 13.6% of patients aged .40 years, and total sperm count was lower (P,0.0001).…”

“…7,12,13 Age-related erectile dysfunction has also been associated with endothelial dysfunction due to atherosclerosis of the penile arteries and a reduction in the production of nitric oxide. 7 In a retrospective study of 3698 infertile patients, the incidence of infection in the accessory glands increased from 6.1% among males aged ,25 years to 13.6% of patients aged .40 years, and total sperm count was lower (P,0.0001). 14 Numerous studies have examined the age-related effect on semen characteristics.…”

“…This change is accompanied by alterations in testicular histomorphology observed in older men. 7,8 In a multivariate analysis, follicle-stimulating hormone (FSH), inhibin B and testosterone were independently associated with bilateral testicular volume in the elderly. This moderately decreased bilateral testicular volume observed in elderly men was strongly associated with a decrease in the inhibin B/FSH ratio, and was consistent with a reduced Sertoli cell mass, compensated by increased FSH stimulation resulting in only limited decrease of Sertoli cell function.…”