Aging of the Male Reproductive System Spring 2007 PS Timiras.

Aging of theMale Reproductive

SystemSpring 2007PS Timiras

Dr. Brown Sequard (Physiologist, Univ. Sorbonne, Paris) introduced the idea that some glands secrete internally (in the blood) potent substances that affect the whole organism.

In 1905, these substances were called “hormones” by the British physiologist E.H. Starling.

Comparison between the relative simplicity of the male reproductivesystem and the complexity of the female reproductive system.

Anatomy of the Male Reproductive Tract

TESTISPrimary sex organ suspended outside of the body in the scrotum

Secondary male sex organs include:

EPIDIDYMIS,VAS DEFERENS,EJACULATORY DUCTSwhich carry sperm to the urethra

SEMINAL VESISCLES, PROSTATE, & BULBOURETHRAL GLANDS

which secrete seminal fluid

PENIS with URETHRAthrough which flow both urine

and semen

In humans the principal reproductive organ is the brain

In addition to the brain, the male reproductive system consists of the:

A simplified version of the

male reproductive endocrinology:

The hypothalamus releases GnRH into the circulatory system and, through blood, directly into the pituitary.

GnRH triggers the release of the pituitary LH and FSH that stimulate the testes to testosterone secretion and sperm production.

the GERM CELLS or GAMETES,involved in fertilization.

the INTERSTITIAL CELLS of LEYDIGthat secrete testosterone, the

major androgen

the SERTOLI CELLSwith secretory and reproductive

functions

The testis, the male primary reproductive

organ, contains three types of cells, all

necessary for reproduction:

With Age:

• On the average, the male reproductive function remains normal (or only slightly diminished in some individuals) until advanced old age (80+ years) when it decreases

• Subtle changes include: GnRHSensitivity of androgen secretion

to LHSensitivity of negative feedback

between GnRH and LH

Figure 12.2Differences in

levels (total,

bioavailable, and percentage)

of free/bioavailable

testosterone

Young

Young

Young

Old

Old

Old

Serum LH concentration

With aging, loss of high-amplitude LH pulses despite normal or increased pituitary LH stores

Serum testosterone concentration

With aging, decreased responsiveness of testis androgen secretion to LH

Young OlderYoung Older

TABLE 12-2SELECTED NEUROENDOCRINE MODELING ISSUES IN THE

AGING MALE REPRODUCTIVE AXIS

1. How does the timing of GnRH pulse-generator change with age?

2. Which alterations in the aging male reproductive axis reflect pathophysiology versus secondary adaptations?

3. What mechanisms account for greater inter-subject heterogeneity in aging of GnRH-LH testosterone secretion?

Aging of the Prostate

Figure 19.7

Table 19-12 The Prostate and Testosterone

The healthy prostate is dependent on androgens for growth

In the prostate: testosterone dihydrotestosterone (DHT)

The enzyme catalyzing this reaction is 5--reductase

DHT stimulates growth of the prostate

Table 19-13 Normal Aging of the Prostate

After age 40:Outer regions:Atrophy of smooth muscle and proliferation of connective tissueFlattening of secretory epitheliumInner region:Increase in the number of cells present (hyperplasia)

After age 60:Slower, but more uniform atrophy of the prostateAccumulation of prostate concretions

Figure 19.8

Table 19-14 Synopsis of Benign Prostatic Hyperplasia (BPH)Characteristics

• Caused by g rowt h of th e prost at e f rom about age 40 un t il deat h• Af fect s 50 % of m en > 50 years o ld• Af fect s 95 % of m en > 70 years o ld• Clinical sympt oms due t o obstru cti on of th e ureth ra are present up to

25% of men w it h histo logic evidence of BPH• BPH t issue resembles normal prosta t e t issue wit h increased am ount s

of smoot h muscle, g landular, and/ or str omal component s• An enlarged prost at e can str angle th e ureth ra

• BPH is not found in men who have been castr at ed or men who lack 5-α-reducta se

Table 19-15 Possible Risk Factors for Benign ProstaticHyperplasia (BPH) and Prostate Cancer

Possible Risk Factors for BPH Possible Risk Factors for Prostate Cancer• Aging • Genet ic predisposit ion• Use of a nabolic st eroids • To bacco exposure• Dieta ry f act ors • Cadmium exposure• Genet ic predisposit ion • Vit amin A def iciency• Environment al to xins • Vasecto my• No oth er major risk fa cto rs • Sexually t ransmit t ed d iseases

• Muta genic hormonal facto rs• Dieta ry f act ors (part icularly h igh level of

animal fa t)

Treatment of Prostate CancerDepends on

Life expectancyOverall health statusPersonal preferencesSize of the prostate

State of disease

Treatments include:Watchful waiting

SurgeryRadiation TherapyHormonal Therapy

Cryotherapy

**PSA controversy pp. 353, 354**