Male Reproductive Pathophysiology – Bullet-Point Study Notes
Acknowledgement of Country
RMIT University acknowledges the people of the Woi wurrung and Boon wurrung language groups of the eastern Kulin Nation on whose unceded lands we conduct the business of the University. RMIT University respectfully acknowledges their Ancestors and Elders, past and present. RMIT also acknowledges the Traditional Custodians and their Ancestors of the lands and waters across Australia where we conduct our business.
Preamble to Reproductive Lectures
Some people are born with an intersex variation, meaning they are born with physical sex characteristics that don’t fit medical and social norms for female or male bodies. These variations will not be covered in these lectures.
The male and female reproductive organs of transgender people may be different from the typical organs described in this unit.
Not all trans and gender diverse people choose to affirm their gender via surgery.
Important to avoid and challenge heteronormativity by identifying heteronormative and cisnormative language and practices and what these concepts mean within the context of the reproductive system.
Learning Objectives
Describe the pathophysiology of the common male reproductive disorders including infections, trauma, hypertrophy and neoplasia, including:- Sexually Transmitted Diseases (STDs) such as Epididymitis and Orchitis
Testicular cancer
Squamous Cell Carcinoma (SCC) of the Penis
Prostatitis
Benign Prostatic Hypertrophy (BPH)
Prostate Cancer
Identify and describe the pathogenesis, clinical features and complications of the common male reproductive disorders.
Common Conditions of the Male Reproductive System
Sexually transmitted infections (STIs) include HPV, HSV, HIV, Syphilis, Chlamydia, gonorrhoeae, Trichomoniasis.
Conditions of the Testis: Epididymitis, Hydrocele, Cancer.
Condition of the Penis: Squamous cell carcinoma (SSC).
Condition of the Prostate Gland: Prostatitis, Benign Prostatic Hypertrophy (BPH), and Cancer.
Sexually Transmitted Infections (STIs)
STIs are common in the male genital system and can be bacterial, viral or parasitic.- Bacterial: Neisseria gonorrhoeae, Chlamydia trachomatis
Viral: Syphilis (Treponema pallidum is the causative organism for syphilis; note this is a bacterium, but listed under a viral/bacterial/parasitic framing in the slide), HIV, Herpes simplex virus (HSV-1 & HPV-2 in the slide text; note actual labeling is HSV-2 for herpes and HPV for human papillomavirus)
Parasitic: Trichomoniasis – Trichomonas vaginalis
Transmission/entry:- STIs invade the body through microscopic abrasions within mucosal membranes (penis, vagina, anus, or other mucosal surfaces).
Transmission can include intravenous drug use and exposure during childbirth or breastfeeding.
Pathophysiology:- Organisms invade normal cells and overwhelm the immune system, producing typical signs and symptoms of the disease.
Signs and Symptoms (general):- Genital, extragenital, or disseminated manifestations depending on the pathogen.
Dysuria, testicular pain, pain with defecation (rectal inflammation or prostate involvement).
Urethral discharge, burning or itching in the penis, pain around the pelvis, sores/bumps/blisters on genitals, anus, or mouth.
Consequences of untreated STIs:- Infertility, scarring, chronic pain, sexual dysfunction, cancers.
Epididymitis
Epididymis inflammation may be caused by:- STI-related: Neisseria gonorrhoeae and Chlamydia trachomatis
Non-sexually transmitted organisms: Pseudomonas and Escherichia coli
Complications of urinary or prostatic infection
Trauma (surgery, urinary catheter, groin impact)
Epididynmo-orchitis: infection can spread to the testis; epididymo-orchitis is more common than orchitis (partly reduced by mumps vaccination).
Signs and Symptoms:- Enlarged, reddened, tender scrotum
Pain radiating along the spermatic cord into the inguinal area
Fever, urethral discharge, cystitis, cloudy urine
Laboratory:- Elevated white blood cell count; urine culture may reveal the organism
Epididymitis (Histology) [Normal vs. Chronic]
Normal epididymis: ductules lined by ciliated tall columnar epithelial cells; underlying basal cells; lamina propria; circular smooth muscle; stroma with blood vessels.
Acute epididymitis: infection may persist and become chronic.
Chronic epididymitis: marked chronic inflammation and fibrosis with induration, scarring, and distortion of tubules; ductules may be cystically dilated with spermatozoa; lining epithelium flattened.
Testicular Cancer
Epidemiology:- One of the most common malignancies in men aged 15-45 years; peak incidence in adolescence to early adulthood.
Most curable malignancies with cure rates as high as 0.90 and >0.95 (5-year survival).
Pathogenesis:- Multifactorial: genetic and environmental factors contribute.
Family history: relative risk increased to about 6-10 fold in brothers or sons.
Cryptorchidism (undescended testis): in approximately 10% of cases.
Infections (including HPV, EBV, CMV, and HIV); prior history of cancer in one testis increases risk for contralateral neoplasia.
Testicular trauma; high maternal estrogen levels.
Histology:- Tumours can be germ cell (95%) or non-germ cell (5%);
Germ-cell tumours are classified as seminomas and non-seminomas; seminomas
~
50% of germ cell tumours; non-seminomas include various subtypes.Germ cell tumours: most are malignant; Sertoli or Leydig cell tumours are uncommon and usually benign.
Classical (
~
85%), Spermatocytic (
~
5%), Anaplastic (
~
10%) subtypes for germ cell tumours.Non-seminomatous components include embryonal carcinoma, yolk-sac tumor (endodermal sinus tumor), teratoma, choriocarcinoma.
Other germ cell lineage lesions and metastases; Lymphoma can occur.
Diagnosis and staging:- Histology (cell type: germ cell vs sex cord-stromal, etc.)
Staging systems to classify disease extent (multiple systems described).
Clinical signs and imaging:- Painless, solid testicular mass
Swelling of the testis or scrotum
Acute or dull testicular pain
Testis heaviness; gynecomastia; back pain in advanced disease
Ultrasound useful for detection; seminoma cells and stroma with characteristic patterns
Squamous Cell Carcinoma (SCC) of the Penis (Penile SCC)
About 95% of penile cancers are squamous cell carcinoma; usually involve the glans or inner foreskin
Invasive SCC often develops from SCC in situ (SCCIS)
Etiology:- HPV-associated PSCC more common in younger men with multiple sexual partners
HPV-independent PSCC affects mainly older men; etiology less well understood
Phimosis with chronic inflammation is a risk factor; poor hygiene
Circumcision markedly lowers incidence
Risk factors:- Low-income status, poor hygiene, smoking
Phimosis or uncircumcised foreskin
Chronic inflammation; HPV infection; exposure to UV radiation
Clinical signs and diagnosis:- Ulcerative and fungating lesions on foreskin or shaft
Bleeding, urethral discharge
Inguinal adenopathy present in >50% at diagnosis
Local inflammatory response to lesion
Benign Prostatic Hypertrophy (BPH)
Epidemiology:- Approximately 80% of males >60 years experience some degree of BPH
Most common reproductive disorder in men aged 50-80 years; roughly 50-90% prevalence depending on age group
Pathophysiology:- Abnormal increase in the number of normal prostate cells (hyperplasia) leading to enlargement (hypertrophy)
Surrounding prostatic urethra enlargement causes urinary obstruction
Dihydrotestosterone (DHT) is the primary androgen driving prostatic growth
Aging-related endocrine changes:
Increased conversion of testosterone to DHT
Increased aromatization of androgens to estrogens
Estrogens may act with DHT to stimulate epithelial and stromal growth (both express estrogen receptors)
Modifiable/non-modifiable risk factors:- Genetic predisposition; metabolic syndrome (diabetes, obesity, hypertension)
Diet, alcohol, caffeine; localized inflammation associated with BPH histology
PSA relation:- BPH can raise PSA levels but is not a risk factor for prostate cancer
Zonal anatomy:- BPH occurs mainly in the central/transitional zone; most cancers arise in the peripheral zone
Signs and symptoms:- Frequent or urgent urination; nocturia; urinary hesitancy
Weak urine stream; start-stop stream; dribbling; incomplete bladder emptying
Less common: urinary tract infection, urinary retention, hematuria
Prostatitis
Prostatitis is the inflammation of the prostate gland
It is the most common urinary tract problem for men <50 years and the third most common for men >50 years
Etiology:- Bacterial urinary tract infection
Acute infection may become chronic
Sometimes the prostate is inflamed without an infection (unknown cause)
Bacterial Prostatitis (BP):- Pathogenesis: ascending infection from urethritis, cystitis, epididymo- bronchitis; direct inoculation from biopsy/surgery
Common in young men: ascending urethral infection after intercourse
In the elderly: prolonged catheterization/instrumentation
Acute vs Chronic BP:- Acute: sudden fever, chills, fatigue, dysuria, perineal pain, bladder outlet obstruction
Chronic: back pain, dysuria, perineal and suprapubic discomfort
Risk factors:- Phimosis; unprotected intercourse; urinary tract infections; indwelling catheter; transurethral biopsy/surgery; congenital ureteral abnormalities
Prostate Cancer
Epidemiology:- Prostate cancer is the most commonly diagnosed cancer in Australia; about 1:6 males will be diagnosed by age 85 years
95% of prostate cancers are adenocarcinomas (malignant proliferation of prostatic glandular epithelium)
Pathogenesis:- Androgens, genetic factors (somatic mutations, heredity), environmental factors (dietary, viral)
Most cancers are small, nonpalpable lesions; discovered via elevated serum PSA or digital rectal examination (DRE)
A subset detected incidentally after histologic examination for BPH
Risk factors:- Older age (most cases >65 years)
Family history (father or brother; higher if younger age at diagnosis)
Genetic predisposition (e.g., BRCA1/BRCA2 mutations)
Obesity; high testosterone and other hormones
Chemical exposure (pesticides)
Previous prostate conditions (prostatitis, high-grade PIN)
Geographic location (higher in North America/Europe than Asia/Africa)
Clinical signs and symptoms:- Often asymptomatic in early stages
Later: voiding pattern changes similar to BPH and prostatitis (frequency, urgency, nocturia, hesitancy, dysuria, hematuria)
Prostate may be nodular and fixed on exam
Back pain may indicate bone metastasis
Histology (adenocarcinoma):- Predominant cell type is glandular epithelium; cancer cells may form glandular structures
Classification overview:- Classical adenocarcinoma; variants and metastases; not all details supplied in the transcript
Learning Objectives Recap
Describe the pathophysiology of common male reproductive disorders (infections, trauma, hypertrophy, neoplasia)
Identify and describe pathogenesis, clinical features and complications of common disorders