What is hypogonadism?

Definition of Hypogonadism

Hypogonadism is a clinical condition characterized by symptoms and biochemical evidence of testosterone deficiency that impacts multiple organ systems and quality of life. 1

Types of Hypogonadism

Hypogonadism occurs in two main forms:

• Primary (hypergonadotropic) hypogonadism: Caused by testicular dysfunction, resulting in low testosterone and high gonadotropin levels 1
• Secondary (hypogonadotropic) hypogonadism: Results from impairment of the hypothalamic-pituitary-gonadal (HPG) axis 1
• Compensated hypogonadism: Characterized by normal testosterone levels with elevated luteinising hormone production 1
• Functional hypogonadism: Diagnosed when low testosterone levels occur in the absence of organic alterations in the HPG axis, often as a consequence of comorbidities 1

Clinical Manifestations

Hypogonadism presents with various symptoms affecting multiple systems:

• Sexual symptoms: Diminished libido, erectile dysfunction 1
• Physical symptoms: Reduced muscle mass and strength, increased body fat, diminished bone density, anemia 1
• Psychological symptoms: Diminished energy, increased fatigue, depressed mood, impaired cognition 1

Etiology

Primary Hypogonadism Causes

• Congenital disorders: Chromosomal abnormalities (e.g., XX male, 47 XYY syndrome), Down syndrome, Noonan syndrome 1
• Developmental disorders: Uncorrected cryptorchidism, bilateral congenital anorchia 1
• Acquired disorders: Testicular trauma, orchitis, radiation damage 2

Secondary Hypogonadism Causes

• Congenital disorders: Idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, Prader-Willi syndrome 1
• Acquired disorders: Pituitary tumors, traumatic brain injury, radiation to the brain 1
• Drug-induced: Opiates, GnRH agonists/antagonists, glucocorticoids, estrogens, anabolic steroids 1

Systemic Conditions Associated with Hypogonadism

• Metabolic disorders: Type 2 diabetes mellitus, metabolic syndrome 1, 3
• Chronic diseases: HIV infection, chronic organ failure, chronic inflammatory arthritis 1, 3
• Other conditions: Cushing syndrome, eating disorders, endurance exercise, acute and critical illness, aging 1

Diagnosis

Diagnosis of hypogonadism requires:

• Clinical symptoms: Assessment of sexual function, energy levels, mood, and physical changes 1, 4
• Biochemical testing: Low serum testosterone levels 1
• Additional hormonal assessment: Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to differentiate between primary and secondary hypogonadism 4, 5

Treatment Considerations

Treatment depends on the type of hypogonadism and patient goals:

• Testosterone replacement therapy (TRT): Standard treatment for most forms of hypogonadism 2, 6
• Gonadotropin therapy: Alternative for men wishing to preserve fertility 6
• Treatment of underlying conditions: Particularly important in functional hypogonadism 1, 3

Monitoring and Potential Risks

Patients on testosterone therapy require monitoring for:

• Erythrocytosis: Risk varies by administration route (3-18% with transdermal, up to 44% with injections) 1
• Cardiovascular effects: Current evidence suggests neutral or possibly beneficial effects 1
• Prostate health: Requires long-term monitoring 1
• Other side effects: Fluid retention, sleep apnea, gynecomastia, skin reactions, and testicular atrophy 1

Hypogonadism significantly impacts mortality, morbidity, and quality of life, making proper diagnosis and treatment essential for optimal patient outcomes 1, 7, 5.