Hypogonadism in Males - Late-Onset

Definition

Late-onset hypogonadism (LOH) in males is characterized by a decline in serum testosterone levels with associated clinical symptoms in middle-aged and older men, often linked to aging and comorbidities.

Epidemiology

• Prevalence increases with age, affecting up to 20–30% of men over 60
• Higher prevalence in men with obesity, diabetes, or metabolic syndrome
• Associated with decreased physical activity and chronic illness
• Underdiagnosed due to non-specific symptoms and overlap with aging
• Significant impact on quality of life, sexual function, and bone health
• Global prevalence varies by population and diagnostic criteria
• Men with cardiovascular disease or type 2 diabetes are at higher risk

Etiology

• Age-related decline in Leydig cell function
• Comorbid conditions: obesity, type 2 diabetes, chronic illness
• Medications: glucocorticoids, opioids, androgen deprivation therapy
• Chronic systemic inflammation
• Sleep disorders (e.g., sleep apnea) reducing testosterone production
• Genetic predisposition in some cases
• Secondary causes less common but may contribute: pituitary or hypothalamic dysfunction

Pathophysiology

• Reduced testosterone synthesis by Leydig cells in the testes
• Altered hypothalamic-pituitary-gonadal axis signaling
• Decreased bioavailable testosterone due to increased sex hormone-binding globulin (SHBG)
• Impact on muscle mass, bone density, and fat distribution
• Altered libido and sexual function due to androgen deficiency
• Metabolic consequences: insulin resistance, dyslipidemia
• Potential contribution to mood disorders and cognitive changes