Obesity

Obesity is a chronic complex disease characterized by excessive body fat accumulation (defined as a BMI of 30 kg/m² or higher) that impairs health and increases the risk of serious medical conditions including diabetes, cardiovascular disease, and certain cancers.

Low testosterone and obesity form a vicious metabolic cycle where each condition worsens the other. Obesity causes testosterone deficiency through multiple mechanisms including increased aromatase activity in fat tissue (converting testosterone to estrogen), elevated inflammatory markers, and disrupted HPG-axis function. Conversely, low testosterone promotes further weight gain by reducing lean muscle mass, decreasing metabolic rate, and increasing visceral fat accumulation. This bidirectional relationship often creates a self-perpetuating cycle that significantly increases risks for diabetes, cardiovascular disease, sexual dysfunction, and metabolic syndrome. Breaking this cycle requires addressing both conditions simultaneously through lifestyle interventions (diet, exercise) and potentially testosterone replacement therapy in appropriately selected hypogonadal men.

Bidirectional Link: Obesity ↔ Low Testosterone

Obesitas → low testosterone: Visceral fat produces aromatase enzyme that converts testosterone to estrogen. Increased estrogen gives negative feedback to the brain → suppresses LH/FSH → less testosterone production. Chronic inflammation from obesity disrupts the hypothalamic-pituitary-gonadal axis

Low testosterone → obesity: Less testosterone → reduced muscle mass → lower basal metabolic rate. Testosterone deficiency promotes fat storage (especially visceral). Lower energy and motivation → less exercise and poor food choices. Insulin resistance increases → more difficult to lose weight.

Vicious circle: More fat → more aromatase → lower testosterone → more fat → etc.

Effect of TRT

• Weight Loss: TRT produces significant and sustained weight loss in obese men with low testosterone, with obese men experiencing the most dramatic improvements - over 20% average weight loss compared to untreated controls who gained weight.
• Body Composition Changes: TRT increases lean body mass by approximately 1.96 kg while reducing fat mass, leading to improved overall body composition and enhanced metabolic function through increased resting energy expenditure.
• Waist Circumference Reduction: Significant reductions in waist circumference occur with TRT (2.78-12.9 cm depending on baseline obesity level), indicating decreased visceral adiposity and improved metabolic health markers.
• BMI Improvements: TRT consistently reduces BMI by 0.57 kg/m² on average, with greater improvements in more severely obese men, representing clinically meaningful weight loss comparable to bariatric surgery outcomes.
• Metabolic Benefits: TRT improves insulin sensitivity, reduces fasting blood glucose by 0.53 mmol/L, decreases HbA1c by 0.52%, and lowers HOMA-IR by 1.89, indicating enhanced glucose metabolism.
• Lipid Profile Enhancement: TRT reduces triglycerides by 0.22 mmol/L and improves overall lipid profiles, while also decreasing blood pressure and reducing cardiovascular risk markers.
• Bidirectional Relationship: Obesity causes low testosterone through increased aromatization and inflammation, while low testosterone worsens obesity - TRT breaks this vicious cycle by addressing the hormonal component.
• Long-term Sustainability: Unlike other obesity treatments, TRT produces progressive weight loss without recidivism over extended periods (up to 11 years), making it uniquely effective for long-term weight management.
• Mortality Benefits: TRT significantly reduces all-cause mortality (19.5% deaths in untreated vs 5.4% in treated groups) and major cardiovascular events in obese hypogonadal men.
• Safety Profile: No major side effects like increased prostate cancer risk were noted, though hematocrit increases by 3.19% requiring monitoring, and treatment adherence remains high.