The "endocrine evolution" of the aging male refers to the gradual, progressive decline in androgen activity—specifically testosterone—mediated by the degradation of the hypothalamic-pituitary-gonadal (HPG) axis. Unlike female menopause, this process (often termed Late-Onset Hypogonadism or LOH) involves a slow attrition of testosterone at a rate of approximately 1% to 2% per year after age 30 or 40.

Clinical Physiology and Symptoms

This decline is characterized by a "saturation model," where physiological functions become impaired once testosterone falls below a critical threshold. Symptoms are categorized into three primary domains:

• Sexual: Loss of libido, erectile dysfunction (ED), and fewer morning erections are considered the specific "core triad" of symptoms.
• Physical/Metabolic: Includes sarcopenia (muscle loss), increased visceral fat, reduced bone density, and anemia.
• Psychological/Cognitive: Manifests as fatigue, "brain fog," irritability, and depressive symptoms.

Diagnostic Controversy

Clinicians face significant debate regarding diagnostic thresholds. The American Urological Association (AUA) recommends a total testosterone cutoff of <300 ng/dL, while the Endocrine Society advises a stricter limit of <264 ng/dL. Guidelines universally emphasize that diagnosis requires two separate early-morning blood tests combined with unequivocal symptoms, as non-specific symptoms frequently overlap with comorbidities like obesity, diabetes, and sleep apnea.

The TRT Safety Resolution (TRAVERSE Trial)

For nearly a decade, Testosterone Replacement Therapy (TRT) was clouded by a 2015 FDA "black box" warning regarding potential cardiovascular (CV) risks. This controversy was effectively resolved by the 2023 TRAVERSE Trial, a large-scale study demonstrating that TRT does not increase the risk of heart attack, stroke, or cardiovascular death in hypogonadal men. Consequently, the FDA updated its guidance in 2025 to remove the cardiovascular boxed warning, though monitoring for atrial fibrillation and blood pressure remains necessary.

Modern Perspectives: Optimization vs. Necessity

Current clinical practice struggles with the "medicalization of aging." While TRT is the standard of care for pathological deficiency, a booming telehealth industry often promotes "optimization" for men with normal age-adjusted levels. Experts caution against this, advocating for lifestyle interventions as first-line therapy. Recent data indicates that significant weight loss and sleep optimization can restore natural testosterone levels as effectively as medication in men with functional hypogonadism, avoiding risks like infertility and polycythemia (thickened blood).