Late-onset Hypogonadism: Current perspective on diagnosis, management and impact on healthy aging

Abstract

Late-onset hypogonadism (LOH), also termed age-related testosterone deficiency, is a clinical and biochemical syndrome affecting aging men. It is characterized by persistent hypogonadal symptoms paired with low serum testosterone levels. Unlike classical organic hypogonadism, LOH stems from a complex multifactorial mechanism involving age-related Leydig cell senescence, altered hypothalamic-pituitary-testicular (HPT) axis feedback, increased sex hormone-binding globulin (SHBG) levels, and reciprocal metabolic crosstalk driven by visceral obesity. Diagnosis requires a strict two-step protocol: identification of key clinical manifestations—predominantly core sexual symptoms such as decreased morning erections, erectile dysfunction, and low libido—and confirmation through two separate fasting morning serum total testosterone draws (typically < 300 ng/dL or 10.4 nmol/L). In borderline cases, calculated free testosterone (< 6.5 ng/dL) is decisive. Left untreated, LOH acts as an accelerator of multi-system physiological decline, compounding sarcopenia, osteopenia, metabolic syndrome, type 2 diabetes, and cardiovascular risk, thereby reducing functional independence and overall quality of life. Management begins with non-pharmacological lifestyle interventions, particularly weight loss and resistance training, which can restore endogenous testosterone in functional/obesity-related cases. For persistent hypogonadism, exogenous testosterone replacement therapy (TRT)—delivered via transdermal gels, intramuscular injections, or subcutaneous pellets—provides effective symptomatic relief. In men desiring preserved fertility, alternative agents such as selective estrogen receptor modulators (SERMs) or human chorionic gonadotropin (hCG) are preferred to prevent HPT axis suppression. Landmark clinical trials, such as the TRAVERSE study, confirm the cardiovascular safety (non-inferiority for major adverse cardiovascular events) of TRT in high-risk populations while highlighting the necessity of ongoing safety monitoring for erythrocytosis (hematocrit > 54%), prostate-specific antigen (PSA) elevations, and atrial fibrillation. Overall, structured diagnosis and tailored therapy allow clinicians to mitigate age-related frailties and promote healthy aging. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S12]