Hypogonadism in Males - Late-Onset Disease Background

Last updated: 19 September 2025
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Introduction

Late-onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome caused by androgen deficiency characterized by older age, a set of typical symptoms, and deficiency in serum testosterone levels. This is a type of hypogonadism that has normal pubertal development, thus having developed normal male secondary sex characteristics. Quality of life may be decreased, and multiple organ systems may be adversely affected.

Epidemiology

The prevalence of hypogonadism increases with age. Testosterone deficiency affects approximately 2–6% of adult males, while 2.1–5.7% of men aged 40–79 years old experience symptomatic hypogonadism.

Despite methodological differences among studies, the core features of late-onset hypogonadism appear to be consistent across different populations and cultures. The prevalence of late-onset hypogonadism varies by population, with studies reporting 7.8% in middle-aged and elderly Chinese men and 25.6% in Korean men aged 40–79 years.

Pathophysiology

After the age of 40 years, testosterone levels decline by approximately 1–2% annually. Suppression of the hypothalamic-pituitary-gonadal axis or a decrease in hypothalamic-pituitary and/or Leydig cell function may occur in association with obesity, diabetes, chronic inflammatory conditions, and other comorbidities. This suppression is often reversible but may become permanent with aging. Evidence also suggests that the chronic elevation of pro-inflammatory cytokines in individuals with obesity, known as low-grade inflammation, contributes to reduced testosterone levels by disrupting the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus.

Risk Factors

Hypogonadism in Males - Late-Onset_Disease BackgroundHypogonadism in Males - Late-Onset_Disease Background




Several factors may increase the risk of hypogonadism, and these include components of metabolic syndrome, such as central obesity, hypertension, dyslipidemia, impaired glucose regulation and insulin resistance (eg diabetes), a prothrombotic tendency, and chronic inflammation. Other associated conditions include HIV-related illnesses, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, kidney disease, vitamin D deficiency, vascular disease, chronic stress, and psychological disorders (eg depression). Low testosterone levels may also be associated with the use of substances and medications such as glucocorticoids, antipsychotics, anabolic steroids, and alcohol, which can impair testosterone production or metabolism.