What are the causes of hypogonadism (low testosterone)?

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From the Guidelines

Low testosterone, or hypogonadism, is primarily caused by a gradual, age-associated decline in serum total testosterone levels, which begins in men in their mid-30s and continues at an average rate of 1.6% per year 1. This condition, referred to as age-related low testosterone, is accompanied by clinical symptoms associated with androgen deficiency. Some of the key factors contributing to low testosterone include:

  • Aging, with a natural decrease in testosterone levels by about 1-2% per year after age 30
  • Obesity, as fat tissue converts testosterone to estrogen
  • Chronic illnesses, such as diabetes, kidney disease, liver disease, and HIV/AIDS, which can reduce testosterone production
  • Certain medications, particularly opioids, glucocorticoids, and some psychiatric medications, which can suppress testosterone
  • Genetic conditions, such as Klinefelter syndrome and hemochromatosis, which may cause low testosterone from birth or early adulthood
  • Injury or infection of the testicles, pituitary gland disorders, and radiation or chemotherapy treatments, which can damage testosterone-producing cells
  • Excessive alcohol consumption, poor sleep, chronic stress, and nutritional deficiencies, which can contribute to lower testosterone levels It is essential to note that there is no well-defined, universally accepted threshold of testosterone levels below which symptoms of androgen deficiency and adverse health outcomes occur 1. If experiencing symptoms like fatigue, reduced libido, erectile dysfunction, or mood changes, it is crucial to consult a healthcare provider for proper testing and potential treatment options. The American College of Physicians suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function 1.

From the FDA Drug Label

• Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals • Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation

The causes of hypogonadism (low testosterone) include:

  • Primary hypogonadism: testicular failure due to conditions such as
    • Cryptorchidism
    • Bilateral torsion
    • Orchitis
    • Vanishing testis syndrome
    • Orchiectomy
    • Klinefelter's syndrome
    • Chemotherapy
    • Toxic damage from alcohol or heavy metals
  • Hypogonadotropic hypogonadism: gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from
    • Tumors
    • Trauma
    • Radiation 2

From the Research

Causes of Hypogonadism

The causes of hypogonadism, also known as low testosterone, can be primary (hypergonadotropic) or secondary (hypogonadotropic) 3.

  • Primary hypogonadism is caused by testicular disorders, while secondary hypogonadism is caused by hypothalamic or pituitary disorders.
  • Hypogonadism associated with aging, also known as andropause, may present a mixed picture with low testosterone levels and low to low-normal gonadotropin levels 3.
  • Functional hypogonadism, a condition characterized by a decline in testosterone levels due to factors other than chronological aging, such as obesity and other comorbidities, can also cause hypogonadism 4.

Lifestyle Factors and Chronic Disease Status

Lifestyle factors and chronic disease status can also contribute to the development of hypogonadism.

  • A study found that free testosterone levels were associated with increased age, diet, diabetes, and hypertension 5.
  • Another study found that obesity, metabolic syndrome, diabetes, and cardiovascular disease are associated with an increased risk of hypogonadism 5.
  • Smoking, diet, and exercise may also be associated with reduced testosterone levels, although the evidence is not conclusive 5.

Other Factors

Other factors that can contribute to the development of hypogonadism include:

  • Pituitary or hypothalamic disorders 3
  • Testicular disorders 3
  • Chronic diseases such as obesity, metabolic syndrome, diabetes, and cardiovascular disease 5
  • Certain medications, such as glucocorticoids and opioids 6
  • Age, with hypogonadism becoming more common with increasing age 3, 4, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Male hypogonadism : an update on diagnosis and treatment.

Treatments in endocrinology, 2005

Research

Ageing male (part I): Pathophysiology and diagnosis of functional hypogonadism.

Best practice & research. Clinical endocrinology & metabolism, 2022

Research

Emerging medication for the treatment of male hypogonadism.

Expert opinion on emerging drugs, 2016

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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