What are the causes of hypogonadism (low testosterone)?

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From the Guidelines

Low testosterone, or hypogonadism, can result from various causes affecting the testes or the pituitary gland, including aging, testicular injury or infection, chemotherapy, radiation treatment, and genetic conditions like Klinefelter syndrome, as well as secondary causes such as problems with the hypothalamus or pituitary gland, medications, obesity, chronic illnesses, and excessive alcohol consumption 1.

Causes of Hypogonadism

The causes of hypogonadism can be categorized into primary and secondary causes. Primary causes include:

  • Aging, with testosterone naturally declining about 1% annually after age 30
  • Testicular injury or infection
  • Chemotherapy
  • Radiation treatment
  • Genetic conditions like Klinefelter syndrome Secondary causes involve problems with the hypothalamus or pituitary gland, including:
  • Pituitary tumors
  • Medications, especially opioids, glucocorticoids, and some psychiatric drugs
  • Obesity
  • Chronic illnesses, such as diabetes, kidney or liver disease, HIV/AIDS
  • Excessive alcohol consumption Lifestyle factors such as poor sleep, chronic stress, and inadequate nutrition can also contribute to hypogonadism 1.

Symptoms and Treatment

Symptoms of hypogonadism may include reduced libido, erectile dysfunction, fatigue, decreased muscle mass, increased body fat, and mood changes. Treatment depends on the underlying cause and may include testosterone replacement therapy, weight loss, stress management, improved sleep habits, and addressing any underlying medical conditions 1.

Importance of Proper Diagnosis

If experiencing symptoms, consulting a healthcare provider for proper diagnosis through blood tests is essential before starting any treatment, as substantial proportions of men who receive testosterone therapy do not have testosterone levels tested before initiation of therapy 1.

Clinical Guidelines

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, and consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone 1.

From the FDA Drug Label

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

The causes of hypogonadism (low testosterone) are:

  • Primary hypogonadism: defects of the gonads, such as
    • Klinefelter's syndrome
    • Leydig cell aplasia
    • testicular failure due to conditions such as
      • cryptorchidism
      • bilateral torsion
      • orchitis
      • vanishing testis syndrome
      • orchiectomy
      • chemotherapy
      • toxic damage from alcohol or heavy metals
  • Hypogonadotropic hypogonadism: failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH) due to
    • gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency
    • 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 or secondary. Primary hypogonadism is caused by a genetic anomaly or a defect in the testes, while secondary hypogonadism is caused by a defect in the hypothalamus or pituitary gland 3.

Types of Hypogonadism

Hypogonadism can be classified into two types: primary and secondary. Each type can be caused by congenital and acquired factors, including genetic and developmental disorders, infection, kidney disease, liver disease, autoimmune disorders, chemotherapy, radiation, surgery, and trauma 4.

Factors Contributing to Hypogonadism

Several factors contribute to the occurrence of hypogonadism, including:

  • Genetic and developmental disorders
  • Infection
  • Kidney disease
  • Liver disease
  • Autoimmune disorders
  • Chemotherapy
  • Radiation
  • Surgery
  • Trauma 4
  • Aging, with testosterone levels declining progressively after age 40 3, 5, 6

Late-Onset Hypogonadism

Late-onset hypogonadism (LOH) is defined by reduced serum testosterone levels and the careful exclusion of any form of classical hypogonadism. LOH can cause detrimental physiological and mental effects, including lethargy, fatigue, decreased sense of well-being, reduced physical and mental activity, diminished libido, and erectile dysfunction 5, 6.

Complications of Male Hypogonadism

Male hypogonadism can lead to several complications, including:

  • Osteoporosis
  • Metabolic alterations
  • Cardiovascular disorders 7
  • Diabetes
  • Heart failure 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hypogonadism, ADAM, and hormone replacement.

Therapeutic advances in urology, 2010

Research

Testosterone deficiency in older men: a problem worth treating.

The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists, 2012

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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