What are the causes of low free testosterone?

From the Guidelines

Low free testosterone is primarily caused by a combination of factors including obesity, aging, chronic illnesses, and certain medications, which can lead to decreased libido, erectile dysfunction, and other health issues in men. The causes of low free testosterone can be attributed to various factors, including:

• Obesity, which can lead to low concentrations of sex hormone-binding globulin and increased aromatization of testosterone to estradiol in adipose tissue 1
• Aging, as testosterone levels naturally decline after age 30 1
• Chronic illnesses, such as diabetes or kidney disease, which can disrupt hormone production and regulation 1
• Medications, particularly opioids and glucocorticoids, which can suppress testosterone production 1
• Pituitary gland disorders, testicular injuries or infections, and genetic conditions, which can affect hormone production and regulation 1

It is essential to diagnose low testosterone through blood tests measuring both total and free testosterone levels, and to consider lifestyle modifications like weight loss, regular exercise, adequate sleep, stress reduction, and limiting alcohol to improve testosterone levels naturally 1. Testosterone replacement therapy (TRT) may be considered for men with low testosterone levels, but its efficacy and safety are still being studied, and long-term effects are unknown 1.

The diagnosis of testosterone deficiency requires both a low testosterone measurement and the presence of select symptoms and/or signs, and clinicians should use a total testosterone level below 300 ng/dL as a reasonable cut-off in support of the diagnosis of low testosterone 1. The clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels combined with symptoms and/or signs, and clinicians should consider measuring total testosterone in patients with a history of unexplained anemia, bone density loss, diabetes, exposure to chemotherapy, exposure to testicular radiation, HIV/AIDS, chronic narcotic use, male infertility, pituitary dysfunction, and chronic corticosteroid use even in the absence of symptoms or signs associated with testosterone deficiency 1.

In patients with obesity, treatment with testosterone-replacement therapy should be considered when the morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments, and the hypogonadism workup has been completed to rule out an etiology of hypogonadism unrelated to obesity 1. The method of testosterone replacement should be individualized for each patient, and transdermal testosterone preparations are suggested for most hypogonadal men because they usually produce normal serum testosterone concentrations, and patients typically find them the most convenient 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 low free testosterone include:

• Primary hypogonadism: defects of the gonads, such as
  • Klinefelter's syndrome
  • Leydig cell aplasia
  • Cryptorchidism
  • Bilateral torsion
  • Orchitis
  • Vanishing testis syndrome
  • Orchiectomy
  • Chemotherapy
  • Toxic damage from alcohol or heavy metals
• Secondary hypogonadism: failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH) due to:
  • Tumors
  • Trauma
  • Radiation
  • Pituitary-hypothalamic injury 2

From the Research

Causes of Low Free Testosterone

The exact causes of low free testosterone are not explicitly stated in the provided studies. However, several factors can contribute to hypogonadism, a condition characterized by low testosterone levels:

• Aging: Low testosterone levels are common in men over 60 years of age 3
• Hypogonadotropic hypogonadism: A condition caused by a dysfunction in the hypothalamus and/or the pituitary gland, leading to low gonadotropin levels and low total testosterone levels 4
• Testosterone replacement therapy: Can impair spermatogenesis and decrease serum gonadotropins and intratesticular testosterone 5

Related Factors

Several factors are related to low free testosterone, including:

• Decreased libido
• Erectile dysfunction
• Decreased vitality
• Decreased muscle mass
• Increased adiposity
• Depressed mood
• Osteopenia
• Osteoporosis 6, 3
• Use of certain medications, such as clomiphene citrate, which can stimulate gonadotropin secretion and increase endogenous testosterone production 7

Treatment-Related Factors

Certain treatments can also affect free testosterone levels, including:

• Testosterone replacement therapy: Can decrease serum gonadotropins and intratesticular testosterone, impairing spermatogenesis 5
• Gonadotropin therapy: Can stimulate spermatogenesis and support puberty in patients with hypogonadotropic hypogonadism 4
• Combination therapy with human chorionic gonadotropin and FSH: Can promote testicular growth, spermatogenesis, and pregnancy rates in patients with hypogonadotropic hypogonadism 4