What are the causes of hypogonadism (low testosterone)?

From the Guidelines

Low testosterone is primarily associated with decreased sex drive, erectile dysfunction, and reduced muscle mass, and can result from aging, obesity, and certain medical conditions. The symptoms of low testosterone in men can be diverse, including decreased sex drive, erectile dysfunction, reduced muscle mass, increased body fat, decreased bone density, fatigue, low energy, depressed mood, irritability, and difficulty concentrating 1. According to the American College of Physicians, low testosterone can be 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. Some of the key factors that contribute to low testosterone include:

• Aging (levels naturally decline after age 30)
• Obesity
• Certain medications (particularly opioids and glucocorticoids)
• Chronic illnesses (diabetes, kidney disease, liver disease, HIV/AIDS)
• Pituitary gland disorders
• Testicular injuries or infections
• Genetic conditions like Klinefelter syndrome The diagnosis of low testosterone typically involves blood tests measuring total testosterone levels, with values below 300 ng/dL considered low 1. Treatment options for low testosterone should be individualized, but may include testosterone replacement therapy, lifestyle modifications like weight loss and exercise, and addressing underlying medical conditions that may be causing the hormone deficiency. It is essential to note that the American College of Physicians suggests that clinicians discuss the potential benefits, harms, costs, and patient's preferences when considering testosterone treatment for men with age-related low testosterone and sexual dysfunction 1.

From the FDA Drug Label

Testosterone Cypionate Injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. Males Testosterone Enanthate Injection, USP is indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) – Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy Hypogonadotropic hypogonadism (congenital or acquired) – Gonadotropin or luteinizing hormone‑releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

Low testosterone can be caused by:

• Primary hypogonadism:
  • Congenital conditions such as cryptorchidism
  • Acquired conditions such as testicular failure due to bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy 2, 3
• Hypogonadotropic hypogonadism:
  • Congenital conditions such as idiopathic gonadotropin or LHRH deficiency
  • Acquired conditions such as pituitary-hypothalamic injury from tumors, trauma, or radiation 2, 3

From the Research

Low Testosterone Causes and Effects

• Low testosterone concentrations are associated with an increased risk of metabolic syndrome and type 2 diabetes in middle-aged and older men 4
• Central adiposity is a risk factor for metabolic syndrome and diabetes, and also predisposes to lower testosterone concentrations 4
• Testosterone deficiency is linked to several co-morbidities, including metabolic syndrome, visceral obesity, and cardiovascular disease (CVD) 5
• Obesity is thought to contribute to testosterone deficiency, creating a complex bidirectional interplay between the two conditions 5
• Age-related testosterone decline is closely associated with sarcopenia, muscle deterioration, and an increased risk of diseases such as angina pectoris, arteriosclerosis, obesity, metabolic syndrome, and dementia 6

Health Implications of Low Testosterone

• Low testosterone is associated with a range of health problems, including decreased bone mineral density, insulin resistance, and increased risk of fractures 7, 8
• Testosterone therapy has been shown to improve sexual function, bone mineral density, and insulin sensitivity in men with functional hypogonadism 7, 8
• Testosterone replacement therapy can improve health-related quality of life in patients with late-onset hypogonadism (LOH) 6
• Recent landmark trials have found that testosterone therapy can have modest but clinically significant benefits on energy, mood, sexual function, and satisfaction in middle-aged and older men with symptoms of hypogonadism 8