What causes hypogonadism in a 35-year-old male?

From the Guidelines

Hypogonadism in a 35-year-old male is most likely caused by primary or secondary hypogonadism, often classified as organic or classical hypogonadism, which can be due to disorders of the hypothalamus, pituitary gland, or testes.

Possible Causes of Hypogonadism

• Primary hypogonadism is the result of testicular failure, where testosterone levels and sperm counts are below normal, and serum LH and FSH are above normal 1.
• Secondary hypogonadism is a disease of the pituitary or hypothalamus, where serum testosterone levels and sperm counts are subnormal and serum LH and FSH levels are normal or reduced 1.
• Adult-onset hypogonadism is characterized by a deficiency of testosterone and a failure of the body to produce an adequate compensatory response, where low testosterone levels are associated with normal or low levels of gonadotropins, suggesting physiologic failure of both the testicles and hypothalamic-pituitary system 1.

Age-Related Low Testosterone

• A gradual, age-associated decline in serum total testosterone levels begins in men in their mid-30s and continues at an average rate of 1.6% per year 1.
• This condition is referred to as age-related low testosterone and is accompanied by clinical symptoms associated with androgen deficiency.

Diagnosis and Evaluation

• The diagnosis and evaluation of hypogonadism should include measurement of testosterone levels and assessment of clinical symptoms associated with androgen deficiency 1.
• Guidelines by the Endocrine Society and the American College of Physicians provide recommendations for the diagnosis and treatment of hypogonadism 1.

Treatment

• Testosterone treatment is approved by the U.S. Food and Drug Administration (FDA) for replacement therapy for men with primary or secondary hypogonadism caused by disorders of the hypothalamus, pituitary gland, or testes 1.
• The American College of Physicians suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition, due to low-certainty evidence 1.

From the Research

Causes of Hypogonadism

The causes of hypogonadism in a 35-year-old male can be attributed to various factors, including:

• Primary hypogonadism, which results from testicular damage or disease 2, 3
• Secondary hypogonadism, which is caused by dysfunction of the hypothalamic-pituitary unit 2, 3
• Genetic conditions, anatomic abnormalities, infection, tumor, and injury 4
• Defects in the hypothalamic-pituitary-gonadal axis, which may be caused by type II diabetes mellitus and treatment with certain medications 4
• Intensive exercise training, which can cause functional hypogonadism 5

Pathophysiology

The pathophysiology of hypogonadism is complex and involves the interplay of various factors, including:

• Low testosterone levels, which can affect sexual function, cognitive function, and body composition 2, 3, 4
• Metabolic dysfunction, which can perpetuate a cycle of low testosterone and metabolic disease 6
• Obesity and insulin resistance, which can suppress the hypothalamic-pituitary-gonadal axis and contribute to hypogonadism 6

Clinical Presentations

The clinical presentations of hypogonadism can vary depending on the time of onset and the underlying cause, and may include:

• Absence or regression of secondary sex characteristics 4
• Reduced fertility, anemia, muscle wasting, and reduced bone mass 2, 3, 4
• Sexual dysfunction, reduced sense of vitality, depressed mood, and hot flushes 4