From the Guidelines
Hypogonadism in middle-aged males is primarily caused by a combination of factors including aging, lifestyle factors, and underlying medical conditions, with the most recent evidence suggesting that low testosterone levels are associated with increased mortality and cardiovascular disease risk 1.
Causes of Hypogonadism
The causes of hypogonadism in middle-aged males can be categorized into primary and secondary causes. Primary causes include:
- Testicular damage from trauma, infections like mumps orchitis, chemotherapy, radiation therapy, or autoimmune disorders
- Genetic conditions like Klinefelter syndrome Secondary causes involve:
- Pituitary or hypothalamic dysfunction, which may result from tumors, medications (particularly opioids, glucocorticoids, and certain antipsychotics), chronic illnesses, obesity, and metabolic disorders like diabetes
- Lifestyle factors such as excessive alcohol consumption, chronic stress, poor sleep, and lack of exercise
- Certain medications including spironolactone, ketoconazole, and some HIV medications that can suppress testosterone production
Association with Mortality and Cardiovascular Disease
Recent studies have associated low testosterone levels with increased all-cause and cardiovascular mortality, with a meta-analysis of 10 longitudinal studies finding that testosterone levels were significantly lower in patients with incident overall and cardiovascular mortality compared with controls 1.
Treatment and Management
Treatment depends on the underlying cause but may include testosterone replacement therapy, which can be administered as injections, transdermal gels, patches, or pellets. Lifestyle modifications such as weight loss, improved sleep, stress reduction, and limiting alcohol consumption can also help improve testosterone levels naturally in some cases.
Recent Guidelines and Recommendations
The American College of Physicians has issued guidelines recommending that testosterone therapy may provide small improvements in sexual functioning and quality of life in older men with low testosterone levels without well-established medical conditions known to cause hypogonadism, but long-term efficacy and safety are unknown 1.
Key Takeaways
- Hypogonadism in middle-aged males is a complex condition with multiple causes
- Low testosterone levels are associated with increased mortality and cardiovascular disease risk
- Treatment should be individualized and may include testosterone replacement therapy and lifestyle modifications
- Recent guidelines recommend cautious use of testosterone therapy, with careful consideration of potential benefits and harms 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 in a middle-aged male are:
- Primary hypogonadism: defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia
- Secondary hypogonadism: failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH) 2
From the Research
Causes of Hypogonadism in Middle-Aged Males
The causes of hypogonadism in middle-aged males can be classified into primary and secondary hypogonadism, with various congenital and acquired factors contributing to its occurrence.
- Primary hypogonadism is caused by testicular disease or failure, while secondary hypogonadism is caused by dysfunction of the hypothalamic-pituitary unit 3, 4, 5.
- Common causes of primary hypogonadism include Klinefelter's syndrome, anorchia, and acquired disturbances of testicular function 4, 6.
- Secondary hypogonadism can be caused by pituitary tumors, hypothalamic defects, and other factors affecting the production of gonadotropins 4, 6, 5.
- Other factors that can contribute to hypogonadism include genetic and developmental disorders, infection, kidney disease, liver disease, autoimmune disorders, chemotherapy, radiation, surgery, and trauma 3.
- Age-related hypogonadism is also a common cause of hypogonadism in middle-aged males, with approximately 15-25% of men over 50 years old experiencing low serum testosterone levels 4.
Classification of Hypogonadism
Hypogonadism can be classified into different types based on the underlying cause and the level of the defect.
- Primary (hypergonadotropic) hypogonadism: caused by testicular disease or failure 6.
- Secondary (hypogonadotropic) hypogonadism: caused by dysfunction of the hypothalamic-pituitary unit 6.
- "Peripheral" hypogonadism: results from androgen receptor polymorphism 6.
Symptoms and Diagnosis
The symptoms of hypogonadism depend on the age of onset and the severity of the condition.