What are the effects of elevated Sex Horming Binding Globulin (SHBG) in a young man?

From the Guidelines

Elevated Sex Hormone Binding Globulin (SHBG) in a young man can lead to reduced free testosterone levels, causing symptoms of hypogonadism, despite normal total testosterone levels, as the bound testosterone is unavailable to tissues 1.

Effects of Elevated SHBG

The effects of elevated SHBG in a young man can be far-reaching, including:

• Reduced free testosterone levels, leading to symptoms of hypogonadism such as decreased libido, erectile dysfunction, and reduced muscle mass
• Increased body fat, particularly in the abdominal area, due to the lack of available testosterone for fat metabolism
• Fatigue, decreased body hair, and mood changes such as depression or irritability
• Decreased bone density over time, leading to an increased risk of osteoporosis
• Potential impact on fertility due to altered sperm production

Causes of Elevated SHBG

Common causes of elevated SHBG include:

• Liver disease
• Hyperthyroidism
• Aging
• Estrogen excess
• Certain medications
• Genetic factors

Treatment and Management

Treatment depends on identifying and addressing the underlying cause of elevated SHBG, which may include:

• Lifestyle modifications
• Treating primary conditions such as liver disease or hyperthyroidism
• In some cases, testosterone replacement therapy under medical supervision to restore hormonal balance and alleviate symptoms, as supported by studies on testosterone replacement in men with obesity and hypogonadism 1 It is essential to note that the measurement of morning serum free testosterone is crucial in evaluating low total testosterone clinically in a man with obesity, as men with obesity and hypogonadism who have low total testosterone due solely to low sex hormone-binding globulin have normal free testosterone levels 1.

From the FDA Drug Label

Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins.

The effects of elevated Sex Hormone Binding Globulin (SHBG) in a young man are not directly addressed in the provided drug labels.

From the Research

Effects of Elevated SHBG in Young Men

• Elevated Sex Hormone Binding Globulin (SHBG) levels in young men may have various effects on their health, including:
  • Association with nonalcoholic fatty liver disease (NAFLD) in midlife, as found in a study where lower SHBG levels in young men were linked to a higher risk of NAFLD later in life 2
  • Influence on the bioavailability of testosterone, with higher SHBG levels potentially reducing the amount of biologically available testosterone 3, 4
  • Potential impact on cardiovascular health, with some studies suggesting that SHBG may have cardioprotective effects 5
• Factors that may contribute to elevated SHBG levels in young men include:
  • Genetic factors, such as certain polymorphisms 6
  • Hormonal factors, such as insulin and glucose levels 6
  • Lifestyle-related factors, such as body composition and physical activity 6

Association with Testosterone and Other Hormones

• Elevated SHBG levels may be associated with higher total testosterone levels, but not necessarily with higher levels of non-SHBG-bound testosterone 4
• SHBG levels may also be influenced by other hormones, such as insulin and IGF-1, which can negatively affect SHBG levels 6

Clinical Implications

• Elevated SHBG levels in young men may be a marker for increased risk of certain health conditions, such as NAFLD 2
• SHBG testing may be useful in clinical practice to assess the risk of these conditions and to monitor the effects of interventions aimed at reducing this risk 3, 2