From the Guidelines
Low sex hormone-binding globulin (SHBG) and low total testosterone are often caused by obesity, which leads to increased aromatization of testosterone to estradiol in adipose tissue, resulting in low free testosterone levels and subsequent negative feedback suppressing pituitary luteinizing hormone secretion 1.
Causes of Low SHBG and Total Testosterone
The causes of low SHBG and total testosterone can be multifactorial, including:
- Obesity, which is a common cause due to its association with increased estrogen production and insulin resistance, both of which suppress SHBG production in the liver 1
- Insulin resistance and metabolic syndrome, which can directly inhibit SHBG synthesis and reduce testosterone production
- Certain medications like glucocorticoids, opioids, and anabolic steroids, which can lower both SHBG and testosterone levels
- Chronic illnesses, inflammatory conditions, and nutritional deficiencies, particularly zinc and vitamin D, which may contribute to low hormone levels
Importance of Evaluating Morning Serum Free Testosterone
When evaluating low total testosterone clinically in a man with obesity, the measurement of morning serum free testosterone is essential to distinguish between low total testosterone due to low SHBG and frankly low free testosterone levels 1. This is crucial in determining the appropriate treatment approach.
Treatment Approach
Addressing the underlying cause is essential for treatment, which might include:
- Weight loss and improved diet
- Exercise and better management of diabetes or thyroid conditions
- Possibly testosterone replacement therapy if hypogonadism is confirmed through multiple blood tests 1
- Lifestyle modifications like reducing alcohol consumption, improving sleep quality, and stress management can also help improve hormone levels naturally.
From the Research
Causes of Low SHBG and Low Total Testosterone
- Low sex hormone-binding globulin (SHBG) and total testosterone levels can be associated with various health conditions, including adult onset hypogonadism (AOH) 2 and metabolic syndrome 3.
- In men with AOH, low SHBG levels are common, and SHBG is highly positively correlated with total testosterone levels 2.
- Low SHBG and total testosterone levels can also be predictive of metabolic syndrome, particularly in non-obese men 3.
- Additionally, low SHBG and total testosterone levels have been linked to increased mortality in men with type 2 diabetes 4.
Relationship Between SHBG and Testosterone
- SHBG regulates testicular negative feedback, which can affect testosterone levels 2.
- The level of SHBG is inversely proportional to BMI in both untreated and testosterone-treated men 2.
- Calculated free testosterone (cFT) is also an important factor in diagnosing hypogonadism, as reliance on total testosterone alone may lead to missed diagnoses 5.
Potential Underlying Factors
- Central hypogonadism, characterized by impaired function of the hypothalamus or pituitary gland, can lead to low testosterone levels 6.
- HIV infection can also affect sex hormone levels, including SHBG and testosterone, and may contribute to hypogonadism 5.
- Age-related decline in testosterone levels can also impact SHBG and mortality in men with type 2 diabetes 4.