From the Guidelines
Low SHBG (Sex Hormone-Binding Globulin) does not typically cause low total testosterone, as men with obesity and hypogonadism who have low total testosterone due solely to low sex hormone-binding globulin have normal free testosterone levels. According to the study published in Gastroenterology in 2017 1, low SHBG is often associated with normal or even high total testosterone levels, as it is a protein that binds to testosterone in the bloodstream, making it unavailable for use by the body. When SHBG levels are low, more testosterone exists in the "free" or bioavailable state, which is the active form that can enter cells and exert effects.
Some key points to consider:
- Total testosterone measures both bound and free testosterone, while free testosterone measures only the unbound portion.
- Low SHBG can be caused by conditions like obesity, insulin resistance, hypothyroidism, and use of certain medications including androgens, glucocorticoids, and growth hormone.
- If a patient has low SHBG and is experiencing symptoms of low testosterone despite normal total testosterone levels, their doctor might consider measuring their free testosterone levels, which could be normal or high despite a lower total testosterone reading.
- Treatment would focus on addressing the underlying cause of low SHBG rather than directly supplementing testosterone, as stated in the study 1.
It's essential to evaluate low total testosterone clinically in a man with obesity by measuring morning serum free testosterone, as suggested in the study 1. This approach helps determine if the low total testosterone is due to low SHBG or other factors, such as increased aromatization of testosterone to estradiol in adipose tissue, with subsequent estradiol-mediated negative feedback suppressing pituitary luteinizing hormone secretion.
From the Research
Relationship Between Low SHBG and Total Testosterone
- Low serum SHBG levels have been found to contribute to low serum total testosterone concentrations in obese men 2.
- A study on men with adult onset hypogonadism found that low SHBG levels were associated with low total testosterone levels, and that SHBG was highly positively correlated with total testosterone level in untreated men 3.
- Another study found that low serum SHBG and total testosterone levels were predictive of the development of the metabolic syndrome in nonobese men 4.
- Low levels of SHBG and testosterone have also been associated with smaller, denser low density lipoprotein in normoglycemic men 5.
Mechanism of Low SHBG and Total Testosterone
- The exact mechanism of how low SHBG contributes to low total testosterone is not fully understood, but it is thought that SHBG regulates testicular negative feedback, which can affect testosterone production 3.
- Low SHBG levels may also allow exogenously supplied testosterone to be excreted, leading to low total testosterone levels 6.
Clinical Implications
- Low SHBG and total testosterone levels have been associated with various health conditions, including erectile dysfunction, metabolic syndrome, and cardiovascular disease 2, 6, 4.
- The relationship between SHBG, total testosterone, and these health conditions suggests that low SHBG and total testosterone may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men 4.