What is Sex Hormone Binding Globulin?
Sex Hormone Binding Globulin (SHBG) is a protein that binds to and transports sex hormones, like testosterone and estrogen, through the bloodstream. It safeguards these hormones so that they are not eliminated by the body too quickly.
When SHBG is bound to testosterone or estrogen, these hormones cannot exert their effects on the body. In this state, they are not active or not bioavailable. When not bound to SHBG or other protein carriers, these sex hormones are active or bioavailable. In this state, they can exert their effects on the body. Other proteins, like albumin, also help transport testosterone through the bloodstream and act in the same way.
Why is sex hormone binding globulin important? In the case of testosterone, SHBG levels determine free testosterone levels. Most testosterone is bound (not active) in the bloodstream. Normally, 45% of testosterone is bound to SHBG and 53% is bound to albumin.1 The remaining 2% of testosterone exists in a free (unbound) active state. Therefore, only a very small amount of testosterone is biologically active at any given time.
(Advanced Note: Historically only the free T was thought to be the bioavailable component. However, testosterone that is bound to albumin dissociates easily. As a result, it is readily available for tissue uptake. Therefore, all non-SHBG bound testosterone is considered bioavailable. Based on this definition, approximately 55% is bioavailable at any given time.)
Relationship Between SHBG and Free Testosterone
The amount of testosterone that is free depends on the level of sex hormone binding globulin. With all else being equal, higher levels result in lower free T levels. Conversely, lower levels result in higher free T levels. This relationship is important because free, unbound testosterone is the active form of testosterone. As a result, men with normal total testosterone levels but high SHBG levels may experience symptoms of low testosterone.
Normal Sex Hormone Binding Globulin Levels
Normal sex hormone binding globulin levels in adult men fall between 20 to 60 nmol/L. A value below 20 nmol/L is considered low. A value above 60 nmol/L is considered high.2
Normal SHBG Levels in Adult Men (nmol/L)
As mentioned above, high sex hormone binding globulin levels are not ideal. Too much SHBG will reduce the amount of free, unbound testosterone. In this state, most testosterone will be unavailable for healthy tissues. If this is the case, a man may have normal total testosterone levels but less than normal free T levels.3
Low sex hormone binding globulin levels are also not ideal. In men, low total testosterone and low SHBG are associated with higher rates of obesity and diabetes (insulin resistance).4-6 Insulin plays an important role in the management of SHBG levels, and insulin resistance lowers these levels.7-8
Sex Hormone Binding Globulin and Aging
Unfortunately, as a man ages, sex hormone binding globulin levels increase by a little over 1% per year after early adulthood.9-14 This increase decreases free T levels. Coupled with the fact that total testosterone levels decrease with aging, free T levels decrease even more.
Total testosterone decrease by about 30% in healthy men between the ages of 25 and 75, while free T levels decline by about 50%. This more dramatic decline in free T levels is directly linked to the increase in SHBG.15-23 As a result of this increase, aging men may potentially experience signs of feminization. The increased SHBG levels prevent testosterone from exerting its effects. Also, since SHBG binds testosterone better than estrogen, this increase also leaves estrogen’s physiological impact on the male physiology unchecked.
What Causes SHBG Levels to Increase?
The exact reason why sex hormone binding globulin levels typically increase with age is unknown. It is known that SHBG levels decrease with high levels of growth hormone (GH) and insulin growth factor (IGF-1). One possibility is that the age-related decline in GH and IGF-1 levels might contribute to the increase.7 It is also known that low levels of estrogen and thyroid hormones decrease SHBG levels. Therefore, high levels of estrogen and thyroid hormones likely increase SHBG.
Interestingly, obese men tend to have lower sex hormone binding globulin levels than non-obese men because these men often have some level of insulin resistance. Insulin plays an important role in the management of SHBG levels, and insulin resistance lowers these levels.7-8 While obese men have lower SHBG levels, they do not necessarily have higher free T levels. Because obesity significantly reduces total testosterone levels, they still have less free, unbound testosterone than their non-obese counterparts.
|Conditions associated with decreased SHBG concentrations||Conditions associated with increased SHBG concentrations|
|Nephrotic syndrome||Hepatic cirrhosis and hepatitis|
|Use of glucocorticoids, progestins, and androgenic steroids||Use of anticonvulsants|
|Acromegaly||Use of estrogens|
|Diabetes mellitus||HIV disease|
Should SHBG Levels Be Lowered?
The amount of testosterone that is bioavailable depends on the level of sex hormone binding globulin. Thus, it would seem like any man would always want to lower his SHBG. However, low levels are correlated with heart disease, diabetes, and obesity. While high levels are certainly not good either, the medical community does not treat high levels directly. Rather, the standard approach is to address any underlying causes associated with either increased or decreased concentrations. If high levels are contributing to lower than normal free T levels, the standard protocol is to treat the low testosterone directly via testosterone replacement therapy.
External Resource: Wikipedia: Sex Hormone Binding Globulin
Updated: April 26, 2015
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