Sex Hormone Binding Globulin (SHBG): Is It Good or Bad?

Testosterone is the primary and dominant male hormone. It is responsible for numerous functions within the human body in men and women, and when levels are too low, it can lead to multiple health issues. Unfortunately, as many know, testosterone levels naturally decline as we age. Numerous external factors can contribute to lower levels of testosterone. In either case, age or external, symptoms occur, problems arise, and solutions are needed to stop the decline. For many men, testosterone replacement therapy (TRT) is the answer to this problem.  Men should ensure that their testosterone free and total, estradiol and other hormone factors are within normal levels. One of those hormone tests to monitor is the Sex Hormone Binding Globulin (SHBG) test.

 

SHBG and the Free Testosterone Relationship

 

When our body produces testosterone or provides it exogenously, a set level of testosterone flows through the body. This testosterone blood level can be measured precisely through a simple blood test aptly referred to as the Total Testosterone blood test. For most adult men, when testing their total testosterone, if it falls in the 350 ng/dl to 1100 ng/dl range, this will be considered medically optimal. Such individuals, even exhibiting low testosterone symptoms, will often not be prescribed TRT. In some cases, this may be a correct diagnosis; in other cases, symptoms exist for different reasons, but in most cases, something else is at play, which makes SHBG important.

 

While useful, measuring total testosterone is only useful with also measuring Free Testosterone. Free testosterone is a small fraction of your total testosterone. It is often referred to as "unbound," meaning the testosterone your body will use for its intended androgenic function. Free testosterone is so important that if your total testosterone levels are within range, if free testosterone levels are low, in most cases, the man will be symptomatic of low testosterone. This issue is often due to high levels of SHBG in the body.

 

For this reason, many men will attempt to lower their SHBG or even fret over it. However, SHBG serves an essential purpose. As is with estrogen, too much can be problematic, but so can too little. SHBG is no different.

 

Of all the testosterone flowing through your body, only 2% is what we can refer to as unbound or free testosterone. From a layman's perspective, to increase free and unbound testosterone, they'd need to increase their total testosterone. Unfortunately, it doesn't always work that way – it often helps and often fixes the issue, but not always – and here's why: our testosterone is bound to albumin and sex hormone-binding globulin (SHBG). Approximately one-third of total testosterone binds to albumin, and the rest to SHBG.

 

Albumin is a protein that binds testosterone, and we can say it does so loosely. This protein carries testosterone through the bloodstream and releases it as needed. The testosterone detaches and becomes what's often referred to as bioavailable or free testosterone. The testosterone that separates from albumin becomes the testosterone that influences your body's functions from sex organs, muscle tissue, brain function, and a host of other areas of bodily function. Testosterone attached to SHBG cannot do this; it is attached and does not detach.

 

What Causes High SHBG?

 

As testosterone attached to SHBG is relatively useless, if SHBG levels increase within the body, there will be more attaches and less free testosterone to circulate. Conversely, lower levels of SHBG are associated with higher levels of free testosterone, which is often associated with positive influences on bodily functions, such as libido, mood, muscle mass, etc.

 

Numerous factors influence how much sex hormone-binding globulin we have in our bodies. Age is one of the primary factors that affect SHBG. Often as we age, SHBG levels increase, and as a result, free testosterone levels go down. Even if our total testosterone levels remain high or optimal, our bioavailable testosterone decreases if SHBG levels increase.

 

Other factors that can contribute to high SHBG include:

• Fatty Liver
  • Excessive or what we might call chronic alcohol consumption can lead to a fatty liver and impending higher levels of SHBG and corresponding lower levels of free testosterone. The disease can also be a factor, such as cirrhosis or cancer.
• Thyroid issues
  • An underactive and overactive thyroid can lead to elevated SHBG, not to mention issues associated with the thyroid. Overactive thyroid or hyperthyroidism is often associated with graves' disease, thyroid nodules, or thyroiditis. It can also exist due to abuse of thyroid medications, such as Cytomel (T3). Underactive thyroid or hypothyroidism may be caused by inflammation of the thyroid gland, pituitary damage, too little iodine in the diet, or genetic factors, along with other possible reasons.
• Elevated estradiol
  • High levels of estradiol can occur for numerous reasons, which are not limited to using certain antibiotics, some mental health medications, obesity, and abuse of exogenous testosterone.
• Obesity & High triglycerides
  • While not as expected of a factor for increasing SHBG, being overweight with a low lipid profile can negatively impact.
• Inflammation
  • While some level of inflammation is necessary for general health in the fight against disease or injury, what we might call chronic inflammation can lead to increases in SHBG and corresponding lower levels of free testosterone

 

Get Your Levels Checked: SHBG Test, Free & Total Testosterone Test

 

Testing your SHBG levels along with both total and free testosterone is particularly important if one wants to get to the bottom of hypogonadism (low testosterone) symptoms they may be experiencing. Remember, a total testosterone test alone, which some physicians will run, is not enough. For most adult men, SHBG levels will run between 10 nmol/L and 60 nmol/L if in the optimal range. If SHBG levels are greater than 60 nmol/L and your free testosterone is less than 2% of your total testosterone, there is a good chance your SHBG levels are too high.

 

Discounted Labs sells several lab test panels that measure SHBG levels that you can buy without a doctor's visit:

 

• Testosterone (Total and Free), SHBG, CBC - Hematocrit, Ultrasensitive Estradiol and PSA

 

• Testosterone, Free, Bioavailable and Total (Upper Limit T 1,500 ng/dL) plus SHBG

 

• CBC, CMP, TT, FT, Lipids, Prolactin, Ultra-Sensitive Estradiol, and SHBG

 

• Testosterone, Free, Bioavailable, and Total, LC/MS (No Upper Limit) plus SHBG

 

As we now understand SHBG, our next question is what can be done to lower it, increasing free testosterone in the body? There is nothing we can do about aging. As each day passes, we grow older, but there are still things we can do that will improve this factor.

 

How to Lower SHBG Levels:

 

The most obvious answer to the problem of low free testosterone and high levels of SHBG is to increase testosterone. Exercise more, consume a cleaner diet, and lose weight; all of these things will increase your testosterone levels. Your levels may not increase massively, but some increase means a higher total to pull from and a greater amount of free testosterone based on the 2% fraction. If this isn't enough - perhaps you're not reaching a 2% fraction due to elevated SHBG – one may need to consider talking to their doctor about testosterone supplementation. However, even if supplementing with exogenous testosterone, the habits mentioned are good for overall health and can only have a positive impact.

 

Another possible solution, and one of the more commonly needed, is lowering estradiol levels in the body. We tend to think estrogen hormones are needed for females only, but they are also crucial for men, granted in smaller amounts. As it pertains to estrogen, too much estradiol can lead to elevated levels of SHBG. If testosterone levels are also low, this can lead to even more negative factors. But it's important not to get carried away as estradiol that's too low will bring with it numerous symptoms; in fact, your life could be miserable in that regard.

 

Many men who are at least somewhat familiar with testosterone have been wrongly been told that too much testosterone can lead to gynecomastia due to elevated levels of estrogen in the body due to the aromatization of testosterone to estrogen. But low levels of testosterone in the body with present high levels of SHBG and estradiol can have the effect of causing gynecomastia. In order to combat high levels of estradiol, avoiding certain foods, especially those that are soy-based, will be important. Equally important is living a healthy lifestyle and incorporating what was mentioned above: adequate exercise, a healthy diet, and getting enough sleep. These things will help lower estradiol. Some men will also need medical help through medications known as aromatase inhibitors if they have gynecomastia, although most men on TRT do not need an AI. Too many men have relied on aromatase inhibitors out of fear for too many years. In reality, most men who supplement with exogenous testosterone can, in fact, control estrogen via non-medicated factors.

 

Some studies have shown that supplementation with DHEA (Dehydroepiandrosterone) may also lower SHBG. However, more study is needed to understand this properly, as too much DHEA can prove problematic. High doses of DHEA supplements have been associated with increased estradiol, so you must speak to your doctor first before beginning such a supplementation regimen.

 

Very Low SHBG :

 

We are then left with one factor we've yet to discuss much because it isn't all that common: low SHBG, or rather, levels of SHBG that are too low. Levels of SHBG that are too low may be an indicator of other underlying health issues. This may be an indicator of a metabolic problem. Low levels of SHBG are a standard indicator of those with diabetes. It doesn't appear, as data suggests, that insulin resistance is caused by low SHBG, but it may be a useful marker. More data is currently needed on this topic.

 

An A1c test will be needed to know with certainty in terms of your diabetic health.

 

While low SHBG is not a common concern for most men, new data has produced interesting results and information. A recent study published in the Journal of Clinical Endocrinology and Metabolism provides such information.

 

The process showed a man with undetectable levels of SHBG and low levels of testosterone accompanied by nearly a decade of hypogonadism symptoms. They discovered a family with a missense mutation in the SHBG gene from studying this individual. Interestingly enough, they found this issue did not interfere with the individual's spermatogenesis or general gonadal development. This leads the study to conclude SHBG may not play a significant role in the maturation of the male species physiologically or sexually.

 

More interesting than the JCEM study is things that new data suggest may negatively impact all men. Low levels of SHBG have recently been associated with three medical conditions that are known to be the silent killers of many men: heart disease, metabolic syndrome, and diabetes. Again, currently, it is being viewed as a marker and not as direct causation, but this new information is important as it acknowledges that more studies must be done.

 

Low SHBG has also been associated with:

 

• Obesity
  • Obesity is a factor we all well understand and is an issue that leads to problems in many health areas, and often in numerous possible directions.
• Cushing Disease
  • It is associated with extended exposure to high levels of cortisol.
• Hypothyroidism
  • It is associated with an under-active thyroid.
• Excessive levels of growth hormone
  • Exceedingly rare for most, although possible via genetic factors or abuse of exogenous forms.
• Abuse through anabolic steroids

 

 

Is SHBG an Enemy of Hormone? - Emerging Studies

 

As we mentioned, androgens like testosterone and DHEA and estrogens are transported to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex hormones inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, some researchers have demonstrated that megalin, a receptor in ovaries and testicles, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. We will see more data on this newly found receptor that actually enables the body to use hormones bound to SHBG in the near future.

 

In endocrinology, the body has no “harmful” or “good” hormone. Their balance and harmony with each other matters for the best health.

 

 

References:

 

Ding et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. The New England Journal of Medicine. Aug 2009.

Vos et al. Sex Hormone Binding Globulin Deficiency Due to a Homozygous Missense Mutation. Journal of Clinical Endocrinology and Metabolism. Sept 2014

SHBG and Free Testosterone - Everything You Need to Know

Hammes et al. Role of Endocytosis in Cellular Uptake of Sex Steroids. Cell. Sept 2005