SHBG stands for Sex Hormone Binding Globulin. It is a protein produced by the liver that binds primarily to testosterone in order to transport it through the body. It also binds to dihydrotestosterone and estradiol. It can be a “canary in the coalmine” for chronic disease states, and is an important part of the whole hormone picture for both men and women. 

Conventional medicine often misses the importance of looking at SHBG in conjunction with total and free testosterone levels, and therefore can quite easily overlook the root cause of your hormone related symptoms. Not considering SHBG levels when prescribing hormone replacement therapy or monitoring while taking certain medications can put your health at risk, and contribute to worsening hormone imbalances. 

How Does SHBG Work?

The first thing to remember about SHBG is that it is a binding protein so it is designed to transport inactive things either to a target tissue, or out of the body. Anything that is bound to it cannot unbind very easily at all- consider it stuck and unavailable for use. Testosterone is the primary hormone that sticks to SHBG. So, when there is a lot of SHBG in the blood, there is a lot of testosterone stuck to it and inaccessible. 

That means if SHBG is high, then free testosterone will be low because more of your total testosterone is stuck (bound) to SHBG. If it wasn’t bound by SHBG it would be free, therefore, you would have a higher Free Testosterone level. Free testosterone is what can readily be used by the body at any given time. Total testosterone level from a blood draw is not able to distinguish between free testosterone and that which is bound to SHBG, so you can’t rely on only a total testosterone level to tell you if you’ve got an issue with testosterone or not. 

SHBG and testosterone are inversely related. This means when SHBG is low, testosterone is likely high. This is often seen in women with PCOS, hypothyroid, and other issues where testosterone levels are too high (compared to estrogen levels). In men, SHBG is often high when testosterone levels are low. Low SHBG in men can be an indicator, especially in conventional medical settings, of underlying chronic disease states that are emerging. Low or high SHBG should never be ignored. Anytime hormone levels are checked, SHBG should be checked as well and interpreted by a practitioner who understands how this protein is affected by, and effects both testosterone and estrogen levels. 

Medications That Increase SHBG

An often overlooked, but very detrimental hormone issue is the ways in which medications can affect hormone balance, even when the reason for the medication is not at all related to hormones. There are many medications that increase SHBG. This means more testosterone gets stuck (bound to) by SHBG, and is inaccessible. Therefore, symptoms of low testosterone can develop as an unintended consequence of some medications. 

It is important to note that many of these medications are used for mental health conditions which are often worsened by hormone imbalances. If the increase of SHBG caused by the medication is resulting in hormone imbalances, then mental health and mood related issues can further negatively affected. 

Here are the types of medications that are well known to cause an increase in SHBG. If you have taken, or at any time find yourself needing to take any of these medications, it is important to monitor your hormone health. 

  • Antipsychotics (typical and atypical)
  • Antidepressants (SSRI’s, Tricyclics, MAOI inhibitors)
  • Xanax
  • Tamoxifen
  • Spironolactone
  • H2 Antagonists
  • Metformin
  • Oral contraceptives (birth control pills)
  • Exogenous insulin for Type 2 DM

Also consider a full hormone assessment from a functional medicine practitioner even if any of these medications have been taken in the past since the hormones may not have been able to recover from the artificial shift on their own. 

How To Keep SHBG in Check?

Manage Stress

A primary reason for SHBG levels to increase is from high cortisol levels. High cortisol levels occur from both a short term and long term stress response of any type (physical or emotional). The connection between SHBG and cortisol is a primary reason stress takes such a toll on hormone balance. This is especially true in men who rely on adequate amounts of available testosterone to feel well and maintain optimal hormone and metabolic functions. 

Determine Root Cause of High or Low SHBG

It will be much more effective long term to treat the REASON your SHBG is high or low, rather than trying to change the SHBG directly. This means you need to keep digging to discover which metabolic system is challenged and needs support. SHBG being low or high can tell a lot about how the body is managing stress, insulin, and how effective the hormones are at doing their jobs. SHBG is kind of like a “check engine” light for all the hormone related systems in the body. When it is high or low, it indicates further investigation of a problem needs to occur. 

For most people, the places to dig deeper to determine what body system has a “check engine” light on are these: 

  • Insulin and blood sugar management: poor insulin sensitivity and blood sugar related metabolic functions are often a driving cause of SHBG getting out of balance. Cortisol levels, amount, type, and frequency of refined carbohydrate foods, and the body’s detox systems all play a role in maintaining good insulin sensitivity. 
  • Estradiol balance: even in men, the female hormone systems of estrogen play a role in the body’s balance of estrogen and testosterone. Estrogen dominance can occur when too much free testosterone is bound up by SHBG. This can be overlooked if the full hormone panel is not assessed since total testosterone and total estrogen levels may be well within normal range, even though estrogen dominance is occurring since the level of available testosterone (free T3) may be too low compared to the estrogen circulating in the bloodstream.  
  • Thyroid function: The thyroid system is a complex mechanism that is intricately connected to the entire hormone network. This means thyroid, insulin, and sex hormones like estrogen and testosterone, are all connected. SHBG is a transport hormone so it can be good indicator of how other systems are working too. SHBG impacts estrogen and estrogen impacts thyroid function. 

Clean Up Your Environment

In this case, your environment is your body. The toxicity of normal, everyday life is taking its toll on our hormones. This means the toxic burden of anything you put in or put on your body needs to be taken into account. We agree with another functional medicine practitioner who said regard to toxic burden, “do all that you can and don’t get weird about it.” The need to consider the effect of plastics, water quality, air quality, chemical exposure from everyday household items and body care products is proven time and time again even by mainstream medical literature. Switching to non-toxic cleaning products, safer/cleaner beauty products, investing in water filtration in your home, and eliminating plastics whenever possible needs to be part of your lifestyle just like recycling. 

The other aspect of cleaning up your environment is the food quality you choose to eat. Eliminating food additives, synthetic colors/food dye, and choosing organic whenever possible will go further than you may think in regard to supporting good hormone health. Heavy metal toxicity from environmental and food sources are often a root cause of or a serious contributor to all kinds of thyroid, metabolic, and hormone issues. A good functional medicine practitioner will be able to guide you towards resources for how to clean up your food and lifestyle to lessen the load the body systems have to carry. 

If you have a history of any of the medications listed above, a thyroid condition, are or ever have ever been on HRT (hormone replacement therapy), or are experiencing symptoms of hormone imbalance, be sure you are looking at the full picture of your hormone and metabolic health by working with a practitioner who understands the importance of, and treatment options for SHBG. 

Dr Corey Priest, DC - Functional medicine practitioner

About the author

Dr. Corey Priest has been practicing functional medicine since 2001. in2GREAT was founded in 2014 by Dr Priest after 13 years of experience with his other practices. Over his career, Dr. Priest has worked with and helped well over 10,000 patients under a functional medicine model.