The Importance of Sex Hormone-Binding Globulin (SHBG) for Healthy Testosterone Levels

Posted by Dr. Michael White, Updated on March 9th, 2024
Reading Time: 6 minutes
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Hormone Balance is the key to maintaining and facilitating optimal wellness.

The way that our hormones work is highly complex.

When we discuss Testosterone, Estrogen, or Human Growth Hormone Production, this is a short-hand for an entire branch of highly-interconnected processes that lead to the production of a vital hormone. Hormone Replacement Therapy tends to revolve around the replacement of the vital hormone which provides the broadest range of benefits.

For example, HGH and Testosterone are both further processed into metabolites which offer the full range of benefits associated with the hormones. The goal of this article is to explain the role of Sex Hormone-Binding Globulin (SHBG) in the function and utilization of Testosterone.

How Does the Body Make Testosterone?

Sex Hormone Production begins in the hypothalamus — the control center of the brain. The Hypothalamus receives signals from the body to produce Testosterone or Estrogen, and sex hormone precursors are released.

Gonadotropin-Releasing Hormone is issued by the Hypothalamus, where it then travels to the Pituitary.

The Pituitary Gland responds to this stimulation by releasing Luteinizing Hormone and Follicle-Stimulating Hormone, which then travel to the sex organs, promoting normal function in both men and women.

For men, Testosterone Production is triggered primarily by Luteinizing Hormone, which triggers interstitial cells in the Testes and Adrenal Glands to produce Testosterone.

What is the Importance of Sex Hormone-Binding Globulin?

After Testosterone is produced, it is then distributed throughout the body via Sex hormone-binding Globulin.

SHBG is responsible for binding to Estrogen, Testosterone, and Dihydrotestosterone (DHT), so that they can perform their essential duties. SHBG is secreted by the liver and is responsible for controlling the level of these hormones that remain unbound in the bloodstream.

SHBG is incredibly essential, but when it is present in concentrations that are too high, it depletes existing reserves of Free Testosterone.

Though SHBG helps distribute these hormones, unbound Testosterone is the reactive form that benefits the human body. SHBG production is highly correlated with Cortisol Levels in the blood.

Cortisol is the body's primary stress hormone. It helps us wake up in the morning, and it also increases dramatically in times of stress, triggering the fight-or-flight response.

Perhaps as a result of our highly evolved brains, we are prone to a condition known as Chronic Stress.

In the case of Chronic Stress, the body releases consistently elevated levels of Cortisol, which has a profoundly adverse effect on human physiology.

Since Cortisol causes Free Testosterone Levels to drop, it is associated with impaired metabolism and anabolism, meaning that it makes it both easier to gain weight and harder to lose muscle.

SHBG Sequesters Testosterone

Though SHBG plays an integral role in hormone maintenance, when Hormone Levels fall out of balance, either due to stress, age, or other factors, this harms your body's ability to utilize sufficient Testosterone to maximize health and vitality.

Because SHBG plays such a dominant role in Testosterone utilization, it's vital to test Free Testosterone, Total Testosterone, and SHBG Concentrations when evaluating for Low-T.

Total Testosterone is the combination of Bound Testosterone and Free Testosterone, which measure the amount of Testosterone present in the bloodstream, whereas Free Testosterone reveals the amount of Testosterone actively available for your body to use.

If you have elevated SHBG Levels, this is a strong suggestion that your Testosterone-Related Issues are the result of underlying factors such as depression, anxiety, and stress.

Under most circumstances, SHBG Levels are antagonistic to Free Testosterone Levels — The more SHBG in the bloodstream, the less Free Testosterone.

Having Low Levels of Free Testosterone is just as bad as having low levels of Total Testosterone, meaning that your libido, cognitive focus, energy levels, and metabolism are highly at risk. SHBG can even provide insight into the effectiveness of your body's insulin production!

What is Unbound Hormones?

Another term for Free Testosterone is Unbound Testosterone.

Most hormones are affected by transport hormones in the bloodstream, which means that there are both Unbound and Bound Hormones in the blood at any given time.

There has been a significant shift in how we understand Testosterone over the last generation, leading to an increased emphasis on evaluating SHBG Levels and how they impact the overall physiological activity. Sometimes this means that Testosterone Replacement Therapy isn't necessary.

Other times this means that Low-T Treatment is modified as a result of the impact of SHBG.

The most important thing that has changed is that Hormone Clinics and HRT Specialists recognize that healthy Total Testosterone Levels don't tell the whole story.

In fact, Low Levels of SHBG aren't ideal either, because they could be indicative of other issues such as Insulin Resistance and Diabetes. As is valid with any hormone, neither elevated nor suppressed Hormones are healthy.

What's important is to strike a balance in the normal range, also known as the Goldilocks Zone. Not too High; Not too Low — Just Right.

What Causes Elevated SHBG Levels in Men?

As we mentioned earlier, there are a wide variety of factors that can lead to increased SHBG Levels and impaired Testosterone Activity. The following is a brief list:

  • Testicular Cancer
  • Liver Detox due to heavy metals, alcohol, medication, etc.
  • Rapid Weight Loss
  • Hyperthyroidism
  • Elevated Estrogen Levels in Men
  • Cirrhosis of the Liver
  • Aging

What Leads to Suppressed SHBG Levels in Men?

  • Testosterone Overdose
  • Elevated Prolactin Levels
  • Insulin Resistance/Diabetes
  • Hypothyroidism

What Elevates SHBG Levels in Women?

  • Elevated Estrogen/Phytoestrogen Levels
  • Stress
  • Pregnancy
  • Liver Detox
  • Hyperthyroidism
  • Some Medications
  • Smoking
  • Anorexia
  • Birth Control Pills
  • Cirrhosis
  • High Testosterone Levels

What Suppresses SHBG Levels in Women?

  • Hypothyroidism
  • Elevated Testosterone Levels
  • High Levels of Prolactin in the Blood Stream
  • Polycystic Ovarian Syndrome
  • Pre-Diabetes/Diabetes

How Can We Use Our Knowledge of SHBG Levels to Improve HRT Treatment Options?

As you can see, there are a wide variety of factors that impact SHBG Levels, and these factors are also largely dependent on the gender of the patient.

For men, assessing SHBG Levels is one of many pieces of the puzzle that represents your Hormone Balance. When evaluating your SHBG Levels, your doctor will use this as a starting point to pinpoint the specific issues which are negatively impacting your Testosterone Activity.

If SHBG Levels are ignored, this can hurt your treatment, leading to side effects associated with Elevated Testosterone Levels, poor results, or masking of the underlying health issue which is causing your Hormone Imbalance in the first place, which can be dangerous or even deadly.

How Does Stress Affect SHBG Levels?

A patient's stress levels have a powerful impact on SHBG Levels and therefore affect Free Testosterone. As mentioned, chronic stress leads to an influx of Cortisol, which also causes SHBG Levels to skyrocket.

When SHBG Production increases for an extended period due to Chronic Stress, Free Testosterone Levels can fall to such an extent that it mimics the symptoms of Testosterone Deficiency. Bio-Identical Low-T Therapy can benefit the patient, but does not resolve the underlying stress, and would not be the appropriate form of treatment in this case.

SHBG Affects Men and Women Differently

Because women produce much less Testosterone than men (around 1/10th as much of the hormone), they are much more sensitive to changes in SHBG concentration and the effects of Low-T.

It's especially crucial for women to have both Free and Total Testosterone Levels checked because they are particularly susceptible to Low Free Testosterone resulting from the influence of SHBG.

Many physicians neglect to check Free Testosterone Levels, which is why you should work with a qualified, reputable HRT Clinic.

SHBG as a Diabetes Signifier

Perhaps contrary to what you would believe, Diabetes has a suppressive effect upon SHBG Levels.

The hormonal changes associated with Diabetes cause SHBG Levels to plummet, whereas cortisol causes SHBG Levels to rise. This does not lead to increased Testosterone Levels; however, as Diabetes also causes Total Testosterone Levels to drop dramatically.

Serum SHBG can also be used as a predictive tool because recent studies have shown that patients with abnormally low SHBG Levels are more likely to experience Diabetes in their lifetime.

This means that if a patient is not currently suffering from Diabetes, but does have Low SHBG Levels, they know to take steps to protect themselves from Diabetes.

Reference

Bisphenol A differentially affects male reproductive function biomarkers in a reference population and agro pesticides users from Djutitsa, Cameroon.

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