Life Extension Magazine®

Issue: May 2011

Do You Know Your Sex Hormone Status?

Hundreds of published studies link imbalances of testosterone and estrogen (in men and women) with the onset of age-related pathologies. A little-known blood marker of hormonal balance is sex hormone-binding globulin or SHBG. Newly published studies reveal how SHBG interacts with testosterone and estrogen—and how maturing individuals can use this blood test to optimize their sex hormone status.

By Zach White

Do You Know Your Sex Hormone Status?

Life Extension® has long emphasized the importance of maintaining a balanced and robust sex hormone profile as a core anti-aging strategy.

Hundreds of published studies link improper testosterone and estrogen balance (in men and women) with the onset of age-related pathologies such as coronary artery disease, stroke, osteoporosis, and bone fracture.1-5

But in order for you to optimize your sex hormone status, precise and accurate measurement is of paramount importance.

In this article you will learn of a critical blood marker of hormonal balance called sex hormone-binding globulin or SHBG. Newly published studies reveal that the interaction of SHBG with testosterone and estrogen affects overall hormonal balance—yet very few doctors test for it.

As you will read, sex hormone imbalances precipitated by SHBG abnormalities are associated with multiple diseases of aging in both sexes. These include cardiovascular disease (especially in women), cancer, type 2 diabetes, metabolic syndrome, and sleep apnea.6-10

SHBG: The Master Regulator for Testosterone and Estrogen

SHBG is a protein produced primarily in the liver, although the testes, uterus, brain, and placenta also synthesize it. It serves as a transport carrier, shuttling estrogen and testosterone to sex hormone receptors throughout your body.11,12 SHBG also safeguards these vital hormones from degrading too rapidly and prevents their clearance from the body.

It thus acts as the master regulator of your sex hormone levels, maintaining the delicate balance between estrogen and testosterone critical to overall health in aging humans.

New evidence further indicates that the SHBG molecule itself plays another key role in the body: conveying essential signals to the heart, the brain, and adipose (fat) tissue that ensure their optimal function.13 There’s even a special SHBG receptor molecule on cell surfaces that functions much like the ubiquitous vitamin D receptor protein, helping cells communicate with one another.14,15 In other words, SHBG itself functions much like a hormone.

Knowing your SHBG levels, along with testosterone and estrogen, thus gives you and your doctor a more precise picture of your overall health—and enables you to take preventive measures against life-threatening conditions for which you may be at greater risk.

Aging Humans and Increasing SHBG: An Overlooked Threat

Aging Humans and Increasing SHBG: An Overlooked Threat

As you age, SHBG levels may steadily rise, even though your production of sex hormones continues to decline.8,16 The result? SHGB binds to what few sex hormones you have remaining and reduces their bioavailability to cells in your body.

With elevated SHBG in the blood, too much testosterone may be sequestered and thus functionally unavailable to healthy tissues. Because testing for SHBG is largely overlooked, many older men (and their doctors) may be led to believe through standard testing that they have “normal” total testosterone levels—but since most of it may be bound to elevated levels of SHBG, in actuality they may be testosterone deficient.16

Why? Testosterone, like all steroid hormones, is derived from cholesterol, a fat molecule.16 Fats don’t dissolve in water, so the amount of testosterone floating freely in your bloodstream is small (about 0.5-2% of the total amount).16,17 Most of the circulating testosterone in your blood is either bound to the protein albumin or to SHBG.18-20

It is the combination of free and albumin-bound testosterone that ultimately determines your bio-available testosterone status.16,21-24

As a result of imprecise testosterone measurement, aging men may experience signs of feminization as their increased SHBG binds testosterone, preventing testosterone from exerting its effects and leaving estrogen’s physiological impact on the male physiology unchecked.16 These may include gynecomastia (the development of fatty breast tissue in men), diminished libido and poor sexual performance, cognitive decline, and chronic fatigue.

Combating Metabolic Syndrome

While excess SHBG creates problems with sex hormone balance, having SHBG levels that are too low is associated with other disorders. Nowhere is the impact of low SHBG so profound as in the cluster of conditions known as the metabolic syndrome, which encompasses obesity, insulin resistance, lipid abnormalities, and chronic high blood pressure.9

In men, low total testosterone and low SHBG are predictors for a higher incidence of metabolic syndrome and many of its components.9,25-29

In late postmenopausal women, low SHBG and high estrogen levels correlate with the inflammatory state associated with metabolic syndrome.30 SHBG abnormalities have also been linked to an increased risk of acne, infertility, polycystic ovary syndrome, and uterine cancer in overweight women.6,31-33

The high insulin levels found in people stricken with metabolic syndrome have also been shown to suppress SHBG, creating a vicious cycle of abnormal SHBG activity.34,35

The good news is that testosterone supplementation for men, and bioidentical hormone replacement for women, may safely and effectively reverse many of these adverse, age-related metabolic changes.36,37 Obtaining accurate measurement of sex hormone levels through SHBG blood testing thus enables you and your doctor to prevent or combat common medical disorders.

Low SHBG Is a Key Marker of Cardiovascular Disease

SHBG levels have an important relationship with nearly every biomarker of cardiovascular disease, from C-reactive protein (CRP) to arterial calcification.38,39 Low SHBG is also associated with elevated triglycerides and low-density lipoprotein (LDL).40

Calcification of blood vessels, an early finding in cardiovascular disease, is also associated with lower SHBG levels, especially in women.10,38 Low SHBG in women is associated with higher levels of C-reactive protein (CRP), an important marker of inflammation and cardiovascular risk.39 In men, low SHBG indicated an increased risk of death from cardiovascular disease.35 In both men and women, low SHBG levels are strongly correlated with obesity.41

SHBG, alone and in the context of specific sex hormone levels, thus constitutes an integral predictor of a major chronic age-related condition. Some experts are now recommending SHBG measurements as another means of evaluating cardiovascular and metabolic risk.42

What You Need to Know: Sex Hormone-Binding Globulin
  • Sex Hormone-Binding Globulin
    Optimal sex hormone status, including a healthy balance of testosterone and estrogen, is a core component of any anti-aging strategy.
  • New scientific evidence has revealed the crucial importance to hormone balance of a widely overlooked active protein called sex hormone-binding globulin or SHBG.
  • SHBG is an important regulator of your testosterone and estrogen levels, responsible for distributing sex hormones throughout your body—yet few doctors test for it.
  • SHBG abnormalities are associated with multiple killer diseases of aging in both sexes, including cardiovascular disease (especially in women), cancer, type 2 diabetes, metabolic syndrome, sleep apnea, and osteoporosis.
Protection from Cancer

Protection from Cancer

Many kinds of cancers of the breast and prostate are stimulated by the sex hormones estrogen and testosterone. However, SHBG interpretations differ for men and women, which is why the SHBG test requires professional interpretation for accurate application.

For example, in human breast cancer cells, higher levels of SHBG inhibit cell proliferation and promote programmed cancer cell death (apoptosis), by blocking the estrogen-related survival mechanisms that most breast cancer cells exploit.43-46

For men, it is the opposite. Higher SHBG levels predict more severe and invasive tumor growth in men with prostate cancer.47 The association is so strong that some urologists have suggested using SHBG levels as a standard pre-operative measurement to identify patients at high risk of invasive cancers who should undergo a more aggressive surgical procedure.48

Optimizing Bone Health

It has long been known that declining estrogen levels in both sexes are significant contributors to bone mineral loss with aging. Experts now recognize that the steady rise in SHBG with aging is directly correlated with bone loss and osteoporosis in both men and women.49-56 As a general rule the higher the SHBG level, the less estrogen is available to contribute favorably to bone health.

New studies, however, are finding a direct role for SHBG and its cell surface receptor in bone loss.57 That suggests an effect that may be independent of estrogen levels. The association is so strong that some experts are now suggesting routine measurement of SHBG as a useful new marker for predicting severity of osteoporosis.57

Understanding Sex Hormone Levels

The terminology for the different measurements of sex hormones in your blood can be confusing, but it needn’t be. Here’s a simple way to think about the levels, using testosterone as an example:16

Total Testosterone (T) is just that—a measurement of all of the testosterone in a given blood sample. It includes free T, T bound to SHBG, and T bound to albumin.

Free Testosterone is equally simple in concept, though harder to measure. Free T is that small proportion (0.5-3%) of testosterone not bound to SHBG or to albumin.17

Bioavailable Testosterone (bioT) is simply the combination of the small amount of free T, plus the much larger amount of T that is loosely bound to albumin. You can also think about bioT as the amount of T that is not bound to SHBG, and some scientists refer to it that way.22,24,61 In general, higher SHBG will mean there’s less T that is bioavailable, while lower SHBG means there’s more bioavailable T, though that is a bit of an oversimplification.

The test for SHBG is useful for understanding and optimizing your sex hormone levels in combination with your other test results. When you receive your blood test results back, if you have any questions about your sex hormone status (including SHBG levels), please reach out to a Life Extension Wellness Specialist at 1-866-864-3027.

Detecting Obstructive Sleep Apnea

Sex hormone-binding globulin may provide an important clue that an individual is affected by obstructive sleep apnea,7,58 a relatively common condition that increases the risk of heart disease and stroke.59

Obstructive sleep apnea occurs when breathing repeatedly stops and starts during sleep due to blockage of the upper air passages. Frighteningly, many people are unaware that they suffer from this disorder. Sleep apnea often manifests with loud snoring, waking up feeling unrested, morning headaches, daytime sleepiness, fatigue, and unexplained high blood pressure. An overnight sleep study (polysomnography) is essential in order to definitively diagnose the condition.60

Scientists have found that obstructive sleep apnea is associated with disruptions in the endocrine system in men, including decreased levels of SHBG as well as free and total testosterone.7,58 Lower levels of SHBG, free testosterone, and total testosterone correlate with more severe sleep apnea.7,58 In one study, men’s SHBG and total testosterone rose significantly following 3 months of sleep apnea treatment with continuous positive airway pressure (CPAP).7

Detecting Obstructive Sleep Apnea

Low SHBG combined with low testosterone may represent a novel marker for sleep apnea in men and may provide helpful information regarding which individuals should consider having a sleep study to diagnose the condition.

Summary

Maintaining optimal sex hormone status, including a healthy balance of testosterone and estrogen, is a core component of any anti-aging strategy. New scientific evidence has revealed the crucial importance to hormone balance of a widely overlooked active protein called sex hormone-binding globulin or SHBG. It is an important regulator of your testosterone and estrogen levels, responsible for distributing sex hormones throughout your body—yet few doctors test for it.

SHBG abnormalities are associated with multiple killer diseases of aging in both sexes, including cardiovascular disease (especially in women), cancer, type 2 diabetes, metabolic syndrome, sleep apnea, and osteoporosis.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

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