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
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 testoste-rone 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
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