[Lotus]

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

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

http://www.lef.org/magazine/mag2011/may2...tus_01.htm

[Lotus]

This next post is a pretty important step in NBE, by not eliminating the 'bad E's' on a regular basis you run the risk of stalling:

We also know that too much E turns off those receptors and feedback is locked, so what to do?.

Well you have to think in terms of reactivating those receptors, you know!!, clear them out to start the process over,

I have often wondered the same thing! I think its crucial to metabolize these active hormones efficiently or they will build up in the liver much sooner than they normally do, causing the receptors to shut down/ feedback loop effect. For ex, as much as DIM is apart of men's formulas and women's to rid E excess, I think the most important part of what we need from it is actually being able to use these hormones as they flush out of the system. The liver is so important in nbe and metabolizing hormones. The abundance of free running hormones in the blood can be from poor liver function.

I think that is why the Cycling of "hormones" format is so important. It creates the re sensitivity factor consistently. I'm starting to think this is why plateaus happen after a while, loaded receptors and acute poor functioning of the liver.

This totally explained why my first attempt in nbe went detrimental. I had blood tests confirm free high estrogen and testosterone ( from high DHEA) and progesterone (though lowest of them all). And of course, I got some serious androgen conversion. I had no nbe success at all and the worst bumpy skin after months of taking all sorts of herbs (mainly estrogenic).So one can have high levels of E hormones and have no breast developmental effects at all, yet have mild masculating effects . I sadly developed some nice little stray hairs on my areola that were never there before
They were gone thankfully after cleansing months in.

Im convinced, that DHT is the little devil that breaks nbe success. I would personally like to raise my T levels as I am naturally low, but I am so sensitive to DHT conversion from my wonky adrenals.

Hi Tibetan,

Thank you-Brilliant!!,

I wish we focused on what you just posted more often, there's so many things out there that's robbing breast growth these days. Xeno-hormones comes to mind, but this statement struck me, matter of fact the whole article did.

The good estrogen causes no damage and drives immediately to the colon or to the bladder where it leaves the body. The bad estrogen backfires, gets stuck in reverse, and speeds back to the breast where it wreaks havoc. If this bad estrogen finds a parking spot on a breast cell, it will rapidly speed up cell division. If you have a lot of bad estrogen in your body, your risk of breast cancer goes up significantly.

Ok the rest of this is a read, but I think it's very important and won't (shouldn't) harm the brain, so press on my pretties.

http://www.womenswellnessconsulting.com/...index.html

Okay, with this understanding of all the different kinds of estrogen, lets look at how estrogen is processed within the body. Understanding how estrogen is produced, used, broken down and eliminated by your body – the estrogen pathway - is important. It will help you to understand the protocol better and make choices that support your optimum level of wellness.

I am going to quote Christine Horner, M.D. directly, from her book, Waking the Warrior Goddess, (which I highly recommend.) She has an analogy that is very simple and easy to understand.

"To understand the estrogen pathway better, lets use the analogy of a car ride. Your trip begins in the ovaries where estrogen is made and then is released into the blood. The blood vessels are like highways and estrogen flows through these blood vessel highways to get to its target destinations. When estrogen travels in the blood, it either travels alone or is attached to a substance called a "protein binder" (HSBG, Human Sex Binding Globulin), -the difference between driving alone and carpooling. When you carpool in certain cities, you can use a special high-speed lane, usually on the far left. In this lane, you can't exit from the highway. If you're driving alone, you can't use these high-speed lanes. You must travel in lanes that have access to exit lanes. Like the person driving alone, only the estrogen that travels alone – without a protein binder, SHBG – can exit from the blood-vessel highway. In this case, we are concerned about the off-ramp for only one destination: the breast tissue.

When estrogen reaches the breast, it looks for a place to "park". Parking spaces represent the "estrogen receptors", which estrogen binds to on the breast cell membranes. There are estrogen receptors all over your body, but the highest concentrations are found in the uterus and breast. Because of the relatively large number of estrogen receptors in these tissues, they respond more to estrogen than the other tissues in the body do.

When estrogen binds to an estrogen receptor, it "turns it on". A turned-on receptor causes cells to start dividing. Estrogen receptors don't turn on like a simple on/off switch. Instead, they turn on like a rheostat, a light switch with a dimmer.

The rate at which cells divide in response to estrogen is affected by many factors. First, the rate depends on the strength of the estrogen. There are strong estrogens (ESTRADIOL, ESTRONE, XENOHORMONES) and weak estrogens (ESTRIOL, PHYTOESTROGENS). Strong estrogens speed up cell division and therefore, increase the risk of cancer. Weak estrogens slow down cell division, therefore reducing the risk for cancer.

Parking at an estrogen receptor causes a lot of wear and tear on the estrogen. After awhile, it needs to go in for service. So, the estrogen leaves the estrogen receptor and heads for the liver (service station). The liver is the great detoxifier of the body. It breaks down toxins and other natural substances to prepare them for elimination.

Estrogen is broken down in the liver, and is influenced by the presence of certain chemicals. It is either broken down into a "good" kind of estrogen (Technically known as 2-hydroxyestrone) or a "bad" kind of estrogen (16-alpha hydroxyestrone). For instance substances in cruciferous vegetables and flax create more of the good kind, while environmental toxins (xenohormones) create more of the bad kind. The difference between good and bad estrogen is that good estrogen causes the cells to divide very slowly, whereas bad estrogen causes them to divide rapidly. Bad estrogen can also cause mutations or mistakes in how the cells grow that increase your risk of cancer even more.

The good estrogen causes no damage and drives immediately to the colon or to the bladder where it leaves the body. The bad estrogen backfires, gets stuck in reverse, and speeds back to the breast where it wreaks havoc. If this bad estrogen finds a parking spot on a breast cell, it will rapidly speed up cell division. If you have a lot of bad estrogen in your body, your risk of breast cancer goes up significantly.

In the colon, estrogen is either eliminated or absorbed back into the blood. If it is absorbed back into the blood, it adds to the total amount of estrogen in your body, and therefore, adds to your risk. There is a simple solution: eat more fiber. Fiber binds to the estrogen in your colon and eliminates it."

I would like to add a little bit here to Dr. Horner's reference to the "protein binder" sex hormone-binding globulin- SHBG. Understanding this protein can make a big difference in your understanding of the "big picture" of hormone health and balance. It is a critical player with a big impact on all our hormones.

As Dr. Horner mentioned, estrogen (and other hormones) that are bound to SHBG are in the "carpool lane" and cannot make random exits from the bloodstream. Only "free" (unbound) estrogen can roam through various tissues of the body searching for estrogen receptor sites to lock on to. In terms of our risk for breast cancer, it is only the free estrogen that concerns us. However, there is more to the story.

The inner intelligence of the body doesn't want hormones running wild or falling below a certain level. It wants normalcy, hormonal law and order. To achieve this, your body utilizes these sex hormone-binding globulins, which are produced by the liver.

These proteins chaperone individual hormone molecules though the blood. Should the hormones reach too high a level, the protein binds and inactivates them – sort of like a handcuffing effect. The protein not only transports but also regulates and assists in the access process at target cell sites.

If the estrogen level goes too high, an alarm goes off in the liver, the body's master chemical factory. It pumps out extra SHBG. In reaction to a high tide of estrogen, your liver can produce up to three times the normal amount of SHBG.

The problem is that this special protein doesn't just bind up some of the excess estrogen. It binds up – and inactivates – some of the other important hormones, such as thyroid hormone, growth hormone and testosterone (which is more important for women than you might think!)

You may have heard of a condition referred to as "Estrogen Dominance". This is where the body is flooded with higher than necessary levels of estrogens, which might be produced by your own body, or come from a toxic source, xenoestrogens. Usually it is a combination of both.

In addition to the deleterious effects we have already discussed in regards to excess estrogen in the body, there is now a complicating factor. High levels of estrogen in the body trigger the release of sex hormone-binding globulin, as the body tries to maintain balance by inactivating some of the excess estrogen. But, at the same time the estrogen is being inactivated, the release of high amounts of SHBG causes other important hormones to become bound and inactive as well.

In this way estrogen dominance not only raises our risk for breast cancer, but can cause a cascade effect on other important hormones as well.

The effect on you is not immediate. It takes about six weeks before you usually start to experience the fallout from the lowered hormonal activity. Quantities of your important anti-aging hormones have now been taken out of commission. In essence, the available amount of these hormones falls to levels you might have when you are years older. The body becomes less "alive". Perhaps the skin becomes less radiant, the vagina drier. Lowered thyroid, for instance, can cause weight gain, fatigue, coldness and dry skin. These are all signs of a thyroid deficiency. Elevated SHBG can cause such multiple effects.

[Lotus]

What are free and bioavailable testosterone?

Testosterone is present in the blood as "free" testosterone (1-4%) or bound testosterone (~98%). The latter may be loosely bound to albumin (38%), the main protein in the fluid portion of the blood, or bound to a specific binding protein called Sex Hormone Binding Globulin (SHBG) (60%), also called Sex Steroid Binding Globulin (SSBG). The binding between testosterone and albumin is not very strong and is easily reversed, so the term bioavailable testosterone (BAT) refers to the sum of free testosterone plus albumin-bound testosterone.

It is suggested that bioavailable testosterone represents the fraction of circulating testosterone that readily enters cells and better reflects the bioactivity of testosterone than does the simple measurement of serum total testosterone. Also, varying levels of SHBG can result in inaccurate measurements of bioavailable testosterone. Decreased SHBG levels can be seen in obesity, hypothyroidism, androgen use, and nephritic syndrome. Increased levels are seen in cirrhosis, hyperthyroidism, and estrogen use. In these situations, measurement of free testosterone may be more useful.

Women's bodies also produce testosterone but in small amounts. It is needed for hormonal balance and to help women's bodies to function normally. If your body is producing too much testosterone, you may have more body hair than average, have abnormal or no menstrual periods, or be infertile. A testosterone test, in conjunction with measuring other hormone levels, can help your doctor to understand what is causing your symptoms.

http://labtestsonline.org/understanding/...ab/faq#top


So what then controls your free testosterone? It turns out that your level of albumin is relatively fixed with minimal fluctuation in most men. However, SHBG can vary widely and lab results clearly show that as SHBG goes up, the percentage of free testosterone as a percentage of total goes down and, as SHBG goes down, the percentage of free testosterone goes up. Thus, it is SHBG that has tremendous control over free testosterone.

Normal aging, as many of us know all too painfully, leads to substantial drops in androgens such as testosterone and a corresponding rise in SHBG. Think how ugly this is: decreasing testosterone leads to increasing SHBG which leads to decreased free testosterone. And, practically speaking, low free testosterone levels will yield low testosterone symptoms just as surely as low total testosterone will.

There are also many other reasons for low and high SHBG, including liver dysfunction, estradiol levels, thyroid function and much more. I cover these in my links on Low SHBG and High SHBG.

NOTE:  Men on HRT (Hormone Replacement Therarpy or testosterone therapy) will often have an elevated free testosterone percentage, because HRT tends to lower SHBG. Also, some men have low SHBG even before starting HRT. These men often have great difficulty with achieving successful results from testosterone therapy for reasons that are not totally understood.
http://www.peaktestosterone.com/Free_Tes..._SHBG.aspx




   

[GoneGirl]

Interesting chart in your previous post, Lotus. I have a question for you:

Where is DHT in the chart? Part of the available or unavailable testosterone? Or is it a separate thing altogether?

Clara

[Lotus]

Interesting chart in your previous post, Lotus. I have a question for you:

Where is DHT in the chart? Part of the available or unavailable testosterone? Or is it a separate thing altogether?

Clara

Good question, I doubt if one exists lol, it would come from free T, I remember seeing another figure somewhere on a slightly similar percentage.

Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase, an enzyme highly expressed in male sex organs and hair follicles. Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1) an enzyme expressed in the brain, liver, and adipose tissues.

Here's something interesting,

The total estradiol production rate in the human male has been estimated to be 35-45 μg (0.130-0.165 μmol) per day, of which approximately 20% is directly produced by the testes. Roughly 60% of circulating estradiol is derived from direct testicular secretion or from conversion of testicular androgens. The remaining fraction is derived from peripheral conversion of adrenal androgens.

[Lenneth]

Interesting chart in your previous post, Lotus. I have a question for you:

Where is DHT in the chart? Part of the available or unavailable testosterone? Or is it a separate thing altogether?

Clara

Good question, I doubt if one exists lol, it would come from free T, I remember seeing another figure somewhere on a slightly similar percentage.

Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase, an enzyme highly expressed in male sex organs and hair follicles. Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1) an enzyme expressed in the brain, liver, and adipose tissues.

Here's something interesting,

The total estradiol production rate in the human male has been estimated to be 35-45 μg (0.130-0.165 μmol) per day, of which approximately 20% is directly produced by the testes. Roughly 60% of circulating estradiol is derived from direct testicular secretion or from conversion of testicular androgens. The remaining fraction is derived from peripheral conversion of adrenal androgens.

interesting, how does that compare with that of biological females?

[GoneGirl]

Interesting chart in your previous post, Lotus. I have a question for you:

Where is DHT in the chart? Part of the available or unavailable testosterone? Or is it a separate thing altogether?

Clara

Good question, I doubt if one exists lol, it would come from free T, I remember seeing another figure somewhere on a slightly similar percentage.

Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase, an enzyme highly expressed in male sex organs and hair follicles. Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1) an enzyme expressed in the brain, liver, and adipose tissues.

Here's something interesting,

The total estradiol production rate in the human male has been estimated to be 35-45 μg (0.130-0.165 μmol) per day, of which approximately 20% is directly produced by the testes. Roughly 60% of circulating estradiol is derived from direct testicular secretion or from conversion of testicular androgens. The remaining fraction is derived from peripheral conversion of adrenal androgens.

Still wondering, is DHT included in total testosterone or not?

[Lotus]

Still wondering, is DHT included in total testosterone or not?

Good question, I doubt if one exists lol, it would come from free T, I remember seeing another figure somewhere on a slightly similar percentage.

Yes, DHT would come from free T. (As far as a percentage DHT has in the pie chart, slice out 7% of that 2% of free T, lol).

[Lotus]

interesting, how does that compare with that of biological females?

According to the National Institutes of Health, the normal range of testosterone is 30 to 95 nanograms per deciliter (ng/dL) for women and 300 to 1,200 ng/dL for men, but individual laboratories might have a slightly different range that they consider normal. Also keep in mind that the levels vary with age. In women, the level of testosterone in the blood is lowest during puberty and adolescence, and is highest in pre- and post-menopausal women. For men, the levels increase during puberty and stay steady for much of their young adult life. They then slowly begin to decline during middle and older age.
http://www.livestrong.com/article/239396...r-a-woman/


Men and women produce exactly the same hormones, but in different amounts: as a rule, men produce 20 times more testosterone than women, while women produce more estrogen and progesterone. As with most things in nature, this "norm" can become imbalanced, and some women may have higher levels of testosterone, causing a unique set of symptoms.


I probably have enough info on all the useless info on T you can image, lol. A fact sheet should be in order.

[GoneGirl]

Still wondering, is DHT included in total testosterone or not?

Good question, I doubt if one exists lol, it would come from free T, I remember seeing another figure somewhere on a slightly similar percentage.

Yes, DHT would come from free T. (As far as a percentage DHT has in the pie chart, slice out 7% of that 2% of free T, lol).

So if I want to know my DHT level, I would need a separate test for that, right?

Clara