Nolvadex for Low SHBG

[Kwirion]

My SHGB = 20 or 22, I thought I read that having a low reading is a good thing? not so?

if your SHBG is low---- what are the symptoms?

On this page You will find the table with SHBG optimal values by age: Testosterone: What’s a Normal Testosterone Level in Men? | The Art of Manliness

In simple terms: too low SHBG -> testosterone and estradiol levels roller-coaster.

 

[James23]

Note that the average SHBG for the youthful range is 35.

 

[Dr JIM]

Because having a "low" SHBG level only increases free testosterone levels, why someone interested in anabolic metabolism would want to "increase it" is beyond reason, IMO!

 

[James23]

Because having a "low" SHBG level only increases free testosterone levels, why someone interested in anabolic metabolism would want to "increase it" is beyond reason, IMO!

I don't know where to start with this one, Dr. 1990. You need to start by picking up a modern text on male hormones.

From Andrology: Male Reproductive Health and Dysfunction:

The main dissociation of testosterone from binding proteins takes places in capillaries. The interaction of binding proteins with the endothelial glycocalyx leads to a structural modification of the hormonal binding site and thereby to a change in affinity. As a result, testosterone is set free and can diffuse freely into the target cell or binds together with SHBG to megalin, a cell importer protein.(Hammes et al 2005).

In the serum 98-99.5% of the sex steroids are protein-bound and endocytosis is quantitatively more relevant for tissue delivery of biologically active steroid hormones than free diffusion.

SHBG is one of the PRIMARY delivery mechanisms of steroid hormones to selected tissues.

SHBG, with 100 times the binding affinity for testosterone when compared to albumin, is the primary mechanism by which the body regulates the excretion and metabolism of testosterone. Impaired SHBG expression leads to hyper excretion and over conversion of testosterone to metabolites.

SHBG is required to bind estradiol. Proportional expression of SHBG is required to keep testosterone within serum and protected from excretion. Proportional expression of SHBG is required to maintain a balance of FT, E2 and DHT that matches the body's overall T concentration.

In "Dr JIM"-talk, this equates to "m0ar E2". To a more sophisticated student of endocrinology, it also means that with inadequate SHBG the ratio of free estrogen to total estrogen will also be disturbed.

Also, Jim, you've made the dirt stupid assumption that we are advocating increasing SHBG. Don't be ridiculous, and please pay attention.

This discussion is about impaired expression of SHBG. It is not about indiscriminately increasing SHBG. SHBG has an ideal range, just like any other hormone. Some men have impaired SHBG expression and fall too low. Other men express too much SHBG. Both cases are undesirable.

Furthermore, the imbalance of T:SHBG is usually caused by the indiscriminate, hammer-handed administration of exogenous testosterone (or through forced LH expression of use of LH analogues) without taking into consideration that the body's reluctance to naturally elevate androgen levels is, in fact, due to an imbalance caused by the liver's inability to express the requisite storage, binding, delivery and balancing protein that we know as sex hormone binding globulin (SHBG.) In other words, it is something we only see revealed in cases artificial hormone replacement.

It's also quite rare, and occurs mainly in young patients.

 

[Dr JIM]

My comment was made in isolation and with reference to alterations of SHBG ALONE causing sexual dysfunction, NOT!

However I'll also emphasize the chicken comes BEFORE the egg!

Furthermore your assertion that alterations in SHBG has a greater effect on E-2 is bogus from a clinical perspective and is nothing more than theoretical garbage James!

(I am implying SHBG does INDEED have a greater affinity for testosterone than E-2 BUT that difference even at lower SHBG levels remains minuscule, especially relative to the increase of free testosterone)

Therrfore if you believe modulating E-2 levels thru the use of a SERM (because of lowered SHBG) is an appropriate methodology for treating the signs or symptoms of SD from "low T", rather than testosterone replacement itself good luck treating that EGG!

 

[BBC3]

Just consider that Serum SHBG levels MAY in fact be indicative of JSUT enough SHBG to go around. Either due to lack of androgenic demand principles, and even due to OVERUSE by estrogenic priciples. In short, I guy with no ass aint got much use, and when he does, his reseves wind up shorted. OR a fat guy is using a lot to maintenance those fat cells, and with little variation in demand due to the inherent nature of fat.

Be sure that Hormones most likely SERVE the Proteeis, and it is NOT the SHBG which is placed in our bodies to "protect" the hormones. LOL. The cell is looking for FOOD/Protien. The hormone attached simply MODULATES/REGULATES the action incurred. There can be no other way.. THIS IS THE REDICULOUS STATE OF MEDICAL SCIENCE AND WHY WE ARE THE LAUGHING STOCK OF THE UNIVERSE..... All sitting around splitting hairs over conjectured unproven incorrect bullshit. Hell, Newton and Einstien as EVEN FUCKED as far as I am concerned....

Consider the word "Free" in real medical terms as really just "proof of life". If there is ANY "Free" left in circulation - then DEMANDS MUST BE MET...

Its sad to think that the average "informed doc" thinks that a high "free level" is a good thing in ANY scenario, when if means squat. They should have known that there was free hormone when the patient was able to walk in the door, and not dead on a cart...!! But lets not dare think to due to locigal battery of testing to actually learn something.!!!! LOL Too risky, some may Loo$e out. Some docs dont even know what testosterone does. These are folks that should be lined up out back in front of a firing squad, or were already accidentally lobotomized in med school. Dont play with the paddles..!

The powers that be, and the hiarchy in place is SET IN STONE. This is why nothing has changed, and we have made ZERO progress, other than the acorn we stumble on to from time time. YOU WILL NOT CHANGE THIS. NO ONE WILL. To de-thrown a ruler is next to impossible, and how could you when no one can even see the wrong. Who wants to. DEATH is the one thing we DARE NOT THINK ABOUT.. Therefore MEDICAL SCIENCE is INTIMENTLY PROTECTED like no other. Its the ultimate money pit smashing oil & gas money, banking, and all other institutions. IT IS THE DOLLAR.. Politics, business, another lab, MO MONEY..!!!!! Let them get ill or we wont eat. The best part is that they could not stop "US" from harming ourselves and make us live a "good Life" if they wanted. Things are the way they are for a REASON....

But I'll play, I'm bored and thats what we are here for, right??!?? Consider an "ADOLESCENT" is in the growth stage which is nothing more than a BIOLOGICAL HORMONE CASCADE MYRIAD. This is the reason science doesnt benchmark by this age. After that, we stop growing. And most of us stop "working". Hence reduced serum counts OR "Blood Buffers/Actviity potential".

We all sit around on the couch pointing fingers, when the truth is we have not been outside to play since we were fourteen...! IT HAS GOT TO BE someone elses fault. I am on board with this. Big time.... LOL[)]:drooling:

But I am - how else would I sleep at night.....

I don't know where to start with this one, Dr. 1990. You need to start by picking up a modern text on male hormones.

From Andrology: Male Reproductive Health and Dysfunction:


SHBG is one of the PRIMARY delivery mechanisms of steroid hormones to selected tissues.

SHBG, with 100 times the binding affinity for testosterone when compared to albumin, is the primary mechanism by which the body regulates the excretion and metabolism of testosterone. Impaired SHBG expression leads to hyper excretion and over conversion of testosterone to metabolites.

SHBG is required to bind estradiol. Proportional expression of SHBG is required to keep testosterone within serum and protected from excretion. Proportional expression of SHBG is required to maintain a balance of FT, E2 and DHT that matches the body's overall T concentration.

In "Dr JIM"-talk, this equates to "m0ar E2". To a more sophisticated student of endocrinology, it also means that with inadequate SHBG the ratio of free estrogen to total estrogen will also be disturbed.

Also, Jim, you've made the dirt stupid assumption that we are advocating increasing SHBG. Don't be ridiculous, and please pay attention.

This discussion is about impaired expression of SHBG. It is not about indiscriminately increasing SHBG. SHBG has an ideal range, just like any other hormone. Some men have impaired SHBG expression and fall too low. Other men express too much SHBG. Both cases are undesirable.

Furthermore, the imbalance of T:SHBG is usually caused by the indiscriminate, hammer-handed administration of exogenous testosterone (or through forced LH expression of use of LH analogues) without taking into consideration that the body's reluctance to naturally elevate androgen levels is, in fact, due to an imbalance caused by the liver's inability to express the requisite storage, binding, delivery and balancing protein that we know as sex hormone binding globulin (SHBG.) In other words, it is something we only see revealed in cases artificial hormone replacement.

It's also quite rare, and occurs mainly in young patients.

 

[James23]

My comment was made in isolation and with reference to alterations of SHBG ALONE causing sexual dysfunction, NOT!

However I'll also emphasize the chicken comes BEFORE the egg!

Furthermore your assertion that alterations in SHBG has a greater effect on E-2 is bogus from a clinical perspective and is nothing more than theoretical garbage James!

(I am implying SHBG does INDEED have a greater affinity for testosterone than E-2 BUT that difference even at lower SHBG levels remains minuscule, especially relative to the increase of free testosterone)

Therrfore if you believe modulating E-2 levels thru the use of a SERM (because of lowered SHBG) is an appropriate methodology for treating the signs or symptoms of SD from "low T", rather than testosterone replacement itself good luck treating that EGG!

Do you have ADD, perhaps?

This is not about using a SERM to increase SHBG without a prerequisite boost in testosterone.

Let me see if I can phrase this in a way that you can comprehend:

Without adequate SHBG expression, increases in testosterone (from TRT) will fail to alleviate sexual dysfunction due to inappropriately high levels of FT (4-5% vs. 2% norm.) leading to excess E2, excess free E2, and hyper excretion and metabolism of the free testosterone excess.

A healthy body expresses the right amount SHBG to match the T:E envrionment. If SHBG expression is impaired, it is impossible to use TRT alone to restore balance. SHBG needs to increase, but can not increase, and therefore can not regulate transport, delivery, excretion or metabolism (including aromatization) for the new level of testosterone.

If one with congenitally low SHBG requires TRT, they must first address the low SHBG. Nolvadex is, theoretically, one such method of increasing SHBG.

----

Notes:
For the average 650 ng/dL testosterone level, an average SHBG of ~30 is required keeps E2 and FT within the normal range.

In the same individual, if SHBG is as low as 15 while TT remains artificially elevated at 650 ng/dl, both FT and E2 will be soar twice as high. In addition, testosterone will be removed from circulation twice as rapidly, cutting the half-life of free testosterone in your body... in half.

 

[idmd]

I don't know....I really don't fit this theory James. Last labs:

tT = 778 (350-1100)
fT = 25 (9-25)
E2 = 22
SHBG = 14 (15-58)

Libido decent, no SD dysfunction what so ever, feel great mentally and physically.

 

[James23]

I don't know....I really don't fit this theory James. Last labs:

tT = 778 (350-1100)
fT = 25 (9-25)
E2 = 22
SHBG = 14 (15-58)

Libido decent, no SD dysfunction what so ever, feel great mentally and physically.

Your FT is disproportionately high, but it's probably calculated and not actually measured by your lab (see below.) Are you not using an AI?

This isn't entirely unreasonable. SHBG binding capacity can differ between individuals.

"This information will need to be assessed in relation to a wide range of diseases that have already been associated with SHBG polymorphisms. In addition, algorithms designed to calculate free testosterone or estradiol levels will need to take into consideration the effects of these new SHBG variants.

SHBG T48I and SHBG R123H have reduced steroid-binding affinity; SHBG R154W is dimerization deficient and has a lower binding affinity for estrogens but a normal affinity for androgens; SHBG G195E is not produced or secreted efficiently, probably due to misfolding during synthesis.

Your SHBG requirements depend on which type of SHBG your body makes. To know if your SHBG is too low, you look at E2 and FT values.

Yes, it is this complex.

 

[Dr JIM]

Your comparing apples to oranges fella and it's obvious you don't know what the hell your talking about.

Apparently your bored and/or depressed and have nothing more to do than pursue lame insular "theories" using science blogs as a basis, "for learning and development"

The crap your posting is theoretically contrived garbage.

Absent any STUDIES from peer reviewed journals to support your commentary, continue the misguided pontification as desired clown!

 

[James23]

Your comparing apples to oranges fella and it's obvious you don't know what the hell your talking about.

Apparently your bored and/or depressed and have nothing more to do than pursue lame insular "theories" using science blogs as a basis, "for learning and development"

The crap your posting is theoretically contrived garbage.

Absent any STUDIES from peer reviewed journals to support your commentary, continue the misguided pontification as desired clown!

I have posted plenty of studies. The quotes from this thread are from modern endocrinology textbooks for use in medical universities.

The role of SHBG is well-known. The only garbage here is your 1990-era view of SHBG solely as a steroid action inhibitor. It's a vehicle of delivery, transport, signaling and the primary mediator of androgen:estrogen balance, metabolization and excretion.

Dr. Jim knows one thing about TRT. If T is low, add it. If E is high, remove it. Minute-clinic level knowledge that will absolutely fail with all but the most basic cases of primary hypogonadism in men over 40.

You are just plain wrong, and every modern study and modern textbook backs up what I am saying.

 

[Dr JIM]

You have not posted anything supporting the bizarre notion a lowered SHBG contributes to SD because it "raises E-2 levels disproportionately compared to fT"!

You further contend a lowered SHBG mediates enhanced fT metabolism, because more is "available" (probably no more than a ONE PERCENT increase) for metabolism which shortens testosterones half life, from roughly 30 min, to what bimbo? (Have an article on this lame supposition? NOT!)

Post ONE STUDY which supports your assertion that either a lowered E-2 or decreased SHBG are known contributors, even remotely, for SD, providing TT is greater than the second quartile AND no underlying metabolic/genetic disorder is responsible!

Otherwise JAMES YOUR FOS! (But I knew that from the outset!)

 

[PharmD518]

While I'm not going to get involved in this SHGB debate I do want to chime in and give an update on my condition. As James knows, I was going to experiment with T-3 to see if raising my SHGB helps my libido. Well, I just ordered T-3 tablets from ManPower research so they will be here in a few days and I will update my findings soon.

In the past though, when my SHGB was around 5 or 6 I did a cycle of Nolvadex and while my libido improved very slightly, my SHGB did go up to about 12, so those two may very well be related.Twelve was in the normal range but just barely. I am prescribed testosterone right now but as test in the past has done absolutely nothing for me I am holding out on my first dose until the T-3 arrives. Hopefully I will start feeling better.My TSH was 4.1 last time I checked a few months ago. If it had been 4.2 then I could have gotten on thyroid medication so will have to do it on my own for now.

My SHGB has always been very low my whole life. I am 20 years old and libido sucks, always has.

 

[Dr JIM]

Phd
I wish you well and hope improvement is in short course.

However as you've already eluded to, although thyroxine therapy often does lead to increased SHBG levels, it is also very effective for the treatment of sexual dysfunction because of hypothyroidism.

However since you have already mentioned TRT as a part of your earlier therapy I am disinclined to believe any significant improvement in SD will be noted absent appropriate TT and thyroid hormone levels.

The point is bioavailable testosterone is primarily responsible for our physiological responses to androgens (excluding one's psyche) and SHBG is not a major player in that arena because it binds it's substrate hormones so tightly maintaining a saturation of between 80-90% in males,

The latter of which DOES NOT change until TT reaches the lower quartile for age.

Ergo unless TT levels are adequate the treatment of SD is almost always a miserable failure, because the "chicken comes before the egg" a concept James is incapable of grasping! (Yea this guy "treated" his ED caused by a "low SHBG" with Novladex, in spite of a TT greater than, 600ng/dl) LOL!

 

[Tyler81]

James,

What you write here reflects my own experience.

I have low shbg (around 13) and even 50mg/wk dose for me is way too high.

I believe what happens is that my Free T SKYROCKETS shortly after injection and this makes me feel like shit. After three days my Free T comes down and i feel much better.

I am trying to solve this by injecting much less/wk than most.

The real solution for guys with low shbg is transdermals imho.

I also think pellets have potential with the slow daily release (versus dump of injections)

Without adequate SHBG expression, increases in testosterone (from TRT) will fail to alleviate sexual dysfunction due to inappropriately high levels of FT (4-5% vs. 2% norm.) leading to excess E2, excess free E2, and hyper excretion and metabolism of the free testosterone excess.

A healthy body expresses the right amount SHBG to match the T:E envrionment. If SHBG expression is impaired, it is impossible to use TRT alone to restore balance. SHBG needs to increase, but can not increase, and therefore can not regulate transport, delivery, excretion or metabolism (including aromatization) for the new level of testosterone.

If one with congenitally low SHBG requires TRT, they must first address the low SHBG. Nolvadex is, theoretically, one such method of increasing SHBG.

----

Notes:
For the average 650 ng/dL testosterone level, an average SHBG of ~30 is required keeps E2 and FT within the normal range.

In the same individual, if SHBG is as low as 15 while TT remains artificially elevated at 650 ng/dl, both FT and E2 will be soar twice as high. In addition, testosterone will be removed from circulation twice as rapidly, cutting the half-life of free testosterone in your body... in half.

 

[James23]

Phd
I wish you well and hope improvement is in short course.

However as you've already eluded to, although thyroxine therapy often does lead to increased SHBG levels, it is also very effective for the treatment of sexual dysfunction because of hypothyroidism.

However since you have already mentioned TRT as a part of your earlier therapy I am disinclined to believe any significant improvement in SD will be noted absent appropriate TT and thyroid hormone levels.

The point is bioavailable testosterone is primarily responsible for our physiological responses to androgens (excluding one's psyche) and SHBG is not a major player in that arena because it binds it's substrate hormones so tightly maintaining a saturation of between 80-90% in males,

The latter of which DOES NOT change until TT reaches the lower quartile for age.

Ergo unless TT levels are adequate the treatment of SD is almost always a miserable failure, because the "chicken comes before the egg" a concept James is incapable of grasping! (Yea this guy "treated" his ED caused by a "low SHBG" with Novladex, in spite of a TT greater than, 600ng/dl) LOL!

I tried baby talking you, but you still don't get it.

Normal TT levels are absolutely required for sexual function. I'm saying that normal TT, without BOOSTING SHBG, will lead to failure.

I presume the concept that breezes by you, each time, while you mention chickens and eggs, is that in certain men, SHBG will NOT INCREASE NO MATTER THE LEVEL OF ANDROGEN OR ESTROGEN. This is a serious problem.

PharmD, Tyler and over 20 other members on this board alone who are all:

- Under 25
- Clinically hypogonadal
- Experience complete sexual dysfunction
+ SHBG does not increase in response to TRT

... ALL have zero physiological response to TRT, despite high TT, FT and even with E2 kept artificially in bounds with AIs.

This is indisputable, and trust me... these men have tried every possible means of balance, administration and ancillaries, including "tuning" their thyroid levels.

An SHBG level that is half of normal for a given normal level of TT, leads to a 200% increase of FT and therefore a direct 200% increase in E2. Not 1%. Just ask me or any of these men for our labs, and you will see.

Without the right SHBG, normal TT is worthless (in most individuals.)

 

[Dr JIM]

I'll ask again, post ONE study that supports your claim LOW SHBG is an sole etiology for SD clown, or does the concept of "evidence based" medicine just breeze by you!

Otherwise your commentary is GARBAGE!

Oh and incidentally how many patients have you treated "to cure" for low SHBG?

You spew BOGUS NONSENSE and 99% of the people on this forum know it Clown!

 

[James23]

I'll ask again, post ONE study that supports your claim LOW SHBG is an sole etiology for SD clown, or does the concept of "evidence based" medicine just breeze by you!

Otherwise your commentary is GARBAGE!

Oh and incidentally how many patients have you treated "to cure" for low SHBG?

You spew BOGUS NONSENSE and 99% of the people on this forum know it Clown!

Dr. Doofus,

99% of people on the forum have seen the disaster that low SHBG causes.

This is the most widely accepted theory of the role of SHBG. Your theory is from 1990. Pick up a book.

Here's the first thing I found, from a related study, showing the effects of impaired SHBG on the utilization of testosterone in the male body:

First pass metabolism of orally administered
oxandrolone may decrease hepatic synthesis of SHBG, allowing exogenously supplied testosterone to be excreted.

Low Sex Hormone-Binding Globulin and Testosterone Levels in Association with Erectile Dysfunction among Human Immunodeficiency Virus-Infected Men Receiving Testosterone and Oxandrolone - Wasserman - 2007 - The Journal of Sexual Medicine - Wiley Onlin

Here we see that exogenous testosterone is urinated out of the body at an accellerated rate if one cannot adequately produce SHBG. In this study, the oxandrolone was impairing SHBG expression.

Per Dr. Mariano, a doctor this board actually respects:

The primary purpose of a binding protein such as SHBG is to prolong the life of testosterone in the body. Otherwise, with a half-life of 10-100 minutes - testosterone would be almost totally eliminated from the body within 50 minutes to 8.3 hours without constant production or frequent application of testosterone.

 

[cvictorg]

Dr. Doofus,

Per Dr. Mariano, a doctor this board actually respects:
Quote:
The primary purpose of a binding protein such as SHBG is to prolong the life of testosterone in the body. Otherwise, with a half-life of 10-100 minutes - testosterone would be almost totally eliminated from the body within 50 minutes to 8.3 hours without constant production or frequent application of testosterone.

Unless you're injecting test suspension - which NOBODY would use for TRT/HRT - the half life for cypionate or entantate is appx 6-7 days."

What Dr Mariano is talking about is this
http://www.steroidology.com/forum/anabolic-steroid-forum/81826-testosterone-almost-everything-you-could-possibly-want-know.html

"The plasma half-life of testosterone reportedly ranges from 10–100 minutes. The plasma half-life of testosterone cypionate after IM injection is approximately 8 days.

Roid Calculator - half lifes steroids ester half-life

Testosterone Cypionate Official FDA information, side effects and uses.
"The half-life of Testosterone Cypionate when injected intramuscularly is approximately eight days."

 

[James23]

Per Dr. Mariano, a doctor this board actually respects:
Quote:
The primary purpose of a binding protein such as SHBG is to prolong the life of testosterone in the body. Otherwise, with a half-life of 10-100 minutes - testosterone would be almost totally eliminated from the body within 50 minutes to 8.3 hours without constant production or frequent application of testosterone.

Unless you're injecting test suspension - which NOBODY would use for TRT/HRT - the half life for cypionate or entantate is appx 6-7 days. SO - tell me how testosterone would be "almost totally eliminated from the body within 50 minutes to 8.3 hours without constant production or frequent application of testosterone."

Roid Calculator - half lifes steroids ester half-life

The testosterone cypionate ester (TC) itself has a half-life of 6-7 days. The TC ester is useless to the body. Once the T molecule separates from the ester it is free in the blood, available for excretion or metabolism. It must first bind to albumin, SHBG or cortisol binding gobulin (yes, 1%) in order to remain in circulation after separation from the ester.

With IM esterized T, the ester itself works as a slow delivery system, but fails to buffer the release of T metabolites, and has no value or signaling properties of its own as does SHBG. Esters are only somewhat equivalent to "constant production or frequent application of testosterone."

TLDR: The TC remains in the body, not T. The T that is continually separating out of the TC will be rapidly excreted.

Low SHBG does not force all T out of the body, it simply doubles or triples the rate of excretion.