Re: Low T after pellets - Ideas?

[Guest guest]

Well I have more of a question than even a SWAG - can the liver

metabolize T if it is deliverd in means other than orally?

Mark

[Guest guest]

> Well I have more of a question than even a SWAG - can the liver

> metabolize T if it is deliverd in means other than orally?

>

> Mark

The drug needs to go through your gut for first pass metabolism.

Brad

[Guest guest]

Very doubtful.

> Well I have more of a question than even a SWAG - can the liver

> metabolize T if it is deliverd in means other than orally?

>

> Mark

[Guest guest]

Hi,

The liver is not involved when it goes thru the skin or is an injection.

Pellets also dissolve directly into the blood stream.

Oral meds have to go thru the liver.

ernestsnolan

> Well I have more of a question than even a SWAG - can the liver

> metabolize T if it is deliverd in means other than orally?

>

> Mark

[Guest guest]

Hi folks-

Doctor Schwartz' plan is to switch me to another delivery method,

this coming Thursday. The pellets didn't work. Rare and

unexpected, but I get that a lot. Whether the problem was the

pellets or my metabolism is not immediately important to me.

Thanks for all your ideas and support. I'll be in touch shortly

about the new delivery method.

Peace,

Bruce

[Guest guest]

Hi,

Please keep us informed.

The liver is not involved in metabolizing the hormone as it is already

in the right chemical form as it dissolves into the blood stream.

You trust the doctor so it must have been the correct number of

pellets. Could you hear them dropping in the tin pan as he popped open

the glass container or feel them being squirted out the end of the

trocar surgical tool?

Really puzzled!!!

ernestnolan

> Hi folks-

>

> Doctor Schwartz' plan is to switch me to another delivery method,

> this coming Thursday. The pellets didn't work. Rare and

> unexpected, but I get that a lot. Whether the problem was the

> pellets or my metabolism is not immediately important to me.

>

> Thanks for all your ideas and support. I'll be in touch shortly

> about the new delivery method.

>

> Peace,

> Bruce

[Guest guest]

ernestnolan,

I think I heard pellets dropping in the pan, but in my state I would

have lost count after two :-) I could feel something coming out of

the trocar (through local anesthesia). I trust the doc, but he's not

God (one reason I trust him is HE knows he's not God).

So I don't know why my pellet implantation failed or if a future one

would work. Fortunately I'm not " married " to pellets as long as I

get a working delivery system. I'm going back to injections, this

time with E2 management and a responsive doctor who

understands low T causes CFS-like disabling symptoms.

My unusual experience doesn't mean pellets aren't great for

other people. It doesn't even conclusively prove they wouldn't be

great for me. Right now I would rather go back to injections than

try another implantation.

Thanks,

Bruce

> > Hi folks-

> >

> > Doctor Schwartz' plan is to switch me to another delivery

method,

> > this coming Thursday. The pellets didn't work. Rare and

> > unexpected, but I get that a lot. Whether the problem was the

> > pellets or my metabolism is not immediately important to

me.

> >

> > Thanks for all your ideas and support. I'll be in touch shortly

> > about the new delivery method.

> >

> > Peace,

> > Bruce

[Guest guest]

Hi,

Using my wild imagination...........

Could he have given you estrogen instead??

ernestnolan

> > > Hi folks-

> > >

> > > Doctor Schwartz' plan is to switch me to another delivery

> method,

> > > this coming Thursday. The pellets didn't work. Rare and

> > > unexpected, but I get that a lot. Whether the problem was the

> > > pellets or my metabolism is not immediately important to

> me.

> > >

> > > Thanks for all your ideas and support. I'll be in touch shortly

> > > about the new delivery method.

> > >

> > > Peace,

> > > Bruce

[Guest guest]

ernestnolan,

Nope, but I envy your range of speculation.

My doctor spoke with Dr. Shippen, who said he thought I was a

" rapid metabolizer " . My first reaction: Bullshit. But then I thought

about it some more.

It's not that the pellets didn't work. THE PELLETS DID WORK for

3 or 4 weeks, THEN STOPPED WORKING. I felt better than I had

in years, with real energy, improved stamina, clear thinking,

ambition & motivation, improved muscle tone, increased libido &

sexual function. Then I slipped back, with T going down

confirmed by lab tests 2 weeks apart. So the action of the pellets

was as expected. Duration was not. Considering that, the " rapid

metabolizer " theory isn't as crazy as I first thought. It may not be

right, but it explains the short duration.

Peace,

Bruce

> > > > Hi folks-

> > > >

> > > > Doctor Schwartz' plan is to switch me to another delivery

> > method,

> > > > this coming Thursday. The pellets didn't work. Rare and

> > > > unexpected, but I get that a lot. Whether the problem was

the

> > > > pellets or my metabolism is not immediately important to

> > me.

> > > >

> > > > Thanks for all your ideas and support. I'll be in touch

shortly

> > > > about the new delivery method.

> > > >

> > > > Peace,

> > > > Bruce

[Guest guest]

Hi,

Don't think so, female dosing wouldn't have had the delightful

(yet short-lived) effect of helping my sticker peck up...

________

Conservatives whine about Liberals whining about

Conservatives whining about Liberals.

>

> >

> >Hi,

> >

> >Using my wild imagination...........

> >

> >Could he have given you estrogen instead??

>

>

> Or female dosing?

>

> ________

> Conservatives whine about the Liberals controlling the world

> like the Nazis whined about the Jews controlling the world.

[Guest guest]

Bruce,

Maybe you get your doctor to try putting them in more often?

Mark

[Guest guest]

Phil,

That was a different person, I think he got 450mg of pellets

because his doctor was overcautions about T.

I think I got enough pellets (supposed to be 1200 mg) because I

got great results, if only for a while.

I have an appointment with my doctor Thursday. He's upset and

puzzled about this as well. I think tests after T-cyp injections will

include trying to figure out if there's anything to the " rapid

metabolizer " theory.

Like you I've had levels go down with other delivery methods. For

example, I had decent results with Androgel, then had to

increase from 5mg to 10mg/day. I suspect that was due to a total

lack of E2 testing and management. Maybe something else is

going on, but at this point I can only speculate.

Peace,

Bruce

> > > > > Hi folks-

> > > > >

> > > > > Doctor Schwartz' plan is to switch me to another

delivery

> > > method,

> > > > > this coming Thursday. The pellets didn't work. Rare and

> > > > > unexpected, but I get that a lot. Whether the problem

was

> the

> > > > > pellets or my metabolism is not immediately important

to

> > > me.

> > > > >

> > > > > Thanks for all your ideas and support. I'll be in touch

> shortly

> > > > > about the new delivery method.

> > > > >

> > > > > Peace,

> > > > > Bruce

>

>

>

[Guest guest]

Hi,

OK. If that is possible, it should be possible to check for the lump

of pellets under the skin. These can usually be felt to diminish in

size as they dissolve. If the lump is gone, that's a good confirmation

of this alternative answer.

ernestnolan

> > > > > Hi folks-

> > > > >

> > > > > Doctor Schwartz' plan is to switch me to another delivery

> > > method,

> > > > > this coming Thursday. The pellets didn't work. Rare and

> > > > > unexpected, but I get that a lot. Whether the problem was

> the

> > > > > pellets or my metabolism is not immediately important to

> > > me.

> > > > >

> > > > > Thanks for all your ideas and support. I'll be in touch

> shortly

> > > > > about the new delivery method.

> > > > >

> > > > > Peace,

> > > > > Bruce

[Guest guest]

Hi,

Possibly.

I guess you are aware there is frequently the effect of fantastic

erections after the level of T begins to increase. It continues until

the level of T levels off at the higher level. Maybe 6-8 weeks. The

good feelings of energy and mental benefits however continue.

I was really ticked off when he told me it was over. I thought I had

found my solution to my ED. Went back to reading and searching. Found

trimix from Dr. Irwin Golstein, Boston Univ. to find the ED cure

mentioned in his book, " The Potent Male " .

ernestnolan

> >

> > >

> > >Hi,

> > >

> > >Using my wild imagination...........

> > >

> > >Could he have given you estrogen instead??

> >

> >

> > Or female dosing?

> >

> > ________

> > Conservatives whine about the Liberals controlling the world

> > like the Nazis whined about the Jews controlling the world.

[Guest guest]

Mark,

It's a fairly expensive procedure. If I'd have to do it often, I'd want

to switch to to a less expensive method.

Thanks. All suggestions welcome.

Bruce

> Bruce,

>

> Maybe you get your doctor to try putting them in more often?

>

> Mark

[Guest guest]

Excellent point! The lump IS still there.

WTF?

Bruce

> > > > > > Hi folks-

> > > > > >

> > > > > > Doctor Schwartz' plan is to switch me to another

delivery

> > > > method,

> > > > > > this coming Thursday. The pellets didn't work. Rare

and

> > > > > > unexpected, but I get that a lot. Whether the problem

was

> > the

> > > > > > pellets or my metabolism is not immediately

important to

> > > > me.

> > > > > >

> > > > > > Thanks for all your ideas and support. I'll be in touch

> > shortly

> > > > > > about the new delivery method.

> > > > > >

> > > > > > Peace,

> > > > > > Bruce

[Guest guest]

That just tells you that the pellets haven't completely dissolved. It

doesn't tell you how fast your liver is metabolizing (clearing)

testosterone from your system.

Brad

> > > > > > > Hi folks-

> > > > > > >

> > > > > > > Doctor Schwartz' plan is to switch me to another

> delivery

> > > > > method,

> > > > > > > this coming Thursday. The pellets didn't work. Rare

> and

> > > > > > > unexpected, but I get that a lot. Whether the problem

> was

> > > the

> > > > > > > pellets or my metabolism is not immediately

> important to

> > > > > me.

> > > > > > >

> > > > > > > Thanks for all your ideas and support. I'll be in touch

> > > shortly

> > > > > > > about the new delivery method.

> > > > > > >

> > > > > > > Peace,

> > > > > > > Bruce

[Guest guest]

Hi,

I knew the liver had to metabolize oral meds to get hormone into the

blood supply.

Never heard the liver cleared it. I heard it is used by all of the

vital organs, (testicles and brain) and consumed in that way.

Would you give me more on what you saying.

ernestnolan

> > > > > > > > Hi folks-

> > > > > > > >

> > > > > > > > Doctor Schwartz' plan is to switch me to another

> > delivery

> > > > > > method,

> > > > > > > > this coming Thursday. The pellets didn't work. Rare

> > and

> > > > > > > > unexpected, but I get that a lot. Whether the problem

> > was

> > > > the

> > > > > > > > pellets or my metabolism is not immediately

> > important to

> > > > > > me.

> > > > > > > >

> > > > > > > > Thanks for all your ideas and support. I'll be in touch

> > > > shortly

> > > > > > > > about the new delivery method.

> > > > > > > >

> > > > > > > > Peace,

> > > > > > > > Bruce

[Guest guest]

> Hi,

>

> I knew the liver had to metabolize oral meds to get hormone into the

> blood supply.

>

> Never heard the liver cleared it. I heard it is used by all of the

> vital organs, (testicles and brain) and consumed in that way.

>

> Would you give me more on what you saying.

>

> ernestnolan

>

Sure.

From the Androgel prescribing info:

Excretion

About 90% of a dose of testosterone given intramuscularly is excreted

in the urine as glucuronic and sulfuric acid conjugates of

testosterone and its metabolites; about 6% of a dose is excreted in

the feces, mostly in the unconjugated form. Inactivation of

testosterone occurs primarily in the liver.

In more detail from Endotext:

http://www.endotext.com/male/male2/maleframe2.htm

Testosterone undergoes metabolism to both bioactive metabolites and to

inactivated oxidised and conjugated metabolites for urinary and/or

biliary excretion. A small proportion of circulating testosterone is

metabolised to biologically active metabolites in specific target

tissues to modulate biological effects. This includes both an

activation pathway and a diversification pathway of androgen action.

The amplification pathway involves conversion of a small fraction

(~4%) of circulating testosterone to a more potent androgen, DHT 29,

30. DHT has higher binding affinity to the androgen receptor and

3-10-fold greater molar biopotency than testosterone. In vitro, DHT is

a more potent androgen than T due to its higher binding affinity 44

and more efficient transactivation of the androgen receptor 45, 46.

Testosterone is converted to DHT, the most potent natural androgen, by

the 5-a reductase enzyme, which exists in two forms (I & II), each

specified by distinct genes 47 with type 1 5a reductase expressed in

liver, skin, and brain whereas type 2 5a reductase is

characteristically expressed strongly in the prostate but also to

lower levels in other tissues such as skin (hair follicles) and liver

47. The functional predominance of prostatic expression of the type 2

5a reductase made it feasible to develop a relatively

prostate-specific 5a reductase inhibitor, finasteride 48. This occurs

extensively within the prostate stroma due to presence of type II 5-a

reductase which converts >95% of testosterone entering the gland into

the more potent androgen DHT 49. DHT circulates at ~10% of blood

testosterone concentrations, partly (50-80%) due to spill-over from

the pool of prostatic DHT 50, 51. Genetic mutations disrupting type II

5-a reductase lead to disorders of sexual differentiation involving

the external genitalia and accessory glands originating from the

urogenital sinus 52, which is developmentally dependent upon local

amplification of testosterone to DHT.

The diversification pathway of androgen action involves a

quantitatively small proportion (0.2%) of testosterone being converted

to estradiol 31 which then acts via estrogen receptors. This

diversification pathway of androgen action is governed by the

cytochrome P450 enzyme (CYP19) aromatase 53. In eugonadal men, most

(~80%) circulating estradiol is derived from extratesticular

aromatisation. The biological importance of aromatisation in male

physiology is highlighted by the striking developmental defects in

bone and some other tissues of a man 54 and mouse line 55 harbouring

genetic mutations that inactivate the estrogen receptor a. By

contrast, genetic inactivation of the estrogen receptor b has little

effect on male phenotype 56. (See chapter on Estrogens in Male

Reproduction).

Testosterone is metabolised to inactive metabolites in the liver,

kidney, muscle and adipose tissue. Inactivation is predominantly by

hepatic mixed function oxidases leading to oxidative degradation at

most oxygen moieties of the molecule and ultimately hepatic

conjugation to glucuronides, which are rendered sufficiently

hydrophilic for renal excretion.

Metabolic clearance rate of testosterone is reduced by increases in

circulating SHBG levels 34 or decreases in hepatic blood flow (eg

posture) 28 or function. Theoretically drugs that influence hepatic

mixed function oxidase activity could alter metabolic inactivation of

testosterone but empirical examples are few. Rapid hepatic metabolic

inactivation of testosterone leads to both a low oral bioavailability

57-60 and a short duration of action when injected parenterally 61,

62. These limitations dictate the need for parenteral depot

testosterone formulations (eg injectable testosterone esters,

testosterone implants or transdermal testosterone) to achieve

sustained androgenic effects, oral delivery systems which involve

portal bypass (buccal 63, 64, sublingual 63, 65, gut lymphatic 58, 66)

or active synthetic androgens 61, 62.

Brad

[Guest guest]

Brad,

Fascinating information! I'm on a number of meds that might

play a hand in this. One is hydrochlorothiazide, a diuretic for high

blood pressure that is also linked to sexual dysfuntion (in some

opinions). Combined with drinking too much coffee, I can see

how my urinary excretion of T might be affected. Another med I've

just stopped is Antabuse (disufiram), which is used as a

deterrent in alcoholism- it modifies alcohol metabolism by the

liver into an extremely unpleasant aldehyde. I don't know if it also

affects T metabolism, but I can get along without the med, so

that's one less thing in my overstuffed pillbox.

Thanks,

Bruce

> > Hi,

> >

> > I knew the liver had to metabolize oral meds to get hormone

into the

> > blood supply.

> >

> > Never heard the liver cleared it. I heard it is used by all of the

> > vital organs, (testicles and brain) and consumed in that way.

> >

> > Would you give me more on what you saying.

> >

> > ernestnolan

> >

>

> Sure.

>

> From the Androgel prescribing info:

>

> Excretion

>

> About 90% of a dose of testosterone given intramuscularly is

excreted

> in the urine as glucuronic and sulfuric acid conjugates of

> testosterone and its metabolites; about 6% of a dose is

excreted in

> the feces, mostly in the unconjugated form. Inactivation of

> testosterone occurs primarily in the liver.

>

>

> In more detail from Endotext:

>

> http://www.endotext.com/male/male2/maleframe2.htm

>

> Testosterone undergoes metabolism to both bioactive

metabolites and to

> inactivated oxidised and conjugated metabolites for urinary

and/or

> biliary excretion. A small proportion of circulating testosterone

is

> metabolised to biologically active metabolites in specific target

> tissues to modulate biological effects. This includes both an

> activation pathway and a diversification pathway of androgen

action.

>

> The amplification pathway involves conversion of a small

fraction

> (~4%) of circulating testosterone to a more potent androgen,

DHT 29,

> 30. DHT has higher binding affinity to the androgen receptor

and

> 3-10-fold greater molar biopotency than testosterone. In vitro,

DHT is

> a more potent androgen than T due to its higher binding affinity

44

> and more efficient transactivation of the androgen receptor 45,

46.

> Testosterone is converted to DHT, the most potent natural

androgen, by

> the 5-a reductase enzyme, which exists in two forms (I & II),

each

> specified by distinct genes 47 with type 1 5a reductase

expressed in

> liver, skin, and brain whereas type 2 5a reductase is

> characteristically expressed strongly in the prostate but also to

> lower levels in other tissues such as skin (hair follicles) and

liver

> 47. The functional predominance of prostatic expression of the

type 2

> 5a reductase made it feasible to develop a relatively

> prostate-specific 5a reductase inhibitor, finasteride 48. This

occurs

> extensively within the prostate stroma due to presence of type II

5-a

> reductase which converts >95% of testosterone entering the

gland into

> the more potent androgen DHT 49. DHT circulates at ~10% of

blood

> testosterone concentrations, partly (50-80%) due to spill-over

from

> the pool of prostatic DHT 50, 51. Genetic mutations disrupting

type II

> 5-a reductase lead to disorders of sexual differentiation

involving

> the external genitalia and accessory glands originating from

the

> urogenital sinus 52, which is developmentally dependent upon

local

> amplification of testosterone to DHT.

>

> The diversification pathway of androgen action involves a

> quantitatively small proportion (0.2%) of testosterone being

converted

> to estradiol 31 which then acts via estrogen receptors. This

> diversification pathway of androgen action is governed by the

> cytochrome P450 enzyme (CYP19) aromatase 53. In

eugonadal men, most

> (~80%) circulating estradiol is derived from extratesticular

> aromatisation. The biological importance of aromatisation in

male

> physiology is highlighted by the striking developmental defects

in

> bone and some other tissues of a man 54 and mouse line 55

harbouring

> genetic mutations that inactivate the estrogen receptor a. By

> contrast, genetic inactivation of the estrogen receptor b has

little

> effect on male phenotype 56. (See chapter on Estrogens in

Male

> Reproduction).

>

> Testosterone is metabolised to inactive metabolites in the

liver,

> kidney, muscle and adipose tissue. Inactivation is

predominantly by

> hepatic mixed function oxidases leading to oxidative

degradation at

> most oxygen moieties of the molecule and ultimately hepatic

> conjugation to glucuronides, which are rendered sufficiently

> hydrophilic for renal excretion.

>

> Metabolic clearance rate of testosterone is reduced by

increases in

> circulating SHBG levels 34 or decreases in hepatic blood flow

(eg

> posture) 28 or function. Theoretically drugs that influence

hepatic

> mixed function oxidase activity could alter metabolic

inactivation of

> testosterone but empirical examples are few. Rapid hepatic

metabolic

> inactivation of testosterone leads to both a low oral

bioavailability

> 57-60 and a short duration of action when injected parenterally

61,

> 62. These limitations dictate the need for parenteral depot

> testosterone formulations (eg injectable testosterone esters,

> testosterone implants or transdermal testosterone) to achieve

> sustained androgenic effects, oral delivery systems which

involve

> portal bypass (buccal 63, 64, sublingual 63, 65, gut lymphatic

58, 66)

> or active synthetic androgens 61, 62.

>

> Brad

[Guest guest]

Hi,

Thanks. I could not understand it as well as I would like. Guess we

need some classes later.

ernestnolan

> > Hi,

> >

> > I knew the liver had to metabolize oral meds to get hormone into the

> > blood supply.

> >

> > Never heard the liver cleared it. I heard it is used by all of the

> > vital organs, (testicles and brain) and consumed in that way.

> >

> > Would you give me more on what you saying.

> >

> > ernestnolan

> >

>

> Sure.

>

> From the Androgel prescribing info:

>

> Excretion

>

> About 90% of a dose of testosterone given intramuscularly is excreted

> in the urine as glucuronic and sulfuric acid conjugates of

> testosterone and its metabolites; about 6% of a dose is excreted in

> the feces, mostly in the unconjugated form. Inactivation of

> testosterone occurs primarily in the liver.

>

>

> In more detail from Endotext:

>

> http://www.endotext.com/male/male2/maleframe2.htm

>

> Testosterone undergoes metabolism to both bioactive metabolites and to

> inactivated oxidised and conjugated metabolites for urinary and/or

> biliary excretion. A small proportion of circulating testosterone is

> metabolised to biologically active metabolites in specific target

> tissues to modulate biological effects. This includes both an

> activation pathway and a diversification pathway of androgen action.

>

> The amplification pathway involves conversion of a small fraction

> (~4%) of circulating testosterone to a more potent androgen, DHT 29,

> 30. DHT has higher binding affinity to the androgen receptor and

> 3-10-fold greater molar biopotency than testosterone. In vitro, DHT is

> a more potent androgen than T due to its higher binding affinity 44

> and more efficient transactivation of the androgen receptor 45, 46.

> Testosterone is converted to DHT, the most potent natural androgen, by

> the 5-a reductase enzyme, which exists in two forms (I & II), each

> specified by distinct genes 47 with type 1 5a reductase expressed in

> liver, skin, and brain whereas type 2 5a reductase is

> characteristically expressed strongly in the prostate but also to

> lower levels in other tissues such as skin (hair follicles) and liver

> 47. The functional predominance of prostatic expression of the type 2

> 5a reductase made it feasible to develop a relatively

> prostate-specific 5a reductase inhibitor, finasteride 48. This occurs

> extensively within the prostate stroma due to presence of type II 5-a

> reductase which converts >95% of testosterone entering the gland into

> the more potent androgen DHT 49. DHT circulates at ~10% of blood

> testosterone concentrations, partly (50-80%) due to spill-over from

> the pool of prostatic DHT 50, 51. Genetic mutations disrupting type II

> 5-a reductase lead to disorders of sexual differentiation involving

> the external genitalia and accessory glands originating from the

> urogenital sinus 52, which is developmentally dependent upon local

> amplification of testosterone to DHT.

>

> The diversification pathway of androgen action involves a

> quantitatively small proportion (0.2%) of testosterone being converted

> to estradiol 31 which then acts via estrogen receptors. This

> diversification pathway of androgen action is governed by the

> cytochrome P450 enzyme (CYP19) aromatase 53. In eugonadal men, most

> (~80%) circulating estradiol is derived from extratesticular

> aromatisation. The biological importance of aromatisation in male

> physiology is highlighted by the striking developmental defects in

> bone and some other tissues of a man 54 and mouse line 55 harbouring

> genetic mutations that inactivate the estrogen receptor a. By

> contrast, genetic inactivation of the estrogen receptor b has little

> effect on male phenotype 56. (See chapter on Estrogens in Male

> Reproduction).

>

> Testosterone is metabolised to inactive metabolites in the liver,

> kidney, muscle and adipose tissue. Inactivation is predominantly by

> hepatic mixed function oxidases leading to oxidative degradation at

> most oxygen moieties of the molecule and ultimately hepatic

> conjugation to glucuronides, which are rendered sufficiently

> hydrophilic for renal excretion.

>

> Metabolic clearance rate of testosterone is reduced by increases in

> circulating SHBG levels 34 or decreases in hepatic blood flow (eg

> posture) 28 or function. Theoretically drugs that influence hepatic

> mixed function oxidase activity could alter metabolic inactivation of

> testosterone but empirical examples are few. Rapid hepatic metabolic

> inactivation of testosterone leads to both a low oral bioavailability

> 57-60 and a short duration of action when injected parenterally 61,

> 62. These limitations dictate the need for parenteral depot

> testosterone formulations (eg injectable testosterone esters,

> testosterone implants or transdermal testosterone) to achieve

> sustained androgenic effects, oral delivery systems which involve

> portal bypass (buccal 63, 64, sublingual 63, 65, gut lymphatic 58, 66)

> or active synthetic androgens 61, 62.

>

> Brad

[Guest guest]

Hi,

For me, the implication Brad's information is: T elimination rates

are as important as T absorption rates. I hadn't thought of that

before. This puts my search for a better delivery method in a new

light. Maybe there's something to me being a " rapid metabolizer "

and no delivery method will work well at my elimination rate.

What to do next? Learn more about it.

Bruce

> > > Hi,

> > >

> > > I knew the liver had to metabolize oral meds to get

hormone into the

> > > blood supply.

> > >

> > > Never heard the liver cleared it. I heard it is used by all of

the

> > > vital organs, (testicles and brain) and consumed in that

way.

> > >

> > > Would you give me more on what you saying.

> > >

> > > ernestnolan

> > >

> >

> > Sure.

> >

> > From the Androgel prescribing info:

> >

> > Excretion

> >

> > About 90% of a dose of testosterone given intramuscularly is

excreted

> > in the urine as glucuronic and sulfuric acid conjugates of

> > testosterone and its metabolites; about 6% of a dose is

excreted in

> > the feces, mostly in the unconjugated form. Inactivation of

> > testosterone occurs primarily in the liver.

> >

> >

> > In more detail from Endotext:

> >

> > http://www.endotext.com/male/male2/maleframe2.htm

> >

> > Testosterone undergoes metabolism to both bioactive

metabolites and to

> > inactivated oxidised and conjugated metabolites for urinary

and/or

> > biliary excretion. A small proportion of circulating

testosterone is

> > metabolised to biologically active metabolites in specific

target

> > tissues to modulate biological effects. This includes both an

> > activation pathway and a diversification pathway of androgen

action.

> >

> > The amplification pathway involves conversion of a small

fraction

> > (~4%) of circulating testosterone to a more potent androgen,

DHT 29,

> > 30. DHT has higher binding affinity to the androgen receptor

and

> > 3-10-fold greater molar biopotency than testosterone. In vitro,

DHT is

> > a more potent androgen than T due to its higher binding

affinity 44

> > and more efficient transactivation of the androgen receptor

45, 46.

> > Testosterone is converted to DHT, the most potent natural

androgen, by

> > the 5-a reductase enzyme, which exists in two forms (I & II),

each

> > specified by distinct genes 47 with type 1 5a reductase

expressed in

> > liver, skin, and brain whereas type 2 5a reductase is

> > characteristically expressed strongly in the prostate but also

to

> > lower levels in other tissues such as skin (hair follicles) and

liver

> > 47. The functional predominance of prostatic expression of

the type 2

> > 5a reductase made it feasible to develop a relatively

> > prostate-specific 5a reductase inhibitor, finasteride 48. This

occurs

> > extensively within the prostate stroma due to presence of

type II 5-a

> > reductase which converts >95% of testosterone entering the

gland into

> > the more potent androgen DHT 49. DHT circulates at ~10%

of blood

> > testosterone concentrations, partly (50-80%) due to spill-over

from

> > the pool of prostatic DHT 50, 51. Genetic mutations

disrupting type II

> > 5-a reductase lead to disorders of sexual differentiation

involving

> > the external genitalia and accessory glands originating from

the

> > urogenital sinus 52, which is developmentally dependent

upon local

> > amplification of testosterone to DHT.

> >

> > The diversification pathway of androgen action involves a

> > quantitatively small proportion (0.2%) of testosterone being

converted

> > to estradiol 31 which then acts via estrogen receptors. This

> > diversification pathway of androgen action is governed by the

> > cytochrome P450 enzyme (CYP19) aromatase 53. In

eugonadal men, most

> > (~80%) circulating estradiol is derived from extratesticular

> > aromatisation. The biological importance of aromatisation in

male

> > physiology is highlighted by the striking developmental

defects in

> > bone and some other tissues of a man 54 and mouse line

55 harbouring

> > genetic mutations that inactivate the estrogen receptor a. By

> > contrast, genetic inactivation of the estrogen receptor b has

little

> > effect on male phenotype 56. (See chapter on Estrogens in

Male

> > Reproduction).

> >

> > Testosterone is metabolised to inactive metabolites in the

liver,

> > kidney, muscle and adipose tissue. Inactivation is

predominantly by

> > hepatic mixed function oxidases leading to oxidative

degradation at

> > most oxygen moieties of the molecule and ultimately hepatic

> > conjugation to glucuronides, which are rendered sufficiently

> > hydrophilic for renal excretion.

> >

> > Metabolic clearance rate of testosterone is reduced by

increases in

> > circulating SHBG levels 34 or decreases in hepatic blood

flow (eg

> > posture) 28 or function. Theoretically drugs that influence

hepatic

> > mixed function oxidase activity could alter metabolic

inactivation of

> > testosterone but empirical examples are few. Rapid hepatic

metabolic

> > inactivation of testosterone leads to both a low oral

bioavailability

> > 57-60 and a short duration of action when injected

parenterally 61,

> > 62. These limitations dictate the need for parenteral depot

> > testosterone formulations (eg injectable testosterone esters,

> > testosterone implants or transdermal testosterone) to

achieve

> > sustained androgenic effects, oral delivery systems which

involve

> > portal bypass (buccal 63, 64, sublingual 63, 65, gut lymphatic

58, 66)

> > or active synthetic androgens 61, 62.

> >

> > Brad

[Guest guest]

I don't know if you are a rapid metabolizer or not, but Shippen's

suggestion is a plausible one. We have had one other rapid

metabolizer that I recall here. He used relatively frequent and

relatively large doses of injectible t and monitored the result with

blood testing till he found what worked. One disadvantage of

implantable pellets is that frequent dosage changes are impractical.

One can easily deliver large amounts of t with injectibles. I would

suggest that you consider that with frequent labs to guide you.

Brad

> Hi,

>

> For me, the implication Brad's information is: T elimination rates

> are as important as T absorption rates. I hadn't thought of that

> before. This puts my search for a better delivery method in a new

> light. Maybe there's something to me being a " rapid metabolizer "

> and no delivery method will work well at my elimination rate.

> What to do next? Learn more about it.

>

> Bruce

>

[Guest guest]

Alcohol certainly has an effect on hormones!

Sometimes though, as with an alcoholic with screwed up hormones, it

might be difficult to figure out if the alcohol is what screwed up

the hormones, or the screwed up hormones is what caused the person

to become an alcholic! Fact.

Armyguy

> :

> : >

> : >Fascinating information! I'm on a number of meds that might

> : >play a hand in this. One is hydrochlorothiazide, a diuretic for

high

> : >blood pressure that is also linked to sexual dysfuntion (in some

> : >opinions). Combined with drinking too much coffee, I can see

> : >how my urinary excretion of T might be affected. Another med

I've

> : >just stopped is Antabuse (disufiram), which is used as a

> : >deterrent in alcoholism- it modifies alcohol metabolism by the

> : >liver into an extremely unpleasant aldehyde. I don't know if it

also

> : >affects T metabolism, but I can get along without the med, so

> : >that's one less thing in my overstuffed pillbox.

> :

> : If you had alcohol issues you may have portal/hepatic issues

affecting

> : metabolism of T.

> :

> :

> :

[Guest guest]

Hi,

What medications are you taking?

ernestnolan

> > > > Hi,

> > > >

> > > > I knew the liver had to metabolize oral meds to get

> hormone into the

> > > > blood supply.

> > > >

> > > > Never heard the liver cleared it. I heard it is used by all of

> the

> > > > vital organs, (testicles and brain) and consumed in that

> way.

> > > >

> > > > Would you give me more on what you saying.

> > > >

> > > > ernestnolan

> > > >

> > >

> > > Sure.

> > >

> > > From the Androgel prescribing info:

> > >

> > > Excretion

> > >

> > > About 90% of a dose of testosterone given intramuscularly is

> excreted

> > > in the urine as glucuronic and sulfuric acid conjugates of

> > > testosterone and its metabolites; about 6% of a dose is

> excreted in

> > > the feces, mostly in the unconjugated form. Inactivation of

> > > testosterone occurs primarily in the liver.

> > >

> > >

> > > In more detail from Endotext:

> > >

> > > http://www.endotext.com/male/male2/maleframe2.htm

> > >

> > > Testosterone undergoes metabolism to both bioactive

> metabolites and to

> > > inactivated oxidised and conjugated metabolites for urinary

> and/or

> > > biliary excretion. A small proportion of circulating

> testosterone is

> > > metabolised to biologically active metabolites in specific

> target

> > > tissues to modulate biological effects. This includes both an

> > > activation pathway and a diversification pathway of androgen

> action.

> > >

> > > The amplification pathway involves conversion of a small

> fraction

> > > (~4%) of circulating testosterone to a more potent androgen,

> DHT 29,

> > > 30. DHT has higher binding affinity to the androgen receptor

> and

> > > 3-10-fold greater molar biopotency than testosterone. In vitro,

> DHT is

> > > a more potent androgen than T due to its higher binding

> affinity 44

> > > and more efficient transactivation of the androgen receptor

> 45, 46.

> > > Testosterone is converted to DHT, the most potent natural

> androgen, by

> > > the 5-a reductase enzyme, which exists in two forms (I & II),

> each

> > > specified by distinct genes 47 with type 1 5a reductase

> expressed in

> > > liver, skin, and brain whereas type 2 5a reductase is

> > > characteristically expressed strongly in the prostate but also

> to

> > > lower levels in other tissues such as skin (hair follicles) and

> liver

> > > 47. The functional predominance of prostatic expression of

> the type 2

> > > 5a reductase made it feasible to develop a relatively

> > > prostate-specific 5a reductase inhibitor, finasteride 48. This

> occurs

> > > extensively within the prostate stroma due to presence of

> type II 5-a

> > > reductase which converts >95% of testosterone entering the

> gland into

> > > the more potent androgen DHT 49. DHT circulates at ~10%

> of blood

> > > testosterone concentrations, partly (50-80%) due to spill-over

> from

> > > the pool of prostatic DHT 50, 51. Genetic mutations

> disrupting type II

> > > 5-a reductase lead to disorders of sexual differentiation

> involving

> > > the external genitalia and accessory glands originating from

> the

> > > urogenital sinus 52, which is developmentally dependent

> upon local

> > > amplification of testosterone to DHT.

> > >

> > > The diversification pathway of androgen action involves a

> > > quantitatively small proportion (0.2%) of testosterone being

> converted

> > > to estradiol 31 which then acts via estrogen receptors. This

> > > diversification pathway of androgen action is governed by the

> > > cytochrome P450 enzyme (CYP19) aromatase 53. In

> eugonadal men, most

> > > (~80%) circulating estradiol is derived from extratesticular

> > > aromatisation. The biological importance of aromatisation in

> male

> > > physiology is highlighted by the striking developmental

> defects in

> > > bone and some other tissues of a man 54 and mouse line

> 55 harbouring

> > > genetic mutations that inactivate the estrogen receptor a. By

> > > contrast, genetic inactivation of the estrogen receptor b has

> little

> > > effect on male phenotype 56. (See chapter on Estrogens in

> Male

> > > Reproduction).

> > >

> > > Testosterone is metabolised to inactive metabolites in the

> liver,

> > > kidney, muscle and adipose tissue. Inactivation is

> predominantly by

> > > hepatic mixed function oxidases leading to oxidative

> degradation at

> > > most oxygen moieties of the molecule and ultimately hepatic

> > > conjugation to glucuronides, which are rendered sufficiently

> > > hydrophilic for renal excretion.

> > >

> > > Metabolic clearance rate of testosterone is reduced by

> increases in

> > > circulating SHBG levels 34 or decreases in hepatic blood

> flow (eg

> > > posture) 28 or function. Theoretically drugs that influence

> hepatic

> > > mixed function oxidase activity could alter metabolic

> inactivation of

> > > testosterone but empirical examples are few. Rapid hepatic

> metabolic

> > > inactivation of testosterone leads to both a low oral

> bioavailability

> > > 57-60 and a short duration of action when injected

> parenterally 61,

> > > 62. These limitations dictate the need for parenteral depot

> > > testosterone formulations (eg injectable testosterone esters,

> > > testosterone implants or transdermal testosterone) to

> achieve

> > > sustained androgenic effects, oral delivery systems which

> involve

> > > portal bypass (buccal 63, 64, sublingual 63, 65, gut lymphatic

> 58, 66)

> > > or active synthetic androgens 61, 62.

> > >

> > > Brad