My Nutts Are Missing

Training Over 35 Lifter
21

[quote]DrSkeptix wrote:

No quarrel with this article. It is directed at a very different subject: using low dose HCG to assist in spermatogenesis in hypogonadotrophic men.

The men in the study were rendered (presumably) infertile with T. Then HCG was used to increase intratesticular T, a necessary precondition for spermatogenesis. The authors provide a complicated warning regarding the timing of the reported benefit (intratesticular testosterone, not circulating hormones): In short, use HCG early if you are going to use it all for the purposes of infertility treatment.

[/quote]

I think that you missed the message that I find in that article.

TRT shuts down the HPTA. In the article, the subjects were HPTA shutdown with T. So far, an exact match for guys on TRT. Next they estabished that around 250iu hCG SC EOD restored ITT. When ITT is restored to baseline levels, then by that measure, the testes are restored to baseline functioning by that measure. [That is a favourable condidion for spermatogenesis, but FSH is also part of the picture, but outside of the scope of the article.]

Yes, ITT is much higher than serum. Obviously serum T is useless as a determinant of T production when on TRT+hCG. It is assumed that one understands that a restored ITT is the objective in hCG dose determination. To assume that “using low dose HCG to assist in spermatogenesis in hypogonadotrophic men” is the point is wrong. That is but one benefit. The research method and data are the only facts.

For old guys on TRT, fertility is not something that is a concern. For the few guys who loose normal hormone production when young, fertility is important and needs to be preserved. The use of hCG has benefits for both groups.

Note effects in the brain

I found this:
"As wel age, we lose pregnenolone production, due to aging of testicles and adrenal glands. When one goes on HRT, HTPA is shut off and testes stop working, hence the pregnenolone production is shut off.

This is also why hcG is so important - we need the testicles alive and well to supplement pregnenolone production, in addition to what we add in as cream. Plus hcG is a source of LH receptor activity! So anyone who thinks that hcG is for cosmetic purposes is simply mis-informed!"

I have found authorative sources for pregnenolone production in the testes and have not book marked those. They are not easy to locate. What I have see are statements that the testes are the largest single source of pregeneolone production.

22

[quote]mistersniffles wrote:
The proposed mechanism of HCG’s effect upon mood in men may not be correct but it is probably genuine. It appears it is the HCG itself as per your speculation. Effects upon mood in women have been documented, men probably respond in some fashion as well.

HCG use is often ideal…one should replace the LH which has been lost due to testosterone administration…otherwise, how is that a true replacement of normal activity? …

The exception to this “rule” of HCG use might be men with primary hypogonadism…those that present with elevated LH and low testosterone, indicating their testicles fail to respond to LH or any analog such as HCG. These men will often times be put on testosterone therapy to normalize their high LH to an in range level. In these cases when LH is still within the normal range during testosterone therapy, no HCG is needed. In any other cases, supplement with it in small amounts as suggested…

[/quote]

Thanks for the heavy lifting!

You also touch on one of my major gripes. Men are put on life-long TRT without analyzing how they have arrived at that state. Very few are primarily hypogonadal (High LH/FSH). Even fewer, nowadays, are provoked with clomiphene, AIs or HCG.
The result is: everyone is treated blindly with T, the opportunity is lost to discover the real problem, and then we wind up with answerable questions: supplemental AIs? HCG? Maybe T alone was the wrong choice to start?

A last thought on HCG: most of the experience with it is short term use. We know that high dose treatment leads to down-regulation of testicular receptors and inefficacy. The article cited by KSMan is a short term observation. Does low-dose chronic use of HCG in T-supplemented men lead to down-regulation and inefficacy? In testicles or brain or both?

23

[quote]KSman wrote:
DrSkeptix wrote:

I think that you missed the message that I find in that article.

[/quote]

Thanks for clarification.

The researchers’ explicit goal was to show that low dose HCG was effective and safe for their purpose: raise ITT in the setting of controlled hypogonadism. They do not like high dose HCG which was a standard therapy for infertile men: here, they show the potential efficacy of a “less toxic” regimen.

I do not doubt that the testicles produce large amounts of pregnenolone: but my understanding is that the enzymatic conversions are almost complete in situ. (Rate-limiting steps and all that.)

Second, although Wiki offers no meaningful citations:
'Pregnenolone and its sulfate, like dehydroepiandrosterone and its sulfate and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas in the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization."

It does not say that the testes produce all the pregnelone that the nervous system uses–it is synthesized there.

Last, I do not know of a “pregnenolone-deficiency state” among castrated men. And trust me…I have known more than a “handful.”

Please, if you have clear studies about my doubts, I would appreciate them. --Always ready to learn and to be corrected!

24

[quote]Chushin wrote:
DrSkeptix wrote:
In short, if you want to use HCG for bigger nuts, ok…If your mood improves, great, but I don’t know why,

Perhaps bigger balls in and of themselves are a real source of pride and happiness? :slight_smile:

[/quote]

OK! Where do I sign up?

25

[quote]DrSkeptix wrote:
KSman wrote:
DrSkeptix wrote:

I think that you missed the message that I find in that article.

Thanks for clarification.

The researchers’ explicit goal was to show that low dose HCG was effective and safe for their purpose: raise ITT in the setting of controlled hypogonadism. They do not like high dose HCG which was a standard therapy for infertile men: here, they show the potential efficacy of a “less toxic” regimen.

I do not doubt that the testicles produce large amounts of pregnenolone: but my understanding is that the enzymatic conversions are almost complete in situ. (Rate-limiting steps and all that.)

Second, although Wiki offers no meaningful citations:

'Pregnenolone and its sulfate, like dehydroepiandrosterone and its sulfate and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas in the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization."

It does not say that the testes produce all the pregnenolone that the nervous system uses–it is synthesized there.

Last, I do not know of a “pregnenolone-deficiency state” among castrated men. And trust me…I have known more than a “handful.”

Please, if you have clear studies about my doubts, I would appreciate them. --Always ready to learn and to be corrected!
[/quote]

Castrated men have have many changes from norms. We can’t learn much from that.

Pregnenolone levels drop with age, also DHEA and testosterone.

Pregnenolone is made everywhere, but that does not change the fact that there are major centers of production. It is also produced in the adrenals glands. DHEA is produced mostly in the adrenal glands from pregnenolone.

My pregnenolone and DHEA dropped significantly when I started testosterone only TRT. Some can supplement with pregnenolone and DHEA levels also lift.

Most while some pregnenolone is converted to other things in the testes, most gets into serum. Most DHEA is produced in the adrenals and most of that gets into serum. DHEA is used in the testes to produce testosterone. It seems that direct conversion from pregnenolone to testosterone in the teste is low.

Men and women make testosterone in the adrenals glands. For premenopausal women, this seems to be around 50%. The adrenal testosterone production for young normal males is not significant compared to total production.

The fact that pregenenolone is produced in the brain does not in any way state that that production is sufficient for brain health. It is known that when serum pregnenolone levels are low, supplementing with pregnenolone improves mental well-being and memory.

Research has been done on rats where they are castrated and then they and the controls are killed and levels of pregnenolone, DHEA etc are measured in brain tissue.

26

I do not know where you get these unreferenced statements but none of them are scientifically substantied and are in fact greatly incongruent with what has been scientifically validated:

To summarize all locatable studies:

  1. Intratesticular pregnenolone levels do not decrease with aging.

  2. The majority of circulating pregnenolone in men comes from the adrenal glands, not the testicles.

  3. The synthesis of pregnenolone occurs in the central nervous system independently, even when men are made to be hypogonadal.

  4. Pregnenolone is synthesized locally in peripheral tissues.

  5. HCG does not influence circulating pregnenolone levels in men.

  6. Circulating, but not locally formed, pregenolone does decline with aging but is due to an age-related decline in adrenal function and little if anything to do with the testicles.

  7. If LH is below normal, use HCG for the simple fact that you should replace it for the effects that lie beyond the testicles.

To be very clear: USE HCG if you are LH deficient. But as a minor point of contention, HCG does not influence pregnenolone levels. The testicles are not the main source of pregnenolone in men, the adrenals are and finally testicular pregnenolone production does not decline with aging, adrenal production does.

(Intratesticular levels of pregnenolone do not decline as men age).

http://jcem.endojournals.org/cgi/content/full/87/5/2225

(“Circulating pregnenolone sulfate is mostly if not entirely of adrenal origin”) (“The majority of circulating pregnenolone is sulfated; though mainly of adrenal origin, it may serve as a supply for EpiTe precursors”)

(“In summary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small decrease in the testis, the activity of the steroid-converting enzymes present in peripheral tissues does not decrease during aging”)

(Followed from birth to adulthood: "The changes induced by adrenal stimulation and suppression and by testicular stimulation were also studied. Plasma PS (Pregnenolone Sulfate) levels rose after either acute or long term stimulation with ACTH and were suppressed by dexamethasone, as were cortisol levels in the same tests. A very close correlation was found between the rise of PS and ACTH levels at the end of metyrapone tests.

In contrast gonadal participation in the production of PS was moderate. These results suggest that the measurement of PS could be a good index of ACTH production in children."

(“These results indicate that the steroidogenic response to ACTH decreases with aging, and that, in the elderly men, an apparent decrease in C17,20 lyase efficiency may be related in part to the decreased secretion of adrenal androgens”)

(“The CSF testosterone, dihydrotestosterone, and androsterone levels were significantly lower during hypogonadism (P=.002, .04, and .046, respectively), but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone”)

http://ajpendo.physiology.org/cgi/content/full/277/6/E1032

(No effect of HCG upon circulating pregnenolone: “With regard to progesterone and pregnenolone, the finding that their plasma levels were not increased by hCG stimulation was also in agreement with a previous report (14).”)

27

[quote]mistersniffles wrote:
(great post with citations)
[/quote]

Thank you for the post and references, mistersniffles!

BD

28

[quote]bigdawg011 wrote:
mistersniffles wrote:
(great post with citations)

Thank you for the post and references, mistersniffles!

BD

[/quote]

Ditto!

What mistersniffles adds is what my understanding has been, but his is an extraordinary effort!
Now I now where I can turn for expert advice!

29

You know I like to keep it simple and compare myself to rat studies as little as possible. Last time I checked I had two legs. Anyway:

  1. HCG will let you keep your nuts while on TRT.
  2. It increases libido for me and elevates my mood.
  3. It’s cheap.

What are we discussing here? If you want to keep your nuts and feel the benefits use it. If not don’t. For $30 a month I’ll keep my nuts and a good mood.

30

[quote]brentf13 wrote:
You know I like to keep it simple and compare myself to rat studies as little as possible. Last time I checked I had two legs. Anyway:

  1. HCG will let you keep your nuts while on TRT.
  2. It increases libido for me and elevates my mood.
  3. It’s cheap.

What are we discussing here? If you want to keep your nuts and feel the benefits use it. If not don’t. For $30 a month I’ll keep my nuts and a good mood. [/quote]

I agree with all of your points. I was merely attempting to provide some insight as to the HOW when it comes to HCG and its potential in affecting mood. Not all are as pragmatic as yourself…some of us like discussing the details and the hows and whys.

31

I believe what’s in all of these studies as much as I believe that 95% of ED is caused by physical problems and TT of 250 is perfectly within range and acceptable. I’m not giving you a hard time but seriously I’m starting to wonder if anyone really knows how anything in the body works.

33

I’m referring to the guy who originally posted. Also what’s the difference between using T (naturally in your body) and using HCG (naturally in your body as LH)? Personally I’m way more concerned about Arimidex than I am HCG.

34

Great stuff Sniffles.

35

Concerning http://ajpendo.physiology.org/cgi/content/full/277/6/E1032

The study examined the effects of 5000iu hCG on young health males. Pregnenolone was not increased when hCG was piled up on top of normal LH/FSH levels. This may be demonstrating that baseline LH drives pregnenolone production to a maximal value and added hCG does not change that.

If the study involved guys on TRT who were shutdown for an extensive amount if time, with some testicular shrinkage and compared pregnenolone levels of that base line to levels achieved after two months with 250iu hCG SC EOD, that would be more to the point.

When I started TRT [without hCG] my pregnenolone levels went down [as my testes shrank]. My DHEA-S also decreased, presumably as a result of lower pregnenolone levels.

36

[quote]KSman wrote:
Concerning http://ajpendo.physiology.org/cgi/content/full/277/6/E1032

The study examined the effects of 5000iu hCG on young health males. Pregnenolone was not increased when hCG was piled up on top of normal LH/FSH levels. This may be demonstrating that baseline LH drives pregnenolone production to a maximal value and added hCG does not change that.

…

[/quote]

There is a much simpler explanation, an explanation which is more consonant with facts.

Clearly, HCG stimulates testosterone production within hours. But as sniffles pointed out in his point # 2 (top of this page), most circulating pregnenolone is made in the adrenals, not the testicles. Stimulating testicular production with HCG would not effect the adrenal production of pregnenolone, especially if it is metabolized in situ, so no effect would be measured in plasma.

Further, the article states clearly: “With regard to plasma pregnenolone and progesterone, hCG administration did not induce significant variations in either placebo aspirin + hCG or aspirin + hCG tests at any time considered (data not shown).”

HCG stimulates the enzymatic cascade that leads from cholesterol to pregnenolone and progesterone to testosterone. If the steps after progesterone (e.g., 17-hydroxylase) are accelerated, then one would see no increase in blood pregnenolone and progesterone, and one would see the increase in testosterone and other derivative steroids.

And this is what the article showed.

(The role of aspirin here is muddled, since tissue cytochromes are altered by COX- 1 and COX-2 activity.)

One conclusion from this data is clear: HCG does not raise blood pregnenolone, which then migrates to nerves and brain. This is in opposition to KSMan’s contention earlier in this thread.

37

But the comparison in the paper was relative to baseline youthful healthy testes which were already which were already LH stimulated. This is clearly not transferable to TRT. That is a technical objection. The paper’s conclusions might be correct, but that is not demonstrated. The research simply increased LH receptor stimulation. More LH receptor stimulation, above a youthful baselines, might not increase pregnenolone production.

Some pregnenolone produced in the testes is exchanged with serum, it works in both directions. We know that supplemental DHEA increases T when DHEA levels are low and T production has been DHEA level rate limited. This is an example of testicular steroid exchange with serum. So the idea that all pregnenolone produced in the testes is metabolized into testosterone seems to be partial understanding. Also, such statements are suspect when the intermediate DHEA is ignored, especially when DHEA is considered to be an adrenal hormone.