Shutdown of the H and P, is that a Bad Thing when on TRT?

Pharma / TRT Testosterone Replacement
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Hey guys,

I’m normally over at the Pharma section but I found something interesting that belongs here.

I’m weighing pros and cons to make up my mind if TRT is going to be in my future or not. While thinking about it, I asked myself: What about the hypothalamus and the pituitary? Is it a bad thing that TRT shuts down these possibly important hormones?

I mean, how realistic is it that LH, FSH, GnRH and the involved peptides have exactly one job in the body? Not very as nearly every transmitter used by the body has a myriad of functions.

Introducing this study:

Here are the main interesting points:

  1. “These studies show that extragonadal expression of LHR not only occurs, but is functional and may play a role in the control of higher processes by the nervous system.”
    So, the LH receptor has functions in the central nervous system. What does it do there?

  2. „LH may regulate cognition and neuroplasticity in an independent fashion. LHR can evoke signaling that has been well linked to learning and memory.
    In rodents LHR is involved in pheromone-driven social behavioral between male and female mice and changes in expression of hippocampal neurogenesis, a neuroplasticity mechanism associated with the regulation of cognitive function.“ So, LH seems to be important for cognitive function and neuroplasticity, two very important functions of the brain which, when dysregulated, result in depression, Alzheimers and other bad stuff.

BUT here’s the Crux: What happens normally with LH during the aging process? Does the hypothalamus stop it’s stimulation of LH production and then T and E decrease?

No it happens the other way round.

T and E2 decrease and therefore the hypothalamus INCREASES its production of GnRH!

LH, which increases 3 fold in women and 2 fold in men throughout the aging process. These changes in LH levels correlate with Alzheimer’s disease progression

So shouldn’t that be good?

Seemingly not. Because here’s Crux number 2:

there seems to be an inverse relationship of LH expression between the brain and bloodstream

So if peripheral LH rises, brain LH decreases because LH doesn’t enter the brain, the brain produces its own LH:

Along with the direct and peripheral effects of hCG, we have recently discovered that LH is produced in the brain. It is expressed in cognition modulating areas such as the hippocampus, the cingulate cortex and midbrain structures such as the thalamus and superior colliculi, and it co-localizes with neuronal markers such as NeuN in pyramidal neurons.

That actually is good for TRT patients because that suggests that the fall in peripheral LH is accompanied by a rise in central LH:

Brain-derived LH protein levels are present in cognition associated areas and reduced by ovariectomy. These levels are normalized by drugs that reduce peripheral LH levels and this normalization of brain-LH positively correlates with markers of neuroplasticity and cognitive improvement.

—> proof of concept

Edit: Graphical abstract

image

What’s the takeaway from the study for TRT patients?

If you like your balls hanging lower than your dick, then don’t overdo it on TRT with hCG.

In parallel, chronic elevations of peripheral human chorionic gonadotropin (hCG), which shares a receptor with LH, impairs working memory and increases levels of total brain amyloid-β40 in a mouse model of Alzheimer’s disease.

So if you’re worrying about LH being decreased by TRT that shouldn’t be an issue. I don’t know how it looks like with FSH and I’d appreciate the input from guys on TRT and their thoughts on this stuff.

If this has been elucidated before by other members, just ignore this.

@readalot @iron_yuppie @unreal24278 @blshaw @dbossa

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I’ve just been reading about how LH affects the adrenal glands and causes secretion of hormones like DHEA.

Its made me want to add HCG into my protocol as my DHEA has dropped and there are studies showing DHEA levels effect erection quality.

I’m struggling to decipher the above that you’ve posted- could someone dumb it down a bit for layman?

Thanks

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Thanks for the opinion!

Are these with or absent of TRT?

My post says:

Low LH in the blood is not bad as that has a positive effect on the brain it seems (Still not enough research but promising) and too much hCG would counter that.

I think many don’t take much hCG, the guys I know of take 250 IU two times per week. The question is, if that’s too much as it has a long half life. It seemingly also affects wakefulness and activity levels.

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I’ll cut it down for ya:

  1. LH is at 0 in the blood during TRT

  2. LH has not only a function in the balls but also in the brain

  3. LHs functions are very important

  4. LH doesn’t enter the brain, it produces its own (not only the pituitary produces LH)

  5. Brain LH correlates negatively with plasma LH

  6. During aging plasma LH normally rises, in TRT patients it’s at zero

  7. Good for the TRT patient, because when LH in the plasma decreases, LH in the brain goes up

  8. HCG and LH activate the same receptor

  9. Don’t inject too much HCG or you’ll hinder brain LH production

  10. TRT maybe has positive effects on degenerative diseases of the brain

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Thanks- that makes sense. Plasma level being in the blood I’ve just realised.

That’s good to know!

Its weird how stuff in the blood cant enter the brain- I’ve read about that with Free T being able to get in to the brain but not SHBG bound T. Amazing as its all carried around in the blood!

Great Post @lordgains will be following this in detail!

Thats a good point about the DHEA levels whether the studies were of TRT patients or non- honest answer is I don’t know- need to do more reading about this!

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Yes. The blood brain barrier is an extremely cool part of the body. It consists of astrocyte end-feet and tight junctions at the vessels and it let’s only specific things in.

There’s also the choroid plexus which filters the blood to produce cerebrospinal fluid which surrounds the brain.

Big proteins like LH generally don’t get into the brain, small molecules often do but only if they don’t have a charge (+ or -).

SHBG is such a big protein.

Free T is an uncharged small lipophilic molecule, it penetrates the BBB quite easily.

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Could this be why some guys feel really great on HCG?

Edit: reading further, could it also be why some guys feel awful on it? I noticed I get amped up, hard to sleep, very anxious on HCG, likely because of either the action in the adrenals or in the brain.

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Could be! Thanks for the chiming in brother. How much did you take per week?

The action on the adrenals for sure has emotional effects. Increased Cortisol is known for what you are describing. It’s very interesting where the body has all these receptors.

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I took 250iu EOD up to 500iu, tried 1000iu in single shots a few times.

I take suboxone daily which lowers cortisol, sometimes have low energy even on TRT, but seems like HCG was too much in the other direction.

Along with gyno lumps coming back. I had read there’s LH receptors in the breast as well, figured that was causing it.

I haven’t tried any HCG in probably 2-3 months, maybe I’ll give it a go again to test

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I’m going strictly from theoretical knowledge here but I’d take it not more than 2 times per week. Maybe start at 250 two times per week.

Is that because of past addiction? The cortisol lowering effects often go by the wayside because of the other 20 effects opioids have on the body, but they are important. Thanks for sharing the experience!

Did you measure E2? Because hCG is known to increase it a good amount.

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Yes, for 3 years now. Pretty low dose tho compared to others.

I didn’t notice e2 being any higher while on HCG, however it did seem much easier to lose weight while taking it. Didn’t have any of those cravings for sugar, and seemed to be able to deal with hunger better

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Congrats!

Very interesting. Cortisol has these effects. Less hunger. But often people don’t calm down and eat sugar and a lot of carbs to feel calmer.

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Want to add to this post some papers I read.

It seems that there’s not only positive correlation for LH levels with cognitive impairment (Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer’s disease | Molecular Psychiatry) but also for FSH levels. It’s only a study from 1999 with bad scientific vigor in my opinion but not everything we get can be thorough.

The authors argue that gonadotropins (especially FSH) are elevated in Alzheimer’s disease patients and they speculate FSH could be part of the etiology of the disease.

It’s funny, at first I thought it couldn’t be good that two peptide hormones vanish for decades on TRT. All evidence seems to be to the contrary.

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It’s funny, at first I thought it couldn’t be good that two peptide hormones vanish for decades on TRT. All evidence seems to be to the contrary.

This was my first thought too and I have been wondering if the absence of LH and FSH would cause me any health issues in the future as I am only 31 on TRT.

Its interesting that it seems to be so far that it is possibly a good thing but time will tell as we discover more about the role of LH and FSH in the body.

Also, HCG makes me feel awful, puts me into an anxious and really dark head space… weird

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Great info in this thread on the topic:

Thank to @MrGrant and contributors

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