Anti-Estrogen for HRT 250-300mg?

Pharma TRT
21

While researching today I came across this article suggesting that extreme E2 levels put the cardiovascular system a risk.

Men with chronic heart failure have a significantly increased mortality risk if their estradiol levels are at the extreme ends of the concentration range, a Polish-led group reported. Action Points Explain to patients that men with chronic heart failure may have an increased risk of dying if their serum estradiol is elevated or very low.

The study was observational and therefore cannot prove that estradiol levels influence mortality risk in men with CHF. Men with low estradiol levels had as much as a 50% lower survival compared with men who had mid-range levels of the female hormone, according to Ewa A. Jankowska, M.D., Ph.D., of the Military Hospital in Wroclaw, and colleagues.

Estrogen has beneficial effects on the myocardium and vasculature, including attenuation of remodeling and cardiomyocyte apoptosis. The cardioprotective effects may explain the association between low estradiol and an increased risk of cardiovascular events in men, the authors said.

Derangement of adrenal androgen metabolism often accompanies heart failure in men and has unfavorable clinical and prognostic implications, they continued. Dr. Jankowska and colleagues hypothesized that similar disturbances in estrogen synthesis might also occur.

During three years of follow-up, 171 (34%) study participants died. Investigators found that men with the lowest estradiol levels had a mortality hazard ratio of 4.17 (P<0.001) compared with patients in the middle quintile. Men in the top quintile had more than double the mortality risk (HR 2.33, P<0.001).

Three-year survival by increasing quintile of estradiol was 44.6%, 65.8%, 82.4%, 79%, and 63.6% (P<0.001 for trend).

The authors found that men with the highest and lowest estradiol levels had distinguishing clinical characteristics.

Those in quintile 1 had higher serum total testosterone, decreased serum DHEA-S, more advanced heart failure, impaired renal function, and decreased fat mass (P<0.05 versus quintile 3).
Friday morning

22

[quote]HiredGun wrote:

[quote]PureChance wrote:
prednisone is a major medication, right? I think I’ve heard bad stories about how it can wreck people’s adrenals.

[/quote]

It is and I thought it was the same thing as hydrocortisone. From a quick lookup prednisone, hydrocortisone, prednisolone are all similar to cortisol. They are all catabolic and also reduce immune inflammation ( my basic problem I am told is an immune system gone wild ).
[/quote]

Hydrocortisone, prednisone, prednisolone, and dexamethasone are all synthetic glucocortocoids, meaning they act similar to cortisol in the body. If you take enough of any of ‘em over time, you will suppress (shut down) your adrenals’ cortisol production, and they may not restart. Likewise, maintenance doses of any will keep you alive if your adrenals do go south.

But that said, they are in fact all different compounds, and have different sides and ranges of effect (and different levels of misery should you need to be on one on an extended basis). Hydrocortisone is closest to bioidentical, but needs to be taken 2 or 3 times a day.

23

2-3 weeks at 40mg or higher and your shutdown. I have been on 100. A little asthma for a child or grandma might be 10mg. Your body produces around 7-8 per day so you can chop from 60 to 30 but you must ride the brakes below 10. I had to cut the pills into 2.5 mg pieces to avoid adrenal shock. Solumedrol is what you get in the when the prednisone does not work and that is IV drip in the hospital.

After finding 640 T from a 2006 blood test I must have demanded from the doctor I really wonder if I need to be on HRT all. Its a long story but I am intending to try and do some variation of PCT and find out for sure. Hmmm old girlfriend flying out in July, may be best to experiment AFTER that. I am older by 5 years but I no longer drink alcohol so perhaps they balance out.

24

“HCG also drives conversion of Progesterone to 17-hydroxyprogesterone one of the primary paths needed to create Cortisol.”

Is that improving things or making things worse. Your wording leaves that up in the air. What else creates the same ‘drives’? Only hCG?

And LH does not to any degree? Is ‘drives’ misleading? And what amounts of hCG are a problem if so?

HANS: We know the protocol for anastrozole dose and adjustment. Please post the protocols for aromasin and what the E2 targets are. Give us something useful.

25

[quote]KSman wrote:
Is that improving things or making things worse. [/quote]

For many probably worse. For me specifically it would be welcome. The only way to naturally boost cortisol I have found is long intense workouts not followed by waxy maize.

I have seen an article that HCG boosted cortisol, it even helped a womans UC unintentionally. Got my ampule of HGC yesterday in the mail, what and odd thing to work with.

26

Anyone have any more info/links on prednisone and the adrenals?

Pretty sure my course of prednisone wrecked mine (started at 40mg for a crohn’s flare).

Feel like absolute shit and saliva cortisol test reflected very low cortisol throughout the day.

GI Dr put me back on 10mg and tapered down over 20 days and felt much better. Then a week or two after concluding the taper, felt like shit again.

New HRT Dr, got on T + AI and HC. Up to 30mg a day of HC (+DHEA and Preg) and still don’t feel any different.

Looking for any ideas. thanks.

27

[quote]j-man1 wrote:
Feel like absolute shit and saliva cortisol test reflected very low cortisol throughout the day.
thanks.[/quote]

Well this is not the best advice but I have too much to do, I cannot be sitting around. I have not been an employee in 5 years, I just keep going after high pressure consulting gigs to basically make stuff run faster, longer.

I need to run faster longer too. So after all that nasty prednisone I just up and told the doc that people noticed I have ADD or whatever they call it these days and answered the one page questionare correctly and I got what I wanted - Vyvanse. Works for 12-14 hours unless I screw it up with caffeine. I get it all done and her comes my daughter just like every weekend - never a break.

It seems to jazz up my cortisol and keep me on an even keel with the cortisol and the mental focus is exactly what I need. When I am tired I cannot do this work with 3 Giant monitors and 50 research windows open. It is 9:30 PM and I been going since 6:30 AM.

All I am saying is it definately has not hurt my adrenals. Now White flood that shit was starting to give me headaches.

28

LH is what drives the conversion to 17-hydroxyprogesterone.

taking external T shuts down your LH production.

no LH = no or too little 17-hydroxyprogesterone.

HCG replaces the missing LH and helps boost 17-hydroxyprogesterone. I was taking 150iu of HCG, my 17-hydroxyprogesterone came back at below range. I upped my dosage and experienced an immediate response to my symptoms which seem to indicate increased cortisol production. a new blood test will confirm this week I hope.

some people can replace 100% of their cortisol by going through other pathways, but some(most?) have issues - the then lower cortisol is what I think drives the excess aromatase to estradiol issues we normally see + stressing thyroid function due to lack of sufficient cortisol.

I can’t find the bookmarked study I have showing the 1 for 1 connection, but I think came across it with a simple google search of 17-hydroxyprogesterone + hcg.

29

In females, ovulation of mature follicles on the ovary is induced by a large burst of LH secretion known as the preovulatory LH surge. Residual cells within ovulated follicles proliferate to form corpora lutea, which secrete the steroid hormones progesterone and …

I understand the above. But progesterone in males is created in the adrenals. Are you stating that this is controlled by LH receptors in the adrenals? If a male is severely secondary hypogonadism, then it would follow that progesterone levels would not support cortisol production, sort of fatal.

LH levels are low in childhood too. So children seem to manage to have a functional progesterone–>cortisol pathways.

“”“LH is what drives the conversion to 17-hydroxyprogesterone.”“”

Conversion of what to 17-hydroxyprogesterone?

30

[quote]KSman wrote:
“HCG also drives conversion of Progesterone to 17-hydroxyprogesterone one of the primary paths needed to create Cortisol.”

Is that improving things or making things worse. Your wording leaves that up in the air. What else creates the same ‘drives’? Only hCG?

And LH does not to any degree? Is ‘drives’ misleading? And what amounts of hCG are a problem if so?

HANS: We know the protocol for anastrozole dose and adjustment. Please post the protocols for aromasin and what the E2 targets are. Give us something useful.[/quote]

LH-like activity (provided by LH or hCG) upregulates CYP45011A1 (also known as P450scc (side-chain cleavage)) gene transcription in the adrenal cortex (this all takes place in the mitochondria). This is the step that cleaves the side-chain of the 27-carbon cholesterol to form a 21-carbon molecule, which is then converted to pregnenolone through other enzymes in the CYP family (all located in the adrenal cortex mitochondria). As a side note, presence of P450scc in the mitochondrial inner-membrane defines a cell as steroidogenic or not. ACTH also upregulates P450scc transcription, and slight upregulation can be induced through angiotensin II.

In short, suppressing LH-like activity can suppress steroid synthesis (especially glucocorticoids and mineralcorticoids) if ACTH isn’t subsequently upregulated and activity of STARD1 (a receptor that regulates transport of cholesterol to the inner mitochondrial membrane) exceeds that of P450scc (which only occurs under chronic stimulation). The latter case (chronic STARD1 stimulation) then makes P450scc the rate-limiting step in steroid synthesis.

Therefore, for some individuals (certainly not all; probably more limited to those under chronic stress (work, diet, etc.)) hCG may normalize low cortisol levels.

31

That is great, but still does not address how children manage proper cortisol with low LH levels, unless they have higher ATCH levels. I guess that upregulation does not mean that activity shuts off without LH.

I guess that my point is that children manage cortisol with little or no LH, then this effect can’t be huge.

Mitochondria do make pregnenolone, did not know about progesterone there. Perhaps the host cell donates P450scc to mitochondria. Seems odd that LH would alter gene expression rates in cellular nuclei and within mitochondria.

32

great questions, but this is normally where I bail out. There are just way too many rabbit holes that I could go down chasing endless questions.

I found a study that linked HCG to 17-hydroxyprogesterone and showed the HCG stimulates 17-hydroxyprogesterone which also correlates directly to intratesticular testosterone (freaking ouch… needle biopies were used to confirm those levels) and that 17-hydroxyprogesterone is a precursor of Cortisol.

I tested and found my 17-hydroxyprogesterone was low on 150iu HCG EOD. I increased my dosage back to 250iu and seem to be doing better. When I increase my HCG further, I seem to feel the results of increased Cortisol - was able to reduce my hydrocortisone during that test with no side effects - and then increased back up when I dropped my HCG back to 250iu EOD. I am hoping the upcoming blood test will show some correlation and support the readings of my symptoms.

why and how it all works is beyond me.

33

[quote]KSman wrote:
That is great, but still does not address how children manage proper cortisol with low LH levels, unless they have higher ATCH levels. I guess that upregulation does not mean that activity shuts off without LH.

I guess that my point is that children manage cortisol with little or no LH, then this effect can’t be huge.

Mitochondria do make pregnenolone, did not know about progesterone there. Perhaps the host cell donates P450scc to mitochondria. Seems odd that LH would alter gene expression rates in cellular nuclei and within mitochondria. [/quote]

Children are not under chronic stress and their ACTH levels are enough to support normal cortisol production. For those under chronic stress, ACTH (and angiotensin II) only regulation of P450scc may make it the rate limiting step in steroidogenesis, whereas STARD1 is normally the rate-limiting enzyme of steroidogenesis.

P450scc is not donated to the mitochondria. Mitochondria have their own DNA (mtDNA)and synthesize electron transport chain (ETC) complex enzymes and proteins, along with the Cytochrome P450 family of enzymes. These enzymes are inner mitochondrial transmembrane proteins.

The LHCG receptor (which LH and hCG interact with) are G-protein coupled receptors. They are found on the plasma membrane, and activation by LH/hCG induces signal transduction and activation of the cAMP pathway.

Many G-protein coupled receptors induce signals that have a greater effect on mitochondrial function (especially cleavage of cardiolipin acyl chains which leads to IP3 upregulation and induces Ca2+ influx (has many downstream effects, notably apoptosis when overstimulated)) than the nucleus (this is not odd, rather normal biology).

The mitochondria has a large role in many diseases and disorders, and is at the heart of many of these disorders (many of these are primary mitochondria dysfunction with secondary nuclear dysregulation (very notably Warburg’s theory of Cancer, epilepsy, PD, AD)).

34

Thank you everyone for the contributions. The flow of conversation in this thread has lead to interesting posts. It seems like everyone has had their important facts right. Rather than a heated argument, it’s a cordial debate about a question which science hasn’t answered yet. I’m not sure what that question, that people are debating, is, though.

Are you debating: is cortisol good, or is cortisol bad? Or, are you debating: does TRT lead to a deficiency of cortisol, and can hCG help produce more cortisol to fix that deficiency.

It could be that children have a different regulatory mechanism for cortisol. Assuming, hCG stimulates the production of cortisol (although I think it mostly regulated by the hypothalamus) then it could be that puberty changes the body’s sensitivity to cortisol releasing hormone. Cortisol can also be synthesized in the actual brain tissue, not just the adrenals or testis, because it’s a neurosteroid. Neurosteroids can be synthesized and utilized almost in the same way as neurotransmitters.

1198×898 74.3 KB

My question is: would someone with low-normal cortisol benefit from supplementing with cortisol? The benefits ‘high-normal’ testosterone are obvious. What would be the benefits of cortisol? I know PureChance is supplementing with cortisone. Why are you doing that, PureChance? He’s the first person I’ve heard of who does that, but maybe cortisol supplementation is popular with the crazy LEF people.

And my main question is this: is cortisol a neurosteroid? Would it have a subtle calming effect, countering the anxiety which can happen while on TRT. I’m not talking about an immediate change in mood, more like a subtle mood change similar to that of an antidepressant.

If exo testosterone is administered, it lowers the production of all sex hormones and prohormones, including some neurosteroids. It could be beneficial to supplement with some of the exotic sex steroids, such as pregnenolone, to counter some of the effects of TRT.

Neurosteroids are really interesting. I’d very much enjoy reading more posts about the topic, and it’s relevant to TRT.

35

there are tons of people taking hydrocortisone for short term boost to cortisol with the end goal to taper off and stop once (or if) all of your systems are able to pick up the slack. just not many on this forum. The STTM site has good information on it, and other sites talk about fixing cortisol and thyroid first before HRT.

I had Cortisol tests results of 5, 11, and 9 (ideal being 15-20 for an 8am draw). that plus high Reverse T3 and problems with excess aromotase of T to E2. Taking 22.5mg Hydrocortisone plus 40mg T3only medication has greatly helped me balance my system - I feel that it has helped lowered my E2, lowered my RT3, increased my energy - no sudden afternoon crashes, and has helped me focus. I am getting another blood test this week so I will be able to post an update soon.

36
37

[quote]PureChance wrote:
there are tons of people taking hydrocortisone for short term boost to cortisol with the end goal to taper off and stop once (or if) all of your systems are able to pick up the slack. just not many on this forum. The STTM site has good information on it, and other sites talk about fixing cortisol and thyroid first before HRT.

I had Cortisol tests results of 5, 11, and 9 (ideal being 15-20 for an 8am draw). that plus high Reverse T3 and problems with excess aromotase of T to E2. Taking 22.5mg Hydrocortisone plus 40mg T3only medication has greatly helped me balance my system - I feel that it has helped lowered my E2, lowered my RT3, increased my energy - no sudden afternoon crashes, and has helped me focus. I am getting another blood test this week so I will be able to post an update soon.[/quote]

PureChance I currently am paying for everything out of pocket (company went out of business) and from reading your posts you sure seem to have plenty of ongoing tests. That makes for easier customizing of HRT drug amounts.

You suggested going with 50mg per week of T.

Also would their be any difference in lessening of energy levels? Ability to lift weight going
to be about the same? Your posts are always insightful.

38

Yeah, having a pretty nice comprehensive medical coverage does help. I am seeing an out-of-network doctor and paying like $150 for phone consultantions (after my first in office visit to establish the dr/patient relationship). luckily, my insurance covers any blood tests he orders as long as I go an in-network lab (like Quest or LabCorp)

My wife is on IsoCort an OTC supplement (you can find it on Amazon) that has the equivelant of 2.5mg+/- hydrocortisone per pill. 240 pills for ~$25 I think. no prescription necessary.

the 50mg E3D is documented in the Injection Protocol sticky. Tons of advantages, supporting reason, etc.

how long it takes depends on your genetics, how strong or weakened your other systems are, if you are on the correct dose, etc.

I think most people start seeing improvements within a month. I am a fast metabolizer and notice everything within a week.

if you stabilize your testosterone levels you should maintain good energy levels, muscle gain, etc. if you are packing muscle on then you are probably on too much T. T shots aren’t a cure all. They should just return you to a baseline normal level. If you push your T above your personal genetic optimal point, then your system will react by trying to dump the excess T into E2 or DHT. also if your cortisol is not sufficient then your system will think you have excess T and will respond accordingly.