Could the ratio of progesterone to estradiol affect water retention in men on TRT?

[xqfq]

Anymore updates on this? I get massive water retention from hcg. I want to try swapping out hcg for pregnenolone or progesterone to combat water retention.

I will post some long, detailed updates once COVID-19 has settled in March/April (my estimate). I have been consumed with COVID-19 research.

I believe that, as Nelson says, androgens themselves lead to water retention. Make sure you know your true free T - get one of the high-quality free testosterone tests if you are struggling with this.

 

[JoeMatts]

Supplemental progesterone makes my trt-induced water retention immediately melt away.

For those unaware, Ray Peat has done an enormous amount of work on the interaction between estrogen and progesterone, and his model explains exactly why a disturbed balance in-favour of estrogen would result in the swelling of cells (retaining water), but also why an aromatase inhibitor would not fix it.

For anyone interested, here are some of his articles on the topic:

Aging, estrogen, and progesterone.
Estrogen, progesterone, and cancer: Conflicts of interest in regulation and product promotion.
Tissue-bound estrogen in aging.

TL;DR:

Estrogen's role in endogenous physiology is to directly downregulate the metabolic rate of a cell by interphereing with efficient oxidative metabolism during times of stress, tissue damage and energetic deficiency, to facilitate the rapid growth, repair and division of a tissue. Whilst said functions play an important role under specific circumstances (i.e, tissue injury), unopposed estrogen keeps the metabolic rate of the cell chronically suppressed, with water retention being one of the manifestations, as the ability of the cell to extrude it's water (regulated largely by the flux of sodium, potassium, calcium, chloride and magnesium) is an energetically-demanding process.

Progesterone is the bodies primary anti-estrogenic substance, having the opposite effect on the metabolic rate by promoting the efficient oxidative metabolism required to keep it elevated.

Testosterone replacement therapy appears to reduce progesterone production beyond just the loss of gonadal production, as many men find themselves with undetectable serum levels after years of therapy — even with the use of HCG. The decrease in progesterone production combined with the significant increase in systemic estrogen from the abundance of it's precursor testosterone can lead to a progesterone : estrogen ratio skewed heavily towards the latter.

AIs don't help because 1.) they do nothing to address the suppression of progesterone production, so even a significant reduction in estrogen would still leave the p:e ratio itself suboptimal, and 2.) as mentioned at the top of the post, aromatase expression, and subsequently the rate of estrogen production, is increased in response to cellular stress and energetic deficiency — neither of which are addressed by an ai. In many cases, the underlying state which leads to one being prone to aromatization is more problematic than the estrogen itself, which is why elevated levels of baseline estrogen in men not on trt are associated with a cohort of undesirable diseases, but reducing estrogen artificially with an aromatase inhibitor in men on trt has few benefits, and may actually cause harm (won't get into the ai vs no ai debate here).

This is a vast, vast simplification of the content discussed in Ray Peat's articles, so please read the articles directly if you're interested in this topic.

Something to note: Ray Peat has a rather poor reputation, but that is primary off the back of other's interpretation of his work - i.e, the people on the independently-run ray peat forum who do very strange things based upon their misinterpretation of his writings - rather than what the man actually writes. Read his information directly from the source and you'll find there is a lot of incredible knowledge to be gained.

Theoretically, the combination of thyroid (the optimal dose being that required to restore body temperature to optimal) and low-dose progesterone (pregnenolone may be able to fill the role) should be able to eliminate all trt-induced water-retention, but the empahsis there is on theoretically.

Just to be clear: I am not saying all of the above is factually correct, nor am I supporting the use of thyroid or progesterone. All I can say is that my own experience with HRT and overall health has always fallen in line with all of Ray Peat's articles, and many (but not all) of his views are supported by medical literature..

 

[JoeMatts]

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[JoeMatts]

Some more information I've come across from Dr Raymond Peat on the influence of progesterone and estrogen on water retention - from his book, 'From PMS to Menopause':

"In animal experiments, I knew that estrogen causes cells to take up water within a few minutes after it reaches the tissue, and that this is at least partly the result of its interfering with the availability of oxygen. Within 40 minutes of administering a large dose of estrogen, the lungs become extremely inefficient at oxygenating the blood. This involves a sudden thickening of the alveolar membranes and the walls of capillaries, simply by taking up water. So, when I saw bulging veins disappear a few minutes after women took progesterone, along with a sudden lifting of extreme depression, I guessed that their circulation had become more efficient, and that better oxygenation had changed their mood."

"Then, I repeatedly saw physical changes in other people that were visible within an hour, and that involved a sudden movement of water out of edematous tissues. In many people with damaged joint cartilage (confirmed by various types of examination, including arthroscopy), the joints became mobile in an hour, and by the next day, the defect no longer existed. A man who was purple from emphysema changed color within a few hours, and within a few days was going to work. The bulging eyes of exophthalmic Graves' disease receded into their sockets noticeably within an hour, and were normal the next day. Simply improving the circulation couldn't have done those things. Opposing estrogen's edema-promoting action was involved, but I couldn't imagine any mechanism that could 103 explain such rapid movement of water from the swollen tissue into the blood stream."

"One of estrogen's effects is to lower the amount of albumin in the blood. Estrogen causes the liver to synthesize less albumin, partly by causing the messenger RNA to be destabilized and degraded. (Iron can have some similar effects on liver RNA.) When there isn't enough albumin in the blood, water moves from the blood into the tissues. Albumin binds oily substances, and its conformation seems to be opened when it binds them. Progesterone is known to adsorb strongly to proteins- -it has been called a "cardinal adsorbant," meaning that it can bind in ways that cause the protein's adsorptive capacity to change. I believe that progesterone and pregnenolone oppose estrogen in many ways, but the amazing speed with which they can cause major structural changes in the soft tissues convinces me that one of their first sites of action is the albumin molecule, causing its conformation to open in such a way that it is able to more strongly bind water molecules. This physical change in albumin would change the blood's osmotic/oncotic pressure, causing water to flow into capillaries. As the edema is reduced, oxygenation is more efficient, because the pathway for oxygen diffusion becomes shorter."

"Albumin has been described as a first line of defense against toxins, since it binds them until the liver is able to degrade them chemically. Progesterone, pregnenolone, and cholesterol are known to increase the organism's resistance to a great variety of toxins. (Selye coined the name "catatoxic steroids" to describe steroids of this type.) If these steroids bind to albumin in a way that opens the protein to increase its binding capacity, that single process could explain the "catatoxic" effect, as well as the anti-edema effect."

"When the blood is unable to retain its normal amount of water because of insufficient albumin/sodium, the blood volume is reduced as the tissues become water-logged. This causes the hematocrit (the proportion of cells in a volume of blood) to rise, and this increased packing of red blood cells causes the blood to become more viscous. (Knisely studied this phenomenon in a great variety of sickness.) Increased viscosity and slower flow decreases the bloods ability to deliver oxygen and nutrients to the tissues, including the blood vessel walls, modifying their tone. Slower flow, even without any changes in the fibrin-fibrinogen system itself, increases the formation of clots. This description of progesterone's immediate action is intended to take some of the mystery out of its dramatic effects, but it isn't intended 104 to argue against any of its actions within cells. It serves to give a general picture of how progesterone can systematically reduce stress and its harmful consequences, just by making blood circulation more efficient"

 

[Nocalves]

No, I just picked some up from AllDayChemist. You get a package of 200 mg ampules, which will last me years.
Blood test results, all with LabCorp and the 0.0-0.5 ng/mL reference range:
Baseline: 0.1
7 mg scrotal: 0.3
3 mg subQ: 1.2
1 mg subQ: 0.5

In which level do you feel the best?

 

[JA Battle]

In which level do you feel the best?

@Cataceous im interested to know of the 7mg topical solution used? What was the solution comprised of besides the progesterone? Alcohol based or oil based? I’m assuming it was 2 drops of progest e based on the 7mg.

 

[Gman86]

This is such an interesting thread! I’ve never seen it until today. Would love to see this thread revived. Progesterone seems be an extremely overlooked hormone, in regards to male hormone optimization, and may be one of those “missing key” hormones for a lot of men trying to get dialed in. I just started injecting 1mg of prog every night again a few days ago. I tried using preg to raise my prog levels, but just didn’t feel that great using it. So decided to go back to straight prog supplementation

Most men on straight test, without HCG and/ or preg supplementation will tend to have bottom of the barrel prog levels. As we know, all hormones need to be in balance. Having any hormone too high or too low is not good and will usually cause issues. Hell even prolactin can cause issues in men when too low. So it just doesn’t make sense for most men on TRT to have very low progesterone levels and doctors not care/ address it.

 

[Cataceous]

In which level do you feel the best?

I wasn't at the higher serum levels long enough to say if things would be much different there. I titrated fairly soon to the midrange levels.

@Cataceous im interested to know of the 7mg topical solution used? What was the solution comprised of besides the progesterone? Alcohol based or oil based? I’m assuming it was 2 drops of progest e based on the 7mg.

I was using the Progestelle product, which is simply progesterone in coconut oil.

 

[JA Battle]

I wasn't at the higher serum levels long enough to say if things would be much different there. I titrated fairly soon to the midrange levels.


I was using the Progestelle product, which is simply progesterone in coconut oil.

We’re those numbers at 24 hour trough?

 

[Cataceous]

We’re those numbers at 24 hour trough?

No, these are about 9-10 hours post dose

 

[WhatSayYou89]

Some more information I've come across from Dr Raymond Peat on the influence of progesterone and estrogen on water retention - from his book, 'From PMS to Menopause':

"In animal experiments, I knew that estrogen causes cells to take up water within a few minutes after it reaches the tissue, and that this is at least partly the result of its interfering with the availability of oxygen. Within 40 minutes of administering a large dose of estrogen, the lungs become extremely inefficient at oxygenating the blood. This involves a sudden thickening of the alveolar membranes and the walls of capillaries, simply by taking up water. So, when I saw bulging veins disappear a few minutes after women took progesterone, along with a sudden lifting of extreme depression, I guessed that their circulation had become more efficient, and that better oxygenation had changed their mood."

"Then, I repeatedly saw physical changes in other people that were visible within an hour, and that involved a sudden movement of water out of edematous tissues. In many people with damaged joint cartilage (confirmed by various types of examination, including arthroscopy), the joints became mobile in an hour, and by the next day, the defect no longer existed. A man who was purple from emphysema changed color within a few hours, and within a few days was going to work. The bulging eyes of exophthalmic Graves' disease receded into their sockets noticeably within an hour, and were normal the next day. Simply improving the circulation couldn't have done those things. Opposing estrogen's edema-promoting action was involved, but I couldn't imagine any mechanism that could 103 explain such rapid movement of water from the swollen tissue into the blood stream."

"One of estrogen's effects is to lower the amount of albumin in the blood. Estrogen causes the liver to synthesize less albumin, partly by causing the messenger RNA to be destabilized and degraded. (Iron can have some similar effects on liver RNA.) When there isn't enough albumin in the blood, water moves from the blood into the tissues. Albumin binds oily substances, and its conformation seems to be opened when it binds them. Progesterone is known to adsorb strongly to proteins- -it has been called a "cardinal adsorbant," meaning that it can bind in ways that cause the protein's adsorptive capacity to change. I believe that progesterone and pregnenolone oppose estrogen in many ways, but the amazing speed with which they can cause major structural changes in the soft tissues convinces me that one of their first sites of action is the albumin molecule, causing its conformation to open in such a way that it is able to more strongly bind water molecules. This physical change in albumin would change the blood's osmotic/oncotic pressure, causing water to flow into capillaries. As the edema is reduced, oxygenation is more efficient, because the pathway for oxygen diffusion becomes shorter."

"Albumin has been described as a first line of defense against toxins, since it binds them until the liver is able to degrade them chemically. Progesterone, pregnenolone, and cholesterol are known to increase the organism's resistance to a great variety of toxins. (Selye coined the name "catatoxic steroids" to describe steroids of this type.) If these steroids bind to albumin in a way that opens the protein to increase its binding capacity, that single process could explain the "catatoxic" effect, as well as the anti-edema effect."

"When the blood is unable to retain its normal amount of water because of insufficient albumin/sodium, the blood volume is reduced as the tissues become water-logged. This causes the hematocrit (the proportion of cells in a volume of blood) to rise, and this increased packing of red blood cells causes the blood to become more viscous. (Knisely studied this phenomenon in a great variety of sickness.) Increased viscosity and slower flow decreases the bloods ability to deliver oxygen and nutrients to the tissues, including the blood vessel walls, modifying their tone. Slower flow, even without any changes in the fibrin-fibrinogen system itself, increases the formation of clots. This description of progesterone's immediate action is intended to take some of the mystery out of its dramatic effects, but it isn't intended 104 to argue against any of its actions within cells. It serves to give a general picture of how progesterone can systematically reduce stress and its harmful consequences, just by making blood circulation more efficient"

I’ve done a lot of reading on that forum as well in regards to pregnelone and progesterone.

The progesterone I take is otc and applied to the scrotum. I noticed very quickly after taking 1 click (which says 20mg) a libido boost then goes down hill quick.

Hands get tight and low e2 type of feeling. If I apply anymore, immediately or the next day then I don’t get that initial libido surge.

Something I’m curious about is I’ve read that the intake method can also be what causes different levels to rise. For example, scrotum absorption of testosterone cream increases DHT more than if the cream was applied in other areas. Also, injectable testosterone has been reported to have lower DHT conversion than that of testosterone cream.

This sort of feels like the same DHT bump that I got from testosterone cream.

What I find interesting about this is I’ve taken DHT based injectables and don’t notice any libido boost. But with stuff like test cream the conversation into DHT is where the libido boost happens imo.

So I’m starting to think it’s the overall conversion into the hormones is more important than anything.

 

[Omi7276]

Ok

I've been experiencing some water retention and I'm trying to see if I can solve it[1]. My E2 LC/MS/MS was 40.4 pg/mL without HCG, and I've since re-added 300IU HCG EOD.

I had my progesterone tested yesterday, and it was 0.2 ng/mL, or 200 pg/mL. So my progesterone is at the very low end of the male reference range, but my E2 is at the very top end of the male reference range.

So I'm now going to try and raise my progesterone levels. I've read some reports here that guys can raise their progesterone by taking pregnenolone, so I've begun taking 50mg of pregnenolone orally as of today.[2]

I'd like to avoid using a progesterone cream if possible, as I believe it may be inconsistent, especially since the "pump" dosage is designed for women.

I'll be posting updates as I learn more!

---

1. I can usually control this water retention with diet (eating with a potassium: sodium ratio of 2-3 : 1), but when eating out or socializing, it flares up.

I'm not on an AI and my current protocol is 44 mg EOD subQ test-e (154mg / week), 300 IU HCG EOD subQ. I was experiencing water retention even without HCG, on 144mg / week test-e, which had my Total T at 664 ng/dL, Free T "direct" 12.6 pg/mL (Range: 8.7-25.1), E2 LC/MS/MS 40.4 pg/mL (Ref: 8 - 35.0), SHBG 45.3 nmol/L. With the 300IU EOD of HCG, my TT is 860 ng/dL and Free T "direct" is 22.8 pg/mL.

2. I wasn't able to find out any information about the "effective" half life of pregnenolone. From reading around, most guys tend to take a single oral dose each day. Pregnenolone appears to have a "sulfate" form, similar to DHEA / DHEA-S, so I'm hoping the "sulfate" form of pregnenolone allows it to be taken once per day.

From my reading, progesterone has poor oral bioavailability as well as a very short half life. This Wikipedia article is really good and detailed: Pharmacodynamics of progesterone - Wikipedia. Most guys who supplement with progesterone seem to use a cream, from what I can tell from reading here and elsewhere?

I am using source natural progesterone cream, 22mg per 1.3 grams 1/4 teaspoon. I am using even less than 1/4 teaspoon, maybe .2 of a teaspoon. Just rub some on my shoulder. Literately a little less than a "tad" which is the name of a spoon I have. A tad isn't any sort of exact measurement.

My progesterone level measured 0.5 but I only took the blood test after using the cream so I don't what my level was before.

If I use too much, then I can get dizzy during the day, it's kind of an odd experience, a little like drinking too much or being high. Especially when I sit for a while then get up. I assume it was the progesterone, as afterwards I read that is a typical symptom.

progesterone can change stress response, cortisol at baseline, sleep, blood pressure,
,GABA receptors, but I am not sure all of what it affects and how it works.

Nearly always when my blood pressure is measured at a doctors office, it will be higher, like 130/82. but this time on two difference visits it measured 117/75, which never happened before.

I don't take it every day, as I am just experimenting with how much, too much also seems to leave me more lazy.

I am mainly interested in better sleep. Not sure how long before sleep to apply it, not sure how long it lasts, like half life. Lower blood pressure is nice, but mine was not very high even without it.

Any idea how much progesterone is raised by dosing 50 mg pregnenolone?

 

[FunkOdyssey]

Interesting thread with the anecdotes of reduced water retention with progesterone supplementation. Anyone have any updated experiences with this? Might be a healthier answer to bloating and excess water than using an AI.