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

[xqfq]

I've been doing reading on water retention on TRT and I'd like to discuss a hypothetical I haven't seen floated: that the ratio of progesterone to estradiol could play a role.

This is a good post by Nelson: "Water Retention Caused by Testosterone May Have Nothing to Do with Estradiol". The theory of that post is that testosterone itself inhibits the enzyme 11b-HSD2, which then causes increased water retention. While I suspect this could play a role in some men's water retention on TRT, some guys experience water retention while having relatively low free testosterone levels. I've read reports of guys getting water retention with ~400 total T and E2 of 16.

Women experience bloating and water retention during their cycle, but only during the period when the ratio between progesterone and estrogen is at its lowest. Once progesterone rises relative to estrogen, water retention is shed. See this paper for some details: Sex Hormone Effects on Body Fluid Regulation

TRT without HCG reduces progesterone levels, and even with HCG progesterone levels may not be fully restored in all men.

The reference range for progesterone levels in men is 0.1 - 1.2 ng/mL, or 100-1200 pg/mL. The labcorp reference range for E2 LC/MS/MS is 8 - 35.0 pg/mL.

I don't have any answers here, but I do wonder if men with higher (free) estradiol numbers require higher progesterone levels to avoid water retention. If a man had undetectable progesterone levels but "in range" estradiol, I think it's plausible he could experience water retention simply because of that.

I would love to hear anyone's experiences with their progesterone levels in relation to water retention symptoms!

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Please note that the above graphic of a woman's cycle appears to be using two different units (E2 is plotted in pg/mL, progesterone is plotted in ng/mL). When units are adjusted to be the same, a women's progesterone is normally always greater than her estrogen.

 

[Cataceous]

...
The reference range for progesterone levels in men is 0.1 - 1.2 ng/dL, or 1 - 12 pg/mL. The labcorp reference range for E2 LC/MS/MS is 8 - 35.0 pg/mL.

Various articles do say that progesterone is important to balance against estradiol, so it seems plausible that neglecting low levels on TRT can lead to less-than-optimal results.

In the little experimenting I've done with progesterone I haven't thus far observed blatant effects on water retention. With undetectable estradiol I lost several pounds of water weight. Partially restoring estradiol allowed the weight to return, and concurrent progesterone supplementation has not seemed to block that.

One quibble: the units are ng/mL. So the reference range is 10-120 ng/dL or 100-1200 pg/mL,

 

[Nelson Vergel]

xpfq

Thanks for the thought-provoking post. A few guys here have used progesterone, so you may ask them if they experienced less water retention.

progesterone excelmale.com site:www.excelmale.com - Google Search


"Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone." Reference attached.

My gut feeling tells me that water retention on TRT, HCG or anabolic steroids has more to do with their effect on kidneys' sodium excretion.

Testosterone Increases: Sodium Reabsorption, Blood Pressure, and Renal Pathology in Female Spontaneously Hypertensive Rats on a High Sodium Diet

https://academic.oup.com/jcem/article/90/7/3989/2837248

 

[Nelson Vergel]

Another theory: testosterone increases 20-Hydroxyeicosatetraenoic Acid (HETE) in the kidneys, which leads to sodium retention, water retention, and increased blood pressure:

Testosterone-Induced Water Retention - How To Combat It

 

[xqfq]

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!

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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?

 

[DragonBits]

Various articles do say that progesterone is important to balance against estradiol, so it seems plausible that neglecting low levels on TRT can lead to less-than-optimal results.

In the little experimenting I've done with progesterone I haven't thus far observed blatant effects on water retention. With undetectable estradiol I lost several pounds of water weight. Partially restoring estradiol allowed the weight to return, and concurrent progesterone supplementation has not seemed to block that.

One quibble: the units are ng/mL. So the reference range is 10-120 ng/dL or 100-1200 pg/mL,

@xqfq

My labcorp reference range for progesterone was 0.0-0.5 ng/ml, so I am not sure where 0.1 - 1.2 ng/mL comes from?

I supplement with progesterone cream, i have never seen an effect on water or weight. It did seem to lower blood pressure a little, I feel like I sleep better and makes me more calm, but too much progesterone caused some dizziness and daytime drowsiness.

 

[xqfq]

@xqfq

My labcorp reference range for progesterone was 0.0-0.5 ng/ml, so I am not sure where 0.1 - 1.2 ng/mL comes from?

I supplement with progesterone cream, i have never seen an effect on water or weight. It did seem to lower blood pressure a little, I feel like I sleep better and makes me more calm, but too much progesterone caused some dizziness and daytime drowsiness.

That's great to hear about your experience! What kind of cream do you use and how much of it do you use? Did you measure your levels before and after?

I believe that Labcorp recently lowered their reference range (see New Labs - Progesterone high???). Dr. Saya says "Previously the range was 0.0 - 1.2 (or 1.5ng/mL depending on lab)."

RE: blood pressure, I believe blood pressure and fluid balance are connected. So if you noticed a drop in blood pressure, it's possible it's because of less sodium retention / less water retention, even if the water retention was imperceptible before. It's also possible progesterone lowers blood pressure in some other way, too - like maybe it 'relaxes' the blood vessels? I found this interesting article on blood pressure and progesterone from 2001: Weill Cornell Researcher Shows How Progesterone Is Not Just Sex Hormone but Blood Pressure Hormone - NewYork-Presbyterian

 

[Cataceous]

My labcorp reference range for progesterone was 0.0-0.5 ng/ml, so I am not sure where 0.1 - 1.2 ng/mL comes from?
...

The most recent reference range from NIH is 0.2-1.4 ng/mL, so pretty similar.

@xqfq — I never had good results with pregnenolone, but I do like direct progesterone supplementation. I attained pretty consistent results with nightly scrotal applications of progesterone in oil (~7 mg qd). There are a couple brands on Amazon. Currently including progesterone in injections (1 mg qd) for even better consistency. Possible positive effects: better mood, better sleep, better nocturnal erections.

 

[xqfq]

The most recent reference range from NIH is 0.2-1.4 ng/mL, so pretty similar.

@xqfq — I never had good results with pregnenolone, but I do like direct progesterone supplementation. I attained pretty consistent results with nightly scrotal applications of progesterone in oil (~7 mg qd). There are a couple brands on Amazon. Currently including progesterone in injections (1 mg qd) for even better consistency. Possible positive effects: better mood, better sleep, better nocturnal erections.

Thanks for the comment - this is very helpful!

I have some progesterone cream (purchased on Amazon), but I want to try out pregnenolone first because it seems more sustainable (pills are easier, especially with travel, etc) if it works for me. From reading studies on oral pregnenolone for depression and loneliness (!), high daily doses in the range of 200 - 500mg are used, which seems way higher than doses guys here have played with. Of course, these researchers are likely just trying to see if there's an effect so they may be mega-dosing..

Did your doctor prescribe the injectable progesterone?

 

[DragonBits]

That's great to hear about your experience! What kind of cream do you use and how much of it do you use? Did you measure your levels before and after?

I believe that Labcorp recently lowered their reference range (see New Labs - Progesterone high???). Dr. Saya says "Previously the range was 0.0 - 1.2 (or 1.5ng/mL depending on lab)."

RE: blood pressure, I believe blood pressure and fluid balance are connected. So if you noticed a drop in blood pressure, it's possible it's because of less sodium retention / less water retention, even if the water retention was imperceptible before. It's also possible progesterone lowers blood pressure in some other way, too - like maybe it 'relaxes' the blood vessels? I found this interesting article on blood pressure and progesterone from 2001: Weill Cornell Researcher Shows How Progesterone Is Not Just Sex Hormone but Blood Pressure Hormone - NewYork-Presbyterian

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.

 

[Cataceous]

...
Did your doctor prescribe the injectable progesterone?

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

 

[xqfq]

Hey everyone, I wanted to give a little update here.

As far as I can tell, increasing my progesterone seems to have eliminated my water retention[1].

I've been logging my water retention status in the AM and PM daily for the past several months. Here's my findings so far:

When I experimented with ~5mg - 10mg of progesterone cream applied to my deltoid, my water retention seemed to disappear. But I didn't use the cream for that long (just a couple days) so I can't say for sure it worked to remove the water retention. I found the cream very sedating; I almost felt too lazy to work -- I felt a bit like "The Dude" from the Big Lebowski!

Next, I tried oral pregnenolone, 60mg/day 3x day (180mg/day), spaced out: wake, afternoon, before bed. I used this brand (I'm not sure that it's 'micronized'). After a couple days on this I noticed my water retention disappear.

I "tested" this by attending outdoor concerts, consuming beer and alcohol, pizza, fries, burgers, etc. Nothing I ate or did could increase my water retention beyond what I remember having pre-TRT; if I felt a tad 'puffy' it was completely gone by morning[2].

I got my progesterone level tested yesterday: the pregnenolone raised it from 0.2 ng/mL to 1.3 ng/mL. I tested ~3 hours after taking my morning pregnenolone, so this may be my 'peak'.

Problems I see with using pregnenolone to raise progesterone as I'm doing:

• I have no idea what the half life of oral pregnenolone is. It seems to have a "sulfate" form, like how "DHEA" has "DHEA-S." But from what I read it's probably only around in the body for ~3-5 hours. Progesterone has a very short half life in the body from what I can tell. I'm fine with dosing 3x a day; I'd just like to know this stuff so I know how much my e.g. 'peak' differs from my 'trough' progesterone.
  
  
• Pregnenolone may also raise other upstream hormones, e.g. DHEA, which I may not need. Raising e.g. DHEA could raise E2, or raise ER-binding hormones like androstenediol; meaning I could require more progesterone than otherwise.
  
  
• It's possible that pregenolone itself may require LH activation (see the post by Nelson here) to convert to progesterone; or maybe for 'full conversion' LH activation is needed. I'd really like a solution that doesn't depend on my always having HCG on hand to function.

I will be lowering my pregnenolone to 30mg 3x a day (90mg/day) and seeing how I feel over the next two weeks and testing again. I may experiment again with direct progesterone usage if pregnenolone proves too unreliable. As Cataceous may have figured out above, injectable progesterone seems to be the best form for men who want to achieve lower, steady levels.

I've been doing a ton of research on progesterone; I'll write more here soon and write up an 'article' of my findings when I've ironed this out for myself. And I'll follow up with my status as I learn more!

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1. Some more personal background: When I started TRT in December of 2018 I didn't notice much of any water retention. I was dieting / losing weight at the time, and I believe it's just harder to have water retention in that circumstance. It wasn't until I started gaining weight (eating in a surplus) in mid-May that I started experiencing water retention. As noted, I could somewhat control my water retention issues by micro-managing my potassium / sodium intake and avoiding alcohol, but boy is that annoying! What use is feeling better with TRT if I can't leave the house and socialize?

I do not want to take an aromatase inhibitor if I can avoid it. I have a family history of cardiovascular disease and I want to do everything possible to minimize my risk. Many people I spoke to told me this was a problem with my estrogen level and that I should take an AI. As a note, my free testosterone levels were barely above the mid-point and I was already injecting EOD (and my SHBG is ~45 nmol/L), so reducing my dose likely wasn't going to work for me, either.

I initially tried stopping HCG to reduce my water retention; I had read stories of HCG increasing water retention either by E2 or some other mechanism. Instead, I noticed that when I stopped HCG it may have gotten even..worse?! Bizarre, right? As an additional note, I notice a profound mental effect with HCG when it works well - I feel like a fog lifts, I feel relaxed and my libido increases; it has a *profound* effect on me.

Without the HCG, I started to notice 'joint aches', I had serious trouble sleeping and I started feeling strong anxiety and irritability. Results: 664 ng/dL, FT ('direct') 12.6 pg/ml (8.7-25.1), E2 40.4 pg/mL LC/MS/MS, SHBG 45.8 nmol/L.

It was unbearable! So I added HCG back in. Those symptoms were all gone within a few hours of re-adding HCG (300IU EOD). My testosterone was low without the HCG, so maybe my symptoms were due to that. But I'm inclined to believe that the minor increase in progesterone from my HCG dose may have played a role in alleviating my issues. E.g. the HCG could have taken my progesterone from ~0 to 0.2 ng/mL or something.

While HCG fixed these issues, I still had some water retention. I also don't like the idea of requiring HCG to function; I can't always travel with it, the 'kick' it gives me seems to vary depending on how old the bottle is or on what phase the moon is in..I wanted a reliable solution to my problems, and that's why I started investigating progesterone.

2. Previously, if I e.g. went to a baseball game and had salty food and beer, my ankles would have a small amount of pitting edema (that only I would ever notice) by the end of the day. This never happened before TRT, and I'm an otherwise extremely healthy 35 year old. Honestly, most people wouldn't be bothered by it - it's minor, but I am not happy with increased water retention as I believe it plays a role in hypertension. I want to feel in control of my body.

 

[Nelson Vergel]

Hey everyone, I wanted to give a little update here.

As far as I can tell, increasing my progesterone seems to have eliminated my water retention[1].

I've been logging my water retention status in the AM and PM daily for the past several months. Here's my findings so far:

Wow...this is what I call a well-researched post. You've got me super curious now! Water retention is my number one problem. I am looking into my histamine response and issues related to sodium retention by the kidneys as part of my research.

Testosterone Caused Horrible Water Retention

I have searched a lot for studies that explain why water retention is so much more common in some men than others when starting testosterone replacement. I have only found one that was done in men with low pituitary output who were exposed to growth hormone alone, testosterone alone and GH+T combination. They speculate that either GH or testosterone may affect water balance (increasing water outside the cells or extracellular water) by an effect on kidney tubules.

Independent and Combined Effects of Testosterone and Growth Hormone on Extracellular Water in Hypopituitary Men

"Testosterone treatment alone did not change the IGF-I concentration, whereas cotreatment with GH induced a marked increase. Testosterone alone increased (P < 0.05) ECW (extracellular water), and the effect was augmented (P < 0.01) by cotreatment with GH. Although PRA and ANP did not change, plasma Aldo (aldosterone) decreased after single and combined treatments.

Conclusion: GH and testosterone exerted independent and additive effects on ECW. The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules. This is the first direct evidence that testosterone increases ECW."


I find that when I consume more carbs than I should, my water retention considerably goes up. Eating meats, eggs, dark green vegetables, nuts, etc and avoiding sweets, sodas, white bread/crackers, high salt consumption, alcohol and pasta also help me not hold water so much. Cardio also helps me lower water retention considerably.

I created this panel but I am yet to use it:

The Role of Aldosterone, ACTH, and Renin in Water Retention and High Blood Pressure

Another theory is that TRT can increase cortisol (and water retention): Water Retention Caused by Testosterone May Have Nothing to Do with Estradiol

 

[xqfq]

Wow...this is what I call a well-researched post. You've got me super curious now! Water retention is my number one problem. I am looking into my histamine response and issues related to sodium retention by the kidneys as part of my research.

Testosterone Caused Horrible Water Retention


I have searched a lot for studies that explain why water retention is so much more common in some men than others when starting testosterone replacement. I have only found one that was done in men with low pituitary output who were exposed to growth hormone alone, testosterone alone and GH+T combination. They speculate that either GH or testosterone may affect water balance (increasing water outside the cells or extracellular water) by an effect on kidney tubules.

Independent and Combined Effects of Testosterone and Growth Hormone on Extracellular Water in Hypopituitary Men


I have been reading a few bodybuilding sites that say that increasing water intake may help decrease water retention. Also, some bodybuilders use diuretics once in a while to decrease water retention.

I find that when I consume more carbs than I should, my water retention considerably goes up. Eating meats, eggs, dark green vegetables, nuts, etc and avoiding sweets, sodas, white bread/crackers, high salt consumption, alcohol and pasta also help me not hold water so much. Cardio also helps me lower water retention considerably.

Thanks Nelson! I hope to learn and share more here soon.

I was able to lessen my water retention previously by ensuring my potassium was 2-3x my sodium, but it felt limiting.

Here's a table of what I think various progesterone : e2 levels are for men and women:

I never measured my progesterone prior to TRT, but it certainly wasn't any less than it is now. So my progesterone : estrogen ratio pre-TRT was at least 10, though it was likely higher - maybe 20-30. On TRT, before my experiments, it was 4.9.

 

[Nelson Vergel]

So, you have no water retention now?

 

[xqfq]

So, you have no water retention now?

Yup, at least as far as I can tell. I've been logging AM and PM. My body weight hasn't changed much but I no longer have (very mild) edema in my lower ankles. My abs also look sharper, but it was the very mild peripheral edema that was the most obvious sign for me.

I think there may be multiple kinds of water retention in the body[1]. So it's possible that my increase in progesterone changed where the fluid goes in my body - perhaps away from the 'surface'.

I certainly hope it sticks and I'll be following up here as I learn more. Of course, the changes in my water retention could be unrelated to progesterone level, etc. But I will monitor and report back!

1. From this overview paper Sex Hormone Effects on Body Fluid Regulation

 

[Maca]

Yup, at least as far as I can tell. I've been logging AM and PM. My body weight hasn't changed much but I no longer have (very mild) edema in my lower ankles. My abs also look sharper, but it was the very mild peripheral edema that was the most obvious sign for me.

I think there may be multiple kinds of water retention in the body[1]. So it's possible that my increase in progesterone changed where the fluid goes in my body - perhaps away from the 'surface'.

I certainly hope it sticks and I'll be following up here as I learn more. Of course, the changes in my water retention could be unrelated to progesterone level, etc. But I will monitor and report back!

1. From this overview paper Sex Hormone Effects on Body Fluid Regulation

Hey xqfq, I'm currently got low progesterone as well and trying to decide what protocol to do to get it up. I've ordered some progesterone cream as well as some pregnenolone 10mg capsules. I'm on HCG but it causes a lot of estrogen issues with gyno and I'm taking a lot of Aromasin to control it. I think this is due to estrogen dominance and will be easier once I get my progesterone levels up.

What did you find worked out best for you?

 

[Nelson Vergel]

@Maca water retention is not due to high estradiol. Have you measured your estradiol.

Testosterone and all androgens disrupt the way kidneys process sodium. Please read the above posts.

 

[apples4oranges]

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.

 

[Nelson Vergel]

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.

Have you tried a Keto diet?

You will lose water weight fast.

Keto Diet General "How-to"

I don't know much about this web site, but I found the article regarding the Keto Diet interesting. I know it is popular right now. The keto diet, explained

www.excelmale.com