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    • Water Retention Caused by Testosterone May Have Nothing to Do with Estradiol


      I get a lot of emails from men on testosterone replacement therapy (and/or HCG) that feel they have water retention (some with ankle swelling) and they are puzzled that their estradiol is low or below 35 micrograms/ml. They may have tried anastrozole treatment without any success in decreasing water retention.

      This study was pointed out by a previous article written by Patrick Arnold.

      "There is an enzyme that is localized primarily in the kidneys whose function is to protect the kidneys from circulating cortisol. The kidneys have receptors called mineralcorticoid receptors (MRs) which are meant to bind to specific adrenal hormones (called mineralcorticoids) in the body such as aldosterone. The result of this binding is a signal to increase sodium and water retention in the body, while stimulating the excretion of potassium. This is an important mechanism to maintain fluid and electrolyte balance in the body.
      A problem exists though in that cortisol can also bind activate these receptors. Cortisol is a widely circulating hormone and serves a multitude of functions throughout the body. However its intended biological functions do not include mineralcorticoid action in the kidneys, so to prevent this from happening the kidneys are rich in the enzyme 11b-hydroxysteroid dehydrogenase 2 (11b-HSD2). This enzyme deactivates cortisol by converting it into cortisone before it can bind to the renal MRs."


      Testosterone and anabolic steroids have been shown to inhibit 11b-HSD2.

      Heres how it works: throughout the course of the day, the adrenal gland releases the hormone cortisol, either due to normal circadian (daily) and ultradian (hourly) rhythms, or in reaction to stress. Cortisol is an important stress hormone, but many of its effects, while good in a fight-or-flight scenario, are bad over time in terms of diabetes and obesity: cortisol increases glucose production and release in the liver; increases appetite in anticipation of any necessary reaction to the stress-causing situation; and alters metabolic processing such that fat is preferentially stored in the central abdominal region. So, for diabetics, this means stored glucose directly increases blood sugar, new calories are ingested and increase both blood sugar and weight, and, to top it all off, the new weight tends to be the bad, visceral, disease-causing weight.

      There are a couple of therapeutically important pit-stops for cortisol throughout this process, though; the active hormone cortisol can be converted in the kidney, colon, and some other tissues into the inactive molecule cortisone. The enzyme 11β-HSD2 aids this conversion, and allows cortisol to be stored out of the bloodstream.


      Inhibiting 11b-HSD 2 can cause glucocorticoid-mediated MR activation, potassium excretion, sodium and water retention, and increased blood pressure.





      Full Paper: http://toxsci.oxfordjournals.org/content/126/2/353.long

      This article was originally published in forum thread: Water Retention Caused by Testosterone May Have Nothing to Do with Estradiol
      Comments 20 Comments
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        I will be trying this drug soon to see the effect on mild water retention, bloating and BP increase that sometimes I get on HCG + TRT. Eplerenone is a selective aldosterone blocker (SAB) approved for the treatment of essential hypertension. It works like Spironolactone but without the testosterone lowering effects.

        Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction


        "
        Eplerenone is a next-generation mineralocorticoid antagonist. Like spironolactone it acts as a diuretic and helps to prevent mineralocorticoid-induced cardiovascular damage and reduces high blood pressure. Like spironolactone, eplerenone can cause a dangerous build-up of potassium in the blood (called hyperkalemia) so extreme care must be taken when using these drugs. Unlike spironolactone, eplerenone has no antagonist activity at the androgen receptor so it is unlikely to cause gynecomastia. Eplerenone is virtually unknown in the steroid using public because it is very new and is not available in generic form. Epleronone has distinct advantages over spironolactone but like other brand name only medications, is much more expensive than the readily available generic versions of spironolactone. The inhibition of 11-beta hydroxylase by certain AAS results in elevated levels of deoxycorticosterone in the blood. Deoxycorticosterone is a mineralocorticoid and will result in sodium and water retention, high blood pressure and adverse cardiovascular effects. Employing a mineralocorticoid antagonist could, theoretically, reduce these side effects of those AAS that inhibit 11-beta hydroxylase. The largest concern in doing so would be the potential for hyperkalemia with the use of antimineralocorticoids since some AAS have been reported to cause potassium retention as well."

        http://mindandmuscle.net/articles/eplerenone/



        Note: High potassium can happen in men with low kidney function.
      1. magnus68's Avatar
        magnus68 -
        whats wrong with plain old lasix?
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        Great question!!

        Lasix (furosemide ) increases insulin resistance and blood glucose. Insulin resistance has been associated with fat and lipid increases. Lasix can also decrease potassium and magnesium.


        http://www.sciencedirect.com/science...14299988901756


        Eplerenone does not cause insulin resistance. The only problem is for those with eGFR (kidney function) under 30. They can have increases in potassium.


        http://www.ahjonline.com/article/S00...659-9/abstract
      1. Mike Lauer's Avatar
        Mike Lauer -
        Nelson- I'd be interested in the update once you start. Is this a research Chemical, or a prescribed compound?
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        It's a prescribed product (Generic. Approved in 2002)

        https://en.wikipedia.org/wiki/Eplerenone


        Price:

        http://www.goodrx.com/eplerenone?drug-name=eplerenone
      1. Tommy Wall's Avatar
        Tommy Wall -
        Nelson do you think Eplerenone and Losartan could be a good combo?
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        Quote Originally Posted by Tommy Wall View Post
        Nelson do you think Eplerenone and Losartan could be a good combo?
        I would try Eplerenone alone first starting at 25 mg and then 50 mg and see what BP effects you have. I would not combine them right away.

        I will start it on Friday (it is on back order at my pharmacy)

        I found no combination studies. Here is one comparing the two drugs:

        Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients.
      1. Tommy Wall's Avatar
        Tommy Wall -
        OK pls let us know how it goes.
      1. BryanCooke's Avatar
        BryanCooke -
        Great post shared..
      1. Tommy Wall's Avatar
        Tommy Wall -
        Nelson how are you doing with Eplerenone?
      1. Chivato's Avatar
        Chivato -
        Quote Originally Posted by Nelson Vergel View Post
        I will be trying this drug soon to see the effect on mild water retention, bloating and BP increase that sometimes I get on HCG + TRT. Eplerenone is a selective aldosterone blocker (SAB) approved for the treatment of essential hypertension. It works like Spironolactone but without the testosterone lowering effects.

        Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction


        "
        Eplerenone is a next-generation mineralocorticoid antagonist. Like spironolactone it acts as a diuretic and helps to prevent mineralocorticoid-induced cardiovascular damage and reduces high blood pressure. Like spironolactone, eplerenone can cause a dangerous build-up of potassium in the blood (called hyperkalemia) so extreme care must be taken when using these drugs. Unlike spironolactone, eplerenone has no antagonist activity at the androgen receptor so it is unlikely to cause gynecomastia. Eplerenone is virtually unknown in the steroid using public because it is very new and is not available in generic form. Epleronone has distinct advantages over spironolactone but like other brand name only medications, is much more expensive than the readily available generic versions of spironolactone. The inhibition of 11-beta hydroxylase by certain AAS results in elevated levels of deoxycorticosterone in the blood. Deoxycorticosterone is a mineralocorticoid and will result in sodium and water retention, high blood pressure and adverse cardiovascular effects. Employing a mineralocorticoid antagonist could, theoretically, reduce these side effects of those AAS that inhibit 11-beta hydroxylase. The largest concern in doing so would be the potential for hyperkalemia with the use of antimineralocorticoids since some AAS have been reported to cause potassium retention as well."

        http://mindandmuscle.net/articles/eplerenone/



        Note: High potassium can happen in men with low kidney function.
        Nelson, I have been on Eplerenone for over a year now, starting at 25mg and now at the maximum dosage of 100mg for control of my blood pressure. For me it has had no side effects and has not increased my potassium beyond the normal range.
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        Yes, I have been taking it also without side effects or loss of sex drive/orgasmic quality
      1. meelord's Avatar
        meelord -
        Quote Originally Posted by Nelson Vergel View Post
        Yes, I have been taking it also without side effects or loss of sex drive/orgasmic quality
        Are you still taking this Nelson. Is it something I could ask my cardiologist for?
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        Yes, I am. No side effects after over 3 months.
      1. UserNameGoesHere's Avatar
        UserNameGoesHere -
        Quote Originally Posted by Nelson Vergel View Post
        Yes, I am. No side effects after over 3 months.
        Hey Nelson,

        So you're on Eplerenone now? How is it handling water retention on hcg? I had to stop due to the 10+ lbs of water weight I add after about 2 weeks. I'm tired of my boys shrinking so looking for something that will help.

        Thank you!
        JJ
      1. fitnessguy's Avatar
        fitnessguy -
        Quote Originally Posted by Nelson Vergel View Post
        Yes, I am. No side effects after over 3 months.
        Hey Nelson, what is your dosage of Eplerenone, and is it ED or what?
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        I no longer take eplerenone. For some strange reason, my bloating decreased dramatically when I started taking Metformin 500 mg twice per day.

        My reduced bloat may be due to these benefits found with the use of Metformin:

        Metformin may work by changing gut bacteria makeup

        Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

        I still take losartan once daily for blood pressure.
      1. fitnessguy's Avatar
        fitnessguy -
        Oh wow, well good to know. Are you a diabetic Nelson or pre-diabetic? Do you just take this for the bloat? Any other positive benefits you have seen from taking it?
      1. Nelson Vergel's Avatar
        Nelson Vergel -
        No, my glucose has always been good. I took it because of these benefits:

      1. Bevaro's Avatar
        Bevaro -
        I remember patrick arnold used to say it had to do with cortisol