Nelson Vergel
Founder, ExcelMale.com
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 in 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 (MR's) 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.
Here's 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 11 beta-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: Anabolic Androgenic Steroid Fluoxymesterone Inhibits 11β-Hydroxysteroid Dehydrogenase 2–Dependent Glucocorticoid Inactivation
Another reason: sodium retention
Why can testosterone increase water retention?
www.excelmale.com
Swelling is one of TRT's most troublesome and hard to manage side effects. It occurs (in my estimate) to about 20 percent of users. The potential causes could be cortisol build up, increase sodium retention, in rare cases high estradiol, or cardiovascular issues. I am enclosing several posts on these issues.
Most cases of lower extremity (peripheral) edema has nothing to do with estradiol and a lot to do with cardiovascular issues. My number one suggestion if edema does not get better after a month on TRT is to get a full cardio work up by a cardiologist.
Some men report decreased edema after a short cycle of a diuretic like HTZ, so that is something to explore. Low sodium intake and plenty of water plus cardio may also help. Cardio exercise and sweating in a sauna have also been reported to help. But these are speculations that should not replace a good cardiovascular work up.
Pulmonary hypertension caused by sleep apnea has also been reported as a cause.
Obstructive Sleep Apnea Associated with Leg Edema
"A common but under-recognized cause of edema is pulmonary hypertension, which is often associated with sleep apnea. Venous insufficiency is treated with leg elevation, compressive stockings, and sometimes diuretics. The initial treatment of idiopathic edema is spironolactone. Patients who have findings consistent with sleep apnea, such as daytime somnolence, load snoring, or neck circumference >17 inches, should be evaluated for pulmonary hypertension with an echocardiogram."
edema[swelling] what is the cause
Ankle swelling after starting testosterone injections
Here are excerpts from another interesting paper that links testosterone related water retention to sodium retention:
"This is the first controlled study demonstrating that testosterone increases extracellular water ECW. Previous data concerning the effects of testosterone on plasma volume (19, 20) and urinary sodium excretion (18, 21) are limited and conflicting. The underlying mechanism is unknown, but several possibilities exist. Testosterone could act directly on the kidney, because androgen receptors are expressed in renal tubules (31). There is evidence that androgens stimulate the expression of the angiotensinogen gene in the kidney (32, 33). Therefore, androgens could activate the local renal RAASto stimulate sodium and water retention through an autocrine or paracrine mechanism (34). The epithelial sodium channel plays an important role in the sodium balance, as demonstrated by genetic abnormalities in its activity, such as in Liddle's syndrome (35). It has recently been reported that androgens increase mRNA expression of the α-subunit of the epithelial sodium channel in a human renal cell line (36), providing a potential mechanism of sodium and water retention by testosterone.
Plasma aldosterone Aldo levels fell significantly during testosterone treatment, whereas a modest fall, which failed to reach significance, occurred during GH treatment. During combined treatments, a significant fall in Aldo was also observed. The uniform trend toward a fall in Aldo levels observed with single and combined treatments suggests an adaptive response to ECW expansion. The observation that the fall in Aldo was greater in the presence of testosterone suggests that additional androgen-mediated mechanisms are probably involved. Androgen receptors have been identified in human adrenocortical cells and appear to exert an inhibitory influence. In vitro studies have demonstrated that testosterone reduced the proliferation of human adrenal adenoma and adrenocortical cancer cell lines (38). It is possible that testosterone directly suppresses Aldo biosynthesis or secretion, but this remains to be demonstrated.
More on aldosterone
The effects of testosterone on the volume and distribution of ECW could theoretically occur secondary to aromatization to estrogen in peripheral tissues. Estrogen may cause fluid retention through reduction of the plasma antidiuretic hormone (arginine vasopressin)-plasma osmolality set point (39, 40) or stimulating the synthesis of hepatic angiotensinogen (41), enhancing the overall activity of RAAS and leading to sodium retention. However, this postulate is not supported by the observation that urinary sodium excretion is increased during oral contraceptive use (42) or that the plasma renin concentration is reduced in women receiving estrogen treatment (43). Moreover, estrogen reduces the plasma renin concentration, the activity of angiotensin-converting enzyme, and the Aldo response to angiotensin II (44, 45). These actions of estrogen putatively generated from aromatization of androgens could explain the slight reduction in plasma Aldo levels in response to testosterone in our study." Source
I notice that I hold more water when I eat higher sodium foods, drink alcohol, and skip the gym for more than 3 days. Higher simple carb intake also worsens water retention. I weigh myself every morning. If I am not careful, I can gain 3-4 pounds of water in 1 or 2 days. Not drinking enough water also makes the body retain water. My kidney function (eGFR) is good (80).
I think decreasing sodium and sweets intake, increasing water consumption, and doing some cardio are ways to control water weight. If it gets bad, the use of a diuretic only once can stabilize this issue during days where I go off the wagon at my family's parties.
Water retention causes increase blood pressure which is treated with weight loss or medications.
What high blood pressure meds are the most erection friendly?
This study was pointed out in 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 (MR's) 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.
Here's 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 11 beta-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: Anabolic Androgenic Steroid Fluoxymesterone Inhibits 11β-Hydroxysteroid Dehydrogenase 2–Dependent Glucocorticoid Inactivation
Another reason: sodium retention
Why can testosterone increase water retention?
Testosterone increases water retention in hypogonadal men by affecting kidneys
The effects of growth hormone (GH) on sodium retention and extracellular fluid (ECF) are well established. The mechanisms are not clear but are thought to involve the GH/IGF-I (insulin-like growth factor I) axis. Men and women differ in their ECF and this contributes to men’s higher fat-free...
www.excelmale.com
Swelling is one of TRT's most troublesome and hard to manage side effects. It occurs (in my estimate) to about 20 percent of users. The potential causes could be cortisol build up, increase sodium retention, in rare cases high estradiol, or cardiovascular issues. I am enclosing several posts on these issues.
Most cases of lower extremity (peripheral) edema has nothing to do with estradiol and a lot to do with cardiovascular issues. My number one suggestion if edema does not get better after a month on TRT is to get a full cardio work up by a cardiologist.
Some men report decreased edema after a short cycle of a diuretic like HTZ, so that is something to explore. Low sodium intake and plenty of water plus cardio may also help. Cardio exercise and sweating in a sauna have also been reported to help. But these are speculations that should not replace a good cardiovascular work up.
Pulmonary hypertension caused by sleep apnea has also been reported as a cause.
Obstructive Sleep Apnea Associated with Leg Edema
"A common but under-recognized cause of edema is pulmonary hypertension, which is often associated with sleep apnea. Venous insufficiency is treated with leg elevation, compressive stockings, and sometimes diuretics. The initial treatment of idiopathic edema is spironolactone. Patients who have findings consistent with sleep apnea, such as daytime somnolence, load snoring, or neck circumference >17 inches, should be evaluated for pulmonary hypertension with an echocardiogram."
edema[swelling] what is the cause
Ankle swelling after starting testosterone injections
Here are excerpts from another interesting paper that links testosterone related water retention to sodium retention:
"This is the first controlled study demonstrating that testosterone increases extracellular water ECW. Previous data concerning the effects of testosterone on plasma volume (19, 20) and urinary sodium excretion (18, 21) are limited and conflicting. The underlying mechanism is unknown, but several possibilities exist. Testosterone could act directly on the kidney, because androgen receptors are expressed in renal tubules (31). There is evidence that androgens stimulate the expression of the angiotensinogen gene in the kidney (32, 33). Therefore, androgens could activate the local renal RAASto stimulate sodium and water retention through an autocrine or paracrine mechanism (34). The epithelial sodium channel plays an important role in the sodium balance, as demonstrated by genetic abnormalities in its activity, such as in Liddle's syndrome (35). It has recently been reported that androgens increase mRNA expression of the α-subunit of the epithelial sodium channel in a human renal cell line (36), providing a potential mechanism of sodium and water retention by testosterone.
Plasma aldosterone Aldo levels fell significantly during testosterone treatment, whereas a modest fall, which failed to reach significance, occurred during GH treatment. During combined treatments, a significant fall in Aldo was also observed. The uniform trend toward a fall in Aldo levels observed with single and combined treatments suggests an adaptive response to ECW expansion. The observation that the fall in Aldo was greater in the presence of testosterone suggests that additional androgen-mediated mechanisms are probably involved. Androgen receptors have been identified in human adrenocortical cells and appear to exert an inhibitory influence. In vitro studies have demonstrated that testosterone reduced the proliferation of human adrenal adenoma and adrenocortical cancer cell lines (38). It is possible that testosterone directly suppresses Aldo biosynthesis or secretion, but this remains to be demonstrated.
More on aldosterone
The effects of testosterone on the volume and distribution of ECW could theoretically occur secondary to aromatization to estrogen in peripheral tissues. Estrogen may cause fluid retention through reduction of the plasma antidiuretic hormone (arginine vasopressin)-plasma osmolality set point (39, 40) or stimulating the synthesis of hepatic angiotensinogen (41), enhancing the overall activity of RAAS and leading to sodium retention. However, this postulate is not supported by the observation that urinary sodium excretion is increased during oral contraceptive use (42) or that the plasma renin concentration is reduced in women receiving estrogen treatment (43). Moreover, estrogen reduces the plasma renin concentration, the activity of angiotensin-converting enzyme, and the Aldo response to angiotensin II (44, 45). These actions of estrogen putatively generated from aromatization of androgens could explain the slight reduction in plasma Aldo levels in response to testosterone in our study." Source
I notice that I hold more water when I eat higher sodium foods, drink alcohol, and skip the gym for more than 3 days. Higher simple carb intake also worsens water retention. I weigh myself every morning. If I am not careful, I can gain 3-4 pounds of water in 1 or 2 days. Not drinking enough water also makes the body retain water. My kidney function (eGFR) is good (80).
I think decreasing sodium and sweets intake, increasing water consumption, and doing some cardio are ways to control water weight. If it gets bad, the use of a diuretic only once can stabilize this issue during days where I go off the wagon at my family's parties.
Water retention causes increase blood pressure which is treated with weight loss or medications.
What high blood pressure meds are the most erection friendly?
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