Ankle swelling after starting testosterone injections

ankleswelliing.webp




I got this question from a friend of mine today who started testosterone replacement 3 weeks ago (injections of 100 mg per week):

"I've been gaining a lot of weight. Does this mean my estradiol is high? I don't have any nipple soreness or severe bloating but my ankles and wrist are swelling."

Here was my answer:

Testosterone is anabolic, and it will cause some nitrogen, sodium and water retention. Some men have water retention (edema) during the first few weeks of TRT which can be reflected as increased weight or ankle swelling. This edema may or may not be associated with high estradiol (only knowing your blood level of estradiol can tell this). Edema may be worsened in patients with preexisting cardiac, renal, or hepatic disease (watch for high liver enzymes and/or decreased creatinine clearance). Edema can be worsened by NSAIDs (Tylenol, Advil, etc), so they should be discontinued to see if it resolves. Sometimes switching from injections to testosterone creams is sufficient to decrease edema. Some physicians also prescribe a short round of diuretics.

If edema does not resolve after 4 weeks on therapy, referral to cardiology is suggested for vascular tests.

What Is Peripheral Arterial Disease?


Comments anyone?
 
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I started to notice very slight swelling in my ankle on one leg and it progressively swelled more each day, by day 4 or 5 my ankle was not discernible <sp?>.
This am the swelling was down considerably and throughout the day it has somewhat returned to about 50% of what it was on the highest swelling level.
Do I need to be concerned about this?
Im on 100 im weekly Bi-Test, administered 2x/ wk , and 1000 HCG admin daily
Duane
 
Your TRT weekly dosage is not clear from your post. Is it 100mg per week, or 200mg per week?

I believe you're saying it's 100mg per week split into two injections of 50mg per week. Is that correct?
 
dang man, 1000 iu of hcg per week, my clinic only recommended 500 iu once per week, but i discovered 1 shot of 250 iu 1 time per week worked great for me both when i was on test @ 200 mlg per week and when i lowered the dosage to 100 mlg per week, id pin test at 50 mlg 2 times per week and hcg on wednesdays at 250 iu's and anastrozole 1 mlg 1 time per week...

at that amount of hcg it has to be e2, have u had it checked?

might also try sub q test a few times per week along with hcg 2 times per week at 125 per pin? ive seen blood levels level out better and e2 stay controllable at those dosages ive stated...ur total test ust be thru the ruff? unless u have extremely low test and or perhaps teste issues?
 
not sure why, but myorig mess was truncated............clarification and correction

1000iu HCG / week........I break this up into daily subq..........

500 iu Bi-Test/weekly ..........separate half doses 2x/week sub q
 
I have seen guys having this issue even with low estradiol (treated with anastrozole)

They tend to have more than one comorbidity like diabetes, hypertension, high body mass and fat content, etc
I started TRT 7 weeks ago, and have moderate swelling in right ankle and lower calf only, pain along inside edge of right shinbone. I was on 100mg/wk to start, lowered down to 50mg the 7th week as I was having side effects, poor sleep, gut issues, insomnia, and no real benefits noticed.
Around week6, I did 8 days of 500mg 2x/day Amoxicillin (was supposed to be 10 days but stopped), which made me feel even worse, and could be the reason for the ankle swelling and shin pain... jeeze!
I was going to start low dose HCG, but am now so frustrated I am leaning towards stopping the TRT completely... would it be advisable to take the HCG, maybe 200iu 2x/day to help me stop the TRT? Do you think I will feel even worse stopping the T after 8 weeks? I have always been sensitive to all drugs/chemicals, so maybe this struggle is no surprise. 64 yrs old, good shape, not overweight, not diabetic... my Free T was 5.2ng before starting TRT... been a one very small dose nightly marijuana user for many years... maybe that was what dropped my Free T so low? Sure helped me sleep, I stopped smoking it when I went on TRT...
Sorry for the long-winded comment!
 
I tell everyone experiencing this issue to at least get this test done from your primary care physician to ensure blood flow issues. I also recommend a keto diet to lose a lot of that excess water retention (and diuretics for a few days if needed).



I would not start HCG yet.

Ankle-brachial index (ABI): a painless exam that compares the blood pressure in your feet to the blood pressure in your arms to determine how well your blood is flowing. This inexpensive test takes only a few minutes and can be performed by your healthcare professional as part of a routine exam. Normally, the ankle pressure is at least 90 percent of the arm pressure, but with severe narrowing it may be less than 50 percent.


The Ankle-Brachial Index (ABI) is a non-invasive diagnostic tool used predominantly for detecting Peripheral Artery Disease (PAD), a condition characterized by narrowing of arteries, which reduces blood flow to the arms and legs[2][3]. In addition to its role in diagnosing PAD, the ABI has also been shown to be a predictor of mortality and adverse cardiovascular events, independently of traditional cardiovascular risk factors[3].
The ABI is calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressure at the arm[1][3]. The blood pressure values are taken from both arms and both ankles, typically focusing on systolic values[4]. This test is performed after the patient has been at rest in the supine position for at least 10 minutes[3].
The ABI results are interpreted as follows:
  • An ABI of 1.0-1.4 is considered normal.
  • An ABI of less than 0.9 suggests the presence of PAD. This indicates that there is significant narrowing or blockage of the arteries in the legs, leading to reduced blood flow[5].
  • An ABI of 0.9-1.0 is considered borderline for PAD.
  • An ABI greater than 1.4 might indicate calcified and stiff arteries, a condition often seen in patients with diabetes or renal disease. In such cases, the vessels are so hard that they resist compression, leading to falsely high systolic pressure measurements at the ankles and thus an elevated ABI[7].
In addition to the ABI values, waveforms obtained during the measurement can provide further information about the state of the peripheral circulation, although interpreting these requires specific expertise[7].
The ABI test is particularly advised for smokers over 50 years old, diabetics over 50, and all patients over 70[3]. It is also important for those with symptoms of PAD, which include intermittent leg pain or cramping, slow-healing leg wounds, and legs that feel colder or have changed color[8].
It is worth noting that the ABI is a valuable tool for tracking the progress of treatment
 
Seems odd that if it is water retention, that only one ankle is swollen... that Amoxicillin sure made me feel worse... and has very similar side effects as testosterone...
I am leaning towards stopping TRT. After 7 weeks of pretty low dose, only 55mg last week, 100mg/wk before that... will stopping be a problem? I sure don't want to feel any worse!
And you don't recommend taking HCG for a few weeks to help get off TRT and restore some Ball function? My LH and FSH re both VERY low, as to be expected I guess... estradiol last test was 30... hematocrit fine...
BTW: I find that 200-300mg+ of L-Theanine really takes the edge off...
THANKS!
 
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It is not uncommon to have one ankle swollen instead of the two. This is an opportunity for you to get flow flow measured (while swollen) on that leg to make sure everything is OK.

hCG does not increase LH or FSH. It acts like LH (and has some FSH qualities) but it is not picked up by the LH and FSH test. If you add hCG now, the swelling may worsen.

I say do not get off TRT. Get the test done.

What "edge" are you talking about?
 
It is not uncommon to have one ankle swollen instead of the two. This is an opportunity for you to get flow flow measured (while swollen) on that leg to make sure everything is OK.

hCG does not increase LH or FSH. It acts like LH (and has some FSH qualities) but it is not picked up by the LH and FSH test. If you add hCG now, the swelling may worsen.

I say do not get off TRT. Get the test done.

What "edge" are you talking about?
Got it... the "edge" is the inside edge of my right shinbone... really more "tender" than painful...
I will definitely ask my next Doc visit for a ankle BP test... but as I research, ankle swelling is somewhat common as a side effect for BOTH testosterone AND Amoxicillin... so while a blood flow problem IS a concern... not as much to see other guys having the same side effects. Ankle selling is down a bit today...
I screwed up, I had problems a long time ago with penicillin, didn't realize that Amoxicillin was in same class.
What do you think of me reducing my T dose to 50mg a wk for a while to see how I do and settle in? From the start, I had some side effects from the T... low-grade anxiety, faster heart rate, some facial flushing... and no serious benefits... which is why after 7 weeks, I am about to give it up... it just might not be for chemical sensitives like me... I'll ponder...
BTW: Good guy Vince here recommended 12.5 Enclomiphene if I stop TRT... seems to be VERY interesting... enough that I regret not trying it first! Thoughts?
Thx!
 
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Thank you. I raise my feet at night and it helped tremendously. Do i still need to take this test?
 

Peripheral Edema and Testosterone Replacement Therapy

Overview of Peripheral Edema in TRT

Peripheral edema-swelling caused by fluid accumulation, often in the feet or ankles-is a recognized side effect of testosterone replacement therapy (TRT) in men
1​
. This edema is typically mild at therapeutic doses but can be more pronounced in certain individuals or at higher doses. Routine monitoring for signs of fluid retention, such as ankle swelling, is standard during TRT
1​
.

Causes and Pathophysiology of Edema in TRT

Mechanisms of Fluid Retention
  • Renal Effects: Testosterone promotes sodium and water retention, increasing blood volume and leading to edema, hypertension, or exacerbation of heart failure in vulnerable patients
    1​
    . Research shows testosterone increases extracellular water volume by acting directly on the kidneys.
  • Hormonal Conversion (Estrogen): Some testosterone is converted to estradiol, which can also cause fluid retention. Elevated estradiol may further activate the renin-angiotensin system, compounding water retention.
  • Increased Blood Volume and Pressure: Testosterone stimulates red blood cell production (erythropoiesis), sometimes causing polycythemia. This, combined with water retention, raises blood volume and capillary pressure, pushing fluid into tissues. Anabolic-androgenic steroids (AAS) can exacerbate these effects, especially at high doses, leading to significant edema and even heart failure in susceptible individuals.

Edema at Therapeutic vs. Supraphysiologic Doses

TRT Dose LevelTypical Edema PresentationAdditional Risks
Therapeutic (medical)Mild-moderate, often ankles/legs, reversibleOlder men and those with heart/kidney/liver disease at higher risk
Supraphysiologic (AAS)Marked edema, rapid weight gain, hypertensionCardiac hypertrophy, heart failure, kidney injury

Treatment and Management of TRT-Induced Edema

Standard Medical Treatments
  • Adjusting TRT Dose/Regimen: Lowering the dose or switching to a different delivery method can reduce edema.
  • Addressing Underlying Conditions: Optimizing management of heart, kidney, or liver disease is crucial; TRT may need to be paused or discontinued in severe cases.
  • Diuretics: Prescribed to help the body excrete excess fluid; used with caution and under supervision.
  • Managing Estrogenic Effects: Aromatase inhibitors may be considered if high estradiol is contributing to edema, but this is individualized.
  • Monitoring: Regular checks of weight, blood pressure, and labs (hematocrit, electrolytes, kidney function) are standard.
Emerging/Adjunct Therapies
  • SARMs: Selective Androgen Receptor Modulators are being studied as alternatives to TRT, potentially offering anabolic benefits with less fluid retention.
  • Refined Testosterone Formulations: Newer delivery methods (e.g., oral undecanoate) may reduce fluid shifts, though data are still emerging.
Lifestyle and Supportive Measures
  • Dietary Salt Reduction: Reducing salt intake helps manage fluid retention.
  • Leg Elevation: Elevating legs above heart level helps drain excess fluid.
  • Compression Garments: Compression stockings prevent fluid accumulation in the legs.
  • Regular Movement/Exercise: Avoiding prolonged sitting or standing and engaging in regular activity improves circulation.
  • Weight Management: Weight loss can reduce venous pressure and edema.
  • Hydration/Alcohol Moderation: Proper hydration and limiting alcohol intake can help control fluid balance.
  • Medication Review: Certain drugs (NSAIDs, some antihypertensives) can worsen edema and may need adjustment.
  • Self-Monitoring: Daily weight or ankle circumference checks can detect changes early.

Prognosis and Outlook

Most cases of TRT-induced edema resolve with conservative measures or dose adjustments. Persistent or severe edema, especially in the context of supraphysiologic steroid use, may signal underlying cardiac or renal issues that require prompt attention. With careful management, most men can continue TRT with minimal or manageable edema
1​
.

References

  1. Risks of testosterone replacement therapy in men - PMC
  2. Testosterone Replacement Therapy (TRT): What It Is – Cleveland Clinic
  3. Adverse Events Associated with Testosterone Administration - PMC
  4. Androgens and Selective Androgen Receptor Modulators to Treat Functional Limitations Associated With Aging and Chronic Disease - PMC
  5. Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men - PubMed
  6. Foot, leg, and ankle swelling: MedlinePlus Medical Encyclopedia
  7. Anabolic-androgenic steroids and cardiovascular risk - PMC
  8. Testosterone (intramuscular route, subcutaneous route) - Mayo Clinic
  9. Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies - PMC
  10. Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse - PMC
  11. Focal segmental glomerulosclerosis (FSGS) - Symptoms, causes ... - National Kidney Foundation
 
Sodium retention is the main cause of water retention.

www.testosteronewisdom.com

High Blood Pressure and Water Retention on Testosterone ( TRT ) | Testosterone Wisdom

TRT can cause water retention and high blood pressure during the first weeks of treatment. This article mentions ways to deal with that issue
www.testosteronewisdom.com
www.testosteronewisdom.com

Testosterone increases water retention in hypogonadal men by affecting kidneys - Excel Male TRT Forum

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
www.excelmale.com

Here are excerpts from an interesting paper:

"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 RAAS to 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 &#945;-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 were I go off the wagon at my family's parties.
 
I was on 80mg weekly Testosteone Cypionate subq starting in 2018. Early this year my left ankle started to swell. The pattern was swelling the day after injection and returning to normal 4 days after. In March my ankle did not return to normal after injection. My right ankle was perfectly normal and my left ankle stayed huge. An ultra sound on March 27th revealed a blood clot in the vein midway up my leg. I have stopped TRT and am on Eliquis. The swelling is slowly resolving. A combination of 81 years, low heart rate and low Diastolic blood pressure along with the viscosity thickening of testosterone caused my blood to stagnate.
 
I have stopped TRT and am on Eliquis. The swelling is slowly resolving. A combination of 81 years, low heart rate and low Diastolic blood pressure along with the viscosity thickening of testosterone caused my blood to stagnate.
Sorry to hear. What other meds were you taking when the DVT happened?
 
I have psoriatic arthritis, hypothyroidism,and hypertension. I take prednisone,minocycline,pentoxifylline,l-thyroxine,temisatan,terazosin, and bystolic. I have isolatic diastolic hypertension. When my systolic is at 130 with meds. my diastolic is under 60. Couple that with bystolic slowing my heart rate into the 50's, my blood is not moving with much force. These are my thoughts, not what a doctor has told me. My PCP said the blood clot was caused by blood coagolation effects of the testosterone cypionate.
 
Thanks for replying. By any chance, did they test for these tests: Factor V Leiden, Prothrombin gene, Factor VIII and Factor XI. How was your hematocrit ?

I am sorry for so many questions.
 

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