Anyone supplement E2 alongside TRT

[Gjohns28]

Not sure if I should start a new thread.....guess I'll post here first.

I'm also a low aromatiser and seemingly a low responder (T-985; E2-15 on 200 Test C per week) . I'm 2-weeks into supplementing Estradiol Cypionate (2mg per week) to try and change my t/e ratio.

Positives: EQ and erection frequency are up (nocturnal/morning) a lot; sensitivity is up a some (wasn't bad before); libido up a little (wasn't bad before); physically a lot stronger, more energetic; maybe a bit calmer/relaxed.

Negatives: My knees feel like someone inserted glass shards in them...as if I have low E2. Almost debilitating. Hurts to walk, impossible to do any type of athletics that require movement.

I guess I should give this more time/get blood work/etc....but not being in pain and being athletic are important to me. 3-4 more weeks of this feels like an eternity.

Note that my best T/E ratio was once at 600/35 and my joints felt like pillows. But this was with Enclomiphene....so libido was non-existent.

 

[Gjohns28]

I should mention...supplementing E2 was due to physically feeling weak/fatigued, brain fog, and joint pain (knees especially).

 

[Cataceous]

...
The main sexual dysfunction I have experienced is loss of sensitivity on my penis and I am wondering if I can get it back by increasing my estrogen. I just started HCG in the hopes of accomplishing this, did you have the same issue?

Anecdotally, some guys see improvements when reducing testosterone to more realistic levels. Even 80 mg TC/week combined with hCG is fairly high compared to what's natural. However, if my experience is also broadly applicable then the problem is not necessarily something that can be fixed by tweaking testosterone, estradiol and hCG. I believe the issue relates to TRT's disruption of other hormones. I made no headway until I started replacing upstream hormones in earnest. In particular, GnRH supplementation seems to be quite helpful. I've also been supplementing kisspeptin, oxytocin and progesterone. While sensitivity is nothing like teenage levels, the improvement is large in comparison to when I was on more generic TRT protocols.

 

[Gjohns28]

Anecdotally, some guys see improvements when reducing testosterone to more realistic levels. Even 80 mg TC/week combined with hCG is fairly high compared to what's natural. However, if my experience is also broadly applicable then the problem is not necessarily something that can be fixed by tweaking testosterone, estradiol and hCG. I believe the issue relates to TRT's disruption of other hormones. I made no headway until I started replacing upstream hormones in earnest. In particular, GnRH supplementation seems to be quite helpful. I've also been supplementing kisspeptin, oxytocin and progesterone. While sensitivity is nothing like teenage levels, the improvement is large in comparison to when I was on more generic TRT protocols.

Thank you! Lowering T was a thought I'd had and you've underscored it for me. Maybe shoot for that 600-700 level. I'm guessing that would be 120-130mg per week.

 

[Cataceous]

Thank you! Lowering T was a thought I'd had and you've underscored it for me. Maybe shoot for that 600-700 level. I'm guessing that would be 120-130mg per week.

What is your injection frequency and when do you test levels relative to injections? Physiological TRT doses are more like 40-90 mg TC per week in divided doses.

 

[Gjohns28]

Catacecous,

100mg every 3.5 days; testing at trough for levels. SHBG is around 50 so I thought it better to keep the frequency no more than twice a week. Got started at the standard telehealth 200mg per week and thought it may be too much. Then got labs and saw that it wasn't so high after all (in terms of Total/Free/E2).

Their solution to raise e2 was simply add more T but I'm not comfortable doing that. Like you, I feel like a borderline roid abuser @ 200mg. I've since left them as it didn't take me long to figure out they're a TRT-mill and I had become smarter than them after some time online.

 

[Willyt]

I want to get bloods before next phase of experiment. My goal is to experiment between th ratios of 15/1, 22/1, 30/1.

What were your conclusions on the experiment? Did you ever get your ratio down and did it make a difference? My TT to e2 is typically over 35x and I have been wondering if it would make a difference to supplement with estradiol tablets similar to other thread mentioned on page1

 

[Cataceous]

... My TT to e2 is typically over 35x and I have been wondering if it would make a difference to supplement with estradiol tablets similar to other thread mentioned on page1

It sounds like there's more risk in oral delivery. If possible aim for topical gel or injections. If you're still with them, Defy will prescribe these. They're currently offering bi-estrogen gel, which might work, along with estradiol cypionate. You'd want to be able to dose topical estradiol to 0.1 mg resolution->10 µg absorption resolution. The estradiol cypionate (10 mg/mL) would need to be diluted to achieve this resolution.

 

[Willyt]

It sounds like there's more risk in oral delivery. If possible aim for topical gel or injections. If you're still with them, Defy will prescribe these. They're currently offering bi-estrogen gel, which might work, along with estradiol cypionate. You'd want to be able to dose topical estradiol to 0.1 mg resolution->10 µg absorption resolution. The estradiol cypionate (10 mg/mL) would need to be diluted to achieve this resolution.

Thanks Cat. Are you referring to health risk with orals (e.g., liver?) or poor absorption?

I see Defy sells sublingual form as well as tablets. The bi-estrogen gel sounds preferable. Here is weakest one Defy has: Bi-Estrogen (80/20) 0.5mg Gel, (30g)

Gemini summary: For a man with a high 37:1 ratio, Bi-Est gel and sublingual estradiol offer two very different ways to raise your E2 levels.

What is Bi-Est Gel?
Bi-Est (short for Bi-Estrogen) is a compounded bioidentical hormone cream or gel that combines two types of estrogen: Estradiol (E2) and Estriol (E3).

• The Blend: It is typically prescribed in an 80:20 ratio (80% Estriol, 20% Estradiol).
• The "Gentle" Factor: Estriol is the weakest and "gentlest" of the three estrogens. Compounding them together is often described by integrative doctors as "feeling gentler" than pure estradiol-only therapy
• Protective Benefits: Estriol is thought to provide protective effects for skin and tissues while blunting some of the more "intense" side effects (like anxiety or water retention) associated with potent Estradiol.

Bi-Est Gel vs. Sublingual Estradiol

Feature	Bi-Est Gel (Topical)	Sublingual Estradiol (Under Tongue)
Potency	Lower/Milder. Balanced by weak Estriol.	Higher/More Potent. Direct E2 absorption.
Absorption	Slow & Steady. Absorbed through skin over several hours.	Fast Spike. Rapidly enters the bloodstream within minutes.
Metabolism	Bypasses Liver. Goes directly into systemic circulation.	Largely Bypasses Liver. Higher E2:E1 ratio than oral.
Risk of Panic	Low. The slow release is less likely to trigger a "spike" response.	Medium. Rapid spikes in E2 can occasionally trigger anxiety in sensitive men.

Which is Preferable for You?

• Bi-Est Gel is likely preferable. The transdermal route mimics your body's natural, slow production of estrogen. Because it includes the "weaker" Estriol, it provides a much larger safety margin for someone who feels "ill" when hormones shift too quickly.
• Sublingual Estradiol might be "too fast." While effective, the rapid onset creates a pharmacokinetic "spike" similar to the fast-acting testosterones

The Strategy to Discuss:
Ask your doctor about a low-dose Bi-Est 80/20 gel (e.g., 0.5 mg total estrogen). Applying this to thin skin (like the inner forearm) once daily can provide that steady "trickle" of E2 you are missing, helping you move from a 37:1 ratio toward a more stable 15:1 or 20:1

 

[Willyt]

Also relevant thread from @Nelson Vergel on the importance of the TT:E2 ratio staying within sweet spot of 14:1 to 20:1.
This is part I was missing - the ratio matters more than the E2 (sensitive) number in isolation. I appear to one of those men whose E2 does not scale up with TT level when increasing dose.

Thread 'Why Does Low Estradiol Cause Joint Pain in Men on TRT?'

Apr 20, 2026

Curated by Nelson Vergel | ExcelMale.com | Updated April 2026

If you started testosterone replacement therapy expecting to feel younger and stronger, the last thing you expected was new, unexplained joint pain - sharp zaps in your elbows, aching fingers, stiffness in your hips, or a grinding sensation in your knees. For thousands of men on TRT, this is exactly what happens, and the culprit is rarely the testosterone itself. More often, it is the aromatase inhibitor prescribed alongside it.

Here is the paradox that still surprises most men (and...

• Nelson Vergel
• crashed estradiol joint pain Low E2 Joint Pain low estradiol
• Replies: 1
• Forum: Testosterone Side Effect Management

• 

 

[Cataceous]

Thanks Cat. Are you referring to health risk with orals (e.g., liver?) or poor absorption?
...

The former. Here's an AI summary:

The primary risks associated specifically with oral estradiol (compared to transdermal gels or injections) stem from its first-pass metabolism in the liver. Oral forms are absorbed through the gastrointestinal tract and undergo significant hepatic processing before reaching systemic circulation. This leads to disproportionate estrogen exposure in the liver, inducing changes in protein synthesis, clotting factors, and other hepatic functions that non-oral routes largely avoid.​

Key Specific Risks of Oral Estradiol

• Increased venous thromboembolism (VTE) risk, including deep vein thrombosis (DVT) and pulmonary embolism: Oral estradiol is consistently linked to a higher risk of blood clots (e.g., relative risks around 1.6–2x or odds ratios ~4x in some studies vs. non-users), due to hepatic induction of prothrombotic factors (e.g., increased thrombin generation, resistance to activated protein C, elevated clotting proteins). Transdermal gels show little to no increase in VTE risk, and many studies find no significant elevation compared to non-users. Injectable forms also bypass first-pass effects, though high-dose injections may carry some other cardiovascular considerations in specific contexts.
• Potential effects on blood pressure and renin-angiotensin system: Oral forms can increase angiotensinogen production in the liver, potentially activating the renin-angiotensin-aldosterone system and raising angiotensin II levels, which may contribute to hypertension in some users. Non-oral routes generally lack this hepatic impact.
• Altered lipid and inflammatory profiles: Oral estradiol more strongly affects liver-mediated lipid metabolism (e.g., greater increases in triglycerides or changes in HDL/LDL) and markers like C-reactive protein. While this can have mixed cardiovascular implications, it differs from the more neutral profile of transdermal routes.
• Gallbladder disease/cholecystectomy risk: Oral administration is associated with higher risk due to hepatic metabolism and biliary excretion effects, which transdermal avoids.

 

[elroy]

I have considered trying some E2 along with my TRT. My wife gets a vaginal estradiol cream (generic for estrace). I could "borrow" some. I believe it is a 0.1 mg per gram. Don't know how much or how long to see any effects.

 

[Cataceous]

I have considered trying some E2 along with my TRT. My wife gets a vaginal estradiol cream (generic for estrace). I could "borrow" some. I believe it is a 0.1 mg per gram. Don't know how much or how long to see any effects.

I'm not sure how widely applicable this is, but very roughly I was seeing about a 10 pg/mL increase in serum estradiol for every 10 µg absorbed. Topical absorption is generally around 10%, so one gram of that 0.01% cream could get you the 10 µg, a good starting point. Alternatively, scrotal skin absorbs more efficiently, possibly up to 50% or so. You should feel some effects within days, though a month or so is needed to rule out transient effects.

 

[Willyt]

I am still waiting on Defy's Bi-Est cream. I ran comparison in Gemini of Bi-Est cream versus Estrace:

The primary difference lies in the hormonal balance and the delivery vehicle, which significantly impacts how "hard" or "soft" the estrogenic effect feels to a sensitive nervous system.

1. Active Ingredient Profile

• Bi-Estrogen Gel (80/20):
  • The Blend: Contains two estrogens: Estriol (E3) and Estradiol (E2).
  • The Logic: Estriol is the "weakest" estrogen. By making the gel 80% Estriol, it provides a much gentler, broader effect on tissues (like your joints and skin) while minimizing the intense systemic "spikes" that can trigger panic or "amped up" feelings.
  • For Men: This is often preferred in the TRT community because it feels less "feminizing" and more like a steady baseline support.
• Estrace Vaginal Cream (0.1 mg E2/gram):
  • The Blend: Contains only Estradiol (E2), the most potent and bioactive form of estrogen.
  • The Logic: It is pure, bioidentical E2. It is designed for maximum potency in localized tissue, but when used transdermally by men, it hits the system much harder than a Bi-Est blend.
  • For Men: Because it is pure E2, the margin for error is smaller. It is easier to accidentally "overshoot" your E2 levels, which could lead to the mood swings or water retention you are trying to avoid.

2. Base Ingredients (The "Vehicle")

• Bi-Est Gel: Typically uses a specialized VersaBase or similar gel designed for transdermal absorption through the skin (arms, thighs, or scrotum). These are formulated to be non-greasy and to deliver the hormone steadily over several hours.
• Estrace Cream: As a vaginal cream, the base is designed for mucosal absorption. It is often much "heavier" and greasier (containing ingredients like propylene glycol, stearyl alcohol, and white petrolatum). It is not optimized for "dry" skin absorption, so it can feel tacky or leave a residue on the skin.

3. Concentration and Dosing

• Bi-Est: Usually comes in a pump or syringe where the concentration is customized (e.g., 0.5 mg total estrogen per click).
• Estrace: 1 gram of cream equals 0.1 mg of pure E2. For a man, a "standard" dose might be a tiny "pea-sized" amount (approx. 0.25g of cream), which is roughly 0.025 mg of E2.