Relationship between insulin resistance, estradiol, aromatase, testosterone replacement, and water retention

[nathan toney]

Hello gentlemen,
Nate here again. I have struggled to get dialed in on TRT for about 12 years. I have tried every protocol (never less than 8 weeks) other than Nebido (not interested). Everything from 50mg per week to 200mg per week, creams, gels, test prop/cyp blend and AI's. ED, EOD, E3D, E4D, E5D, weekly, 2 weeks, 3 weeks. Every time I reach a point where the water retention, actively feeling weaker, loss of libido, and foggier thinking is my reason for D/C'g TRT. The only time I have a period of time feeling great on TRT is after I have abstained from use for a minimum of 3 months (and I mean F%$@ing GREAT - strong, smart, lean, great sleep, great workouts, great libido, etc - then it passes if I continue TRT). When I come off TRT I pass through a short period of time where I feel slightly better, then I start having muscle tears, injuries, losing muscle, weakness, no libido. Last year my Dr wanted me to try an aromatase inhibitor. Long story short it made things worse. I did a 3 week washout and then most recently started daily TC injections for 8 weeks (no ancillaries) at 200mg/wk. Again I never felt any benefit and water retention, slow thinking, weakness, no libido (my usual reasons for quitting TRT) was my reason for D/C'g TRT this go around. My SHBG is never lower than 29. I am currently off TRT for 8 days. This week I convinced my Dr to prescribe Metformin. I have had fasting BG around 100 for decades. Even on Keto, low carb, fasting. I believe we have put to bed that AI's don't work and that E2 is not the problem (the Danny Bossa guys) but I'm not sure.
Here is what I'm wondering:
Can insulin resistance get worse on testosterone partly due to E2, causing me to pass through a period of time feeling excellent?
Is there a relationship between insulin resistance and E2 that makes some low T men unable to maintain benefit?
Can E2 increase insulin resistance?
I am a seeker by nature, so I won't stop trying to feel better.
Thanks for any responses,
Nate

 

[Cyclingislife]

Nate, I have had a similar experience on trt. Tried on and off for five years, always felt like I gained weight, looked puffy, never felt good. Never got the benefits everyone raved about, it never worked. Ironically, my best days were 2-3 weeks after I came off. I recently tried it again & through a lot of research I figured it out. First check your SHBG level, from what your describing it sounds low. Mine was low too at 19, my fasting BS is usually 99. Also check your free T, if it is well above the max level that’s also an indicator. Here is what the issue is, if you have low shbg you are extremely sensitive to testosterone. And, From what I can tell your dose is way too high. Which will only lower SHBG more & make u feel worse. That’s why when you come off you feel better after a few weeks. When your on at large doses you blow by your sweet spot, never able to dial it in. And, if you inject large doses you’ll also get a huge spike in E2. I can also tell you doctors don’t have any idea how to prescribe for special situations. My doc had me on 60mg 2x per week & I felt like crap & blew up like a balloon. My total was 980, E2 was 63 & free T was above the limit. I finally figured it out on my own. I switched to 12-14mg per day. Remember when you’re younger the max test your body produces naturally is 6-10mg per day. With prescription test cypionate 70% is test, 30% is oil. So at 100mg per week your getting 70mg of test, 10mg per day. Trust me the US docs have guys so over prescribed On TRT that’s why they’re all on here looking for answers trying to get dialed in. Right now I inject .07 per day (14mg). I alternate daily shots between subcutaneous in the stomach using a 27 guage, 1/2 inch & shallow IM in deltoid only using a 25 guage 5/8. This has been a miracle for me, the lower dose makes me feel 100% like I was in my 30’s. When I switched to this I felt like I lost ten pounds in one week. I finally know what it’s like to be in the sweet spot, it’s amazing. Awesome energy, no brain fog, great libido. My total T stays around 600-700, free T in upper middle, E2 is normal around 25 with no AI, zero side effects. Less is more, try it. You need to give it 4-6 weeks once you change your protocol. Hope this helps.

 

[Cataceous]

...
I am a seeker by nature, so I won't stop trying to feel better.
...

This is good, because success requires persistence. Your results show that there can be more to this than testosterone and estradiol. Sometimes it's necessary to go back to basics. Are thyroid and adrenal hormones in good shape? Lowish, but in-range thyroid hormones can be a problem. It's commonly said that TRT won't work well if these other hormones aren't right.

@Cyclingislife has a good suggestion in general; overdosing is a common problem in the TRT world. But it does seem as though you've tried a lot of protocols, including some at fairly low levels. One way to take it a step further is to dose the testosterone so that the daily peak in serum levels is normal and the daily trough is about 40% lower. This can be accomplished with daily injections of an appropriate blend of propionate and a longer ester.

While the dosing stuff is worth trying, I expect it's too subtle for what you're trying to fix. A likely culprit is TRT's disruption of upstream hormones, which include kisspeptin, GnRH, LH, FSH, progesterone, DHEA and pregnenolone. Though tedious, it is possible to restore levels of these hormones to the point of reducing some amount of TRT-induced dysfunction. If this is impractical then the main alternative is to forgo regular TRT and instead boost testosterone in a non-suppressive manner. Two options for this are testosterone nasal gel and enclomiphene.

Another avenue to pursue is neurotransmitters. There's a range of supplements and medications that can be used to boost acetylcholine and dopamine. Some examples here.

 

[gerardo]

Nate, I have had a similar experience on trt. Tried on and off for five years, always felt like I gained weight, looked puffy, never felt good. Never got the benefits everyone raved about, it never worked. Ironically, my best days were 2-3 weeks after I came off. I recently tried it again & through a lot of research I figured it out. First check your SHBG level, from what your describing it sounds low. Mine was low too at 19, my fasting BS is usually 99. Also check your free T, if it is well above the max level that’s also an indicator. Here is what the issue is, if you have low shbg you are extremely sensitive to testosterone. And, From what I can tell your dose is way too high. Which will only lower SHBG more & make u feel worse. That’s why when you come off you feel better after a few weeks. When your on at large doses you blow by your sweet spot, never able to dial it in. And, if you inject large doses you’ll also get a huge spike in E2. I can also tell you doctors don’t have any idea how to prescribe for special situations. My doc had me on 60mg 2x per week & I felt like crap & blew up like a balloon. My total was 980, E2 was 63 & free T was above the limit. I finally figured it out on my own. I switched to 12-14mg per day. Remember when you’re younger the max test your body produces naturally is 6-10mg per day. With prescription test cypionate 70% is test, 30% is oil. So at 100mg per week your getting 70mg of test, 10mg per day. Trust me the US docs have guys so over prescribed On TRT that’s why they’re all on here looking for answers trying to get dialed in. Right now I inject .07 per day (14mg). I alternate daily shots between subcutaneous in the stomach using a 27 guage, 1/2 inch & shallow IM in deltoid only using a 25 guage 5/8. This has been a miracle for me, the lower dose makes me feel 100% like I was in my 30’s. When I switched to this I felt like I lost ten pounds in one week. I finally know what it’s like to be in the sweet spot, it’s amazing. Awesome energy, no brain fog, great libido. My total T stays around 600-700, free T in upper middle, E2 is normal around 25 with no AI, zero side effects. Less is more, try it. You need to give it 4-6 weeks once you change your protocol. Hope this helps.

Did you ever try the 35 mg E3.5D protocol?

 

[goolapsh]

Nate, I have had a similar experience on trt. Tried on and off for five years, always felt like I gained weight, looked puffy, never felt good. Never got the benefits everyone raved about, it never worked. Ironically, my best days were 2-3 weeks after I came off. I recently tried it again & through a lot of research I figured it out. First check your SHBG level, from what your describing it sounds low. Mine was low too at 19, my fasting BS is usually 99. Also check your free T, if it is well above the max level that’s also an indicator. Here is what the issue is, if you have low shbg you are extremely sensitive to testosterone. And, From what I can tell your dose is way too high. Which will only lower SHBG more & make u feel worse. That’s why when you come off you feel better after a few weeks. When your on at large doses you blow by your sweet spot, never able to dial it in. And, if you inject large doses you’ll also get a huge spike in E2. I can also tell you doctors don’t have any idea how to prescribe for special situations. My doc had me on 60mg 2x per week & I felt like crap & blew up like a balloon. My total was 980, E2 was 63 & free T was above the limit. I finally figured it out on my own. I switched to 12-14mg per day. Remember when you’re younger the max test your body produces naturally is 6-10mg per day. With prescription test cypionate 70% is test, 30% is oil. So at 100mg per week your getting 70mg of test, 10mg per day. Trust me the US docs have guys so over prescribed On TRT that’s why they’re all on here looking for answers trying to get dialed in. Right now I inject .07 per day (14mg). I alternate daily shots between subcutaneous in the stomach using a 27 guage, 1/2 inch & shallow IM in deltoid only using a 25 guage 5/8. This has been a miracle for me, the lower dose makes me feel 100% like I was in my 30’s. When I switched to this I felt like I lost ten pounds in one week. I finally know what it’s like to be in the sweet spot, it’s amazing. Awesome energy, no brain fog, great libido. My total T stays around 600-700, free T in upper middle, E2 is normal around 25 with no AI, zero side effects. Less is more, try it. You need to give it 4-6 weeks once you change your protocol. Hope this helps.

This hits home with me. Everyone raves about Dr Saya at defy on this website, but he had me way overdosed for my shbg. I’m right around 16-18 and he had me on 120mg injected daily plus scrotal cream. I felt like shit for months and decided to stop treatment altogether. My free t was way over the range. Actually I’m scared to get back on. That’s how bad I currently feel. I had better success with scrotal cream solo but I didn’t like all the hair loss with it. I wish I could’ve had a better doctor who actually knew what he was doing but now I don’t think I’ll get back on.

 

[Cyclingislife]

I know how you feel. 95% of the docs have no clue how to deal with low shbg guys. I was ready to throw in the towel too. But I would encourage you to give it another try. if you have a doctor who will write you a prescription for Cypionate and you can self administer you’ll be able to dial it in. My shbg was 19. The low dose daily subcutaneous shot is a miracle when you finally get it right. There’s no doubt this is the protocol for low SHBG. I’m actually going to try lowering my dose even further. I think 10mg to 14mg per day is the sweet spot for most guys & you most likely won’t need an AI. Also, I don’t take HCG & my hematocrit is normal. The real secret to TRT is you adjust your dose 100% by how you feel, I learned that from a TRT doc who knows what he is talking about. I keep a daily log of dose/How I feel/etc. I think for low shbg, total T does not matter, you need to keep your free t in mid to 75% of range. If your free T goes too high everything goes to hell & you’ll feel terrible, spike E2, etc. I promise when you get it right it’s nirvana. It took me 5 years to figure it out but now I finally feel like myself again. Also look at this website:
themenshealthclinic.co.uk
I don’t use them, but I learned a lot from their site & videos.

 

[goolapsh]

I know how you feel. 95% of the docs have no clue how to deal with low shbg guys. I was ready to throw in the towel too. But I would encourage you to give it another try. if you have a doctor who will write you a prescription for Cypionate and you can self administer you’ll be able to dial it in. My shbg was 19. The low dose daily subcutaneous shot is a miracle when you finally get it right. There’s no doubt this is the protocol for low SHBG. I’m actually going to try lowering my dose even further. I think 10mg to 14mg per day is the sweet spot for most guys & you most likely won’t need an AI. Also, I don’t take HCG & my hematocrit is normal. The real secret to TRT is you adjust your dose 100% by how you feel, I learned that from a TRT doc who knows what he is talking about. I keep a daily log of dose/How I feel/etc. I think for low shbg, total T does not matter, you need to keep your free t in mid to 75% of range. If your free T goes too high everything goes to hell & you’ll feel terrible, spike E2, etc. I promise when you get it right it’s nirvana. It took me 5 years to figure it out but now I finally feel like myself again. Also look at this website:
themenshealthclinic.co.uk
I don’t use them, but I learned a lot from their site & videos.

Thanks for your reply. How long ago did you start this new protocol? Where does your free t usually land (please include reference range).

 

[Cyclingislife]

I switched to daily injections about 3 months ago. In the first 10 days I felt completely different, TRT finally worked for me! My last labs were 623 total T (264-916 ng/dL), free T 16.4 (7.2-24pg/ml). I’ve also recently gone to just SubQ injections, they work great & are super easy to administer.

 

[Dr Justin Saya MD]

This hits home with me. Everyone raves about Dr Saya at defy on this website, but he had me way overdosed for my shbg. I’m right around 16-18 and he had me on 120mg injected daily plus scrotal cream. I felt like shit for months and decided to stop treatment altogether. My free t was way over the range. Actually I’m scared to get back on. That’s how bad I currently feel. I had better success with scrotal cream solo but I didn’t like all the hair loss with it. I wish I could’ve had a better doctor who actually knew what he was doing but now I don’t think I’ll get back on.

I’m very sorry you feel that way, goolapsh. Low SHBG guys are always a unique challenge, but I’ve probably successfully treated more than most other practitioners. With that said, I certainly don’t have a perfect batting average. Wish I could have helped you more.

 

[Nelson Vergel]

I am just speculating here. After many years of reading posts on here and with my own experience, I think these are the main factors that may explain why someone may not feel better on TRT:

1- They never needed it. They started TRT with baseline total T over 400 ng/dL and did not address issues like sleep quality, sedentary life style, high body weight, and potential stress.

2- They used too high of a dose. This increased their hematocrit considerably with the resulting quality of life issues caused by higher blood viscosity.

3- TRT made their sleep apnea worse (Obstructive or central in nature).

4- They donated blood too frequently and could not catch up in their iron and ferritin loss. Many never got those two levels even tested.

5- They crashed their estradiol with anastrozole.

6- Their water retention was excessive, with increase blood pressure and feeling "out of breath".

7- They did not address and treat their depression. There is so much TRT can do but improving depression unrelated to low T is hard to accomplish without treatment and therapy.

8- They never looked deeply at thyroid dysfunction with a full panel that includes antibodies and reverse T3.

9- They never improved their diet and alcohol use.

10- None of the above...just bad luck.

I will think of more and add later. These are the most obvious ones.

 

[Cyclingislife]

I think you make some great points Nelson. However, I believe you missed a big one.
11. They were truly suffering from Hypogonadism and chose a doctor who didn’t have any idea what they were doing. Said doctor never analyzed the situation, labs correctly & therefore prescribed the wrong protocol. Or they rubber stamped the same protocol regardless of individual labs, low/high shbg etc.

I believe most of us who have struggled is due 100% to the lack of experienced doctors in this field.

 

[Cyclingislife]

I wanted to add. TRT requires a medical prescription for those of us who do it the right way. It is a controlled substance. With that in mind the doctors need more training/resources/accountability. Adjusting ones hormones can have great results and horrible results. I think there’s just too many people/internet sites writing prescriptions without proper training. I believe their are tens of thousands, maybe millions of guys left trying to figure this out on their own. Combing the Internet for answers, self adjusting, spending time on forums, etc. That’s a fundamental problem that should be addressed by the medical community.

 

[Anonymon]

I wanted to add. TRT requires a medical prescription for those of us who do it the right way. It is a controlled substance. With that in mind the doctors need more training/resources/accountability. Adjusting ones hormones can have great results and horrible results. I think there’s just too many people/internet sites writing prescriptions without proper training. I believe their are tens of thousands, maybe millions of guys left trying to figure this out on their own. Combing the Internet for answers, self adjusting, spending time on forums, etc. That’s a fundamental problem that should be addressed by the medical community.

That’s probably not the issue. Many ‘trained physician‘ prescribed TRT is 200mg ever 2 weeks, or 100mg ever 2 weeks. Most of the TRT clinic docs are a far cry better than people with far more ‘training’ in the sense you’re referring to.

I’ve been a problem case as well, but have had more success working with TRT style clinics than the people you’re hoping will help you. The standard way most physicians handle things like this is not to do it and you’re left as you are until you get cancer or diabetes and they prescribe you something for that.