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RP McMurphy

New Member
I’m a 45 yo male, 150 lbs. Prior to starting any testosterone therapy my labs in January 2018 were in range (Total T 601 280-1100ng/dl, Free T 10.43 1.9-27ng/dl), but I wanted to see if increasing testosterone levels would help to improve fatigue. I always had a high sex drive, with decent erections but sometimes room for improvement re the erections...

I trialed clomid monotherapy starting from March 2018 until June 2020 (50mg every three days), with positive results –increased energy, stronger erections.

In the summer of 2020 I started an injectable cypionate/propionate blend (160/40 mg/ml) from Empower. I switched from clomid monotherapy to testosterone injections mainly because clomid seemed to be dropping my IGF-1 into the 70’s, and I was also curious if I would see even better results with injectable testosterone. I also cycled in 22.5mg of clomid a few times a week, but very rarely because of my concerns regarding IGF-1 levels. I’ve also cycled in 1iu of HGH a decent amount of the time (but was not taking at the time or leadup to the most recent labwork).

I’ve experimented with different dosing regimens, mostly lowering my dose over time and decreasing the time between doses. I experienced great sexual function for the first year plus (and increased muscle mass), but the past 4-5 months I’ve had little to no sexual desire, and some ED. This is a complete 180 for me, as I mentioned I’ve always had a high sex drive. I realize that the arena of sexual desire and function is a complicated one, but I believe that this is a side effect of my TRT regimen. Systolic blood pressure also increased from 120 into 130’s on TRT, and at times felt a bit amped up, and possibly fatigued.

Here are my recent labs (trough) from Quest on April 4, 2022 after 8 weeks of dosing 20mg of the cypionate/propionate blend, every other day subq in the thigh. I was also taking my standard regimen of (alot of vitamins), 25mg DHEA, 150mg pregnenolone, 30mg armour thyroid, and I was not on HGH.

TESTOSTERONE, TOTAL, MS 806 250-1100 ng/dL
TESTOSTERONE, FREE (DIALYSIS) 151. 6 35.0-155.0 pg/mL
TSH 3.49 0.40-4.50 mIU/L
T4, FREE 1.2 0.8-1.8 ng/dL
T3, FREE 3.1 2.3-4.2 pg/mL
IGF 1, LC/MS 122 52-328 ng/mL

DHT,LC/MS/MS 56 12-65 ng/dL
HEMOGLOBIN 17 13.2-17.1 g/dL
HEMATOCRIT 50.3 38.5-50%
PROLACTIN 8.6 2.0-18.0 ng/mL
PSA 1.12 < or = 4.00 ng/mL
ESTRADIOL/ULTRASENSITIVE LC/MS 52 <OR=29pg/mL

I’m currently considering:
-Lowering my TRT dose
-HCG monotherapy
-Running a significantly lowered TRT dose with HCG
-Trying an AI

Any input would be much appreciated! And I’d love to hear any thoughts @Nelsonvergel may have. Thank you all in advance.
 

Cataceous

Super Moderator
I believe having testosterone higher than necessary can contribute to some problems, and it would be worthwhile for you to experiment with doses that moderate your free testosterone, perhaps a reduction of 20-25%. But this is unlikely to be a panacea. My hypothesis is that TRT can negatively affect libido and sexual function via its disruption of other hormones, and especially those hormones upstream of testosterone, which include LH, GnRH and kisspeptin. Your idea to add hCG is good, as this replaces the LH you are missing due to TRT. However, hCG is an imperfect replacement, and in particular it can disproportionately raise estradiol, which may be problematic for guys like you who are already aromatizing at an above-average rate. Therefore I would not even bother considering hCG monotherapy, which already has a low overall success rate.

I would hold the AI in reserve for now. Maybe you'd want to experiment if you have problems that are pretty clearly linked to estrogenic action, or if your estradiol/testosterone ratio further increases, which it could with the addition of hCG.

Another option to consider is the use of a testosterone nasal gel, such as Natesto. Think of this as TRT-lite. You get the benefits of boosted testosterone without the drawbacks of a complete HPTA shutdown; your body is still able to produce those upstreams hormones that could be important.
 
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Jucaro

Active Member
I believe having testosterone higher than necessary can contribute to some problems, and it would be worthwhile for you to experiment with doses that moderate your free testosterone, perhaps a reduction of 20-25%. But this is unlikely to be a panacea. My hypothesis is that TRT can negatively affect libido and sexual function via its disruption of other hormones, and especially those hormones upstream of testosterone, which include LH, GnRH and kisspeptin. Your idea to add hCG is good, as this replaces the LH you are missing due to TRT. However, hCG is an imperfect replacement, and in particular it can disproportionately raise estradiol, which may be problematic for guys like you who are already aromatizing at an above-average rate. Therefore I would not even bother considering hCG monotherapy, which already has a low overall success rate.

I would hold the AI in reserve for now. Maybe you'd want to experiment if you have problems that are pretty clearly linked to estrogenic action, or if your estradiol/testosterone ratio further increases, which it could with the addition of hCG.

Another option to consider is the use of a testosterone nasal gel, such as Natesto. Think of this as TRT-lite. You get the benefits of boosted testosterone without the drawbacks of a complete HPTA shutdown; your body is still able to produce those upstreams hormones that could be important.
@Cataceous , I have read that AI are not very helpfull to control estradiol when it comes from HCG use, How much of this is true?
 

Willyt

Well-Known Member
Why not take a break from TRT and see if libido comes back? Your pre-TRT numbers were damn good.

If you stay on TRT, try reducing or eliminating DHEA and Preg. I've read more than a few accounts on here of those two hurting more than helping. Even small amounts of DHEA gives me E2 symptoms by the second day.
 

Cataceous

Super Moderator
@Cataceous , I have read that AI are not very helpfull to control estradiol when it comes from HCG use, How much of this is true?
It's true that aromatase inhibitors operating via competitive inhibition can be less effective in the intratesticular environment due to the much higher concentration of testosterone, typically an order of magnitude greater than serum levels. HCG acutely stimulates aromatization in Leydig cells, while also increasing intratesticular testosterone. This combination makes for a source of estradiol that is resistant to inhibition. The overall effect depends on what fraction of total estradiol is created instratesticularly. This reference cites a figure of 20% for typical males. With this figure it would seem as though serum estradiol could still be influenced significantly. However, I can envision individual cases in which hCG use increases the fraction of estradiol created intratesticularly, perhaps significantly. In these instances aromatase inhibitors such as anastrozole might indeed appear to be weak. The outcome would also be undesirable if local estradiol production in areas like the brain is crushed even as serum levels appear to be ok.
 

RP McMurphy

New Member
Why not take a break from TRT and see if libido comes back? Your pre-TRT numbers were damn good.

If you stay on TRT, try reducing or eliminating DHEA and Preg. I've read more than a few accounts on here of those two hurting more than helping. Even small amounts of DHEA gives me E2 symptoms by the second day.
Thanks for the response, @Willyt, I appreciate it! I've stopped TRT for the moment, cycling in some hCG and clomid to kickstart the system, and currently assessing what move to make next...
 

Guided_by_Voices

Well-Known Member
It sounds like fatigue is at the root of your issues and from what I recall from hearing the stories of people who've overcome fatigue, I don't remember TRT being the primary issue. You may want to consider getting a full work-up done from a holistic functional medicine Doc who specializes in fatigue. I seem to remember that unresolved infections are often an issue. Do a search for the book by P.D. Mangan who overcame chronic fatigue. Personally, I would not have thrown another variable into the mix by trying to come off of TRT until you know what's going on with the fatigue issue since trying to do a restart could create fatigue on its own.
 

RP McMurphy

New Member
I believe having testosterone higher than necessary can contribute to some problems, and it would be worthwhile for you to experiment with doses that moderate your free testosterone, perhaps a reduction of 20-25%. But this is unlikely to be a panacea. My hypothesis is that TRT can negatively affect libido and sexual function via its disruption of other hormones, and especially those hormones upstream of testosterone, which include LH, GnRH and kisspeptin. Your idea to add hCG is good, as this replaces the LH you are missing due to TRT. However, hCG is an imperfect replacement, and in particular it can disproportionately raise estradiol, which may be problematic for guys like you who are already aromatizing at an above-average rate. Therefore I would not even bother considering hCG monotherapy, which already has a low overall success rate.

I would hold the AI in reserve for now. Maybe you'd want to experiment if you have problems that are pretty clearly linked to estrogenic action, or if your estradiol/testosterone ratio further increases, which it could with the addition of hCG.

Another option to consider is the use of a testosterone nasal gel, such as Natesto. Think of this as TRT-lite. You get the benefits of boosted testosterone without the drawbacks of a complete HPTA shutdown; your body is still able to produce those upstreams hormones that could be important.
@Cataceous thanks so much for such a detailed and informative response. Greatly appreciated!

Great suggestion re Natesto. Wondering if Natesto and hCG or Natesto and clomid might be the way to go? I'm leaning towards one of these combos as a next step...

If I decide to stay on TRT, I will add in hCG and also lower the dose...appreciate the target of 20-25% lower FT. I'm also considering cycling in low dose clomid along with a lower dose of injectable testosterone...this was what my doctor (Mark Gordon) initially recommended. I've seen some people on the forum poo poo TRT+clomid use, but from what I can tell there seem to be differing opinions?

I will table hCG monotherapy and put the AI on the backburner based on your recommendation.

Also any thoughts on me going back to clomid monotherapy given the positive experience I had (despite the lowering of IGF-1)?.... I'll likely be supplementing 1iu of HGH anyway...

Thank you.
 

RP McMurphy

New Member
It sounds like fatigue is at the root of your issues and from what I recall from hearing the stories of people who've overcome fatigue, I don't remember TRT being the primary issue. You may want to consider getting a full work-up done from a holistic functional medicine Doc who specializes in fatigue. I seem to remember that unresolved infections are often an issue. Do a search for the book by P.D. Mangan who overcame chronic fatigue. Personally, I would not have thrown another variable into the mix by trying to come off of TRT until you know what's going on with the fatigue issue since trying to do a restart could create fatigue on its own.
@Guided_by_Voices I appreciate you weighing in! You are spot on re attempting to get to the root of fatigue issues with a good functional medicine doctor. I've worked with some of the best functional medicine docs around (spending more than the GDP of a small African country in the process). I've made significant progress over many years combatting fatigue (initially due to toxic mold exposure), and I'm alway tweaking the system and hitting it from multiple angles in an attempt to improve as much as I can. Mold exposure can wreck the pituitary, and I had significant improvements supplementing hormones such as pregnenolone, DHEA, cortisol, and thyroid...which is what led me to experimenting with TRT. I'll have a look at the book you recommended. Thanks so much for you help.
 

TRicker

Member
and I had significant improvements supplementing hormones such as pregnenolone, DHEA, cortisol, and thyroid.
Which of these gave you the best resolution of the fatigue, in your opinion?

The one thing TRT has never done for me is resolve fatigue issues. I recently experimented with T3 (cytomel) for higher Reverse T3, but it did nothing for me. I did not experience increased energy, nor any fat loss, so I ceased the T3 as it appears thyroid was not my problem. I have a cortisol test scheduled, as I've been told by 2 Dr's that I have "adrenal fatigue" from stressful jobs. However, their recommendation is to get more rest and relaxation...LoL...sounds great...LoL. Now I'm interested in cortisol supplementation.
 

Systemlord

Member
Systolic blood pressure also increased from 120 into 130’s on TRT, and at times felt a bit amped up, and possibly fatigued.
The last thing we men think about when fatigued is sex, the estrogen level, excessive androgens may be responsible. Constantly elevated levels could also be the issue.

Be aware DHEA increases estrogen in men, so unless you really need DHEA, maybe try stopping it before starting on an AI.

I have problems on injections, non responder to all but daily and EOD protocols, except very bizarre symptoms (super low blood pressure when sleeping) when levels start getting very steady.

Jatenzo was a very different experience and outcome.
 
Last edited:

Cataceous

Super Moderator
@Cataceous thanks so much for such a detailed and informative response. Greatly appreciated!

Great suggestion re Natesto. Wondering if Natesto and hCG or Natesto and clomid might be the way to go? I'm leaning towards one of these combos as a next step...

If I decide to stay on TRT, I will add in hCG and also lower the dose...appreciate the target of 20-25% lower FT. I'm also considering cycling in low dose clomid along with a lower dose of injectable testosterone...this was what my doctor (Mark Gordon) initially recommended. I've seen some people on the forum poo poo TRT+clomid use, but from what I can tell there seem to be differing opinions?
...
Also any thoughts on me going back to clomid monotherapy given the positive experience I had (despite the lowering of IGF-1)?.... I'll likely be supplementing 1iu of HGH anyway...
If you can get it, enclomiphene is preferred over Clomid/clomiphene. Clomid is just enclomiphene and zuclomiphene. The latter is estrogenic and usually unhelpful. Resuming SERM monotherapy is a reasonable option, especially since you did well with Clomid. I would not use hCG with Natesto or a SERM because it can be suppressive and work against the HPTA function you're trying to maintain or stimulate. Natesto with a SERM is potentially viable and maybe even beneficial. Natesto still suppresses the HPTA a little and a SERM would tend to counteract that.

I believe that adding a SERM such as enclomiphene to conventional TRT will most often fail to significantly stimulate the HPTA. The matter has not been decided definitively, as there are anecdotes going both ways. It's true that estrogens form the most potent mechanism of negative feedback in the HPTA, and SERMs can block this feedback. However, androgens also provide negative feedback at the hypothalamus, and SERMs do not affect this. I use enclomiphene with TRT, but this is in conjunction with gonadorelin (GnRH), which effectively bypasses the hypothalamus and directly stimulates the pituitary to make LH. I also see a drop in IGF-1 with enclomiphene use, though not as dramatic as yours. In a way it's beneficial to me because it allows me to use ipamorelin as a sleep aid with less worry about elevating IGF-1.
 

RP McMurphy

New Member
Which of these gave you the best resolution of the fatigue, in your opinion?

The one thing TRT has never done for me is resolve fatigue issues. I recently experimented with T3 (cytomel) for higher Reverse T3, but it did nothing for me. I did not experience increased energy, nor any fat loss, so I ceased the T3 as it appears thyroid was not my problem. I have a cortisol test scheduled, as I've been told by 2 Dr's that I have "adrenal fatigue" from stressful jobs. However, their recommendation is to get more rest and relaxation...LoL...sounds great...LoL. Now I'm interested in cortisol supplementation.
For my specific situation pregnenolone had the biggest positive impact...my natural levels were close to undetectable due to my history with mold. Hydrocortisone helped for a period of time when I needed an adrenal reboot...I've found that a saliva cortisol test is the best way to check. I always start slow and cautiously with hydrocortisone (can raise blood glucose among other things) and consider dessicated adrenal glandular as a starting point.
 

sammmy

Well-Known Member
It doesn't sound like TRT (that you didn't need) or the excessive number of other supplements that you take resolved your original issues.

It is best to stop them all and start testing supplements one by one searching for an actual benefit. If you are currently taking external cortisol, it has to be tapered off, since it shuts down the natural body production and suddenly stopping it may lead to adrenal crisis.
 

GreenMachineX

Well-Known Member
I believe having testosterone higher than necessary can contribute to some problems, and it would be worthwhile for you to experiment with doses that moderate your free testosterone, perhaps a reduction of 20-25%. But this is unlikely to be a panacea. My hypothesis is that TRT can negatively affect libido and sexual function via its disruption of other hormones, and especially those hormones upstream of testosterone, which include LH, GnRH and kisspeptin. Your idea to add hCG is good, as this replaces the LH you are missing due to TRT. However, hCG is an imperfect replacement, and in particular it can disproportionately raise estradiol, which may be problematic for guys like you who are already aromatizing at an above-average rate. Therefore I would not even bother considering hCG monotherapy, which already has a low overall success rate.

I would hold the AI in reserve for now. Maybe you'd want to experiment if you have problems that are pretty clearly linked to estrogenic action, or if your estradiol/testosterone ratio further increases, which it could with the addition of hCG.

Another option to consider is the use of a testosterone nasal gel, such as Natesto. Think of this as TRT-lite. You get the benefits of boosted testosterone without the drawbacks of a complete HPTA shutdown; your body is still able to produce those upstreams hormones that could be important.
How does Natesto not shut one down?
 

sammmy

Well-Known Member
Natesto shuts down gonadotropins by a lesser degree:

Testosterone shutdown.JPG
 
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