A treatment candidate to reduce HPTA suppression under TRT. Possible hCG alternative?

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Cataceous

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TL;DR: Some research suggests that echinacoside may complement a SERM in reducing TRT-induced negative HPT-axis feedback at the hypothalamus.

Background: In testosterone replacement therapy, elevated levels of testosterone and estradiol apply negative feedback to the hypothalamus. This suppresses the release of kisspeptin, which in turn suppresses the production of gonadotropin releasing hormone (GnRH). The lack of GnRH in turn suppresses production of LH and FSH at the pituitary,† which can then lead to a loss of endogenous testosterone production, testicular atrophy and infertility. It's hypothesized that some men experience other side effects caused directly by the reduction in upstream hormones.

Various treatments have been used to counteract HPTA suppression under TRT:

HCG Human Chorionic Gonadotropin (hCG) is the best known. HCG acts as a replacement for LH. It stimulates the Leydig cells, which can lessen testicular atrophy and restore fertility in many cases. Subjective benefits are often reported. HCG does not help with the loss of FSH and the upstream hormones.

SERMs Because selective estrogen receptor modulators (SERMs) are known to stimulate the HPTA in normal men and women, they have been used with TRT in an attempt to keep the HPTA going. However, this appears to fail most of the time. The reason why is that SERMs are limited to blocking negative feedback from estradiol at the hypothalamus and pituitary. The negative feedback of testosterone at the hypothalamus is left unchecked.

High-dose GnRH Royal Medical Center has published numerous case studies suggesting that once- or twice-weekly high doses of GnRH can stimulate production of LH and FSH. It may be that the relatively high doses overcome estradiol's negative feedback at the pituitary. Our assumption is that each isolated injection results in only single pulses of LH and FSH, a far cry from endogenous patterns. It's unclear if this is sufficient to do things like reverse testicular atrophy or restore fertility.

Low-dose GnRH Described here, this complicated treatment bypasses the hypothalamus, using pulsed physiological doses of GnRH to stimulate the pituitary to produce LH and FSH. A SERM is used to prevent negative feedback from estradiol at the pituitary.

Discussion: In commenting over the years on the failure of TRT + SERM to maintain HPTA function, I have noted that we need a selective androgen receptor modular (SARM) to add to this to make it work; the ideal SARM would block negative feedback from androgens at the hypothalamus. Now, thanks to a tip from @ajax31, I see that there is a potential candidate that has been hiding in plain sight:

... these data demonstrate that [echinacoside] blocks [androgen receptor] activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats.

Those in-the-know may already have recalled that echinacoside is a significant component of plants in the Cistanche genus. In the U.S., Cistanche plant extracts are readily available as dietary supplements. Cistanche is mentioned a few times in the forum, sometimes in the context of post-cycle treatment. This supplement has definitely been on the radar as an HPTA stimulator. It's just not obvious to me if it has been used in conjunction with TRT.

Conclusion: There is a chance that adding enclomiphene and Cistanche plant extract to a TRT protocol would result in HTPA activity. Even if this works, there is uncertainty about the subjective results. Anecdotally, we have seen several men experiencing poor subjective results with enclomiphene monotherapy, in spite of good numbers. Would the same apply to this combo therapy, or does the exogenous testosterone create a different situation? Speaking for myself, I continue to have good results with a protocol that includes both exogenous testosterone and enclomiphene. I could be an outlier, but only time and experimentation will tell.

†Estradiol also applies negative feedback directly to the pituitary.
 
Defy Medical TRT clinic doctor
Great information!
I have used cistanche successfully multiple times post cycle but never while on trt.
I'm currently using Natesto but doing to well with long-term.
After reading this post I will certainly try injection plus trt to see what happens.
Would consider enclomiphene to if available without to much hassle.
S.J.
 
Historically my numbers would drop off to around 250 to 280 TT when stopping cypionate.
Cistanche would bring me back to base sooner @ around 500 TT.
There is a slight bump in sex drive and a better sense of well being.
I have my blodwork scattered throughout my email.
I'll see if I can find some to reflect the use of Cistanche.
Though Natesto shouldn't affect HPTA all that much I'm going to add Cistanche back into my regimen until I switch back to injectable.
Also I'm going to try the Lost Empire Herbs brand of Cistanche. It's pricey @ $70.00 but potent stuff.
I'm currently using their Pine Pollen which is a good product at a lesser price.
Pine Pollen has helped my morning wood to reappear more consistently.
We'll see how long this is to last.
S.J.
 
My protocol is Test Cyp 20mg IM MWF, HcG 250 IU MWF and FSH 75 IU MWF. This keeps my TT 900-1000, E2 40-50 and I feel like a machine. Yes, I only take 60mg of total Test per week. The HcG is potent for me. Also had a sperm count of 40 million with normal forms and motility. I’m 54 years old.
 
My inability to take hcg is what lead me down the road to herbs
for recovery. Particularly Cistanche.
HCG in any amount sends me into sweats and anxiety like crazy.
If not for that I'm sure that my protocol could be similar.
 
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My protocol is Test Cyp 20mg IM MWF, HcG 250 IU MWF and FSH 75 IU MWF. This keeps my TT 900-1000, E2 40-50 and I feel like a machine. Yes, I only take 60mg of total Test per week. The HcG is potent for me. Also had a sperm count of 40 million with normal forms and motility. I’m 54 years old.
It's good that you're doing well on a protocol with sensible dosing. Hopefully my worries about GnRH suppression are unfounded. But given the improvements I saw when I began supplementation, along with the information in the posts below, I personally would no longer use a protocol that keeps GnRH at low levels.
 
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