Building a TRT protocol around hCG

[FunkOdyssey]

Are we talking about Pregnyl pharma brand name HCG or compounded HCG? From the threads I've read here, it sounds like most are having more success with Pregnyl

There is no longer any such thing as compounded hCG due to changing regulations. My impression is that most people these days are using Indian generic brands of hCG due to the drastically lower cost than pregnyl. The eutrig brand I'm using is a urine-derived hCG with a good reputation for potency.

 

[FunkOdyssey]

This experiment has not gone very well for me so far. I've been on hCG for over a month now, with some varying doses at first but settling at 150 iu daily, combined with 15 mg test cyp daily. I did feel some improved sensitivity in the beginning, which went away. I also noticed signs of life in the testicles, like sensations of pressure or tingling.

There are two serious issues that developed though. First, very bothersome (painful, itchy) cystic acne on my chest and back. In the past, I've recorded free T as high as the 90's ng/dL and E2 also ~90 pg/mL without encountering this problem, so I am confident the mechanism is not related to either of those hormones. The potential mechanisms here are interesting (GPT):

1. Direct activation of sebaceous LH/hCG receptors​

• Human epidermis, hair follicles and sebaceous glands express full-length luteinizing-hormone / hCG receptors capable of binding radiolabeled hCG.PubMed
• In cultured SEB-1 sebocytes, hCG (or db-cAMP/forskolin) boosts de-novo testosterone synthesis from cholesterol, showing that the receptor is not just decorative.Wiley Online Library
  Why this matters: you can keep serum T/DHT modest while still delivering a local “micro-dose” of androgens right inside the follicle where acne starts.

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2. Adrenal back-door androgens​

Adrenal cortex (zona reticularis) also carries LHCGR. hCG infusions or tumors that over-secrete hCG raise DHEA-S and androstenedione independent of ACTH.PMC These weak androgens are ideal sebocyte fuel because they are rapidly converted to T → DHT inside the skin. In some men they rise more than T does, tipping the local androgen balance.

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3. Progesterone & pregnenolone surge​

hCG stimulates the whole Δ5 steroid pathway in the testis; pregnenolone and progesterone can jump 5- to 20-fold in classic stimulation tests.

• Sebaceous glands express functional progesterone receptors as well as 5α-reductase; progesterone metabolites (5α-dihydroprogesterone, allopregnanolone) have been shown to up-regulate sebocyte lipogenesis in rodents and some human models.PubMed
  Even if serum levels stay in the “normal male” range, the combo of higher substrate plus receptor activation can amplify sebum output.

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4. IGF-1 crosstalk​

hCG up-regulates IGF-1 receptor mRNA and surface density in steroidogenic cells through a cAMP pathway.PubMed IGF-1, in turn, is a well-established sebocyte mitogen that also boosts IL-1β, IL-6, IL-8 and TNF-α production.Annals of Dermatology
If your baseline diet/hormone milieu already keeps IGF-1 on the higher side, the receptor up-regulation makes sebocytes hypersensitive to the same IGF-1, adding an inflammatory layer to the androgen hit.

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5. Inflammatory priming via cAMP → NF-κB​

LHCGR is a Gs-coupled receptor; in sebocytes the resulting cAMP/PKA signal can feed into CREB and NF-κB, transiently raising pro-inflammatory cytokines even without bacteria. That helps explain why some users report red, inflamed papules within 24–48 h of each hCG shot before any comedones mature.

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Secondly, this protocol absolutely crushed my libido, taking my previous 3-4 out of 10 on 35 mg test cyp EOD (no hCG) down to zero. I am finding my attractive wife almost repulsive right now. Again, I have had very high E2 before without experiencing anything like this, so that seems unlikely as the culprit. I ran some comprehensive bloodwork a couple days ago which will hopefully shed some light on this, including DHT, preg, prog, 17-OH prog and prolactin along with the usual markers. I would guess that the progesterone and allopregnanolone surge is probably involved, as I have reacted similarly with dead libido after previous experiments with injected and topical progesterone. Perhaps a dropping DHT/E2 ratio relative to my TRT monotherapy baseline could also be a factor.

If I were not going on a family vacation next month where my shirt was going to be off all the time, I might experiment with a lower hCG dose like 75 IU daily. For now, I have to prioritize clearing up my skin, so the hCG experimentation is over for the moment.

 

[Willyt]

Damn that is disappointing. I was inspired by this post to order some Pregnyl from Defy.

Any comments on other areas such as sleep, mental cognition, energy levels, athletic performance?

 

[FunkOdyssey]

Damn that is disappointing. I was inspired by this post to order some Pregnyl from Defy.

Any comments on other areas such as sleep, mental cognition, energy levels, athletic performance?

I still think it is going benefit most people, and hope you won't be discouraged from your own experimentation. With my history of accutane and SSRI use, I am likely broken in some unique ways. And I will probably still try a lower dose again, when I return from vacation.

Sleep has not been noticeably affected. Was cognition a little better? Maybe - it is hard to say. I should probably have tried to quantify that with some cognitive testing. Energy and lifting progress was not different either.

 

[Willyt]

I still think it is going benefit most people, and hope you won't be discouraged from your own experimentation. With my history of accutane and SSRI use, I am likely broken in some unique ways.

Sleep has not been noticeably affected. Was cognition a little better? Maybe - it is hard to say. I should probably have tried to quantify that with some cognitive testing. Energy and lifting progress was not different either.

So overall nothing positive. Bummer. Let us know your test results and if you try the 75 iu daily after your trip.

 

[FunkOdyssey]

So overall nothing positive. Bummer. Let us know your test results and if you try the 75 iu daily after your trip.

All I got out of hCG was a bunch of E2. The preg/prog/17-OHP and presumably allopregnanolone that I was expecting to rise all remained bottomed out. DHT/E2 ratio almost halved.

ChatGPT led me to believe this low dose daily hCG was going to be an efficient way to raise most of the TRT-disrupted neurosteroids into the normal range, but it now claims they are mostly derived from the adrenal glands, and only large bolus doses of hCG are able to produce measurable increases. I think I receive about 50% useful advice and 50% gaslighting from this tool.

Why your labs look “backwards”​

1. Most of the pregnenolone→progesterone pathway is paracrine inside the testis.
   hCG triggers cholesterol import (StAR) and side‑chain cleavage (P450scc), so intratesticular pregnenolone and progesterone rise quickly, but very little of either leaks into the systemic circulation — they are immediately converted downstream to androgens and estrogens inside the Leydig cell. In a classic spermatic‑vein study, pregnenolone, progesterone and 17‑OH‑progesterone shot up after an hCG bolus, yet peripheral venous levels barely changed.
2. Estradiol does spill into the bloodstream.
   The testis contains abundant aromatase; even a low dose such as 150 IU/day can create a disproportionately large increase in E2, which then persists because estradiol’s plasma half‑life (2‑3 h) is longer than that of the upstream pro‑hormones. That is exactly what happened in your panel: Sensitive E2 jumped from 30 → 51 pg/mL, while pregnenolone stayed at 10 ng/dL and 17‑OHP remained low.
3. Serum pregnenolone and 17‑OHP are mostly adrenal in origin.
   Low‑dose hCG has no effect on ACTH, so the adrenal contribution can stay flat or even fall if TRT has already quieted the HPA axis. That further masks any small testicular contribution in a peripheral blood draw. A Belgian cohort on long‑term hCG + rFSH showed lower serum progesterone than controls despite vigorous spermatogenesis, underscoring this dissociation.
4. Timing matters.
   Peak testicular pregnenolone after an hCG shot occurs within ~1 h locally and decays within 3‑4 h; your blood was drawn the afternoon after a morning injection, when any transient systemic bump would already be gone.

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How common is “big E2, flat pregnenolone / 17‑OHP”?​

• Quite common at doses ≤ 250 IU SC per shot. Clinicians who track 17‑OHP as a surrogate for intratesticular T see meaningful rises mainly at ≥ 500 IU 2–3×/wk; below that, ~50 % of men show no serum change even though IT‑T does rise in biopsy studies.
• Anecdotal TRT forums echo this: many users report sharp estradiol increases without noticeable movement in pregnenolone or progesterone until they exceed 350–500 IU per injection or measure spermatic‑vein levels directly.

So your pattern is expected, not an outlier.

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What it means for your protocol​

If the goal is…	Then hCG at 150 IU/day will…	What to adjust
Raise intratesticular T for fertility	Probably adequate (17‑OHP is insensitive at this dose)	Confirm with semen analysis or bump to 250–500 IU EOD if IT‑T is critical.
Lift neurosteroid precursors for mood/libido	Unreliable; serum pregnenolone stayed very low	Direct pregnenolone (e.g., 20–30 mg AM) or modest DHEA may be needed.
Avoid a big estradiol swing	Failed (E2 +70 %)	Lower to 75 IU/day or switch to two 250 IU shots per week to blunt daily aromatase stimulation.
Boost DHT‑driven libido	Inefficient (DHT flat)	Consider adding 5 mg DHT enanthate or a low‑dose DHT cream while holding hCG dose steady.

Key take‑away: low‑dose hCG is excellent at re‑igniting the aromatase arm of the Leydig cell but is too small, too transient, and too “local” to show up as higher pregnenolone/progesterone/17‑OHP in a routine venous draw. That biochemical profile is seen in many men and becomes obvious only when you compare peripheral labs to how you feel.

 

[Seagal]

ChatGPT imitates MDs
With deepseek deep thinking activated I can follow the internal reasoning and ask critical follow-up questions. After few follow-up questions the output seems reasonable to me whether it's then accurate and unbiased is another problem.

 

[Seagal]

Great experiment. Thank you for sharing!

 

[Willyt]

Appreciate the results @FunkOdyssey . That is quite a jump in E2.

Why would the bolus from larger, presumably less frequent dose improve the disrupted neurosteroids verus daily?

 

[FunkOdyssey]

Appreciate the results @FunkOdyssey . That is quite a jump in E2.

Why would the bolus from larger, presumably less frequent dose improve the disrupted neurosteroids verus daily?

If I understand correctly, the precursor hormones to testosterone that are produced in the testicles are not supposed to "leak out" under normal circumstances. They are instead consumed in the process of manufacturing testosterone. It is only with relatively massive doses of hCG that you can bottleneck some of the intermediate steps, and consequently some of the precursor hormones now accumulate and spill into the blood.

Nothing about the infrequent bolus dosing is stable or mimicking normal physiology. But, some guys seem to do very well on it anyway.

 

[Willyt]

If I understand correctly, the precursor hormones to testosterone that are produced in the testicles are not supposed to "leak out" under normal circumstances. They are instead consumed in the process of manufacturing testosterone. It is only with relatively massive doses of hCG that you can bottleneck some of the intermediate steps, and consequently some of the precursor hormones now accumulate and spill into the blood.

Nothing about the infrequent bolus dosing is stable or mimicking normal physiology. But, some guys seem to do very well on it anyway.

So are you officially done with the HCG? Or will you adjust and try again?

 

[FunkOdyssey]

So are you officially done with the HCG? Or will you adjust and try again?

I'm a glutton for punishment so I will be trying again with a lower dose. DHT enanthate first though.

 

[Seagal]

Estradiol non-linearity
DHT up and E2 down seems a direction to explore. What you pointed out, your DHT to E2 ratio.

No new information to you however nice plots

Relation of Testosterone, Dihydrotestosterone, and Estradiol With Changes in Outcomes Measures in the Testosterone Trials - PMC

Many effects of testosterone are mediated through dihydrotestosterone (DHT) and estradiol. To determine the relative contributions of each hormone to the observed effects of testosterone treatment in older men with hypogonadism. Using data from the ...

pmc.ncbi.nlm.nih.gov