Don’t run the HCG at the same time as the SERMS. HCG will suppress the pituitary while the SERM tries to increase its function.
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Yes I will be doing 1000iu eod first 2 week then nolva clomid
I know it will be a roller coaster but this is my last resort
Ok, doing HCG first is fine.
Great explanation, thank you. I think that my next step will be to run clomid every day at 15 mg for 3 months, then get bloods done again. I
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This is good advice.
Understanding HPTA control loop should be a prerequisite for AAS use. If you understand how the loop works, diagnosing issues and making intelligent decisions becomes much easier.
It was mentioned earlier, Clomid monotherapy. Not as common but the results are usually pretty good. Low dose a few times a week can maintain good test levels. But it’s going to be just like testosterone in that when you stop using it your numbers will start to slip again. Without intervention you’ll see a mean reversion.
So then you are basically saying it isn’t even worth it, and I would have to be on it permanently to see lasting results?
Do you believe that if clomid therapy brought my levels up to ~500 from the current 177 ( just for example sake)… then…
Once I stop taking it, the “mean reversion” you speak of will drag the levels back down to the 177 I am at now? You do not believe I could naturally be producing in the 300 range after stopping the clomid therapy or is it just completely unknown until tested?
If stopping clomid therapy, would my natural test levels crash below the 177 level it is at now? I can’t handle another complete test crash, I would rather not even try the therapy.
I have found the main studies where this has been proven to work, but none of them mention testing levels once discontinuing the therapy. Can anyone find one if they are feeling up to it? I’ve found three so far, none of which test after discontinuation.
If 177 is your baseline then you’d likely return to somewhere around there. Possible you stay well above that—like in the 300’s as you mentioned—for a while before nature takes over. I started trt because I was around 300, so it’s not like that’s a number you want to shoot for. If that ends up being your best case scenario as a natty then you’ll have to get to that point and then assess whether or not you can live that way. Maybe for you 300 ends up being not that bad? Hard to predict how individuals will respond to any of this.
Thanks for the response. I really don’t feel “THAT” bad at 177. My mood is good, not depressed, Maybe just slightly lower energy level than used to be. Really the only remaining differences I feel are a bit more lethargic, tad less motivation and concentration, but If I go to the gym everyday, seems to help. So I think if I could get back to 300, I would be very happy.
From all that I have read, you really only need to be around 300 to build and maintain muscle mass. So If my mood is good now, it should be even better at 300, and if I can build and maintain muscle even just a little at 300 I will be stoked. I used to be very big, but now I am ok with just being “Fit” and having some definition.
For me at least, the difference between high and low test is how much fat I hold to be at a certain muscularity. I can be leaner with the same muscle, when I cut, I keep a lot more muscle. When I gain more of it is muscle.
I was big and strong with test around 400 ng/dL, but I was also pretty fat.
I think clomid mono therapy might be a good option for you. It seems doses like 10-15 mg per day can have awesome results in many. There is a log you could dig up from a few years ago where a guy got his TT to 800ish with IIRC 12.5 mg per day. This individual found that increasing dose did not lead to higher TT, so he kept it at 12.5 mg/day.
I think a possibility is that you regain some ball function while on, and upon stopping you may get more out of your natural LH and FSH production. This is a possibility, not a certain at all.
At the same time, I am not sure if you will have any perceived negative side effects from clomid if the dose is low enough. Might be worth running long term. For some it loses effectiveness over time, so that is something to look out for.
I don’t think it’s you. The explanation is clearly without any sense. There’s no need for endogenous LH production when you supplement HCG (exogenous “LH”). The explanation must be wrong. I think the solution could be a desensitization of the LH receptors as happens with leuprorelin administration on the GnRH receptors. There’s two possibilities:
- It was just way too much hCG or
- There was too high a level hCG in the blood over time
And it took me a bit but I found this study supporting my theory:
The testosterone response to hCG in vitro was completely inhibited for about 3 days, then rose to the control level at 5 days, when only a small proportion of the original receptor sites and cyclic AMP response had begun to return
Since I know you love graphs I’ll include this one
Edit: I should note that the response to hCG With functioning testicles is highly individual and the dose-response relationship is not linear
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I think he didn’t know but he knew instinctively it was too much.
One question came to mind as I read the article. Is the doc right about the E receptors in the hypothalamus being the only receptors for the feedback loop?
I did my own research months ago and read a few studies that suggested that there are T receptors responsible for the feedback, too.
Just wanted to get your opinion on this.
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This is nice! Thanks for the input, that’s what I came around to when I researched it but I read other studies so thanks for the support
This natesto seems like it could be a revolutionary step in TRT practice! I’m stunned by the fact that the feedback doesn’t get inhibited (as strongly) by pulsatile administration but since GnRH receptors work the same it’s not that outlandish a thought.
(i) pulsatile T is less effective than continuous T delivery in suppression of LH secretion, (ii) T feedback is reduced by BMI, and (iii) basal and total, but not pulsatile, LH secretion, estimated by deconvolution analysis is negatively correlated to visceral fat and total abdominal fat area, calculated from a single CT slice at L3-L4.
That’s what the study found. I like it, but we always gotta keep statistics in mind. Deconvolution is not the best way of getting data.
What’s also interesting was that free T and LH secretion correlated negatively with BMI (I think we knew that) which shows us again that fat people are hormonally fucked.
This might be a compensatory mechanism to decreased LH secretion in severe obesity
I’m surprised they got this approved by an ethics committee cause I wouldn’t be excited about getting 800 mg of Ketoconazole orally haha!
The discussion in the end about glucocorticoids and emotions is definitely a topic for another day.
A major discovery recently is that the pulsatility of cortisol is required for normal emotional and cognitive responses in man [42]
To the OP: I think you got some really good input here, I wish you and your family the best and report back how your fertility and T levels are going!
Also OP, maybe your Willy grows on HCG:
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Nice find. It seems to be way more difficult to apply HCG right than we thought. I saw studies where people are given 3000 IU (I recently saw one with 5000 IU ED) hCG for a few weeks which should definitely be enough to suppress T production but it didn’t happen (at least not in that limited time frame, think it was 3-4 weeks). As I stated above: the effect is highly individual which shows is again how important bloods are.
If we are on the topic of hCG, there’s one thing I want to point out/discuss.
I repeatedly saw the mantra “AIs won’t stop the aromatization induced by hCG” on this forum and I’d like to get a rationale for that as I couldn’t verify this and my understanding would suggest otherwise. I’ll give my opinion:
HCG increases E2 before it increases T. Several studies show that E2 is highest 24 h after HCG dosing and T 72 h. (Won’t link that) Here you can see an example of acute stimulation of aromatization by hCG in Leydig cells independent of T production:
This could mean that the LH receptor regulates aromatase expression and voila, it does:
With 50 ng/ml oLH, a large augmentation (twofold) of the P450arom mRNA level either without or with testosterone was observed.
With that in mind the only question becomes if AIs get into the Leydig cells (primary T and E2 producers in man) so they can inhibit the aromatase there.
Since the next study shows that non-steroidal AIs readily cross the blood brain barrier, it’s safe to assume they pass the blood testis barrier. They are lipophilic and only anastrozole gets actively transported out of the brain. (I couldn’t find studies about the concentration measured in the testis)
All this info leads me to believe that AIs do
- Get into the Testis and Leydig cells
- Inhibit the aromatase there
- Therefore inhibit aromatization by hCG
Finally this paper shows that AIs do prevent the increase of E2 caused by hCG
In the hCG group, the rate of testicular aromatase activity and testicular E2 level were higher and the diameter of seminiferous tubules was smaller than in the control group. However, these changes were not observed in the hCG+A.I. group
If some of you have evidence suggesting the contrary I’m open to change my opinion.
@anon18050987 I learned a lot too, thanks!
I got a few things I’d like to discuss in the near future: Glucucorticoids (find them extremely interesting and complicated, also in combination with androgens) and then a smaller one would be thyroid hormones (here we could also discuss differences with synthetic and swine derived (I heard it’s a difference but I didn’t research yet, don’t know what it contains right now). I’ll open up new threads then and I’d appreciate your opinion there too.
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My understanding was that the increase of e2 by HCG wasn’t via aromatase, so an AI wouldn’t be able to control it. The studies you linked show that’s not the case, so very interested to learn more about this. I’m one of those guys that doesn’t take HCG regularly for fear of higher e2
I tried to find an answer to that question too but it was difficult. One study wrote “all E2 from the Testis gets created through the aromatase enzyme complex” and others just used the higher aromatase activity as a reason.
Im skeptical myself because a few studies showed an increase in E2 after 1 hour with the peak at 24 h which seems a bit fast for an up regulation of the expression (takes a day usually so 24h makes sense).
It was also difficult to find studies linking LH to an upregulation of aromatase but the one I found supports it.
So we’re left with this non conclusive area. But if my hypothesis is wrong there are many questions:
- What means a higher activity of aromatase if not an increase in expression? It could be that aromatase enzymes are inactive in the cell per example as vesicles because it is an ER associated enzyme.
- If the AIs don’t block the aromatization, it shouldn’t happen through aromatase so what way is there to synthesize E2 in the testis without aromatase? (I touched on it in another lengthy post but I don’t think these ways happen in the testis on a large scale)
- Why does an AI seem to suppress the increase in E2 caused by hCG in some studies?
The easiest thing would be if we guys on here reported their blood results and experiment next time they PCT or are on TRT+hCG. Our own independent, no conflict of interest, crossover study.
I think the evidence I provide is the best we have right now. Let’s see if somebody finds additional knowledge.
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This paper supports everything we wrote about down regulation of LH receptors. It even hints at upregulation (indirectly through T administration).
I’m out for today and I’m excited to read your input tomorrow!
I looked into the intratesticular T concentrations a bit and that’s what I came up with:
LH and FSH were profoundly suppressed to 5% and 3% of baseline, respectively, and ITT was suppressed by 94% (1234 to 72 nmol/liter) in the T enanthate/placebo group. ITT increased linearly with increasing hCG dose (P < 0.001). Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group [all every other day], and 26% greater than baseline in the 500 IU hCG group.
Which leads me to believe, if you inject 500 IU two times weekly your intratesticar T levels are most likely within normal range (if you’re shut down and you inject more, you should also not get crazy high levels otherwise why inject that much when you respond well?) which means even a competitive AI will do it’s job.
For more info on competitive AIs see my Independence Day post here:
Now, even if a competitive AI like anastrozol doesn’t work, you’d always have the option of Exemestane to inhibit Aromatase which has different kinetics (see post) and simply doesn’t care about T level that much.
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