The indirect evidence mostly suggests I have little endogenous production of testosterone; serum levels are predicted pretty well by a proportionality to dose. This in spite of normal testicular volume and a slight positive on a fertility test. I saw the same when I was using hCG. I may be at the lower end of responsiveness.
Pituitary restart while on TRT: promising initial results with GnRH plus enclomiphene
Which makes your test results (TT peak in 600s?) all the more remarkable on such a low dose of 5.6mg daily (4.4 actual T). What is story behind why you ended up on this dose versus your earlier low dose protocols?
I am trying to better understand how low one can go while still experiencing the benefits of TRT.
The most recent TT reading was just a hair shy of 700 ng/dL at peak with the 4.4 mg daily. As for how I got to the current dose, it's a function of the 4:3 enanthate/propionate ratio, the 0.005 mL resolution of my syringes, and the subjective results. I first tried the blend in earnest using the next increment up, which provides 5 mg T daily. I ran this for a few months and it was pretty good. But peak TT was 900 ng/dL, which I felt was too high. Thus the bump down to 4.4 mg, which produced even better subjective results. I think I'd be fine on the next increment down, which provides 3.7 mg of testosterone daily. I've run three trials with this dose and never felt hypogonadal. I believe the subjective results weren't quite as good because I was attempting to go without enclomiphene, leading to a gradual reduction in the already lowish gonadotropins.
This is peak, correct? (4-5 hours post-injection?)
You mentioned that you likely have little endogenous production. But isn't there some minimal level that we produce naturally (e.g., 0.5 to 1mg daily) when on such low daily TRT doses? Otherwise, how could 4.4mg per day produce TT 700? In other words, are we talking about 4.4mg exogenous + [x]mg endogenous?
Perhaps I am just splitting hairs. But I'm just trying to recalibrate in my lizard brain how much TRT we actually need to mimic natural production of healthy non-hypogonadal older guys.
Yes. The indirect evidence suggests my serum testosterone peaks with propionate and propionate blends are around three hours post-injection, which is when this measurement was made.
According to Wikipedia, "The largest amounts of testosterone (>95%) are produced by the testes in men,[4] while the adrenal glands account for most of the remainder." If this figure is accurate then non-testicular production could get lost in the noise.
I'll split some hairs too: It's a tough habit to break, but we need to get away from linking total testosterone to the production rate. Total testosterone is also a reflection of how much SHBG one has. Instead we should use free testosterone, which is likely proportional to production or endogenous dosing. Therefore we'd observe that my Vermeulen free testosterone was 15.5 ng/dL, which is right about at the average for healthy young men. Now you can ask, how I can have that level with 4.4 mg of exogenous testosterone per day when the average natural production rate is 6-7 mg? My first observation is that 4.4 mg is still going to be within a couple standard deviations of average natural production, so it's not so unusual. My second observation is that the metabolic clearance rate drops with age, meaning I can expect more bang for the buck.
I think the vast majority of guys would be covered by 4-8 mg per day if it can be dosed to imitate a diurnal rhythm.
I apologize if you covered this earlier in the thread. But why Enanthate as opposed to cypionate?
When I started TRT I was having pretty significant injection site reactions to the testosterone cypionate product. I switched to enanthate, which improved the situation. I think my sensitivity has decreased over time, so I expect now I could use cypionate without as much discomfort. It's just inertia that keeps me from switching back. In terms of pharmacokinetics, cypionate and enanthate are nearly interchangeable.
FunkOdyssey
Seeker of Wisdom
Let me start by saying your protocol and the results are ground-breaking and fascinating. I'm thankful that you're documenting it so well and sharing it with everyone.
You've explored the impact of enclomiphene on your protocol by discontinuing it, with some confounding by simultaneous dose adjustment and lower serum testosterone. Have you done the same with gonadorelin? I would suggest the combination of dosing as low as yours combined with enclomiphene might result in some measurable HPTA activity without the gonadorelin.
I'm also curious about the impact of enclomiphene on your symptoms. It is widely reported that enclomiphene therapy produces eugonadal lab values in just about everyone with secondary hypogonadism. However, symptom resolution is often partial or nonexistent. When these same individuals progress to full-blown TRT, even with the same lab values, they usually report better results. The common explanation for this phenomenon is that it occurs due to blocking of estrogen receptors, whose activation is essential to fully realize the benefits of TRT. Everyone here knows testosterone doesn't do much besides muscle anabolism on its own -- it's basically a pro-drug for DHT and E2 in most tissues.
In other words, potentially half the benefit of TRT could be jeopardized by enclomiphene's ER antagonism. I'm curious whether you've noticed any negative impact from it. You would be an unusual example if there were truly none.
While I haven't definitively ruled this out, I would bet against it. There are a few anecdotal reports of TRT + enclomiphene yielding HPTA activity, but these are outweighed by reported failures and Dr. Saya's clinical experience. Even on the lower TRT dose my nominal daily peak TT is about 600 ng/dL and the trough is upper 300s. This is likely too much testosterone for too long to activate a hypothalamus that already has an unnaturally low set point.
Having tried going without enclomiphene more than once I can say that for me the results are degraded without it. This is unusual given the conventional wisdom you mention. I've speculated that my relatively high rate of aromatization is a contributing factor. If you start out with your E2/T ratio in the low-to-mid range of 0.3-0.4% then perhaps enclomiphene reduces estrogenic activity by too much in some locations. In contrast, I don't often see E2/T below 0.5%, and my average over the last couple years has been over 0.7%.
JustPanicNoDisco
Member
Great stuff, @Cataceous
I'd like to hear your opinion regarding using GnRH alone as a restart tool -- a potential application you referenced in your initial post.
I've finally decided to get off TRT. I started exogenous T to see if it could help with symptoms of PSSD (post-SSRI...disaster). After playing around with various esters, dosing, schedules, etc., I've concluded it's time to end this 2-year experiment. I feel worse than ever sexually; moreover, I've developed a slew of other symptoms (and even chronic illnesses) that I did not have prior to starting TRT.
I'm currently tapering down, per the recommendation of the doctor with whom I'm working. We agreed that it would be pointless to extend the taper into the "low T" territory, so I plan to cease injections when I hit a daily release of ~4mg test. After cessation, I expect it to take roughly two weeks to fully clear my body.
Onto the application of GnRH:
1) I seemingly "crashed" my estrogen and never recovered. I've been dealing with a huge number of "low E2" sides for the past year and a half. I now respond very poorly to anything that antagonizes estrogen or has AI properties; as such, I plan to avoid using SERMs are all cost.
2) I see that you tried GnRH in the absence of enclom, testing whether it would work without as much negative feedback at the hypothalamus and pituitary from estrogen and testosterone, respectively. It doesn't look like you had any numbers for this trial, as you experienced testicular pain.
I am thinking of trying something similar to this. From what I see online, it typically takes people 9-12 months, on average, to normalize their HPTA after long-term supression. Do you think that starting GnRH without enclomiphene would potentially work to "prime" my pituitary and testicles *before* coming off TRT totally (but while tapering down onto a very low dose, just prior to quitting)? I know there's no certainty here; it just depends whether the pituitary would signal with the current level of suppression from the exogenous hormones still in the blood. Given the very short half-life of GnRH, I see no drawbacks; it shouldn't cause suppression of the anterior pituitary even if it doesn't offer any additional benefit.
When I've finally cleared my body totally of TRT, I think it makes sense to run GnRH/gonadorelin in a pulsatile manner, as you've done, in order to accelerate the recovery of the HPTA. I understand that injecting GnRH bypasses the signaling of the hypothalamus. Do you see any risk in such a protocol?
As I see it:
It seems the hardest part of a restart is getting the pituitary and leydig cells to signal again, as both have become desensitized in the presence of very, very low levels of upstream hormones (GnRH, LHRH, LH). Following that logic, it seems to make sense to get these systems working, and the hypothalamus would follow. However, I do understand that the hypothalamus is mediated by negative feedback, so this could also raise hormone (although I doubt much, at least for a while) levels enough to slow that process down.
I know we don't have research to determine with any certainty what the best approach is; I'd just like to hear your thoughts regarding my current proposal.
I'm writing this from a very, very foggy brain. Apologies for any incoherence.
Thanks!
I'd like to hear your opinion regarding using GnRH alone as a restart tool -- a potential application you referenced in your initial post.
I've finally decided to get off TRT. I started exogenous T to see if it could help with symptoms of PSSD (post-SSRI...disaster). After playing around with various esters, dosing, schedules, etc., I've concluded it's time to end this 2-year experiment. I feel worse than ever sexually; moreover, I've developed a slew of other symptoms (and even chronic illnesses) that I did not have prior to starting TRT.
I'm currently tapering down, per the recommendation of the doctor with whom I'm working. We agreed that it would be pointless to extend the taper into the "low T" territory, so I plan to cease injections when I hit a daily release of ~4mg test. After cessation, I expect it to take roughly two weeks to fully clear my body.
Onto the application of GnRH:
1) I seemingly "crashed" my estrogen and never recovered. I've been dealing with a huge number of "low E2" sides for the past year and a half. I now respond very poorly to anything that antagonizes estrogen or has AI properties; as such, I plan to avoid using SERMs are all cost.
2) I see that you tried GnRH in the absence of enclom, testing whether it would work without as much negative feedback at the hypothalamus and pituitary from estrogen and testosterone, respectively. It doesn't look like you had any numbers for this trial, as you experienced testicular pain.
I am thinking of trying something similar to this. From what I see online, it typically takes people 9-12 months, on average, to normalize their HPTA after long-term supression. Do you think that starting GnRH without enclomiphene would potentially work to "prime" my pituitary and testicles *before* coming off TRT totally (but while tapering down onto a very low dose, just prior to quitting)? I know there's no certainty here; it just depends whether the pituitary would signal with the current level of suppression from the exogenous hormones still in the blood. Given the very short half-life of GnRH, I see no drawbacks; it shouldn't cause suppression of the anterior pituitary even if it doesn't offer any additional benefit.
When I've finally cleared my body totally of TRT, I think it makes sense to run GnRH/gonadorelin in a pulsatile manner, as you've done, in order to accelerate the recovery of the HPTA. I understand that injecting GnRH bypasses the signaling of the hypothalamus. Do you see any risk in such a protocol?
As I see it:
It seems the hardest part of a restart is getting the pituitary and leydig cells to signal again, as both have become desensitized in the presence of very, very low levels of upstream hormones (GnRH, LHRH, LH). Following that logic, it seems to make sense to get these systems working, and the hypothalamus would follow. However, I do understand that the hypothalamus is mediated by negative feedback, so this could also raise hormone (although I doubt much, at least for a while) levels enough to slow that process down.
I know we don't have research to determine with any certainty what the best approach is; I'd just like to hear your thoughts regarding my current proposal.
I'm writing this from a very, very foggy brain. Apologies for any incoherence.
Thanks!
JustPanicNoDisco
Member
By the way, is there ANY literature suggesting that GnRH/gonadorelin can be used as a substitute for hCG with respect to maintaining testicular function (while on TRT, ofc)? Maybe @readalot would know?
I know a lot of clinics chose to switch over, but I can't find any of the clinics citing research showing that this substitution actually works. As cataceous mentioned, it would seem unlikely to work with high hormone levels, unless one was to block E2's negative feedback at the pituitary with a SERM -- and even this is questionable
I know a lot of clinics chose to switch over, but I can't find any of the clinics citing research showing that this substitution actually works. As cataceous mentioned, it would seem unlikely to work with high hormone levels, unless one was to block E2's negative feedback at the pituitary with a SERM -- and even this is questionable
I did try again to forgo enclomiphene while lowering the TRT dose. This time there was not the testicular discomfort, but as I recall, gonadotropin production was basically lost and subjective results deteriorated.
Thus I'm not particularly optimistic about GnRH alone as a restart tool. It depends on how sensitive your pituitary is to negative feedback from estrogen. It should work when the exogenous testosterone is low enough—but if that puts you in hypogonadal territory then it's less helpful. I'd agree there's probably not much risk in trying it.
I hesitate to predict what would happen if GnRH is continued when TRT is completely stopped. I suppose it could be helpful in stimulating the pituitary in the interval before the hypothalamus fully reactivates. As I recall, the research involving administration of GnRH to normal individuals didn't reveal anything very bad happening, at least in the short run.
More as a thought experiment, I've proposed a full restart while on TRT. This includes taking a SERM, kisspeptin, GnRH and hCG. The idea is that you may be able to regain some functionality in each part of the HPTA before ending TRT. There is uncertainly about how long it would take for each element to restart, so it would be difficult to stagger the different drugs in an optimal manner. But presumably you'd still get results in time if you started everything simultaneously.
Do a search for our discussion of the Royal Medical Center results. They have posted lab work from quite a few patients showing that isolated and fairly large doses of GnRH produce robust LH in a lot of men on TRT. The protocol is something like 50-100 mcg twice a week. It's interesting work, but I haven't seen feedback on whether the subjective results make it worthwhile. I'm skeptical that it is comparable to using hCG. The assumption is that the guys only see a single LH pulse shortly after each GnRH injection. I don't think they stated how long guys needed to be on the protocol to see significant LH. A possible implication is that supraphysiological doses can overcome fairly significant negative feedback from estrogen. However, many of these guys were on AIs, so it's not entirely clear what's going on.
Gonadorelin vs hCG - Royal Medical Center
Our new replacement to hCG, Gonadorelin, works more effectively for patients. Gonadorelin will actually raise LH levels during testosterone therapy.
www.royalmedicalcenters.com
JustPanicNoDisco
Member
I appreciate the thoughtful response. Nine to twelve months to get to a baseline level of HPTA function just sounds absolutely brutal, but perhaps it's the way to go in my case, where so many systems are completely out of whack. Maybe throwing it into a tailspin and letting it re-calibrate itself naturally is required to get out of this mess.I did try again to forgo enclomiphene while lowering the TRT dose. This time there was not the testicular discomfort, but as I recall, gonadotropin production was basically lost and subjective results deteriorated.
Thus I'm not particularly optimistic about GnRH alone as a restart tool. It depends on how sensitive your pituitary is to negative feedback from estrogen. It should work when the exogenous testosterone is low enough—but if that puts you in hypogonadal territory then it's less helpful. I'd agree there's probably not much risk in trying it.
I hesitate to predict what would happen if GnRH is continued when TRT is completely stopped. I suppose it could be helpful in stimulating the pituitary in the interval before the hypothalamus fully reactivates. As I recall, the research involving administration of GnRH to normal individuals didn't reveal anything very bad happening, at least in the short run.
More as a thought experiment, I've proposed a full restart while on TRT. This includes taking a SERM, kisspeptin, GnRH and hCG. The idea is that you may be able to regain some functionality in each part of the HPTA before ending TRT. There is uncertainly about how long it would take for each element to restart, so it would be difficult to stagger the different drugs in an optimal manner. But presumably you'd still get results in time if you started everything simultaneously.
Do a search for our discussion of the Royal Medical Center results. They have posted lab work from quite a few patients showing that isolated and fairly large doses of GnRH produce robust LH in a lot of men on TRT. The protocol is something like 50-100 mcg twice a week. It's interesting work, but I haven't seen feedback on whether the subjective results make it worthwhile. I'm skeptical that it is comparable to using hCG. The assumption is that the guys only see a single LH pulse shortly after each GnRH injection. I don't think they stated how long guys needed to be on the protocol to see significant LH. A possible implication is that supraphysiological doses can overcome fairly significant negative feedback from estrogen. However, many of these guys were on AIs, so it's not entirely clear what's going on.
Gonadorelin vs hCG - Royal Medical Center
Our new replacement to hCG, Gonadorelin, works more effectively for patients. Gonadorelin will actually raise LH levels during testosterone therapy.
There is no certainty.
I know some people have used single high-dose shots of GH analogs, like triptorelin, for restarts. My body just appears to be in a very, very fragile state, and I fear blasting it with an extreme LH spike could have unforeseen -- and possibly dire -- consequences.
Rock and a hard place. I suppose I'm leaning toward the fully natural "recovery" at this point if GnRH likely won't confer much additional benefit in isolation and entails some level of risk.
Hyrulewarrior1978
Active Member
It took me four months to regain hpta function when I stopped to get my wife pregnant. I had been on it for three years at the time. Not sure where you’re getting this 9-12 month period from. I think most people recover within the first six months or so. If you’re using steroids that’s a different story.
JustPanicNoDisco
Member
The literature body on people who have experienced shutdown for a prolonged period (however, some of this is using GnRH analogues, as in the case of prostate cancer research).
It does seem most people, anecdotally, recover more quickly than 9-12 months, but often these people were just cycling steroids, not running TRT for a long period (in my case, 2 years). There are a lot of variables at work.
Did you undergo the restart? How did it go?
Just curious, would there be any harm in adding gonadorelin, along with hcg and trt for fertility? Im.using 1666 ius of hcg 3 times a week, coupled with 250 mgs a week of test cyp( down from 500 mgs a week). I'll be adding FSH soon, but in the meantime, I do have unused gonadorelin and will be taking a second semen analysis within the next few weeksI did try again to forgo enclomiphene while lowering the TRT dose. This time there was not the testicular discomfort, but as I recall, gonadotropin production was basically lost and subjective results deteriorated.
Thus I'm not particularly optimistic about GnRH alone as a restart tool. It depends on how sensitive your pituitary is to negative feedback from estrogen. It should work when the exogenous testosterone is low enough—but if that puts you in hypogonadal territory then it's less helpful. I'd agree there's probably not much risk in trying it.
I hesitate to predict what would happen if GnRH is continued when TRT is completely stopped. I suppose it could be helpful in stimulating the pituitary in the interval before the hypothalamus fully reactivates. As I recall, the research involving administration of GnRH to normal individuals didn't reveal anything very bad happening, at least in the short run.
More as a thought experiment, I've proposed a full restart while on TRT. This includes taking a SERM, kisspeptin, GnRH and hCG. The idea is that you may be able to regain some functionality in each part of the HPTA before ending TRT. There is uncertainly about how long it would take for each element to restart, so it would be difficult to stagger the different drugs in an optimal manner. But presumably you'd still get results in time if you started everything simultaneously.
Do a search for our discussion of the Royal Medical Center results. They have posted lab work from quite a few patients showing that isolated and fairly large doses of GnRH produce robust LH in a lot of men on TRT. The protocol is something like 50-100 mcg twice a week. It's interesting work, but I haven't seen feedback on whether the subjective results make it worthwhile. I'm skeptical that it is comparable to using hCG. The assumption is that the guys only see a single LH pulse shortly after each GnRH injection. I don't think they stated how long guys needed to be on the protocol to see significant LH. A possible implication is that supraphysiological doses can overcome fairly significant negative feedback from estrogen. However, many of these guys were on AIs, so it's not entirely clear what's going on.
Gonadorelin vs hCG - Royal Medical Center
Our new replacement to hCG, Gonadorelin, works more effectively for patients. Gonadorelin will actually raise LH levels during testosterone therapy.
Probably no harm, and maybe some benefits. But I doubt any involving fertility—unless you include a SERM such as enclomiphene. With your very large doses of testosterone and hCG you most likely have a lot of negative feedback from estradiol at the pituitary, which suppresses the production of the FSH that you want for fertility. Realistically it would be simpler for you to add FSH to your protocol, either directly or via hMG.
Thanks for the quick input. Gonna drop my test dose to 30 mgs twice a week from 50, keep hcg the same at 1666 ius 3 times a week and up my anastrozole a smidge as well. Do you have any suggestions for dosing of the gonadorelin? My next semen analysis with the fertility center is Monday. Then I'll be adding fsh once I have my numbers. After 3 months, we'll prolly opt for IVF if it dont happen naturally
With respect to gonadorelin stimulating the pituitary, anastrozole can in theory take the place of a SERM. Dosing may be more of a balancing act, and there is somewhat more risk due to the lack of selectivity. On the other hand, you're already taking the drug and high doses of hCG often lead to high estradiol production.
Gonadorelin should be taken as frequently as you can tolerate. Natural GnRH pulses are delivered every 1-3 hours. Apparently isolated large doses of 50-100 mcg can lead to isolated pulses of LH and FSH. But it is unclear what effect this has on fertility. Personally I take 20 mcg 5-6 times daily. Most would find this untenable. Intermediate dosing, e.g. 30-50 mcg once every day or two, is not well studied. You would be running your own experiment.
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